ECMO cart supplies (sample).
\r\n\tThis book will address the various modern, technical, and practical aspects of smart technology for capturing solar radiation and converting it into different forms of energy, as well as enabling it for renewables integration in energy generation and transformation, built environment, transportation, buildings, and agriculture.
\r\n\r\n\tThe book will cover the most recent developments, innovations and applications concerning the following topics:
\r\n\t• Solar radiation – Smart and enabling technologies for measurement, modelling, and forecasting
\r\n\tHigh-resolution measurement sensor and instrument technology (Pyranometers, Albedometers, Pyrheliometers, UV Radiometers, Sun Trackers, Spectroradiometer, Pyrgeometers, etc.), Artificial intelligence techniques for modelling and forecasting of solar radiation, Solar Irradiance forecast with satellite data, Solar potential analysis, Short-term forecasting of photovoltaic power and solar irradiance prediction with sky imagers.
\r\n\t• Renewable energy integration – Smart solutions for integration of RE in distributed generation, energy storage, and demand-side management.
\r\n\tIntegrated Photovoltaics: Smart technology for vehicle-integrated PV, Building Integrated PV, Agrivoltaics, Road-Integrated PV, Floating PV, Product-integrated PV.
\r\n\tRenewable Energy Applications in Built Environment and mobility: Solar cars, solar-powered electric charging stations, passive solar systems, solar heating, and cooling systems, building-integrated vegetation, multifunctional solar systems, solar pumps, solar lighting, solar shading, Natural lighting, Solar dryer, Greenhouse.
Extra-corporeal membrane oxygenation (ECMO) or extra-corporeal life support (ECLS) is quickly becoming a well-established form of therapy for patients presenting in severe respiratory failure and/or cardiogenic shock. The fundamentals of therapy, while technically challenging and involving a complex dynamic human-artificial circuit system, also requires a huge reliance on a multi-disciplinary team and an institutional infrastructure with robust administrative support at all levels to function effectively. While the medical and technical aspects of therapy are covered extensively in this text—and the others in this series [1, 2], a common fundamental question that is often asked is “how do we start and develop a program?” The development of an ECMO/ECLS program is far more complex than organizing a small group of interested providers and acquiring the hardware necessary for support—as such, the goal of this chapter is to outline those steps necessary to help establish a foundation for a successful institutional program.
\nAcute respiratory failure—regardless of the etiology—remains a complex and difficult problem to treat. Management focuses on treating the primary problem and allowing lung healing via lung protective ventilation strategies, while maintaining adequate oxygenation and ventilation [3]. Unfortunately, morbidity and mortality remain high in patients with severe lung injury, despite implementing standard lung protective strategies. Even for those patients who survive, quality of life can be severely impacted for many years after their initial illness [4]. Acute cardiac failure, or cardiogenic shock, also presents a difficult clinical problem for which even contemporary outcomes are less than ideal. While the most common cause of cardiogenic shock remains pump failure after an acute myocardial infarction, other mechanical problems such as acute papillary rupture (with acute mitral regurgitation), ventricular septal rupture, and myocarditis [5] must be considered [6]. While the use of ECMO for either acute respiratory failure or cardiogenic shock (or often a combination of both) is well-described, in part due to more comprehensive reviews of these topics elsewhere in this text, their incidence and challenges—regardless of the circumstances—serve as a foundation for why there is a substantial interest in developing and growing ECMO programs.
\nThere is growing evidence to support the role of ECMO in the management of these very difficult problems. ECMO has been shown to be an important tool in the armamentarium of any program that serves as a tertiary or referral center for complex cardio-pulmonary pathologies. In fact, excluding the survival benefit that has been demonstrated in patients who are supported with ECMO, there is also growing evidence to suggest that overall outcomes of patients with Adult Respiratory Distress Syndrome (ARDS) or cardiogenic shock treated at “ECMO Program Centers” are better regardless of whether they are treated with ECMO. In other words, the multi-disciplinary and administrative commitment to take care of patients (both adults and children) with complex and difficult cardiac and pulmonary problems can lead to improved outcomes independent of the actual use of ECMO [7, 8, 9, 10].
\nTwo randomized clinical trials in patients with severe ARDS support the implementation and increased utilization of ECMO therapy [11, 12]. These randomized trials—again, topics that will be discussed elsewhere in this text—despite their controversies, have demonstrated a clinical benefit of ECMO in the setting of ARDS. These well-conducted randomized trials, in addition to the extensive body of literature (case series, single center reports, and Extracorporeal Life Support Organization (ELSO) registry reviews—far too numerous to reference) combined with growing society guidelines and position papers, serve as a solid foundation of medical science to support the development of ECMO programs worldwide [13].
\nThe clinicians and administrators first determine the need and support for an ECMO program. This multidisciplinary group then operationalizes the care team that needs to be assembled and trained. The team includes clinical, administrative, ancillary, and other stakeholders, which are required to care for the patient and support the infrastructure, while moving the program to implementation.
\nPhysicians from Cardiothoracic Surgery, Pulmonary/Critical Care, and Cardiology form the foundation of physician support for veno-veno and veno-arterial ECMO patient identification, insertion, and management. In addition to the core physician team, there is a need to engage neurologists and infectious disease specialists to understand the therapy and the unique patient care challenges and complications associated with ECMO support. Vascular surgeons often will get involved with cannulation if others are not available or comfortable with placing large bore cannulas—likewise, there is a growing interest by general and trauma surgeons [14].
\nIn addition, the Palliative Care team must be involved from the very beginning of program’s development and some will advocate, especially in pediatric programs (while the focus of this chapter is on adult program development), Palliative Care providers are automatically involved and consulted on every ECMO case. As such, their understanding of the risks and benefits of ECMO are critical given the marginal outcomes associated with ECMO, even in the best of circumstances [15].
\nInclusion of emergency physicians in the team can assist with early identification of patients on presentation to the emergency room, and implementation of protocols in the emergency room for cardiogenic shock and respiratory failure [16].
\nAdministrators from the executive team should be engaged early to help support the creation of structures to accelerate implementation, project management, and assurance of adequate capital and personnel resources for a sustainable program. Financial models, which obviously vary from system (and country) to system, must be considered—and given the amount of resources required to establish and maintain an ECMO program, it is wise to have someone to monitor the financial implications.
\nRespiratory therapists assist with identifying possible candidates and work closely with the team ensuring the implementation of lung protective strategies. The growth of electronic medical records can allow for daily (if not more frequent) reports of those patients who might be considered for ECMO based upon ventilator settings and arterial blood case results.
\nPerfusionists must be engaged to help with setup, oversight of the ongoing treatment and for their skill sets in understanding the complexities of the machines and testing required.
\nFinally, there are implications for laboratory department around testing and blood bank needs; as well as coordinating and consulting with case management, ethics, and chaplains in regard to complex shared decision-making to implement, care for, and remove therapy; and the rehabilitation needs for patients post-ECMO removal.
\nIn addition to leadership described previously, executive nursing leadership, departmental nursing leadership, nursing advanced practice providers (APP), and frontline nursing engagement are fundamental and are essential to assure the success of the program. This includes communication, input and collaboration with policy, procedures and evidence-based protocols, education and competency training of high performing clinical staff, and provision of surveillance and care of patients. Frontline nursing from outside the ICU are often engaged in patient flow and early identification of decompensating acute care patients, who may need to be considered for ECLS. Since patients might require ECMO at any time, day or night, and given the amount of resources required to initiate and care for such patients, nursing administration must be involved to help develop protocols to organize “phone tree” lines of communication and specialized competent staff schedules to help recruit and arrange appropriate resources on very short notice.
\nAs the program grows beyond supporting the host hospital, it is necessary to engage Critical Care Transport to organize a system to transport patients from outside the facility with appropriate support and skill sets. This engagement is discussed more fully later in the chapter.
\nThe IT department can help with order set development and the Medical Staff office will need to support the development of privileging requirements to assure consistent skill sets for new team members.
\nEspecially in the situations with VA-ECMO use, long-term myocardial support may be needed. It is essential to build relationships with centers that can provide bridge to long-term LVAD support or transplant.
\nAdditionally, the marketing and public relations departments engage to help in creating materials to help outlying hospitals and physicians have awareness of the program, with knowledge of how to identify patients and when to transport to higher levels of care for consideration of ECMO support.
\nA rapid pace for implementation is best served by a strong triad leadership: experienced physician leaders and champions who are experts in ECMO; nursing leadership; and hospital executives. All need experience in change management and are given support and authority to use project tools and cross-functional influence to fast track project goals across a wide span of departments. These members then must communicate progress within the executive team.
\nFollowing Kotter’s change management theory, a small group of physicians, nursing leadership, and administrators gather to set a vision, determine the feasibility and challenges of the project, then create a shared project plan for the organization, structure, and timeline for implementation of the program [17]. The creation of a Gantt chart with key requirements and milestones is helpful in the early stages of program development—also useful in a sense of accomplishment and motivation of the team. Regular recurrent frequent meetings with agendas driven by a project management tool to assure progress is made on key deadlines, accountability to the individuals and team, and to create a shared message and plan for continued communication. Initial work should focus on best practice, research-based literature review, professional organization review of standards and data, then develop a gap analysis of clinical guidelines, equipment, skill sets, and organizational readiness. This small group should include Cardiothoracic surgeon(s), Pulmonologists, a “C” level executive, the cardiovascular service line, and Intensive Care nursing leadership. A small tactical group allows for more rapid progress through the initial stages and supports creation of a shared vision to accelerate momentum when the inevitable resistance to change surfaces—as well as working through team dynamics, comfort level, and building relationships. This group must strive to produce early wins, however small, to enable the organization to “feel the progress” as more difficult hurdles are faced. These can include shared clinical guidelines, order sets, and eventually patients that lived thanks to the program—as a true connect to purpose for all involved.
\nPutting screening guidelines in place and educating the teams on the benefits of ECMO to patients who would otherwise be terminal are very compelling when used in a story format.
\nFinally, change in management requires vigilance to newly implemented care processes, or the tendency of the organization will slide back to previous status quo. Tools and strategies that assist in holding on to new skills are most effectively done through audits, constructive timely feedback, continuous process improvement discussions, and accountability to the process. While education can assist in reminding staff of the “why”, it is not a sticky tool in terms of cementing new behaviors into a culture.
\nOnce the ECMO program is up and running, collaboration with the quality abstractionist and review of registry data at regular intervals generates quality improvement projects to assure new practice and clinical referral patterns producing the optimal outcomes. It is also a way of preventing politics and rumors from gaining momentum as the facts are reviewed and discussed in larger quality forums. These forums are ideally multi-disciplinary and followed up with tangible action items that have due dates and closed-loop communication back to the CQI team, as the action items are completed.
\nThe obvious hardware required for the program is the ECMO machine. The variables needed to make the correct choice for the program include need for portability of transport between facilities, as well as within the host organization, ease of use, skill sets of those responsible for managing the process, and the capital budget of the organization.
\nIn addition to the perfusion/ECMO machine, there is a need for a readily available stock of cannulas in various sizes, as well as for the variety of approaches that may need to be used. In addition, a well-stocked cart that allows the necessary equipment for sterile fields, cut-down, suturing, and possible complications of the cannulation procedures should be available to take to the patient’s location, as often the patient is not stable to transport to the OR for the procedure. As these are tools routinely used by perfusionists and cardiothoracic surgeons, they need to be engaged in selecting the appropriate sizes, manufacturers, connectors, introducers, wires and par levels. Many programs, as a function of the need to initiate ECMO therapy on short notice and in many different clinical areas, will create an “ECMO cart” which consist of all the key disposable equipment and tools needed to cannulate anywhere at any time (Table 1 and Figure 1).
\nSupplies | \nSize | \nRef # | \nQty | \n
---|---|---|---|
\n | \n | \n | |
Medtronic bio-medicus single stage venous | \n23Fr | \nCB96605-023 | \n×1 | \n
\n | 21Fr | \nCB96605-021 | \n×1 | \n
Medtronic bio-medicus multi-stage venous | \n25Fr | \n96880-025 | \n×1 | \n
\n | 21Fr | \n96880-021 | \n×1 | \n
Maquet avalon | \n31Fr | \n10031 | \n×1 | \n
\n | 27Fr | \n10027 | \n×1 | \n
Medtronic bio-medicus arterial | \n15Fr | \n96530-015 | \n×1 | \n
Medtronic bio-medicus nexgen arterial | \n17Fr | \n96570-117 | \n×1 | \n
\n | 19Fr | \n96570-119 | \n×1 | \n
\n | 21Fr | \n96570-121 | \n×1 | \n
\n | \n | \n | \n |
\n | \n | \n | |
Medtronic arterial introducer kit | \n\n | 96552 | \n×1 | \n
Medtronic venous introducter kit | \n\n | 96551 | \n×1 | \n
Lunderquist extra stiff | \n\n | G31453 | \n×1 | \n
Amplatz super stiff | \n\n | M0066401080 | \n×1 | \n
Sorrin dilator kit | \n\n | \n | ×1 | \n
4Fr micro puncture | \n\n | \n | ×4 | \n
4Fr introducer | \n\n | \n | ×1 | \n
6Fr introducer | \n\n | \n | ×2 | \n
8Fr Introducer | \n\n | \n | ×1 | \n
\n | \n | \n | \n |
\n | \n | \n | |
Basic pack | \n\n | \n | ×1 | \n
Angiography pack | \n\n | \n | ×1 | \n
\n | \n | \n | \n |
\n | \n | \n | |
Pledgets | \n\n | \n | \n |
2-0 Prolene SH | \n\n | \n | ×4 | \n
2-0 Prolene MH | \n\n | \n | ×4 | \n
3-0 Prolene SH | \n\n | \n | ×4 | \n
3-0 Prolene RB-1 | \n\n | \n | ×4 | \n
4-0 Prolene SH | \n\n | \n | ×12 | \n
4-0 Prolene RB-1 | \n\n | \n | ×12 | \n
4-0 Prolene large needle pledget | \n\n | \n | ×12 | \n
4-0 Prolene small needle pledget | \n\n | \n | ×12 | \n
5-0 Prolene C-1 | \n\n | \n | ×4 | \n
6-0 Prolene BV-1 | \n\n | \n | ×4 | \n
6-0 Prolene C-1 | \n\n | \n | ×4 | \n
7-0 Prolene BV-1 | \n\n | \n | ×4 | \n
#1 Sofsilk | \n\n | \n | ×6 | \n
0 Silk popoffs CT-1 | \n\n | \n | ×4 | \n
1 Vicryl CTX | \n\n | \n | ×2 | \n
0 Vicryl CTX | \n\n | \n | ×2 | \n
0 Vicryl CT-1 | \n\n | \n | ×2 | \n
2-0 Vicryl CT-1 | \n\n | \n | ×4 | \n
3-0 Vicryl SH | \n\n | \n | ×2 | \n
4-0 Vicryl PS-1 | \n\n | \n | ×2 | \n
4-0 Monocryl PS-2 | \n\n | \n | ×2 | \n
3-0 Ethibond SH | \n\n | \n | ×6 | \n
Heavy silk ties | \n\n | \n | ×4 | \n
2-0 Silk ties | \n\n | \n | ×4 | \n
3-0 Silk ties | \n\n | \n | ×4 | \n
4-0 Vicryl ties | \n\n | \n | ×4 | \n
2-0 Ethicon pacing wires | \n\n | \n | ×2 | \n
Orange pacing wires | \n\n | \n | ×4 | \n
Blue pacing wires | \n\n | \n | ×2 | \n
#6 Sternal wires | \n\n | \n | ×2 | \n
Double wires | \n\n | \n | ×2 | \n
\n | \n | \n | \n |
\n | \n | \n | |
Chloraprep | \n\n | \n | ×5 | \n
Duraprep | \n\n | \n | ×1 | \n
Alcohol bottles | \n\n | \n | ×2 | \n
PVP | \n\n | \n | ×2 | \n
CHG surgical scrub brush | \n\n | \n | ×5 | \n
\n | \n | \n | \n |
\n | \n | \n | |
#10 | \n\n | \n | ×10 | \n
#11 | \n\n | \n | ×10 | \n
#15 | \n\n | \n | ×10 | \n
Stryker sternal blade | \n\n | \n | ×4 | \n
Hall redo blade | \n\n | \n | ×2 | \n
\n | \n | \n | \n |
Umbilical tapes | \n\n | \n | ×8 | \n
Tourniquet 4 packs | \n\n | \n | ×6 | \n
Red vessel loops | \n\n | \n | ×2 | \n
White vessel loops | \n\n | \n | ×4 | \n
Shods 10 pack | \n\n | \n | ×2 | \n
Small yellow clip racks Qty 4 | \n\n | \n | ×5 | \n
Small red clip racks Qty 4 | \n\n | \n | ×5 | \n
Small automatic clip applier | \n\n | \n | ×1 | \n
Large automatic clip applier | \n\n | \n | ×1 | \n
\n | \n | \n | \n |
Asepto | \n\n | \n | ×2 | \n
Suction tubing | \n\n | \n | ×3 | \n
Cell Saver tubing | \n\n | \n | ×2 | \n
Yankauer tip | \n\n | \n | ×3 | \n
Poole tip | \n\n | \n | ×2 | \n
\n | \n | \n | \n |
Bovie pencil | \n\n | \n | ×2 | \n
Bovie pad | \n\n | \n | ×2 | \n
Long bovie tips | \n\n | \n | \n |
Short bovie tips | \n\n | \n | \n |
Eye cautery | \n\n | \n | ×2 | \n
\n | \n | \n | \n |
Snake clamp inserts | \n\n | \n | ×1 | \n
86 mm inserts | \n\n | \n | ×2 | \n
61 mm inserts | \n\n | \n | ×2 | \n
33 mm inserts | \n\n | \n | ×2 | \n
\n | \n | \n | \n |
\n | \n | \n | |
Bone wax | \n\n | \n | ×6 | \n
Felt 4×4 | \n\n | \n | ×1 | \n
Felt 6×6 | \n\n | \n | ×1 | \n
GelFoam | \n\n | \n | ×1 | \n
Fibrillar | \n\n | \n | ×5 | \n
Snow | \n\n | \n | ×2 | \n
Nu-Knit | \n\n | \n | ×1 | \n
\n | \n | \n | \n |
Laps | \n\n | \n | ×9 | \n
Baby laps | \n\n | \n | ×5 | \n
Raytec | \n\n | \n | ×5 | \n
\n | \n | \n | \n |
Gowns | \n\n | \n | ×7 | \n
Towel packs | \n\n | \n | ×4 | \n
Gloves | \n\n | \n | \n |
\n | \n | \n | \n |
\n | \n | \n | |
Split sheets | \n\n | \n | ×2 | \n
3/4 Sheets | \n\n | \n | ×6 | \n
Bi-Lat split sheet | \n\n | \n | ×1 | \n
Cardiac drape | \n\n | \n | ×1 | \n
\n | \n | \n | \n |
Tegaderms | \n\n | \n | \n |
4×4s | \n\n | \n | ×5 | \n
Esmark | \n\n | \n | ×1 | \n
Prineo | \n\n | \n | ×1 | \n
Stapler | \n\n | \n | ×1 | \n
Dermabond mini | \n\n | \n | ×5 | \n
Hollister horizontal tube attachment device | \n\n | \n | ×2 | \n
\n | \n | \n | \n |
18 Ga Hypo | \n\n | \n | ×4 | \n
Hep/blunt tip hypo | \n\n | \n | ×4 | \n
60 cc syringe | \n\n | \n | ×2 | \n
20 cc syringe | \n\n | \n | ×2 | \n
10 cc syringe | \n\n | \n | ×2 | \n
5 cc syringe | \n\n | \n | ×2 | \n
\n | \n | \n | \n |
Defib pads | \n\n | \n | ×1 | \n
Pacing cables | \n\n | \n | ×2 | \n
Decanters | \n\n | \n | ×2 | \n
Plasmalyte 1 L | \n\n | \n | ×2 | \n
ECMO cart supplies (sample).
