\r\n\tRisk management aims to develop an efficient organizational development environment through risk planning, assessment, analysis, and control. This process will apply in all areas of activity, and the evaluation framework is the same regardless of the field. This volume will aim to appeal to chapters that address methods, models, evaluation frameworks, benefits, barriers, and other dimensions of risk management. \r\n\tSustainability and the circular economy are approaches approached by many companies and have become activities of global interest. Protecting the environment, streamlining the consumption of organizational resources, reducing the amount of waste generated, and other activities are objectives of these efforts. The circular economy contributes to the sustainable development of the company or country and the achievement of the global objectives of sustainable development. This book will aim to collect various studies for organizational and global sustainability. \r\n\tLeadership has become a globally desirable approach that can help improve organizational competitiveness and reduce organizational risks. Risks and barriers in risk-free management can be well managed through effective organizational leadership. This book will aim to bring together chapters that explore different areas of leadership.
",isbn:"978-1-83768-218-8",printIsbn:"978-1-83769-991-9",pdfIsbn:"978-1-83768-219-5",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!0,isSalesforceBook:!1,isNomenclature:!1,hash:"5d9c14d51cb7e214a9093c454eab1404",bookSignature:"Prof. Larisa Ivascu, Dr. Ben-Oni Ardelean and Dr. Muddassar Sarfraz",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/11937.jpg",keywords:"Technical Risk, Occupational Risk, Operational Risk Management, Economic Risk, Financial Risk, Thematic Mapping, Global Sustainability, Sustainability Models, Life Cycle Assessment, Critical Raw Materials, Global Leadership, Risks",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"May 5th 2022",dateEndSecondStepPublish:"June 2nd 2022",dateEndThirdStepPublish:"August 1st 2022",dateEndFourthStepPublish:"October 20th 2022",dateEndFifthStepPublish:"December 19th 2022",dateConfirmationOfParticipation:null,remainingDaysToSecondStep:"a month",secondStepPassed:!0,areRegistrationsClosed:!1,currentStepOfPublishingProcess:3,editedByType:null,kuFlag:!1,biosketch:"Dr. Ivascu obtained Ph.D. in Management and graduated with an MBA in Production and Transportation from the Faculty of Management, Politehnica University of Timisoara. 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1. Introduction
Once a patient receives kidney transplant, critical attention should be paid to ensure patient’s hemodynamic stability, they should be monitored for any side effects of the new medications and prevent infections that may jeopardize the renal allograft and patients’ general health. Medical problems such as diabetes and hypertension that may be medical complications of transplant immunosuppression need to be managed appropriately. This chapter will go over the medical management of the kidney transplant recipient.
2. Early post operative management
2.1. Assessing fluid status
There are two broad goals to assess fluid status: the transplanted kidney needs to receive adequate perfusion and make adequate amounts of urine.
When patients’ are admitted for kidney transplant, it is preferred to have the patient about 1kg above their dry weight (1). This is to decrease the risk for hypotension intra-operatively, and ensure that the patients are somewhat hypervolemic and there is enough mean arterial pressure to perfuse the new transplanted kidney at the end of the surgery. Post transplant, it is important to assess urine output on hourly basis to ensure that patients are not oliguric, i.e., urine output should at least be greater than 0.5ml/kg/hr or 500ml/24hrs. Patient’s pre-transplant urine output should be known and be accounted for when assessing for urine output adequacy post-transplant. Initial blood pressure and volume status on clinical exam should dictate fluid replacement. If the patient is hypovolemic, patient should be given isotonic saline in 500ml to 1L boluses until mean arterial pressure of at least 65 mm hg can be established. Most patients are hypervolemic. In that scenario, it is not necessary to replace all of the urine output.
There are many different protocols for replacement and maintenance fluids. In general, there is no evidence that crystalloids are better than colloids. Replacement fluid should also account for any other body fluid losses such as in nasogastric tube output. Half normal saline can be used for replacement fluid as urinary sodium after kidney transplant initially tends to be between 60 and 80 mEq/L (1). Maintenance fluids should account for insensible losses which can range in from 500cc to 1500cc in a 24 hour period for surgical patients (3). Typically the maintenance fluid used is 5% dextrose in water at the rate of at least 30cc/hr (1). For cases where electrolyte replacement is needed such as in potassium, this should be carefully given monitoring for any risk of hyperkalemia if patient is oliguric and preferably through a separate intravenous line. Electrolytes including potassium, phosphate, calcium and magnesium should be checked at least every 6 hours (1).