(a and b): Portable ECMO cart that contains all the disposable tools needed for initiating therapy.
The ECMO team skill set crosses a variety of normal reporting structures within the hospital, as well as contracted services used in hospitals, including surgical services, nursing, laboratory, perfusion, physicians—employed and independent. Hence, thought must be placed into creating a strong team-based culture among a group of individuals who may have primary team affiliation across multiple departments.
\nThe use of multidisciplinary teams to develop project goals can serve as the first team building structure. Recognition of the team publicly can serve to bond the team more closely, and debriefings can prevent “silo formation” as individuals must often integrate in and out of the ECMO team due to patient volume and clinical needs. To cement this sense of team, the leaders of the departments that support the ECMO program should have regular meetings to discuss issues that arise, including productivity and interpersonal issues. Finally, the executive champion of the program should assure that there is accountability from all parties to the success of the program through goals and metrics, periodic meetings of the entire group of stakeholders, and shared public recognition of the successes of the program.
\nEarly in the development of any ECMO program, there must be a strategy for establishing “who watches what”—specifically, while nursing will always have bedside management of the patient, there must be consideration given as who has dedicated responsibility for the ECMO pump and circuit. As with any technology or “machine” that is directly connected to a patient—and provides critical life-saving support—there must be institutional guidelines and protocols regarding who monitors the functional status of the pump and circuit assuring safe and continuous functionality. In addition, the specific roles and responsibilities of this individual also need to be clearly defined. Various staffing models exist as described below.
\nPerfusionist is ideal bedside ECMO care providers, while initiating an ECMO program. Their advantages are considerable experiences in managing patients requiring extra-corporeal support as a function of their primary job responsibilities in the operating room supporting cardiac surgery procedures. Their training, credentialing, and licensure will often include formal experiences in managing patients requiring short-term mechanical circulatory support, including ECMO, outside of the operating room environment. A perfusionist-based model is appealing, however there are resource and financial limitations of this model. Perfusionists are usually limited in number (especially if they are also supporting an active clinical cardiothoracic surgical program) and their perspective is from a different care model which is focused around staffing limited time intervals in the operating room rather than 24/7 ICU-based ECMO care management. They are also an expensive resource for 24/7 daily ECMO use in the ICU. Given their availability and cost (and depending on how a program “employs” perfusionists—salary, per diem, hourly, contract employees, etc.), other care models are preferred for providing bedside ECMO support, particularly for veno-veno ECMO patients.
\nRN/RT ECMO specialist staffing models are becoming widely accepted and utilized in programs nationally—these programs and the combination structure of RT and RN staffing pools are mainly volume dependent to maintain competence. RNs have many advantages with regards to their inherent familiarity with the complexities and challenges in managing sick patients who require various life-support therapies. For example, in many programs, nurses manage renal replacement therapy technologies, wean and manage ventilators directly, and even have ownership in the management of both short- and long-term cardiac/ventricular support therapies. An additional advantage is, as a function such nurses are often extremely experienced in the management and assessment of critically-ill patients, they can serve as a valuable resource in other areas of immediate patient care—and potentially with volume and competence that become a primary care model for the more stable ECMO patient. Although respiratory therapists (RT) often have extensive experience in the management—and independent assessment—of patients requiring mechanical ventilatory support, it has only been relatively recently that their experiences and training in pulmonary mechanics and respiratory physiology, have they as a profession, been engaged as ECMO specialists. In theory, since most busy intensive care units are often staffed with a high volume of RNs and RTs, who are clinically high performing and engaged, the addition of monitoring ECMO pumps and circuits might not require a substantial investment in human resources and expanding staffing models. As such, using RNs and RTs might be viewed as being potentially less expensive—it is important to recognize that prior to using this human resource to monitor ECMO patients, a substantial investment in extensive ongoing education and training to maintain competence is needed. There are many courses offered by large ECMO programs, professional societies, and ELSO (see below) that can assist in the training of bedside ECMO specialists. Significant advantages in the ECMO specialist staffing model, already described as financially fiscal, also include continuity of nursing-based care provided by hospital staff who have an investment in the organization and unit, as well as the patients they serve.
\nAnother attractive option is a combination of various specialists—often as a function of the acuity of the patient and the needs of the program at any given time. Such a model takes advantage of the strengths of each type of healthcare professional. Even though such models can be difficult to implement as protocols defining individual roles and when and how handoffs can occur, nevertheless, with a strong collaborative team, a hybrid model can be successful. For example, for “routine” (if such exists) veno-veno cases of isolated respiratory failure in an otherwise hemodynamically stable patient, a perfusionist might help initiate therapy, provide the first 24 hours of support, and once the patient is deemed stable on ECMO, care is handed off to a RT or RN ECMO specialist. On-call perfusion support for technical questions and issues can then be easily provided from home and might not require immediate bedside support. Veno-arterial cases, especially in post-cardiotomy patients, might be more complex, and therefore might require more direct involvement of perfusionists given their experiences of managing such patients in the operating room. The challenge in a hybrid model is to determine either objectively or subjectively—the clinical parameters that would allow for an appropriate hand-off between one type (or level) of provider to another (i.e. perfusionist to RN/RT ECMO Specialist).
\nRegardless of the care model provided, there must be collaboration between the team members to build evidence-based standardized protocols, as well as strong physician buy-in in terms of supporting the individuals who manage the patient and pump at the bedside. Availability for immediate communication, using current technology, should be established between the ECMO specialist and/or perfusionist and the in-house physician. In addition, a strong and collaborative relationship between the ECMO specialist, perfusionist, and the bedside nurse must exist. Everyone must work together—inter-personality or professional conflicts cannot be tolerated and only get in the way of safe and effective patient care. Strong provider leadership, such as a perfusionist team leader, can be extremely effective in helping mentor other providers and serving as a resource for some of the day to day challenges in the management of an ECMO pump and circuit that might involve various disciplines, each of which have various levels of training and experiences.
\nIn addition, while current ECMO pumps and circuits are much more reliable than previous technologies, they will often have more advanced monitoring options. Each specialist involved in the care of the patient must have extensive training and a sound understanding of the functionality and troubleshooting of the entire circuit. Simulation training, as discussed in other chapters, plays a critical role in education and maintaining proficiency and, therefore, should be a key component—when feasible—of every ECMO program.
\nIn a multiple hospital system of care, there is not generally a need for more than one ECMO center for the system to accommodate the needs for non-CT surgery-related ECMO support. A helpful resource to assure patients have rapid transfer to the ECMO program from other hospitals, it is useful to set up a access center process to assure a standardized approach to hand-offs, transport, and tracking of patient movement. Call system personnel trained in the indications for ECMO can assist critical access and other facilities in routing possible ECMO patients for evaluation at the Center of Excellence. Early coordination with the call center leadership will allow them time to develop protocols, education, and coordination with transport services to assure smooth operations when the first patient call is received (Figure 2).
\nPatient access/call center flow.
A question that is often asked early in the development of any ECMO program is “where the patients should be cannulated?” While each institution must identify the ideal location for ideal cases, it is critical to recognize the nature of ECMO often dictates therapy must be able to be initiated anywhere within the hospital, including, but not limited to the following locations:
Emergency department
Operating rooms (cardiac and non-cardiac)
Catheterization labs
Obstetric labor and delivery suites
Intensive care units (medical, cardiac, surgical, neuro, etc.)
In fact, depending on the resources available and the resilience of the team, some centers will often consider initiating therapy in unusual out-of-hospital locations with the extreme example being the recent initiation of ECMO in the Louvre Museum in Paris, France [18].
\nPrior to considering the ideal location for initiating therapy, it is critical to outline those technologies that might be required. As discussed above, while it is important to have an “ECMO Cart” that contains, in a single location, all the key disposables that might be required, there might be a need for less portable equipment. For example, for cannulation, physicians might need immediate access to fluoroscopy and/or transesophageal echocardiography. Such technology might only be readily available in an operating room or catheterization lab. As many operating rooms, especially major trauma centers, and cardiac catheterization laboratories that support STEMI programs will often have access to advanced imaging, the exact ideal location often is dictated not only by physician preference, but also by potential administrative considerations. Such administrative considerations include the availability of a team to support cannulation, how disruptive emergency ECMO cases would be to the scheduling and allocation of OR/Cath lab resources, and often “how comfortable” the team is with the procedures. For example, Cath lab teams who are more comfortable with the catheter and wire-base procedures than surgical team might be a better option for peripheral cannulation of ECMO (arterial and venous)—while operating room teams might be better skilled at assisting with central cannulation (especially if the chest is already open). Nevertheless, a core “ECMO team” of providers beyond physicians and perfusions must be identified and included in all communications so that therapy can be initiated efficiently and safely anywhere needed.
\nOrder sets provide a rapid, standardized, initiation for ECMO. The order set should include guidance for the perfusion team and nursing team to appropriately care for the patient in a variety of settings, as well as give parameters for physician notification to address changes in patient status quickly.
\nOrder set elements should include:
Instructions for ECMO machine priming
ECMO circuit settings
ECMO daily parameters
Instructions for the perfusionist/nurse in charge of the machine
Instructions to leave all catheters in if not functioning and notify physician
Ventilatory settings
Blood products and transfusion parameters
Massive transfusion protocol parameters
Post-cannulation radiology studies
AP abdomen post-cannulation
AP chest post-cannulation
Radiology ◦studies
Echocardiogram for symptoms
Daily and routine laboratory studies
Anticoagulation and associated laboratory monitoring and adjustments
Triggers for notification of the ECMO physician/nurse practitioner
Other
Nursing care
Sedation medications
Physical therapy
Occupational therapy
Case management
Routine ICU parameters
Critically ill patients requiring ECMO can be transported by ground, helicopter, and fixed wing aircraft. Considerations in choice of transport include distance, number of team members required, equipment, electrical and oxygen needs, and cost. Ideally, patients can be identified and transported prior to initiation of ECMO therapy, however there are models of care with good results in which the team goes to the patient and initiates ECMO, and then the patient is transported to the ECMO center.
\nPer the 2015 ELSO guidelines, team members will vary depending on the need to cannulate the patient [19]. An ECMO specialist physician is required in either case, as is an ECMO specialist and a transport RN/RT. If cannulation is required, and the ECMO specialist physician is unable to perform this, there may be the need to add a cannulating physician and a surgical assistant to the team. Each team member has specific roles that should be delineated and understood prior to deployment to the outlying facility.
\nA checklist, should include all the needed equipment for the return trip with the patient, and should be verified prior to departure.
\nThe equipment recommended by ELSO includes [20]:
Suitable blood pump, centrifugal, or roller
Membrane oxygenator, appropriate for the patient size
Device(s) for heating and regulating circuit blood temperature (less critical for adult transports)
Medical gas tanks, regulators, hoses, connectors, flow meters, and blenders for provision and adjustment of blended sweep gas to the oxygenator
Venous and arterial pressure monitoring device(s), according to center-specific practices
Point-of-care anticoagulation monitoring equipment (e.g., activated clotting time)
Emergency pump or manual control mechanism in the event of primary pump failure or power failure
Uninterruptible power source(s) capable of meeting the electrical power needs of all equipment during transfer between vehicles and in the event of vehicle power source failure.
Portable ultrasound machine, if not provided by the referring facility
Additional equipment recommended by 2015 ELSO to improve safety includes:
System for servo-regulation of flow to balance venous drainage rate from the patient and blood return to the patient
Blood flow rate monitor (may be internal or external to the blood circuit)
Monitor(s) for circuit blood temperature, blood gas, oxygen saturation, and hemoglobin (may be internal or external to the blood circuit)
Capacitance “bladder” incorporated into the circuit
Bubble detector with or without automatic pump regulation function
Of note, the requirements for voltage, current, and power for all equipment should be verified for the transport vehicle prior to departure and monitored throughout transport. An adequate oxygen source must also be available with sufficient reserve to support high-flow 100% oxygen delivery for the duration of the transport. Provisions must be made to adequately secure the equipment during transport—brackets, holders, straps, etc. should be tested prior to first-time transport and should be compliance with appropriate regulatory guidelines (i.e., Federal Aviation Administration for the United States) (Table 2).