2.2. Delayed & slow graft function
The consensus definition of delayed graft function (DGF) is lacking, though, it is generally agreed upon that if dialysis is needed within first 7 days of transplant that constitutes delayed graft function (2). Delayed graft function, in reality, is acute kidney injury in transplanted kidney and should be worked up as any other acute kidney injury with attention paid to the special circumstance that is kidney transplant and differential diagnosis broadened accordingly to include acute rejection as well as acute ischemic tubular necrosis.
The long waiting list of patients awaiting kidney transplant and shortage of donors has necessitated accepting expanded criteria donors (ECD) and donation after cardiac death donors (DCD). Not surprisingly, incidence of DGF has increased to 21% for the years 1998-2008 from 14% during 1985-1992 (6,7,9). DGF increases the risk of graft rejection, transplant glomerulopathy and ultimately, decreases the long-term allograft survival (4,11,12). Long-term patient survival after DGF is not known, but it is likely that patients who suffer graft failure compared to patients with functioning grafts may have decrease survival rates. Besides ECD and DCD kidneys, there are several other risk factors for DGF. Donor specific risk factors include: donor age >60, cold ischemia time >15 hours, warm ischemia time > 45 minutes, Non T-cell antibody induction, female gender and obese donor (5,7,8,9,10,13,14,15,16). Recipient risk factors include: maintenance hemodialysis prior to transplantation, obesity, diabetes, male gender, age > 55, African-American race, small-for-size organ and prior immune sensitizing events such as blood transfusions, pregnancy and previous transplant (7,10,15,16,17). Machine perfusion technique for preservation of organ also seems to decrease the risk for DGF in ECD kidneys (7). The underlying mechanisms including molecular pathways and cytogenetic mechanisms are being established and may aid future prevention as well as treatment measures for DGF. For now, focus remains on prevention with controlling for risk factors as well as trying to avoid intra-operative and post-operative hypovolemic states and hypotensive conditions. If patient does have DGF, patient is supported with preventing further nephrotoxicity from all measures and providing dialysis until allograft kidney function recovers.
Indications for dialysis should be dictated by clinical circumstances but persistent acidosis, hyperkalemia especially with EKG changes suggestive of destabilization of cardiac membrane and volume overload that is resistant to high doses of diuretics. Both intermittent hemodialysis and peritoneal dialysis can be used. When hemodialysis is used, close attention should be paid to patient’s blood pressure and unless need for hypervolemic status, ultrafiltration should be avoided. Peritoneal dialysis can be used, though, dwelling volumes may need to be as low as 500ml in order to avoid worsening pain (1). Preferably hemodialysis should be performed, unless peritoneal dialysis catheter is readily available.
There is a subset of transplanted patients that do not require dialysis within the first 7 days, but the serum creatinine is very slow to decrease. This group of patients can be defined as having intermediate graft function or slow graft function (18). The risk factors and the graft outcomes are likely similar to DGF, though less severe (18). This can possibly be explained by lesser severity kidney injury or lesser degree of baseline clinical or subclinical kidney dysfunction in the allograft (18).
2.3. Immunosuppression
Every transplant center has their own immunosuppressive protocol which serves as guides for therapy based on type of transplant (kidney vs. kidney-pancreas) and patient’s risk group determined by pre-formed antibodies, sensitization status, age and race (2). Low-risk group patients such as two-haplotype match may require less immunosuppression. African-Americans, on the other hand, have been shown to require higher doses of immunosuppression.
There are two phases to immunosuppression. Acute rejection risk is highest from time zero to first few months after transplantation (2). The immunosuppresion induced at time zero is called induction phase. Maintenance immunosuppression is also introduced early-on, however, this therapy is maintained for the rest of the patient’s transplant life and constitutes the post-induction phase, the maintenance phase.
Both phases of immunosuppression are described in a separate chapter in this textbook and will not be further discussed here
2.4. Infection prophylaxis
All patients undergoing kidney transplant should received prophylaxis for infection as immunocompromised state post-transplant puts this group of patient at high risk of life-threatening common and uncommon infections. Any infection subsequently also increases risk of allograft failure through primary (e.g. ATN secondary to sepsis) or secondary mechanisms (e.g.. allograft rejection).
The following antimicrobial therapy should be given peri-operatively (1,2):
Standard antibiotic pre-operative prophylaxis per center based guidelines should be used. Prophylaxis should be against common skin and urinary tract pathogens. Cefazolin 1 or 2 grams based on body weight, generally, is the preferred agent.