\nMethod of transport | \nAdvantages | \nDisadvantages | \nDistance for transport | \n
---|---|---|---|
Ground | \n\n
| \n\n
| \nUp to 300 miles | \n
Helicopter | \n\n
| \n\n
| \nUp to 450 miles | \n
Fixed wing | \n\n
| \n\n
| \nUnlimited | \n
Decision-making for ECMO transport options.
No patient should be transported without a means of manually providing circuit flow in the event of an electrical pump failure or malfunction.
\nAs with all areas of medicine, the optimization of patient outcomes must be a priority. This concept is especially important in the context of developing and maintaining an ECMO/ECLS program. Many other disease therapies have an infrastructure for monitoring clinical outcomes and benchmarking them against peer groups, national, and even international programs. These infrastructures typically are in the form of voluntary registries and databases (although some might argue that participation is becoming less and less voluntary and more and more a requirement—especially are payor sources are starting link payments to participation and eventually outcomes in such programs). Examples of these types of programs include the Society for Thoracic Surgeons (STS) Outcomes database (https://www.sts.org/registries-research-center/sts-national-database) and the American College of Cardiology National Cardiovascular Data Registry (ACC NCDR: https://cvquality.acc.org/NCDR-Home). Both organizations also for submission of patient characteristic data, comorbidities, therapies performed, and outcomes with the goal of providing program (and sometimes provider) specific outcome data—often risk adjusted, therapy specific, and benchmarked against other programs with provided summaries that can allow for continuous quality improvement initiatives.
\nCurrently, the Extracorporeal Life Support Organization (ELSO) provides a mechanism for tracking and benchmarking outcomes for ECMO programs (https://www.elso.org/Home.aspx). The organization was founded in 1989 and is headquartered in Ann Arbor, Michigan, USA. While the organization serves many roles to assist ECMO providers and programs—voluntary membership allows for the submission of clinical program outcome data and in return, summary data are provided. The organization also provides access to clinical guidelines, discussion forums, announcements for relevant meetings, links to key publications and references, and overall serves as a hub for ECMO/ECLS-related activities. Membership is strongly encouraged and the organization claims international membership and helps coordinate worldwide activities.
\nIn addition to submitting clinical patient and outcome data for benchmarking to ELSO, programs should also establish a formal case presentation and review process. Much like traditional surgical “morbidity and mortality” reviews, given the high-acuity and resource intensive nature of ECMO, similar periodic reviews of institutional ECMO outcomes should also be reviewed. While the focus should not be in individual practices or decision-making, ideally, each case should be reviewed by the team in a non-judgmental fashion to explore for potential areas of opportunity. Likewise, while good outcomes should be discussion in the context of “what went right”—such cases should also serve as team learning opportunity for growth and improvement. Depending on the number of cases performed, such meetings should be held in a timely manner (monthly, quarterly, etc.) so that real-time assessments can be performed and the nuances of each case might still be relatively fresh in the minds of the providers. While the structure of such meetings can be variable, many “quality” meetings typically will only involve key stakeholders—both providers (i.e. physicians, ECMO specialists, perfusionists, etc.) and appropriate administrators. The benefit of having meetings limited is that there is then the opportunity for open, honest, and transparent conversations—either on a case-by-case basis or from a programmatic standpoint—in a manner that can and should be protected from legal disclosure under the umbrella of a formal peer-review or quality improvement initiative. Appropriate protections of patient data and provider involvement must be maintained and established from the onset.
\nLikewise, summary data of program outcomes—such as the number of cases, types of cases, and overall outcomes should be actively tracked in real-time and made available to institutional leadership as a gauge of program growth and success. Institutional leadership/administration should also be able to provide financial data as profit/loss margins must be tracked in the context of program growth and success. Additional benchmarking information should also be considered and tracked in real-time to help monitor the evolution of a program—and should include, but not necessarily be limited to:
\n(1) Patient demographics (i.e., age, gender, and major comorbidities)
\n(2) Primary indications for support and etiologies of respiratory failure and/or cardiogenic shock
\n(3) Type of support (VV, VA, eCPR, and cannulation)
\n(4) Duration of support
\n(5) Blood and blood product utilization
\n(6) Outcomes
Successful weaning from support
Death on support
Death despite successful weaning
Major factors contributing to patient death (i.e., multi-organ failure, neurologic, etc.)
Such summary data should be in addition to the extensive amount of clinical and circuit data that is collected and tracked in the ELSO registry (see above).
\nAs discussed above, the tracking of outcome data should be a key component to helping measure program growth and success. Such initiatives must be established from the onset and involve the program champions—both clinical and administrative leaders to be successful. While it is important to review cases in the context of tracking outcomes—both good and bad—from a programmatic standpoint, it is also important to examine outcome summary data with the focus of exploring potential opportunity for improvement. It should be a primary objective of the ECMO team to consider periodic continuous quality improvement (CQI) activities. The activities should be viewed as opportunities to review best practices, current literature on various topics, and metrics with the focused goal of improving outcome metrics—while the primary focus should always be on improving patient survival, other metrics, program practices, and guidelines should also be considered as topics for review. Key topics can be identified, champions identified, and a timeline established for review and the development of potential action plans. While the specific details of how to develop and implement CQI is out of the scope of this topic—it does emphasize the importance of engaged administrative leadership individuals and team who have established experiences with these programmatic and institutional activities. By no means, comprehensive, various CQI topics are listed in Table 3.
\nTopics for review | \nPotential desired outcome | \n
---|---|
Anticoagulation protocol | \nReduction in bleeding and bleeding related complication. Reduction in blood product utilization | \n
Antibiotic utilization | \nIntegration in an antibiotic stewardship program Reduction in multi-drug resistant infections Reduction in opportunistic infections | \n
Time from admission/intubation to initiation of ECMO support | \nPotential impact on improving weaning and survival outcomes | \n
Mortality despite successful weaning from ECMO | \nImproving overall outcomes and survival to discharge. | \n
Medication utilization | \nOpportunities for potential cost savings | \n
Family/patient satisfaction scores | \nOpportunities to improve communication with families, Improved satisfaction metrics | \n
Suggested topics for continuous quality initiatives.
Once the complex set of internal processes, personnel, and patient care skills are established, the ECMO program has the potential to serve patients in a wide area around the ECMO center. To assure that other hospitals and emergency facilities have the information to know of the resources available, and when to engage them, the primary facility should engage a multi-pronged approach to raise awareness and clinical decision-making skills of potential patient care partners. As with all endeavors, this should be done in the WIIFM (What’s In It For Me) with the patient and practitioner at the outlying facilities interests’ in mind. A good place to begin this is to address the benefits to the patient, the current science that supports the need for ECMO, the parameters for consideration of ECMO support, the process to easily move the patient, and the resources to enhance education of the topic. This is accomplished by marketing informational materials, individual outreach to create awareness, an education program that includes lectures, publication of successes, a plan for follow-up communication to the referring institution to help them understand the results of their referrals, and finally, by creating branding that helps the referral sources easily retain a connection to the program.
\nMarketing materials should ideally be created to reflect the ECMO program as a larger system of care around ARDS and shock. In addition to the organization housing the ECMO program, clear guidance on referral processes (see Call Center Section), there should also be some succinct explanation of the use of VV and VA ECMO, parameters for initiation of referral, as well as references to studies supporting the decision. Consideration should be given to having two sets of guidance; one for critical access lower acuity facilities/ER’s and one geared toward facilities with ICU care directed by intensivists, as the threshold for referral will be different.
\nThe personal touch of a visit cannot be underestimated when establishing trusted referral center status for complex procedures such as ECMO. It affords a chance to create personal trust, as well as allowing answers to questions are procedures and processes for transfer, and expectations for communication regarding patient status from the ECMO center. The outreach should be well versed on all of these processes, as well as having the ability to provide physician to physician conversations to answer any outstanding issues.
\nEducation is a valued commodity for referring physicians and clinicians when learning a new resource for their patients. The education can include multiple formats to meet the needs of the audience including lectures, educational brochures, webcasts, publications regarding outcomes and patient stories, and conferences at the ECMO center on topics related to ECMO such as current ARDS and shock therapies.
\nWhile clearly an avenue to enhance education, follow-up communication is also an important tool to create the interpersonal relationship that develops trust between the organizations. It is very important for referring provider to learn the “end of the story” regarding patients that were sent for therapy. In addition, this provides a transition of care so that appropriate ongoing care can be provided to the patient in their home medical community. This also establishes that trust of the referring providers that patients sent for a specific therapy will be sent back to the home community for the care that can be provided in that setting.
\nAs the use of ECMO increases, the need to create a memorable brand for the program becomes a key component to establishing the reputation of the ECMO center that is distinguishable from other future programs. The program should ideally be branded as a part of the larger cardiothoracic-vascular/pulmonary/critical care program of the institution. This allows the halo of the organization’s programs to create synergistic enhancement quality outcomes and growth opportunities.
\nThe initiation of an ECMO program is a comprehensive multidisciplinary project, which must be based on the clinical needs of the patients served. It requires advanced clinical capabilities and decision-making, and clear pathways for patient care to make it high quality and financially sustainable. As such, strong leadership is needed from physician leaders, nursing leaders, and administrative leaders working in a triad professional leadership model.
\nOnce the clinical case for implementation is made, a multidisciplinary team should be identified, and given the ability to work across multiple departments and stakeholders to assure all quality and operational details are aligned and accomplished. The team is encouraged to work using change management format and techniques supported with strong project guidelines to assure that the internal and external resources needed to support ECMO care are identified, captured as project goals, and systematically completed prior to initiation of ECMO patient care. Use of tools such as order sets, access center protocols, and education tools support clinical standardization across the team, and provides a consistency of clinical care.
\nQuality metrics are identified at project initiation and can be supported by ELSO tools allowing comparisons across programs internationally. The commitment to high quality and a relentless curiosity to find improvements that can be made, are critical to provide best practices to this high acuity population. The data and outcomes collected can help educate and encourage referrals from other programs that do not have ECMO capabilities, thus providing added advanced patient care options on regional basis.
\nThe literature has previously benchmarked an 18 month ramp up to program initiation as rapid deployment. Using the tools provided by others in the literature, a strong triad leadership process, and a dedicated multidisciplinary team with strong project management support, it is possible to accomplish program initiation in a six-month period in a hospital with an established CV Surgical program. We believe this process is replicable, and provides tools and implementation models that can be used by other hospitals to add needed ECMO support to meet their community needs [8, 9, 10].
\nOver the centuries, humans have depended on nature for their essential needs of food supplies, shelters, apparel, transport means, fertilizers, flavors and fragrances, and the last not but least, medicines. Sophisticated traditional medicine systems have been generated by the plants over thousands of years. Moreover, plants maintain the significant sources of modern remedies for humanity. Additionally, according to WHO, 80% of the world’s population—primarily those of developing countries rely on plant-derived medicines for their healthcare [1]. People continue to consider nature as a source of potential chemotherapeutic agents. Over 50% of clinical drugs all over the world are the product of natural plants and their derivatives. While more than 25% of the total are extracted from higher plants [2].
History of pharmacy was for centuries identical with the history of pharmacognosy, or study of materia medica, which were obtained from natural sources—mostly plants but minerals, animals, and fungi. Chirality is one of the universal phenomena in nature. For instance, chiral biomolecules such as amino acids, sugars, proteins and nucleic acids have created living organisms. In natural surroundings, these biomolecules are present in one of the two possible enantiomeric forms, e.g., amino acids in the L-form and sugars in the D-form. Living organisms show variation in biological responses to one of a couple of enantiomers in medicines due to the chirality [3].
A range of chemicals that accurate enzymatic metamorphosis defines stereochemical configurations. Consequently, there is a certain chirality in most organic compounds in nature. It is important to emphasize that some phytochemicals exist in only one enantiomeric form, while others the optical rotation of the metabolite can be different [4].
Alkaloids are cyclic organic compounds that contain nitrogen in a negative oxidation state. They are generally distributed in flora and are an essential role in plant protection, sprouting and stimulating plant growth. Alkaloids-containing plants are often used as traditional medicines and these compounds usually have marked pharmacological activity [5]. Over 21,000 alkaloids have been identified, which thus constitute the largest group among the nitrogen-containing secondary metabolites [6]. Alkaloids are significantly pharmaceutical, e.g. morphine as pain relief medicines, codeine as an antitussive in cough medicines, colchicine in the treatment of gout and familial Mediterranean fever (FMF), Quinine as an anti-malarial and a muscle relaxant, Quinidine, as an antiarrhythmic agent to prevent ventricular arrhythmias and L-hyoscyamine (in the form of its racemic mixture known as atropine) as antimuscarinic; i.e., as an antagonist of muscarinic acetylcholine receptors [7].
The first isolations of alkaloids in the nineteenth-century new investigation into medicine of several alkaloid-containing drugs and were accidental with the advent of the separation process for the extraction of drugs. In 1803, the French apothecary Derosne probably isolated narcotine. Several years later, the Hanoverian apothecary Sertürner further investigated opium (1806) and isolated morphine (1816) [7].
Based on their structures, alkaloids are divided into several subgroups: non-heterocyclic alkaloids and heterocyclic alkaloids, which are again divided into 7 major groups according to their basic ring structure [8]. Families reported to be rich in alkaloids are: Liliaceae, Amaryllidaceae, Apocynaceae, Berberidaceae, Leguminosae, Papaveraceae, Ranunculaceae, Rubiaceae and Solanaceae [9]. Most of alkaloids are chiral compounds and are clinically administered as the racemic mixture, although its enantiomers have been shown to exert different pharmacological activity.
Phenylethylamine alkaloids in medicinal herbs (i.e. Citrus species and
In the case of C. urantium alkaloids, synephrine has also effect on human metabolism that could help to reduce fat mass in obese people, since it stimulates lipolysis, raises the metabolic rate and promotes the oxidation of fat through increased thermogenesis [14]. Synephrine is a chiral compound and is clinically administered as the racemic mixture, although its enantiomers have been illustrated to apply different pharmacological activity on α- and β-adrenoreceptors. Particularly, (R)-(−)-synephrine is from 1 to 2 orders of magnitude more active than its (S)-(+)-counterpart (Figure 1) [15].
Molecular structure of synephrine and ephedrine alkaloids (*chiral center).
Solanaceae contain mainly tropane alkaloids such as atropine, anisodamine and scopolamine; these plants are extensively used both in traditional medicine and as sources for the extraction of the pharmacologically important (parasympatolytic and anti-cholinergic) alkaloids [10]. Atropine is existed in racemic mixture of (S)-hyoscyamine and (R)-hyoscyamine. (S)-hyoscyamine is original in plants and (R)-hyoscyamine forms under alkaline conditions. (S)-hyoscyamine functions competitive antagonist of muscarinic receptors, thereby inhibiting the parasympathetic activities of acetylcholine on the salivary and sweat glands, as well as gastrointestinal tract, while the (R)-hyoscyamine is mostly inactive. Atropine, which is more often applied than (S)-hyoscyamine, exhibits approximately half of the pharmacological activity of (S)-hyoscyamine. In reverse, Scopolamine is mostly applied as pure enantiomer, e.g. (S)-scopolamine bromide [16].
Anisodamine, a tropane alkaloid isolated from Solanaceae family (Scopolia tangutica Maxim.). In China for decades, Anisodamine is an effective cholinoceptor antagonist and has been used as a spasmolytic drug to effect on smooth muscle by feature of its weaker side effect on the central nervous system than atropine. This kind of alkaloids have biological characteristic including cholinoceptor agonists and antagonists, like most chiral drugs, depend strongly on their stereochemistry. The effectiveness differences among four isomers of anisodamine racemic on muscarinic receptors have been perceived (Figure 2) [17].
Molecular structure of (S)-hyoscyamine, (S)-scopolamine, and anisodamine.
Aconitum plants (Ranuncolaceae) are generally distributed across Asia and North America. In the Chinese Pharmacopeia, two species of them, A. carmichaeli Dexb. and A. kusnezoffiiare were listed. Aconitine and the congener mesaconitine and hypaconitine (Figure 3) are the important diester-diterpene alkaloids of aconitum plants. Although they have toxic effects on human health, they can also be used at low doses because their pharmacological effects such as anti-inflammatory and anti-pain are effectively [10].
Molecular structure of aconitine, mesaconitine and hypaconitine.
In the legume alkaloids, the largest single group is quinolizidine alkaloids. In distribution to species in the more primitive tribes of the Papilionoideae, they appear to be restricted. Because of their toxicity in humans and animals as components of poisonous plants, these compounds become important. In contrast, some of them are potentially useful in pharmacological activities [18]. Radix sophorae flavescentis (
Molecular structures of four quinolizidine alkaloids.
Bis-benzylisoquinoline alkaloids have fascinated by the significant pharmacological impacts; especially, protoberberines are a structural class of organic cations (quaternary ammonium alkaloids) mostly distributed in Ranuncolaceae (e.g., Rhizoma coptidis), Berberidaceae (e.g. Cortex berberdis), Papaveraceae (e.g. Herba chelidoni) and Rutaceae (e.g. Cortex phellodendri) [10]. The most considered chiral isoquinoline alkaloids are tetrahydroprotoberberine backbone structure such as tetrahydropalmatine (THP), tetrahydroberberine (THB), and corydaline [21]. (DL)-THP and (DL)-THB are highly abundant in C. yanhusuo and a variety of Corydalis plants. (L)-THP can also be isolated from Stephania plants [22]. Tetrahydropalmatine is one of the active ingredients isolated from Rhizoma Corydalis (yanhusuo), a traditional Chinese medicine that has been used for the treatment of chest pain, epigastric pain, dysmenorrhea, traumatic swelling, and pain for thousands of years [23]. The analgesic activity of (−)-THP is much higher than that of (+)-THP. Clinically, THP is used as the racemic mixture (Figure 5) [22].
Molecular structures of the enantiomers of tetrahydropalmatine (THP), and tetrahydro-berberine (THB).
Amaryllidaceae alkaloids are an important class of iso-quinoline derivatives; among them galanthamine, that is found in Galanthus and Narcissus species, has been approved for the pharmacological treatment of Alzheimer’s disease [24]. There are several chiral centers in this molecule, but only one S-enantiomer responsible for Alzheimer’s disease, other stereoisomers considered as impurity (Figure 6) [25].
Molecular structures of galanthamine.
Morphinane alkaloids (opium alkaloids) such as morphine, codeine, thebaine, papaverine and narcotine belong to isoquinoline derivatives and show a broad range of pharmacological activities; their major application is in analgesia, sedation and cough depression [26]. Although opiate alkaloids have an important place in medicine, the illegal trafficking and abuse of heroin (the diacetyl derivative of morphine) has become a widespread problem [27]. Opium, the exudates from
Molecular structures of: (1) morphine; (2) codeine; (3) oripavine; (4) thebaine; (5) pseudomorphine.
Although these alkaloids have at present no great medicinal significance, they are important in that they constitute the poisonous hepatotoxic constituents of plants of the genus Senecio (Compositae), well-known for their toxicity to livestock [28]. Pyrrolizidine alkaloids are found in a variety of plant species growing wide world such as Gynura segetum that belongs to the Compositae family and Senecio and Tussilago genera [10]. The majority of naturally occurring pyrrolizidine alkaloids (PA) are hepatotoxic causing liver damage and in some cases liver cancer. Toxic PAs are often responsible for serious health problems through direct consumption of PA-containing herbal teas, herbal medicines, and herbal dietary supplements [29].
The most important pyrrolizidine alkaloids senecionine, seneciphylline, retrorsine and senkirkine, contain the 4-azabicyclo [3.3.0] octane system with senecionine and seneciphylline differing only for the presence in the latter of the C13-C23 double bond (Figure 8) [30].
Molecular structures of four toxic PAs. (1) senkirkine; (2) senecionine; (3) retrorsine; (4) seneciphylline.
Indole alkaloids constitute a wide class of natural products most of them pharmacologically important and characterized by very different activities [31]. In the recent years, attention has been focused on the biological activity of yohimbine which is a monoterpenoid indole alkaloid (Figure 9). It displayed the treatment of erectile functional disturbance and anxiogenic [32]. Hydroindole alkaloids such as mesembrine and congeners (mesembrenone, Δ7 mesembrenone, mesembranol and its stereoisomer epimesembranol) have been isolated from Sceletium species used for the psychoactive effects [33].
Molecular structure of yohimbine and mesembrine.
The vinca alkaloids were isolated from the Madagascar periwinkle, Catharantus roseus G. Don., which included a class of about 130 terpenoid indole alkaloids [32]. In early 1965, people obviously know their clinical quality. And this group of compounds has been taken advantage of as an anticancer servant for more than 40 years and is a symbol of the compound that gives the trend to drug development [34, 35]. Among these base (+)-vincamine exhibits a valuable therapeutic activity in cerebral insufficiencies. Due to the presence of three stereogenic centers eight stereoisomers (four enantiomeric pairs) are in fact possible (Figure 10) [36].
Molecular structure of major vinca alkaloids isolated from
Steroidal alkaloids including verticine and verticinone are distinguished by cholestane carbon skeleton (isosteroid alkaloids) with a hexacyclic benzo [7, 8] fluoreno [2,1-b] quinolizine nucleus (Figure 11). These compounds have been isolated from plants from Liliaceae family typically Bulbus fritillariae used as a traditional medicine in Japanese, Turkish, Pakistani, and south-east Asian folk medicines [10]. Pharmacological studies demonstrate that verticine and verticinone in Bulbus Fritillariaeare the primary active ingredients responsible for the antitussive activity [37].
Molecular structures of verticine and verticinone.
Stemona, belonging to Stemonaceae family, is known in the folk medicine of Southeast Asia, China, and Japan since its Phyto-preparations (primary the roots) are used to treat diseases about bronchitis, pertussis and tuberculosis. Interestingly many alkaloids, structurally defined as pyrido[1,2-α]azepines, have been recognized in this plant species and are considered the important pharmacological activity. All the Stemona alkaloids are polycyclic and contain multiple stereocenters [38]. Up to now, there are about 139 Stemona alkaloids which the scientist isolated (Figure 12).
Molecular structure of stemonamine and parvistemoline.
Analytical methods usually contain several steps, such as sampling, sample preparation, isolation, and quantification. Remarkably sample preparation just recently is concentration as an important analytical step. According to Wen
Ultrasound Assisted Extraction (UAE) technique is based on the using of acoustic waves in the kilohertz range spreading in liquid medium. These waves created by the ultrasound produces regions of compression and rarefaction in the molecules. Then, the cavitation bubbles are formed and collapse giving rise to smaller bubbles that could act as new cavitation nuclei or simply get dissolved. When the bubbles collapse at the surface of the herbal material, a shockwave having very high temperature and pressure is induced, resulting in plant cell disruption which enhances both the mass transfer of alkaloids into solution and the solvent penetration [41]. In addition, the swelling of plant materials can be enhanced by ultrasound, leading to improving of solvent penetration which increases the extraction yield [42]. The UAE procedure is optimized with regard to extraction solvent, temperature and liquid to solid ratio for the plant sample [41]. UAE has some advantageous properties including high extraction efficiency, good reproducibility, low solvent consumption, low cost and environmental friendliness. However, the major disadvantage of UAE is generating heat, leading to the degradation of thermo labile products and racemization of chiral compounds [43]. To avoid such types of drawback, extraction is carried on under an ice bath to reduce the temperature [44]. Table 1 lists examples of protocols that were developed using MAE from various plants.
Plant | Compounds | Solvent | Solvent: biomass (mL: g) | Temp (°C) | Time duration (min) | Ref. |
---|---|---|---|---|---|---|
Macleaya cordata | Protopine Allocryptopine Sanguinarine Chelerythrine Dihydrochelerythrine Dihydrosanguinarine | 1-hexyl-3-methylimidazolium tetrafluoroborate ([C6MIM][BF4]) aqueous solution | 500: 1 | 80 | 15 | [45] |
Catha edulis | Norephedrine Cathine Cathinone | 0.1 N HCl | 600: 1 | — | 45 | [46] |
Ipomoea genera | Ergot alkaloid (ergine, ergometrine, lysergic acid α-hydroxyethylamide) Penniclavine Chanoclavine Lysergol | 70% methanol | 100: 1 | 60 | 30 | [47] |
Carica papaya | Carpaine Pseudocarpaine Dehydrocarpaine I Dehydrocarpaine II | 100% methanol | 100: 7.5 | — | 20 | [48] |
Extraction conditions from various plants using UAE.
The MAE technique uses the electromagnetic radiations with a frequency range of 0.3–300 GHz, that stimulates ion migration and dipole rotation leading to the heating of dielectric materials and the penetration of extraction solvent into the matrix [49]. The released thermal energy is increased gradually with higher dielectric constant, so the effectiveness of MAE is depended on the dielectric properties of both extraction solvent and sample matrix [50]. Therefore, only specific solvents which have high dipole moment as water, methanol and ethanol can be used for extraction solvent in MAE and the moisture of plant sample is an important factor in the extraction efficiency [51]. Basically, higher water content matrices will be expected to give higher extraction yields. Water contained in plant matrices absorbs microwave radiation creating pockets of localized heating in the sample. This heat promotes the plant cell walls rupture which enhances the release of alkaloids into the solvent and the increase of extraction yield [50]. In addition to having a high dielectric constant, the extraction solvents must have a high dissipation factor to reduce the potential of localized sample overheating resulting degradation of alkaloids in plants [43]. Therefore, organic solvent-water mixtures, polar organic solvents and water are usually used as extraction solvent. Moreover, other parameters relating to extraction performance as sample size, sonication power, solid to liquid ratio, extraction time and microwave power should be modified for MAE procedure optimization [34]. The main advantages of MAE are the low solvent consumption, the ability to extract many samples simultaneously and the short extraction time [43, 52]. The major drawbacks of MAE are nonhomogeneous heating distribution and overheating of extract which may cause racemization or thermal degradation of chiral alkaloids [44]. Table 2 lists examples of protocols that were developed using MAE from various plants.
Plant | Compounds | Solvent | Solvent: biomass (mL: g) | Tem (°C) | Time duration | Microwave power (W) | Ref. |
---|---|---|---|---|---|---|---|
Peganum harmala | Vasicine, Harmalin Harmine | 80% ethanol | 30: 1 | 80 | 8 min | 600 | [53] |
Stephania sinica | Sinoacutine Palmatine Isocorydine L-tetrahydropalmatine | 65% ethanol | 24: 1 | 60 | 90 s | 150 | [54] |
Lotus plumule | Liensinine Dauricine Isoliensinine Neferine Nuciferine | 65% methanol | — | — | 4 min | 200 | [55] |
Corydalis decumbens | Protopine Palmatine Allocryptopine Jatrorrhizine Tetrahydropalmatine Corypalmine Bicuculline | 90% methanol | 20: 1 | 40 | 5 min | — | [56] |
Menispermum dauricum | Bianfugedine, Menisporphine, 6-O-demethylmenisporphine Bianfugecine Dauriporphine Dauriporphinoline | 70% ethanol | 20: 1 | 60 | 11 min | — | [57] |
Extraction conditions from various plants using MAE.
The SFE process utilizes pressurized fluids (mainly CO2) as extraction solvents. In this technique, a fluid is heated and compressed to reach above critical point of it’s creating the fluid having physicochemical properties of both liquid and gas states called supercritical fluid [58]. Specifically, supercritical fluid has a density similar to liquid (0.3–0.8 g/cm3), a viscosity similar to gas (10−4 – 10−3 g/s.cm) and a diffusion coefficient that is intermediate between liquid and gas [59]. Therefore, supercritical fluid has higher transport capacity which facilitate to fluid diffusion through plant materials in comparison to traditional extraction solvents [43]. In addition, the density is related to polarity property of fluid which directly impact in solubility of compounds in extraction solvent. This parameter can be modified by controlling temperature and/or pressure so the flexibility and selectivity of the technique is enhanced, enabling selective extraction of different compounds from the plant matrix [60]. Carbon dioxide is commonly used in SFE because it has ideal properties including low critical temperature (31.3°C) and can be easily remove from extracts [51]. However, carbon dioxide is less effective in extraction of polar compounds from matrix because of its low polarity property. Aiming to extract more polar alkaloids, the modifiers such as methanol, ethanol or water are added to extend the range of the solvating strength [43, 47]. For optimization of SFE procedure, these parameters such as pressure, temperature, modifier, flow of carbon dioxide and modifier [51]. Besides, the extraction time also effects on extraction yield, since an inadequate extraction time can result in incomplete extraction, while too long extraction time can cause the degradation of compounds. The major drawback of SFE are the complexity of system configuration and the requirement for a personal training program to operate the instrument [61].
PSE process uses the pressurize solvents to enhance transport capacity of solvents and mass transfer rates which leads to improve extraction performance. In this technique, extraction solvents are heated at/or above the solvent’s boiling points to decrease viscosity while keeping its in liquid state thanks to an elevated pressure [62]. Therefore, the extraction process is enhanced kinetic which leads to decreasing both the extraction time and solvent consumption. Similar to SFE, these parameters such as solvents nature, temperature and pressure should be modified to optimize PSE procedure [51]. Logically, higher temperature would be expected to give higher alkaloid extraction yields. However, excessive temperature may cause degradation and racemization of chiral alkaloids. The main advantages of PSE are utilizing an extensive range of solvents (except strong acids/bases), low solvent consumption, short extraction time, automated instruments and performing an oxygen- and light – free extraction condition. Besides, the major drawbacks of PSE are similar to SFE such as using expensive laboratory equipment and requirement for a professional training to operate instrument [43].
Due to the alkaloids usually exist in plants at low concentration and the complication of plant matrices, samples should be purified and enriched which facilitate to identify and/or quantify process right after extraction step. Liquid–liquid extraction (LLE) and solid phase extraction (SLE) are popular clean-up methods utilized for sample preparation of alkaloids. Moreover, other techniques based on LLE and SPE methods, such as Liquid Membrane Extraction (LME) and Solid-Phase Micro Extraction (SPME) have also been developed.
Liquid–Liquid Extraction (LLE) is the most simple and traditional clean-up method. LLE method is based on the relative solubility of compounds between two immiscible solvents. The alkaloids have polarity varying between pH, so the solubility of alkaloids in specific solvent are also affected by pH [34]. In the acid solutions (pH is lower than pKa of alkaloids), the analytes are protonated which leads to better water solubility so this aqueous phase can be washed with less polar organic solvents such as ethyl acetate, n-hexane and diethyl ether to eliminate hydrophobic interferences. After that, this aqueous layer is alkalinized which leads to the alkaloids becoming non-polarity and can be extracted by organic solvents to eliminate hydrophilic interferences [63]. For enrichment, the organic solvents layer can be collected, vaporized and reconstituted into new solvents which is suitable for analytical instrument. The main disadvantages of this method are requirement for repetitive extraction causing time consuming and solvent wasting [51].
To overcome the drawback of LLE method, solid phase extraction (SPE) has been developed and applied in sample preparation since the 1970s. In this method, extract is loaded onto a sorbent phase which will retain alkaloids. Then, interferences in extract are washed away and the analytes is eluted by suitable solvents [64]. In fact, cartridge is the most popular SPE type due to its convenience. The SPE procedure have five step including conditioning, loading, washing and elution step. Several factors can affect to the extraction efficiency such as concentration of analytes in solvent, loading solvent nature, sorbent types, particle size, volume used for loading – washing – eluting, flow rate and elution solvent. Each factor has specified role which depends on the affinity of analytes and solid phase. Because the chemical structures of alkaloids always have secondary or tertiary amine groups, the strong cation exchange (SCX) sorbents are an ideal choice for sample preparation. When using these sorbents, washing solvent will be water and organic solvent to eliminate both hydrophilic and hydrophobic from plant matrices. After that, alkaloids will be deprotonated for elution by alkalized solvent which has pH at 2 units above pKa of analytes and evaporated to enrich sample [64].
If the analytes are unstable in strong alkaline solutions, the weak cation exchange (WCX) will be use instead. The WCX sorbent has carboxylic acid as functional group which has pKa value about 4.8, so these sorbents should be conditioned by solutions having pH above 6.8 for sorbent ionization. In addition, the loading and washing solvent pH should be adjusted at the value above 6.8 and below 2 value of analytes’s pKa to maintain the ionized state of both sorbent and analytes. Finally, the alkaloids will be eluted by the acidic solutions [63]. Besides, the C18 and C8 sorbents are also applied to extract aromatic alkaloids and eliminate hydrophilic interferences from matrices. In some case, those sorbents could be used for eliminating hydrophobic interferences by loading unretained alkaloids through cartridges [64].
High performance liquid chromatography (HPLC) is currently the most widely used chromatographic enantio-separation technique [65]. HPLC has become one of the most common modern chemical analysis techniques because of its versatility, efficiency, stability, reproducibility and sensitivity. With these advantages, HPLC continues to be one of the best choices for chiral analysis and separation. Basically, chiral separation by HPLC techniques included direct and indirect methods. The indirect method is based on diastereomer formation by the derivatization reaction of analytes and a chiral reagent, then the separation of diastereomeric derivatives is performed by using a column having an achiral stationary phase. In addition, the direct method uses a chiral stationary phase for chiral separation or forms diastereomer by using a chiral mobile phase additive (CMPA).
HPLC using CSPs has demonstrated to be extremely useful, accurate, versatile, and it has been a widely used technique in diverse fields and applications, emphasizing (Table 3). The CSP mode is generally the most straightforward and convenient means for chromatographic enantiomer separation; it is the method of choice for both analytical and preparative applications [66, 67, 68, 69]. A hundred CSPs have been developed and commercialized thirty years ago [70]. Besides, the larger number of CSPs are made in laboratory for specialized separation. CSPs are divided into nine major types by Snyder basing on the interaction mechanism between stationary phase and analytes [71].
Macromolecular selectors of semisynthetic origin (polysaccharides)
Macromolecular selectors of synthetic origin (poly(meth)acrylamides), (poly-tartramides)
Macromolecular selectors of natural origin (proteins)
Macrocyclic oligomeric or intermediate-sized selectors (cyclodextrins, macro-cyclic antibiotics, chiral crown ethers)
Synthetic, neutral entities of low molecular weight (Pirkle-type phases, brush-type CSPs)
Synthetic, ionic entities of low molecular weight that provide for ion exchange
Chelating selectors for chiral ligand-exchange chromatography.
Polysaccharide-derived CSPs are widely used in enantio-separation of a large number of chiral compounds [71]. The development of polysaccharide-derived CSPs has continued for about three decades. It can be roughly divided into two stages (i) the coated CSPs stage, and (ii) the immobilized CSPs stage.
Polysaccharide selectors have been used for enantioselective liquid chromatography technique for a long time. In 1973, a polymeric selector (without supporting matrix) was introduced by Hesse and Hagel named as microcrystalline cellulose triacetate (MCTA) used for enantioselective liquid chromatography. MCTA are widely applied in enantio-recognition and preparative separations due to its ideal loading capacities. However, this material has major disadvantages including poor pressure stability, slow separations, and low chromatographic efficiency. To overcome the mechanical stability problem of MCTA, a solution was found by Okamoto and co-workers in 1984, in which the surface of macro-porous silica beads (100 or 400 nm pore size) was coated by the cellulose derivatives at about 20 wt%. Thanks to this coating, the mechanical stability of this material was remarkably improved resulting in better efficiencies qualified for HPLC enantiomer separations. Such coated polysaccharide-based CSPs were the highest level of polymeric selector developments for several decades [71].
Nowadays, about 200 kinds of polysaccharide derivatives were introduced by using different polysaccharides which includes cellulose, amylose, chitin, chitosan, galactosamine, curdlan, dextran, xylan, and inulin [72] (Figure 13). These materials have been coated on a surface of macro-porous silica gel to create CSPs and followed by the evaluation of chiral recognitions on HPLC.
Structures of the various kinds of polysaccharides: (1) cellulose; (2) amylose; (3) chitin; (4) chitosan; (5) Galatosamine; (6) Curdlan; (7) dextran; (8) Xylan; (9) inulin.
Each of coated polysaccharide-based CSPs exhibit the different enantioselectivity and elution order of the various enantiomers due to the structural differences of CSPs including sugar units, linkage position, and linkage type. In particular, the derivatives of cellulose and amylose usually perform higher recognition abilities than the others, though this property also depends on the structure of a specific racemate. The most useful and successful derivatives of cellulose and amylose are triesters and tricarbamate. It has been claimed by Aboul-Enein and Ali that for the resolution of about 500 test racemates, about 80% of them have been successfully resolved on only two kinds of polysaccharide derivative-based CSPs (cellulose and amylose tris (3,5-diphenylcarbamate) CSPs) [72]. More specifically, three famous commercially available CSPs, CHIRALCEL OD, OJ, and CHIRALPAK AD, have fully or partially resolved 70% racemates among over 100 racemates tested [71].
A current strategy introduced by Snyder for chiral separation method development includes trial-and-error experiments of various polysaccharide-type CSPs under multiple respective mobile-phase conditions using fully automated column- and solvent-switching. Nowadays, more and more studies have focused on developing a more efficient screening procedure to enhance the chance for success and shorten the experiment time: the most favorable CSP in the normal phase mode is
The separation efficiency of column should be tested before conducting screening experiment if serial instead of parallel screening is utilized. The application of coated polysaccharide-derived CSPs has been reviewed in Table 4 including the names of CSPs and their most frequent applications.
Type | CSP | Typical column trade name | Application |
---|---|---|---|
I | Polysaccharide | AD, OD, OJ, AS, IA, IB, IC | Alkaloids, tropines, amines, beta blockers, aryl methyl esters, aryl methoxy esters |
II | Synthetic-Polymer CSPs | Kromasil CHI-DMB and CHI-TBB | Acidic, neutral, and basic compounds |
III | Protein Phases | Chiral HSA, Chiral AGP, Ultron ES-OVM, Chiral CBH | Benzodiazepine, Warfarin and oxazepam, beta blockers |
IV | Cyclodextrin | Cyclobond I, II, III | Beta blockers |
V | Macrocyclic Antibiotic | Chirobiotic V, T, R, TAG; vancomycin | Polar compounds such as underivatized amino acids |
VI | Chiral Crown-Ether | ChiroSil RCA(+); SCA(−); ChiralHyun-CR-1 | Amino acids, amino acid esters, amino alcohols |
VII | Donor-Acceptor Phases | Whelk-O 1, ULMO, Sumichiral 2500, Sumichiral OA 4900 | Amides, epoxides, esters, ureas, carbamates, ethers, aziridines, phosphonates, aldehydes,ketones, carboxylic acids, alcohols |
VIII | Chiral Ion-Exchangers | Chiralpak QN-AX; Chiralpak QD-AX | Chiral carboxylic, sulfonic, phosphonic, and phosphoric acids |
IX | Chiral Ligand-Exchange | Chiralpak MA+, Nucleosil Chiral-1 | Amino acids |
Application of nine major types of CSP and their commercial CSP [72].
Trade name | Chemical name | Applications |
---|---|---|
Cellulose CSPs | ||
Chiralcel OB | Cellulose trisbenzoate | Small aliphatic and aromatic compounds |
Chiralcel OJ | Cellulose tris(4-methyl benzoate) | Aryl methyl esters, aryl methoxy esters |
Chiralcel OC | Cellulose trisphenylcarbamate | Cyclopentanones |
Chiralcel OD | Cellulose tris(3,5-dimethylphenylcarbamate) | Alkaloids, amines, |
Chiralcel OD-Hb | Cellulose tris(3,5-dimethylphenylcarbamate) | Alkaloids, amines, |
Chiralcel OD-Rc | Cellulose tris(3,5-dimethylphenylcarbamate) | Alkaloids, amines, |
Chiralcel OD-RHd | Cellulose tris(3,5-dimethylphenylcarbamate) | Alkaloids, amines, |
Chiralcel OF | Cellulose tris(4-chlorophenylcarbamate) | |
Chiralcel OG | Cellulose tris(4-methylphenylcarbamate) | |
Chiralcel OA | Cellulose triacetate on silica gel | Small aliphatie compounds |
Amylose CSPs | ||
Chiralpak AD | Amylose tris(3,5-dimethylphenylcarbamate) | Alkaloids, tropines, amines, |
Chiralpak AD-Ra | Amylose tris(3,5-dimethylphenylcarbamate) | Alkaloids, tropines, amines, |
Chiralpak AD-RHb | Amylose tris(3,5-dimethylphenylcarbamate) | Alkaloids, tropines, amines, |
Chiralpak AD-H | Amylose tris-(3,5-dimethylphenylcarbamate) | Alkaloids |
Chiralpak AR | Amylose tris(R)-1-phenylethylcarbamate | Alkaloids, tropines, amines |
Chiralpak AS | Amylose tris(S)-1-methylphenylcarbamate | Alkaloids, tropines, amines |
Columns supplied by Daicel Chemical Industries, Tokyo, Japan, Dimension are column size 25 cm X 0,46 cm, particle size 10
Column size 25 cm X 0,46 cm, particle size 5
Column size 15 cm X 0,46 cm, particle size 10
Column size 15 cm X 46 cm, particle size 5
The coated CSPs are formed by coating the polysaccharide derivatives onto surface of silica gel. Due to the weak linkages and interactions between the polysaccharide derivatives (chiral selector) and silicagel (substrate), a number of organic solvents including chloroform, dichloromethane, tetrahydrofuran and ethyl acetate which can dissolve or swell the chiral selector are not allowed using as mobile phase components. Besides, the mixtures of alkanes (n-pentane, n-hexane or n-heptane) and alcohols (2-propanol (IPA), ethanol or methanol (n-pentane, n-hexane or n-heptane)) and alcohols (2-propanol (IPA), ethanol or methanol) are favorable mobile phase solvents used in normal phase mode. The addition of “prohibited solvents” may lead to better separation and greater solubility of racemic analytes than the standard solvent combinations so the performance of separation method is improved. Besides, the better solubility of racemic analytes also facilitates preparative separations. In addition, the spectroscopic techniques used for chiral recognition should ideally be in the “prohibited solvents”. As a result, chemical immobilization of polysaccharide derivatives becomes an interesting research topic to overcome the drawbacks of the coated CSPs (see in Figure 14). In 2005, Daicel and Chiral Technologies introduced a set of three immobilized polysaccharide CSPs as [71]:
Chiralpak®IA (immobilized version of Chiralpak AD)
Chiralpak®IB (immobilized Chiralcel OD) [61]
Chiralpak®IC based on the cellulose tris (3,5-dichlorophenylcarbamate) selector that is not available in coated form.
Effect of column type (immobilized vs. coated polysaccharide-based CSP) and mobile phase on enantioselectivity. Enantiomer separations of N-benzyloxycarbonyl-phenylalanine (a–c) with Chiralpak IB (immobilized) and Chiralcel OD (coated). Flowrate: 1 mL/min; temperature: 25°C; UV detection at 230 nm. Note that the mobile phases used in (a) is forbidden mobile phases for the coated version Chiralcel OD [
Finally, it should be noted that polysaccharide CSPs have now also been established as the first-choice of chiral phases for enantiomer separation.
Analytical applications, including CSPs, separation conditions and analyte, are summarized in Table 5. A review focused mainly on the latest examples of chiral alkaloids separations on CSPs for efficient analyses was prepared.
Columns | Analyte | Plant | Separation conditions | Ref. |
---|---|---|---|---|
CHIRALPAK AS-H column | (12S,22S)-Dihydroxyisoechinulin A (2) and (12R/S)- Neoechinulin A | Cannabis sativ L | Hexane/isopropanol/diethylamine (4:1:0.05) | [73] |
CHIRALPAK AD-H column | Mucroniferanine A | Corydalis mucronifera | n-hexane−2-propanol (70:30) | [74] |
(±)-homocrepidine A | Dendrobium crepidatum | n-hexane/2-propanol (95:5) | [75] | |
(+)-(3R,6R)- and (−)-(3S,6S)-3α,6β-tropanediol | Erythroxylaceae species | n-hexane and 2-propanol (9:1) with 0.1% of diethylamine | [76] | |
Chirobiotic V, Chiralpak-AY3 column | (−) and (+) hyoscyamine | Solanaceaes seeds | Ethanol, 0.1% DEA | [77] |
Chirex 3019 chiral column | S-(−)-canadine and R-(+)-canadine | Hexan:DCE:EtOH:TFA (75:40:7:0.1) | [78] | |
CHIRALPAK AGP column | (R)-nicotine; (S)-nicotine; anabasine, and anatabine | Tobacco | NH4OH- methanol (90:10) | [79] |
A Phenomenex Lux Cellulose-2 chiral column | (+)- and (−)-5-hydroxyl-8-oxyberberine | Coptis chinensis | CH3CN:H2O (40:60) | [80] |
Chiralpak IA column | intermedine and lycopsamine | Symphytum uplandicum | ACN/methanol (80:20) and methanol/methyl-t-butyl ether (90:10) | [81] |
Phenomenex-Chirex-3126 column | dihydrocarneamide A and iso-notoamide B | Paecilomyces variotii | MeCN–H2O (5:95). | [82] |
Summary of CSPs, mobile phase compositions, and applications.
Novel column materials also improved enantiomer separation of tropane alkaloids. Separation of (R, S)-hyoscyamine was achieved using chiral stationary phase with immobilizing α-1-acid glycoprotein (Chiral AGP®) [83], alternatively, enantiomer separation of atropine could be achieved by a chirobiotic V column packed with vancomycin as chiral selector [84]. Anisodamine, the 6β-hydroxyl derivative of (S)-hyoscyamine was separated from its synthetic enantiomer and diastereomers by a Chiralpak AD-H column as chiral stationary phase, which uses an amylose derivative as chiral selector [85]. Satropane, 3α-paramethylbenzenesulfonyloxy-6β-acetoxy-tropane, could be resolved in 3S, 6S-isomer named lesatropane and 3R, 6R-isomer named desatropane. Lesatropane as a novel muscarinic agonist is being under preclinical development in China as a single enantiomer drug for the treatment of primary glaucoma. The separation of lesatropane from desatropane was conducted by both Chiralpak AD-H and Chiralpak AS-RH column [86].
Chiral separation of isoquinoline alkaloid has also achieved by using chiral stationary phase. For example, the determination of tetrahydropalmatine (THP) was performed by using a Chiralcel OJ column with quantification by UV at 230 nm. This developed method was used for determining the pharmacokinetics of THP enantiomers in rats and dogs after oral administration [87]. Another report of isoquinoline alkaloid group is sanguinarine derivatives. Chiral determination of Benzophenanthridine alkaloids from methanol extracts of Hylomecon species was conducted by Chiralcel OD (4.6 x 250 mm) column with mixture of isopropanol-hexane-diethylamine (20/80/0.1, v/v/v) as a mobile phase [88]. The stereochemistry of L-isocorypalmine and the D/L ratio of tetrahydropalmatine, stylopine, and corydaline were established unambiguously by using a chiral Chiralcel OD (4.6 x 250 mm) column; 50% ethanol as mobile phase; wavelength 230 nm [89]. Cularinoids are a group of isoquinoline alkaloids consisting of about 60 members. The HPLC enantiomeric separation of the racemic cularinoid alkaloids N-p-methoxy-1,α-dihydroaristoyagonine and 4′,5’demethoxy-1,α-dihydroaristoyagonine was accomplished using five chiral stationary phases (CSPs), the good enantioselectivity and resolution factor obtained with a polysaccharide-derived CSP (Chiralpak AD) [90].
Indole derivatives are widely used in chiral synthesis, chemical asymmetric catalysis, biological and medicinal chemistry. Recently, the enantiomeric separation of several chiral plant growth regulators and related compounds, such as 3-(3-indolyl)-butyric acid, abscisic acid and structurally related molecules including a variety of substituted tryptophan compounds was reported. Chiral stationary phases such as coated and immobilized were suitable for the separation of indole derivatives; however, the coated CSP possesses a higher resolving power than the immobilized one [91]. Tangutorine, a biogenetically interesting indole alkaloid, was found in the leaves of Nitraria tangutorum in 1999. It was separated from its synthetic enantiomer by chiral stationary phases two polysaccharide-derived CSP (Chiralcel OD and Chiralpak AD) and a network polymer incorporating a bifunctional C2-symmetric chiral selector (Kromasil CHI-DMB) [92]. The HPLC enantiomeric separation of racemic indole alkaloids tacamonine, 17α-hydroxytacamonine, deethyleburnamonine, and vindeburnol was accomplished using Chiralpak AD and Chiralcel OD as chiral stationary phases [93].
The enantiomers of homocamptothecin (hCPT) derivatives which constitute a promising series of potent anticancer agents targeting DNA topoisomerase I were separated by using the combination of two silica-based normal phase column including Chiralcel OD-H (celluloses tris-3,5-dimethylphenylcarbamateand) Chiralcel OJ (celluloses tris-methylbenzoate) or Chiralpak AD (amyloses tris-3,5-dimethylphenylcarbamate) and Chiralpak AS (amyloses tris-(S)-1-phenylethylcar-bamate) [94]. A method for the simultaneous determination of eight Cinchona alkaloids (quinine, quinidine, cinchonine, cinchonidine, and their corresponding dihydro analogs) using a novel strong cation-exchange-type chiral stationary phase (cSCX) column in HPLC has been developed and exemplarily applied to impurity profiling of a commercial alkaloid sample [95].
Most of alkaloids are chiral compounds and are clinically administered as the racemic mixture, although its enantiomers have been shown to exert different pharmacological activity. The complication of sample matrices and low concentration of chiral alkaloids are major challenges for analytical processes. To improve the performance of analytical procedure, we provide the current state of the art in sample preparation focusing on extraction and purification to remove interferences and enrich analyte concentrations. HPLC using CSPs has demonstrated to be extremely useful, accurate, versatile, its mode is generally the most straightforward and convenient means for chromatographic enantiomer separation. The development of CSPs for HPLC is a continuous and challenger issue covering various types of CSPs.
The authors would like to express their hearty gratitude to Can Tho University of Medicine and Pharmacy. We also thank all of our colleagues for their excellent assistance.
The authors declare no conflict of interest.
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There are many hybrid techniques, which arise from CVD and are constantly evolving in order to modify the properties of the fabricated thin films. Amongst them, plasma enhanced chemical vapor deposition (PECVD) is a technique that can extend the applicability of the method for various precursors, reactive organic and inorganic materials as well as inert materials. Organic/inorganic monomers, which are used as precursors in the PECVD technique, undergo disintegration and radical polymerization while exposed to a high-energy plasma stream, followed by thin film deposition. In this chapter, we have provided a summary of the history, various characteristics as well as the main applications of PECVD. By demonstrating the advantages and disadvantages of PECVD, we have provided a comparison of this technique with other techniques. PECVD, like any other techniques, still suffers from some restrictions, such as selection of appropriate monomers, or suitable inlet instrument. However, the remarkable properties of this technique and variety of possible applications make it an area of interest for researchers, and offers potential for many future developments.",book:{id:"5211",slug:"chemical-vapor-deposition-recent-advances-and-applications-in-optical-solar-cells-and-solid-state-devices",title:"Chemical Vapor Deposition",fullTitle:"Chemical Vapor Deposition - Recent Advances and Applications in Optical, Solar Cells and Solid State Devices"},signatures:"Yasaman Hamedani, Prathyushakrishna Macha, Timothy J. Bunning,\nRajesh R. Naik and Milana C. Vasudev",authors:[{id:"181604",title:"Dr.",name:"Milana",middleName:null,surname:"Vasudev",slug:"milana-vasudev",fullName:"Milana Vasudev"}]},{id:"55301",doi:"10.5772/intechopen.68802",title:"Recent Overview on the Abatement of Pesticide Residues in Water by Photocatalytic Treatment Using TiO2",slug:"recent-overview-on-the-abatement-of-pesticide-residues-in-water-by-photocatalytic-treatment-using-ti",totalDownloads:1996,totalCrossrefCites:9,totalDimensionsCites:26,abstract:"The water bodies’ pollution with phytosanitary products can pose a serious threat to aquatic ecosystems and drinking water resources. The usual appearance of pesticides in surface water, waste water and groundwater has driven the search for proper methods to remove persistent pesticides. Although typical biological treatments of water offer some advantages such as low cost and operability, many investigations referring to the removal of pesticides have suggested that in many cases they have low effectiveness due to the limited biodegradability of many agrochemicals. In recent years, research for new techniques for water detoxification to avoid these disadvantages has led to processes that involve light, which are called advanced oxidation processes (AOPs). Among the different semiconductor (SC) materials tested as potential photocatalysts, titanium dioxide (TiO2) is the most popular because of its photochemical stability, commercial availability, non-toxic nature and low cost, high photoactivity, ease of preparation in the laboratory, possibility of doping with metals and non-metals and coating on solid support. Thus, in the present review, we provide an overview of the recent research being developed to photodegrade pesticide residues in water using TiO2 as photocatalyst.",book:{id:"6407",slug:"application-of-titanium-dioxide",title:"Application of Titanium Dioxide",fullTitle:"Application of Titanium Dioxide"},signatures:"Nuria Vela, Gabriel Pérez-Lucas, José Fenoll and Simón Navarro",authors:[{id:"202983",title:"Dr.",name:"Simón",middleName:null,surname:"Navarro",slug:"simon-navarro",fullName:"Simón Navarro"},{id:"202988",title:"Dr.",name:"Nuria",middleName:null,surname:"Vela",slug:"nuria-vela",fullName:"Nuria Vela"},{id:"202989",title:"Dr.",name:"José",middleName:null,surname:"Fenoll",slug:"jose-fenoll",fullName:"José Fenoll"},{id:"206059",title:"Dr.",name:"Gabriel",middleName:null,surname:"Pérez-Lucas",slug:"gabriel-perez-lucas",fullName:"Gabriel Pérez-Lucas"}]}],mostDownloadedChaptersLast30Days:[{id:"55440",title:"Solubility Products and Solubility Concepts",slug:"solubility-products-and-solubility-concepts",totalDownloads:3090,totalCrossrefCites:6,totalDimensionsCites:7,abstract:"The chapter refers to a general concept of solubility product Ksp of sparingly soluble hydroxides and different salts and calculation of solubility of some hydroxides, oxides, and different salts in aqueous media. A (criticized) conventional approach, based on stoichiometry of a reaction notation and the solubility product of a precipitate, is compared with the unconventional/correct approach based on charge and concentration balances and a detailed physicochemical knowledge on the system considered, and calculations realized according to generalized approach to electrolytic systems (GATES) principles. An indisputable advantage of the latter approach is proved in simulation of static or dynamic, two-phase nonredox or redox systems.",book:{id:"5891",slug:"descriptive-inorganic-chemistry-researches-of-metal-compounds",title:"Descriptive Inorganic Chemistry Researches of Metal Compounds",fullTitle:"Descriptive Inorganic Chemistry Researches of Metal Compounds"},signatures:"Anna Maria Michałowska-Kaczmarczyk, Aneta Spórna-Kucab and\nTadeusz Michałowski",authors:[{id:"35273",title:"Prof.",name:"Tadeusz",middleName:null,surname:"Michalowski",slug:"tadeusz-michalowski",fullName:"Tadeusz Michalowski"},{id:"203867",title:"Dr.",name:"Anna Maria",middleName:null,surname:"Michałowska-Kaczmarczyk",slug:"anna-maria-michalowska-kaczmarczyk",fullName:"Anna Maria Michałowska-Kaczmarczyk"},{id:"203868",title:"Dr.",name:"Aneta",middleName:null,surname:"Spórna-Kucab",slug:"aneta-sporna-kucab",fullName:"Aneta Spórna-Kucab"}]},{id:"56162",title:"Phosphoric Acid Industry: Problems and Solutions",slug:"phosphoric-acid-industry-problems-and-solutions",totalDownloads:5273,totalCrossrefCites:3,totalDimensionsCites:10,abstract:"Phosphoric acid (PA) is an important industrial chemical used as an intermediate in the fertilizer industry, for metal surface treatment in the metallurgical industry and as an additive in the food industry. The PA industry is spread out worldwide in Europe, Asia and America, including countries that operate phosphate rock (PR) mines and produce PA, phosphatic fertilizers and phosphate-based products.",book:{id:"5595",slug:"phosphoric-acid-industry-problems-and-solutions",title:"Phosphoric Acid Industry",fullTitle:"Phosphoric Acid Industry - Problems and Solutions"},signatures:"Benjamín Valdez Salas, Michael Schorr Wiener and Juan Ricardo\nSalinas Martinez",authors:[{id:"16436",title:"Dr.",name:"Michael",middleName:null,surname:"Schorr",slug:"michael-schorr",fullName:"Michael Schorr"}]},{id:"62941",title:"Inorganic Coordination Chemistry: Where We Stand in Cancer Treatment?",slug:"inorganic-coordination-chemistry-where-we-stand-in-cancer-treatment-",totalDownloads:2160,totalCrossrefCites:5,totalDimensionsCites:10,abstract:"Metals have unique characteristics such as variable coordination modes, redox activity, and reactivity being indispensable for several biochemical processes in cells. Due to their reactivity, their concentration is tightly regulated inside the cells, and abnormal concentrations are associated with many disorders, such as cancer. As such metal complexes turned out to be very attractive as potential anticancer agents. The discovery of cisplatin was a crucial moment, which prompted the interest in Pt(II) and other metal complexes as potential anticancer agents. This chapter highlights the state of the art on metal complexes in cancer therapy, highlighting their uptake mechanisms, biological targets, toxicity, and drug resistance. Finally, based on the importance of selective target of cancer cells, drug delivery systems will also be discussed.",book:{id:"7549",slug:"basic-concepts-viewed-from-frontier-in-inorganic-coordination-chemistry",title:"Basic Concepts Viewed from Frontier in Inorganic Coordination Chemistry",fullTitle:"Basic Concepts Viewed from Frontier in Inorganic Coordination Chemistry"},signatures:"Pedro Pedrosa, Andreia Carvalho, Pedro V. Baptista and Alexandra R. Fernandes",authors:[{id:"253664",title:"Prof.",name:"Alexandra R",middleName:null,surname:"Fernandes",slug:"alexandra-r-fernandes",fullName:"Alexandra R Fernandes"}]},{id:"57464",title:"General Aspects of the Cobalt Chemistry",slug:"general-aspects-of-the-cobalt-chemistry",totalDownloads:2305,totalCrossrefCites:1,totalDimensionsCites:2,abstract:"This chapter aims to collect and summarize the chemical properties of cobalt and some new cobalt compounds. It deals with the progress of cobalt chemistry. Cobalt has been substantial in both chemical reactions and within many compounds. Some of them are heterocyclic reactions, cobalt-based catalyst and cobalamin. Also, it discusses variety of applications of cobalt in a wide range of areas and toxicity of cobalt. The studies carried out in this area so far have enabled and will be continued to be responsible for producing unknown and difficult reactions. This survey of the recent literature illustrates the fact that many different approaches on cobalt and new cobalt compounds are being used in many different areas.",book:{id:"6133",slug:"cobalt",title:"Cobalt",fullTitle:"Cobalt"},signatures:"Yasemin Yildiz",authors:[{id:"208129",title:"Dr.",name:"Yasemin",middleName:null,surname:"Yıldız",slug:"yasemin-yildiz",fullName:"Yasemin Yıldız"}]},{id:"55301",title:"Recent Overview on the Abatement of Pesticide Residues in Water by Photocatalytic Treatment Using TiO2",slug:"recent-overview-on-the-abatement-of-pesticide-residues-in-water-by-photocatalytic-treatment-using-ti",totalDownloads:1994,totalCrossrefCites:9,totalDimensionsCites:26,abstract:"The water bodies’ pollution with phytosanitary products can pose a serious threat to aquatic ecosystems and drinking water resources. The usual appearance of pesticides in surface water, waste water and groundwater has driven the search for proper methods to remove persistent pesticides. Although typical biological treatments of water offer some advantages such as low cost and operability, many investigations referring to the removal of pesticides have suggested that in many cases they have low effectiveness due to the limited biodegradability of many agrochemicals. In recent years, research for new techniques for water detoxification to avoid these disadvantages has led to processes that involve light, which are called advanced oxidation processes (AOPs). Among the different semiconductor (SC) materials tested as potential photocatalysts, titanium dioxide (TiO2) is the most popular because of its photochemical stability, commercial availability, non-toxic nature and low cost, high photoactivity, ease of preparation in the laboratory, possibility of doping with metals and non-metals and coating on solid support. Thus, in the present review, we provide an overview of the recent research being developed to photodegrade pesticide residues in water using TiO2 as photocatalyst.",book:{id:"6407",slug:"application-of-titanium-dioxide",title:"Application of Titanium Dioxide",fullTitle:"Application of Titanium Dioxide"},signatures:"Nuria Vela, Gabriel Pérez-Lucas, José Fenoll and Simón Navarro",authors:[{id:"202983",title:"Dr.",name:"Simón",middleName:null,surname:"Navarro",slug:"simon-navarro",fullName:"Simón Navarro"},{id:"202988",title:"Dr.",name:"Nuria",middleName:null,surname:"Vela",slug:"nuria-vela",fullName:"Nuria Vela"},{id:"202989",title:"Dr.",name:"José",middleName:null,surname:"Fenoll",slug:"jose-fenoll",fullName:"José Fenoll"},{id:"206059",title:"Dr.",name:"Gabriel",middleName:null,surname:"Pérez-Lucas",slug:"gabriel-perez-lucas",fullName:"Gabriel Pérez-Lucas"}]}],onlineFirstChaptersFilter:{topicId:"83",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:11,numberOfPublishedChapters:91,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:108,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:33,numberOfPublishedChapters:333,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:14,numberOfPublishedChapters:145,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:11,numberOfPublishedChapters:143,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:124,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:112,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:23,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:12,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:"2753-6580",doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. 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Initial biochemical studies have been exclusively analytic: dissecting, purifying, and examining individual components of a biological system; in the apt words of Efraim Racker (1913 –1991), “Don’t waste clean thinking on dirty enzymes.” Today, however, biochemistry is becoming more agglomerative and comprehensive, setting out to integrate and describe entirely particular biological systems. The ‘big data’ metabolomics can define the complement of small molecules, e.g., in a soil or biofilm sample; proteomics can distinguish all the comprising proteins, e.g., serum; metagenomics can identify all the genes in a complex environment, e.g., the bovine rumen. 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Dr. Blumenberg’s research is focused on the epidermis, expression of keratin genes, transcription profiling, keratinocyte differentiation, inflammatory diseases and cancers, and most recently the effects of the microbiome on the skin. He has published more than 100 peer-reviewed research articles and graduated numerous Ph.D. and postdoctoral students.",institutionString:null,institution:{name:"New York University Langone Medical Center",institutionURL:null,country:{name:"United States of America"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:5,paginationItems:[{id:"91",title:"Sustainable Economy and Fair Society",coverUrl:"https://cdn.intechopen.com/series_topics/covers/91.jpg",isOpenForSubmission:!0,editor:{id:"181603",title:"Dr.",name:"Antonella",middleName:null,surname:"Petrillo",slug:"antonella-petrillo",fullName:"Antonella Petrillo",profilePictureURL:"https://mts.intechopen.com/storage/users/181603/images/system/181603.jpg",biography:"Antonella Petrillo, Ph.D., is a professor in the Department of Engineering, University of Naples “Parthenope,” Italy. She received her Ph.D. in Mechanical Engineering from the University of Cassino and Southern Lazio, Italy. 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Her focus is on quality, innovation, leadership, and personalised learning. She works primarily at the strategic and policy levels, both nationally and internationally, and with key international organisations. She is committed to promoting and improving OFDL in the context of SDG4 and the future of education. Ossiannilsson has more than 20 years of experience in her current field, but more than 40 years in the education sector. She works as a reviewer and expert for the European Commission and collaborates with the Joint Research Centre for Quality in Open Education. Ossiannilsson also collaborates with ITCILO and ICoBC (International Council on Badges and Credentials). She is a member of the ICDE Board of Directors and has previously served on the boards of EDEN and EUCEN. Ossiannilsson is a quality expert and reviewer for ICDE, EDEN and the EADTU. She chairs the ICDE OER Advocacy Committee and is a member of the ICDE Quality Network. 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He got his Ph.D. in Animal Ecology at Umeå University in Sweden in 1998. He conducted postdoc research in stream ecology at the University of California at Santa Barbara in the USA. After that, he was a postdoc research fellow at the University of British Columbia in Canada to do research on large-scale stream experimental manipulation and watershed ecological survey in temperate rainforests of BC. He was a faculty member at the University of Hong Kong to run ecological research projects on aquatic insects, fishes, and newts in Tropical Asian streams. He also conducted research in streams, rivers, and caves in Texas, USA, to study the ecology of macroinvertebrates, big-claw river shrimp, fish, turtles, and bats. Current research interests include trophic flows across ecosystems; watershed impacts of land-use change on biodiversity and ecosystem functioning; ecological civilization and water resource management; urban ecology and urban/rural sustainable development.",institutionString:null,institution:{name:"Soochow University",institutionURL:null,country:{name:"China"}}},editorTwo:null,editorThree:null},{id:"95",title:"Urban Planning and Environmental Management",coverUrl:"https://cdn.intechopen.com/series_topics/covers/95.jpg",isOpenForSubmission:!0,editor:{id:"181079",title:"Dr.",name:"Christoph",middleName:null,surname:"Lüthi",slug:"christoph-luthi",fullName:"Christoph Lüthi",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRHSqQAO/Profile_Picture_2022-04-12T15:51:33.png",biography:"Dr. Christoph Lüthi is an urban infrastructure planner with over 25 years of experience in planning and design of urban infrastructure in middle and low-income countries. 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Dr. Adimule has attended, chaired, and presented papers at national and international conferences. He is a guest editor for Topics in Catalysis and other journals. He is also an editorial board member, life member, and associate member for many international societies and research institutions. His research interests include nanoelectronics, material chemistry, artificial intelligence, sensors and actuators, bio-nanomaterials, and medicinal chemistry.",institutionString:"Angadi Institute of Technology and Management",institution:null},{id:"284317",title:"Prof.",name:"Kantharaju",middleName:null,surname:"Kamanna",slug:"kantharaju-kamanna",fullName:"Kantharaju Kamanna",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/284317/images/21050_n.jpg",biography:"Prof. K. Kantharaju has received Bachelor of science (PCM), master of science (Organic Chemistry) and Doctor of Philosophy in Chemistry from Bangalore University. He worked as a Executive Research & Development @ Cadila Pharmaceuticals Ltd, Ahmedabad. He received DBT-postdoc fellow @ Molecular Biophysics Unit, Indian Institute of Science, Bangalore under the supervision of Prof. P. Balaram, later he moved to NIH-postdoc researcher at Drexel University College of Medicine, Philadelphia, USA, after his return from postdoc joined NITK-Surthakal as a Adhoc faculty at department of chemistry. Since from August 2013 working as a Associate Professor, and in 2016 promoted to Profeesor in the School of Basic Sciences: Department of Chemistry and having 20 years of teaching and research experiences.",institutionString:null,institution:{name:"Rani Channamma University, Belagavi",country:{name:"India"}}},{id:"158492",title:"Prof.",name:"Yusuf",middleName:null,surname:"Tutar",slug:"yusuf-tutar",fullName:"Yusuf Tutar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/158492/images/system/158492.jpeg",biography:"Prof. Dr. Yusuf Tutar conducts his research at the Hamidiye Faculty of Pharmacy, Department of Basic Pharmaceutical Sciences, Division of Biochemistry, University of Health Sciences, Turkey. He is also a faculty member in the Molecular Oncology Program. He obtained his MSc and Ph.D. at Oregon State University and Texas Tech University, respectively. He pursued his postdoctoral studies at Rutgers University Medical School and the National Institutes of Health (NIH/NIDDK), USA. His research focuses on biochemistry, biophysics, genetics, molecular biology, and molecular medicine with specialization in the fields of drug design, protein structure-function, protein folding, prions, microRNA, pseudogenes, molecular cancer, epigenetics, metabolites, proteomics, genomics, protein expression, and characterization by spectroscopic and calorimetric methods.",institutionString:"University of Health Sciences",institution:null},{id:"180528",title:"Dr.",name:"Hiroyuki",middleName:null,surname:"Kagechika",slug:"hiroyuki-kagechika",fullName:"Hiroyuki Kagechika",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/180528/images/system/180528.jpg",biography:"Hiroyuki Kagechika received his bachelor’s degree and Ph.D. in Pharmaceutical Sciences from the University of Tokyo, Japan, where he served as an associate professor until 2004. He is currently a professor at the Institute of Biomaterials and Bioengineering (IBB), Tokyo Medical and Dental University (TMDU). From 2010 to 2012, he was the dean of the Graduate School of Biomedical Science. Since 2012, he has served as the vice dean of the Graduate School of Medical and Dental Sciences. He has been the director of the IBB since 2020. Dr. Kagechika’s major research interests are the medicinal chemistry of retinoids, vitamins D/K, and nuclear receptors. He has developed various compounds including a drug for acute promyelocytic leukemia.",institutionString:"Tokyo Medical and Dental University",institution:{name:"Tokyo Medical and Dental University",country:{name:"Japan"}}},{id:"94311",title:"Prof.",name:"Martins",middleName:"Ochubiojo",surname:"Ochubiojo Emeje",slug:"martins-ochubiojo-emeje",fullName:"Martins Ochubiojo Emeje",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/94311/images/system/94311.jpeg",biography:"Martins Emeje obtained a BPharm with distinction from Ahmadu Bello University, Nigeria, and an MPharm and Ph.D. from the University of Nigeria (UNN), where he received the best Ph.D. award and was enlisted as UNN’s “Face of Research.” He established the first nanomedicine center in Nigeria and was the pioneer head of the intellectual property and technology transfer as well as the technology innovation and support center. Prof. Emeje’s several international fellowships include the prestigious Raman fellowship. He has published more than 150 articles and patents. He is also the head of R&D at NIPRD and holds a visiting professor position at Nnamdi Azikiwe University, Nigeria. He has a postgraduate certificate in Project Management from Walden University, Minnesota, as well as a professional teaching certificate and a World Bank certification in Public Procurement. Prof. Emeje was a national chairman of academic pharmacists in Nigeria and the 2021 winner of the May & Baker Nigeria Plc–sponsored prize for professional service in research and innovation.",institutionString:"National Institute for Pharmaceutical Research and Development",institution:{name:"National Institute for Pharmaceutical Research and Development",country:{name:"Nigeria"}}},{id:"436430",title:"Associate Prof.",name:"Mesut",middleName:null,surname:"Işık",slug:"mesut-isik",fullName:"Mesut Işık",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/436430/images/19686_n.jpg",biography:null,institutionString:null,institution:{name:"Bilecik University",country:{name:"Turkey"}}},{id:"268659",title:"Ms.",name:"Xianquan",middleName:null,surname:"Zhan",slug:"xianquan-zhan",fullName:"Xianquan Zhan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/268659/images/8143_n.jpg",biography:"Dr. Zhan received his undergraduate and graduate training in the fields of preventive medicine and epidemiology and statistics at the West China University of Medical Sciences in China during 1989 to 1999. He received his post-doctoral training in oncology and cancer proteomics for two years at the Cancer Research Institute of Human Medical University in China. In 2001, he went to the University of Tennessee Health Science Center (UTHSC) in USA, where he was a post-doctoral researcher and focused on mass spectrometry and cancer proteomics. Then, he was appointed as an Assistant Professor of Neurology, UTHSC in 2005. He moved to the Cleveland Clinic in USA as a Project Scientist/Staff in 2006 where he focused on the studies of eye disease proteomics and biomarkers. He returned to UTHSC as an Assistant Professor of Neurology in the end of 2007, engaging in proteomics and biomarker studies of lung diseases and brain tumors, and initiating the studies of predictive, preventive, and personalized medicine (PPPM) in cancer. In 2010, he was promoted to Associate Professor of Neurology, UTHSC. Currently, he is a Professor at Xiangya Hospital of Central South University in China, Fellow of Royal Society of Medicine (FRSM), the European EPMA National Representative in China, Regular Member of American Association for the Advancement of Science (AAAS), European Cooperation of Science and Technology (e-COST) grant evaluator, Associate Editors of BMC Genomics, BMC Medical Genomics, EPMA Journal, and Frontiers in Endocrinology, Executive Editor-in-Chief of Med One. He has\npublished 116 peer-reviewed research articles, 16 book chapters, 2 books, and 2 US patents. His current main research interest focuses on the studies of cancer proteomics and biomarkers, and the use of modern omics techniques and systems biology for PPPM in cancer, and on the development and use of 2DE-LC/MS for the large-scale study of human proteoforms.",institutionString:null,institution:{name:"Xiangya Hospital Central South University",country:{name:"China"}}},{id:"40482",title:null,name:"Rizwan",middleName:null,surname:"Ahmad",slug:"rizwan-ahmad",fullName:"Rizwan Ahmad",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/40482/images/system/40482.jpeg",biography:"Dr. Rizwan Ahmad is a University Professor and Coordinator, Quality and Development, College of Medicine, Imam Abdulrahman bin Faisal University, Saudi Arabia. Previously, he was Associate Professor of Human Function, Oman Medical College, Oman, and SBS University, Dehradun. Dr. Ahmad completed his education at Aligarh Muslim University, Aligarh. He has published several articles in peer-reviewed journals, chapters, and edited books. His area of specialization is free radical biochemistry and autoimmune diseases.",institutionString:"Imam Abdulrahman Bin Faisal University",institution:{name:"Imam Abdulrahman Bin Faisal University",country:{name:"Saudi Arabia"}}},{id:"41865",title:"Prof.",name:"Farid A.",middleName:null,surname:"Badria",slug:"farid-a.-badria",fullName:"Farid A. Badria",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/41865/images/system/41865.jpg",biography:"Farid A. Badria, Ph.D., is the recipient of several awards, including The World Academy of Sciences (TWAS) Prize for Public Understanding of Science; the World Intellectual Property Organization (WIPO) Gold Medal for best invention; Outstanding Arab Scholar, Kuwait; and the Khwarizmi International Award, Iran. He has 250 publications, 12 books, 20 patents, and several marketed pharmaceutical products to his credit. He continues to lead research projects on developing new therapies for liver, skin disorders, and cancer. Dr. Badria was listed among the world’s top 2% of scientists in medicinal and biomolecular chemistry in 2019 and 2020. He is a member of the Arab Development Fund, Kuwait; International Cell Research Organization–United Nations Educational, Scientific and Cultural Organization (ICRO–UNESCO), Chile; and UNESCO Biotechnology France",institutionString:"Mansoura University",institution:{name:"Mansoura University",country:{name:"Egypt"}}},{id:"329385",title:"Dr.",name:"Rajesh K.",middleName:"Kumar",surname:"Singh",slug:"rajesh-k.-singh",fullName:"Rajesh K. Singh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329385/images/system/329385.png",biography:"Dr. Singh received a BPharm (2003) and MPharm (2005) from Panjab University, Chandigarh, India, and a Ph.D. (2013) from Punjab Technical University (PTU), Jalandhar, India. He has more than sixteen years of teaching experience and has supervised numerous postgraduate and Ph.D. students. He has to his credit more than seventy papers in SCI- and SCOPUS-indexed journals, fifty-five conference proceedings, four books, six Best Paper Awards, and five projects from different government agencies. He is currently an editorial board member of eight international journals and a reviewer for more than fifty scientific journals. He received Top Reviewer and Excellent Peer Reviewer Awards from Publons in 2016 and 2017, respectively. He is also on the panel of The International Reviewer for reviewing research proposals for grants from the Royal Society. He also serves as a Publons Academy mentor and Bentham brand ambassador.",institutionString:"Punjab Technical University",institution:{name:"Punjab Technical University",country:{name:"India"}}},{id:"142388",title:"Dr.",name:"Thiago",middleName:"Gomes",surname:"Gomes Heck",slug:"thiago-gomes-heck",fullName:"Thiago Gomes Heck",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/142388/images/7259_n.jpg",biography:null,institutionString:null,institution:{name:"Universidade Regional do Noroeste do Estado do Rio Grande do Sul",country:{name:"Brazil"}}},{id:"336273",title:"Assistant Prof.",name:"Janja",middleName:null,surname:"Zupan",slug:"janja-zupan",fullName:"Janja Zupan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/336273/images/14853_n.jpeg",biography:"Janja Zupan graduated in 2005 at the Department of Clinical Biochemistry (superviser prof. dr. Janja Marc) in the field of genetics of osteoporosis. Since November 2009 she is working as a Teaching Assistant at the Faculty of Pharmacy, Department of Clinical Biochemistry. In 2011 she completed part of her research and PhD work at Institute of Genetics and Molecular Medicine, University of Edinburgh. She finished her PhD entitled The influence of the proinflammatory cytokines on the RANK/RANKL/OPG in bone tissue of osteoporotic and osteoarthritic patients in 2012. From 2014-2016 she worked at the Institute of Biomedical Sciences, University of Aberdeen as a postdoctoral research fellow on UK Arthritis research project where she gained knowledge in mesenchymal stem cells and regenerative medicine. She returned back to University of Ljubljana, Faculty of Pharmacy in 2016. She is currently leading project entitled Mesenchymal stem cells-the keepers of tissue endogenous regenerative capacity facing up to aging of the musculoskeletal system funded by Slovenian Research Agency.",institutionString:null,institution:{name:"University of Ljubljana",country:{name:"Slovenia"}}},{id:"357453",title:"Dr.",name:"Radheshyam",middleName:null,surname:"Maurya",slug:"radheshyam-maurya",fullName:"Radheshyam Maurya",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/357453/images/16535_n.jpg",biography:null,institutionString:null,institution:{name:"University of Hyderabad",country:{name:"India"}}},{id:"418340",title:"Dr.",name:"Jyotirmoi",middleName:null,surname:"Aich",slug:"jyotirmoi-aich",fullName:"Jyotirmoi Aich",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000038Ugi5QAC/Profile_Picture_2022-04-15T07:48:28.png",biography:"Biotechnologist with 15 years of research including 6 years of teaching experience. Demonstrated record of scientific achievements through consistent publication record (H index = 13, with 874 citations) in high impact journals such as Nature Communications, Oncotarget, Annals of Oncology, PNAS, and AJRCCM, etc. Strong research professional with a post-doctorate from ACTREC where I gained experimental oncology experience in clinical settings and a doctorate from IGIB where I gained expertise in asthma pathophysiology. A well-trained biotechnologist with diverse experience on the bench across different research themes ranging from asthma to cancer and other infectious diseases. An individual with a strong commitment and innovative mindset. Have the ability to work on diverse projects such as regenerative and molecular medicine with an overall mindset of improving healthcare.",institutionString:"DY Patil Deemed to Be University",institution:null},{id:"349288",title:"Prof.",name:"Soumya",middleName:null,surname:"Basu",slug:"soumya-basu",fullName:"Soumya Basu",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000035QxIDQA0/Profile_Picture_2022-04-15T07:47:01.jpg",biography:"Soumya Basu, Ph.D., is currently working as an Associate Professor at Dr. D. Y. Patil Biotechnology and Bioinformatics Institute, Dr. D. Y. Patil Vidyapeeth, Pune, Maharashtra, India. With 16+ years of trans-disciplinary research experience in Drug Design, development, and pre-clinical validation; 20+ research article publications in journals of repute, 9+ years of teaching experience, trained with cross-disciplinary education, Dr. Basu is a life-long learner and always thrives for new challenges.\r\nHer research area is the design and synthesis of small molecule partial agonists of PPAR-γ in lung cancer. She is also using artificial intelligence and deep learning methods to understand the exosomal miRNA’s role in cancer metastasis. Dr. Basu is the recipient of many awards including the Early Career Research Award from the Department of Science and Technology, Govt. of India. She is a reviewer of many journals like Molecular Biology Reports, Frontiers in Oncology, RSC Advances, PLOS ONE, Journal of Biomolecular Structure & Dynamics, Journal of Molecular Graphics and Modelling, etc. She has edited and authored/co-authored 21 journal papers, 3 book chapters, and 15 abstracts. She is a Board of Studies member at her university. She is a life member of 'The Cytometry Society”-in India and 'All India Cell Biology Society”- in India.",institutionString:"Dr. D.Y. Patil Vidyapeeth, Pune",institution:{name:"Dr. D.Y. Patil Vidyapeeth, Pune",country:{name:"India"}}},{id:"354817",title:"Dr.",name:"Anubhab",middleName:null,surname:"Mukherjee",slug:"anubhab-mukherjee",fullName:"Anubhab Mukherjee",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0033Y0000365PbRQAU/ProfilePicture%202022-04-15%2005%3A11%3A18.480",biography:"A former member of Laboratory of Nanomedicine, Brigham and Women’s Hospital, Harvard University, Boston, USA, Dr. Anubhab Mukherjee is an ardent votary of science who strives to make an impact in the lives of those afflicted with cancer and other chronic/acute ailments. He completed his Ph.D. from CSIR-Indian Institute of Chemical Technology, Hyderabad, India, having been skilled with RNAi, liposomal drug delivery, preclinical cell and animal studies. He pursued post-doctoral research at College of Pharmacy, Health Science Center, Texas A & M University and was involved in another postdoctoral research at Department of Translational Neurosciences and Neurotherapeutics, John Wayne Cancer Institute, Santa Monica, California. In 2015, he worked in Harvard-MIT Health Sciences & Technology as a visiting scientist. He has substantial experience in nanotechnology-based formulation development and successfully served various Indian organizations to develop pharmaceuticals and nutraceutical products. He is an inventor in many US patents and an author in many peer-reviewed articles, book chapters and books published in various media of international repute. Dr. Mukherjee is currently serving as Principal Scientist, R&D at Esperer Onco Nutrition (EON) Pvt. Ltd. and heads the Hyderabad R&D center of the organization.",institutionString:"Esperer Onco Nutrition Pvt Ltd.",institution:null},{id:"319365",title:"Assistant Prof.",name:"Manash K.",middleName:null,surname:"Paul",slug:"manash-k.-paul",fullName:"Manash K. Paul",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/319365/images/system/319365.png",biography:"Manash K. Paul is a scientist and Principal Investigator at the University of California Los Angeles. He has contributed significantly to the fields of stem cell biology, regenerative medicine, and lung cancer. His research focuses on various signaling processes involved in maintaining stem cell homeostasis during the injury-repair process, deciphering the lung stem cell niche, pulmonary disease modeling, immuno-oncology, and drug discovery. He is currently investigating the role of extracellular vesicles in premalignant lung cell migration and detecting the metastatic phenotype of lung cancer via artificial intelligence-based analyses of exosomal Raman signatures. Dr. Paul also works on spatial multiplex immunofluorescence-based tissue mapping to understand the immune repertoire in lung cancer. Dr. Paul has published in more than sixty-five peer-reviewed international journals and is highly cited. He is the recipient of many awards, including the UCLA Vice Chancellor’s award and the 2022 AAISCR-R Vijayalaxmi Award for Innovative Cancer Research. He is a senior member of the Institute of Electrical and Electronics Engineers (IEEE) and an editorial board member for several international journals.",institutionString:"University of California Los Angeles",institution:{name:"University of California Los Angeles",country:{name:"United States of America"}}},{id:"311457",title:"Dr.",name:"Júlia",middleName:null,surname:"Scherer Santos",slug:"julia-scherer-santos",fullName:"Júlia Scherer Santos",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/311457/images/system/311457.jpg",biography:"Dr. Júlia Scherer Santos works in the areas of cosmetology, nanotechnology, pharmaceutical technology, beauty, and aesthetics. Dr. Santos also has experience as a professor of graduate courses. Graduated in Pharmacy, specialization in Cosmetology and Cosmeceuticals applied to aesthetics, specialization in Aesthetic and Cosmetic Health, and a doctorate in Pharmaceutical Nanotechnology. Teaching experience in Pharmacy and Aesthetics and Cosmetics courses. She works mainly on the following subjects: nanotechnology, cosmetology, pharmaceutical technology, aesthetics.",institutionString:"Universidade Federal de Juiz de Fora",institution:{name:"Universidade Federal de Juiz de Fora",country:{name:"Brazil"}}},{id:"219081",title:"Dr.",name:"Abdulsamed",middleName:null,surname:"Kükürt",slug:"abdulsamed-kukurt",fullName:"Abdulsamed Kükürt",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/219081/images/system/219081.png",biography:"Dr. Kükürt graduated from Uludağ University in Turkey. He started his academic career as a Research Assistant in the Department of Biochemistry at Kafkas University. In 2019, he completed his Ph.D. program in the Department of Biochemistry at the Institute of Health Sciences. He is currently working at the Department of Biochemistry, Kafkas University. He has 27 published research articles in academic journals, 11 book chapters, and 37 papers. He took part in 10 academic projects. He served as a reviewer for many articles. He still serves as a member of the review board in many academic journals. He is currently working on the protective activity of phenolic compounds in disorders associated with oxidative stress and inflammation.",institutionString:null,institution:{name:"Kafkas University",country:{name:"Turkey"}}},{id:"178366",title:"Dr.",name:"Volkan",middleName:null,surname:"Gelen",slug:"volkan-gelen",fullName:"Volkan Gelen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/178366/images/system/178366.jpg",biography:"Volkan Gelen is a Physiology specialist who received his veterinary degree from Kafkas University in 2011. Between 2011-2015, he worked as an assistant at Atatürk University, Faculty of Veterinary Medicine, Department of Physiology. In 2016, he joined Kafkas University, Faculty of Veterinary Medicine, Department of Physiology as an assistant professor. Dr. Gelen has been engaged in various academic activities at Kafkas University since 2016. There he completed 5 projects and has 3 ongoing projects. He has 60 articles published in scientific journals and 20 poster presentations in scientific congresses. His research interests include physiology, endocrine system, cancer, diabetes, cardiovascular system diseases, and isolated organ bath system studies.",institutionString:"Kafkas University",institution:{name:"Kafkas University",country:{name:"Turkey"}}},{id:"418963",title:"Dr.",name:"Augustine Ododo",middleName:"Augustine",surname:"Osagie",slug:"augustine-ododo-osagie",fullName:"Augustine Ododo Osagie",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/418963/images/16900_n.jpg",biography:"Born into the family of Osagie, a prince of the Benin Kingdom. I am currently an academic in the Department of Medical Biochemistry, University of Benin. Part of the duties are to teach undergraduate students and conduct academic research.",institutionString:null,institution:{name:"University of Benin",country:{name:"Nigeria"}}},{id:"192992",title:"Prof.",name:"Shagufta",middleName:null,surname:"Perveen",slug:"shagufta-perveen",fullName:"Shagufta Perveen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/192992/images/system/192992.png",biography:"Prof. Shagufta Perveen is a Distinguish Professor in the Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia. Dr. Perveen has acted as the principal investigator of major research projects funded by the research unit of King Saud University. She has more than ninety original research papers in peer-reviewed journals of international repute to her credit. She is a fellow member of the Royal Society of Chemistry UK and the American Chemical Society of the United States.",institutionString:"King Saud University",institution:{name:"King Saud University",country:{name:"Saudi Arabia"}}},{id:"49848",title:"Dr.",name:"Wen-Long",middleName:null,surname:"Hu",slug:"wen-long-hu",fullName:"Wen-Long Hu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49848/images/system/49848.jpg",biography:"Wen-Long Hu is Chief of the Division of Acupuncture, Department of Chinese Medicine at Kaohsiung Chang Gung Memorial Hospital, as well as an adjunct associate professor at Fooyin University and Kaohsiung Medical University. Wen-Long is President of Taiwan Traditional Chinese Medicine Medical Association. He has 28 years of experience in clinical practice in laser acupuncture therapy and 34 years in acupuncture. He is an invited speaker for lectures and workshops in laser acupuncture at many symposiums held by medical associations. He owns the patent for herbal preparation and producing, and for the supercritical fluid-treated needle. Dr. Hu has published three books, 12 book chapters, and more than 30 papers in reputed journals, besides serving as an editorial board member of repute.",institutionString:"Kaohsiung Chang Gung Memorial Hospital",institution:{name:"Kaohsiung Chang Gung Memorial Hospital",country:{name:"Taiwan"}}},{id:"298472",title:"Prof.",name:"Andrey V.",middleName:null,surname:"Grechko",slug:"andrey-v.-grechko",fullName:"Andrey V. Grechko",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/298472/images/system/298472.png",biography:"Andrey Vyacheslavovich Grechko, Ph.D., Professor, is a Corresponding Member of the Russian Academy of Sciences. He graduated from the Semashko Moscow Medical Institute (Semashko National Research Institute of Public Health) with a degree in Medicine (1998), the Clinical Department of Dermatovenerology (2000), and received a second higher education in Psychology (2009). Professor A.V. Grechko held the position of Сhief Physician of the Central Clinical Hospital in Moscow. He worked as a professor at the faculty and was engaged in scientific research at the Medical University. Starting in 2013, he has been the initiator of the creation of the Federal Scientific and Clinical Center for Intensive Care and Rehabilitology, Moscow, Russian Federation, where he also serves as Director since 2015. He has many years of experience in research and teaching in various fields of medicine, is an author/co-author of more than 200 scientific publications, 13 patents, 15 medical books/chapters, including Chapter in Book «Metabolomics», IntechOpen, 2020 «Metabolomic Discovery of Microbiota Dysfunction as the Cause of Pathology».",institutionString:"Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology",institution:null},{id:"199461",title:"Prof.",name:"Natalia V.",middleName:null,surname:"Beloborodova",slug:"natalia-v.-beloborodova",fullName:"Natalia V. Beloborodova",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/199461/images/system/199461.jpg",biography:'Natalia Vladimirovna Beloborodova was educated at the Pirogov Russian National Research Medical University, with a degree in pediatrics in 1980, a Ph.D. in 1987, and a specialization in Clinical Microbiology from First Moscow State Medical University in 2004. She has been a Professor since 1996. Currently, she is the Head of the Laboratory of Metabolism, a division of the Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology, Moscow, Russian Federation. N.V. Beloborodova has many years of clinical experience in the field of intensive care and surgery. She studies infectious complications and sepsis. She initiated a series of interdisciplinary clinical and experimental studies based on the concept of integrating human metabolism and its microbiota. Her scientific achievements are widely known: she is the recipient of the Marie E. Coates Award \\"Best lecturer-scientist\\" Gustafsson Fund, Karolinska Institutes, Stockholm, Sweden, and the International Sepsis Forum Award, Pasteur Institute, Paris, France (2014), etc. Professor N.V. Beloborodova wrote 210 papers, five books, 10 chapters and has edited four books.',institutionString:"Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology",institution:null},{id:"354260",title:"Ph.D.",name:"Tércio Elyan",middleName:"Azevedo",surname:"Azevedo Martins",slug:"tercio-elyan-azevedo-martins",fullName:"Tércio Elyan Azevedo Martins",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/354260/images/16241_n.jpg",biography:"Graduated in Pharmacy from the Federal University of Ceará with the modality in Industrial Pharmacy, Specialist in Production and Control of Medicines from the University of São Paulo (USP), Master in Pharmaceuticals and Medicines from the University of São Paulo (USP) and Doctor of Science in the program of Pharmaceuticals and Medicines by the University of São Paulo. Professor at Universidade Paulista (UNIP) in the areas of chemistry, cosmetology and trichology. Assistant Coordinator of the Higher Course in Aesthetic and Cosmetic Technology at Universidade Paulista Campus Chácara Santo Antônio. Experience in the Pharmacy area, with emphasis on Pharmacotechnics, Pharmaceutical Technology, Research and Development of Cosmetics, acting mainly on topics such as cosmetology, antioxidant activity, aesthetics, photoprotection, cyclodextrin and thermal analysis.",institutionString:null,institution:{name:"University of Sao Paulo",country:{name:"Brazil"}}},{id:"334285",title:"Ph.D. Student",name:"Sameer",middleName:"Kumar",surname:"Jagirdar",slug:"sameer-jagirdar",fullName:"Sameer Jagirdar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/334285/images/14691_n.jpg",biography:"I\\'m a graduate student at the center for biosystems science and engineering at the Indian Institute of Science, Bangalore, India. I am interested in studying host-pathogen interactions at the biomaterial interface.",institutionString:null,institution:{name:"Indian Institute of Science Bangalore",country:{name:"India"}}},{id:"329248",title:"Dr.",name:"Md. Faheem",middleName:null,surname:"Haider",slug:"md.-faheem-haider",fullName:"Md. Faheem Haider",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329248/images/system/329248.jpg",biography:"Dr. Md. Faheem Haider completed his BPharm in 2012 at Integral University, Lucknow, India. In 2014, he completed his MPharm with specialization in Pharmaceutics at Babasaheb Bhimrao Ambedkar University, Lucknow, India. He received his Ph.D. degree from Jamia Hamdard University, New Delhi, India, in 2018. He was selected for the GPAT six times and his best All India Rank was 34. Currently, he is an assistant professor at Integral University. Previously he was an assistant professor at IIMT University, Meerut, India. He has experience teaching DPharm, Pharm.D, BPharm, and MPharm students. He has more than five publications in reputed journals to his credit. Dr. Faheem’s research area is the development and characterization of nanoformulation for the delivery of drugs to various organs.",institutionString:"Integral University",institution:{name:"Integral University",country:{name:"India"}}},{id:"329795",title:"Dr.",name:"Mohd Aftab",middleName:"Aftab",surname:"Siddiqui",slug:"mohd-aftab-siddiqui",fullName:"Mohd Aftab Siddiqui",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329795/images/system/329795.png",biography:"Dr. Mohd Aftab Siddiqui is an assistant professor in the Faculty of Pharmacy, Integral University, Lucknow, India, where he obtained a Ph.D. in Pharmacology in 2020. He also obtained a BPharm and MPharm from the same university in 2013 and 2015, respectively. His area of research is the pharmacological screening of herbal drugs/natural products in liver cancer and cardiac diseases. He is a member of many professional bodies and has guided many MPharm and PharmD research projects. Dr. Siddiqui has many national and international publications and one German patent to his credit.",institutionString:"Integral University",institution:null}]}},subseries:{item:{id:"2",type:"subseries",title:"Prosthodontics and Implant Dentistry",keywords:"Osseointegration, Hard Tissue, Peri-implant Soft Tissue, Restorative Materials, Prosthesis Design, Prosthesis, Patient Satisfaction, Rehabilitation",scope:"