Also, bactrim should be introduced as prophylaxis against for UTI, sepsis, nocardia and pneumocystis jiroveci pneumonia (pjp). One single strength tablet daily is the general recommendation. Dosing should be done renally and adjusted to patient’s creatinine clearance. For UTI prophylaxis, patients allergic to bactrim can use any other oral quinolone such as levaquin. In that scenario, patients should also get atovaquone 1500mg daily for pneumocystis jiroveci. Pentamidine monthly nebulized is another option if atovaquone cannot be tolerated. Dapsone 100mg daily may be used for same prophylaxis, though G6PD status must be checked. Any such prophylaxis should be continued for one year for pjp prophylaxis.
CMV status should be checked for both donor and recipient. CMV negative recipients from CMV positive donors are at highest risk for CMV disease as are patients receiving OKT3 or other t-cell depleting agents. CMV positive recipients are at risk for reactivation. All such patients should receive valganciclovir 900mg daily or three times weekly adjusted to renal function for 6 months. Alternatively, ganciclovir 1000mg three times daily or valacyclovir 2g four times daily can be used. All donor and recipient CMV negative patients should receive Acyclovir 400mg twice daily for 3 months.
During induction phase, oral or topical antifungal agents such as clotrimazole or nystatin are used. Systemic antifungal agents are not recommended in uncomplicated renal transplant.
3. Early post-transplant follow-up: First three months
3.1. Immunosuppression
The risk of acute rejection and allograft loss is highest in the first three months, so immunosuppression should be at its highest levels in this time period. The topic of immunosuppression has been reviewed in a separate chapter.
4. Long-term follow-up
4.1. Immunosuppression
All patients should be maintained on 2 or 3 drug regimen as long as the patient has functional graft. Target drug levels may be lowered after the first three months.
4.2. Patient and graft survival
Graft survival (i.e., patient survival with a functioning graft) has steadily improved. Graft survival for deceased donor kidneys in 2009 was 94.4% at 6 months; for transplants in 2008, 92.0% at 1 year; for transplants in 2006, 81.9% at 3 years; for transplants in 2004, 70.0% at 5 years; and for transplants in 1999, 42.7% at 10 years (19). Graft survival for living donor transplants in 2009 was 97.7% at 6 months; for transplants in 2008, 96.5% at 1 year; for transplants in 2006, 90.9% at 3 years; for transplants in 2004, 82.5% at 5 years; and for transplants in 1999, 59.6% at 10 years (19). While one-year graft survival has improved significantly, there is much room for improvement in 10-year graft survival.
The rate of late graft failure is traditionally measured by the graft half-life conditional on 1-year survival, defined as the time to when half of grafts surviving at least 1 year are still functioning. Graft half-lives for deceased and living donor kidneys have increased (19). For deceased donor kidneys, the half-life increased 45%, from 10.1 years for transplants in 1991 to 14.7 years for transplants in 2007 (19). For living donor kidneys, the half-life increased 68.2%, from 15.8 years for transplants in 1991 to 26.6 years for transplants in 2007 (19). Remarkably as per the 2010 Scientific Registry of Transplant Recipients/Organ Procurement and Transplantation Network annual report, the half-life of a deceased donor kidney in 2007 (14.7 years) is less than the half-life of a living donor kidney in 1991 (15.8 years). This suggests there is substantial room to improve the rate of late graft failure, at least for recipients of deceased donor kidneys.
The number of patients with a functioning kidney graft has doubled, from 68,200 in 1998 to 144,180 in 2009 (19).
Besides donor type, DGF and presence of HLA-antibodies also reduces the short-term graft survival. Long-term graft survival is also reduced by DGF, history of known HLA antibodies, HLA mismatching, cold ischemia time and insufficient immunosuppression. Inadequate renal mass for body size, CMV seropositivity, ongoing renal injuries, medical non-compliance, poorly managed hypertension, hyperlipidemia and recurrent or de novo glomerular disease are some of the other risk factors portending shorter graft survivial.
The most common causes of death in kidney transplant recipients include death from cardiovascular disease followed by infection, malignancy and other miscellaneous causes. The miscellaneous causes, such as pulmonary embolus, brain hemorrhage, colon or peptic ulcer perforation etc. can contribute 1-2% each to annual death rate (20). Death from cardiovascular disease remains the leading cause of mortality. It accounts for 40-55% of all deaths in transplant recipients (20). This includes congestive heart failure, coronary artery disease, cerebrovascular disease, and peripheral vascular disease. Renal transplant recipients have up to 10 times the rate of cardiac death and 50 times the annual rate of fatal or nonfatal cardiovascular events as the general population (21). Nearly 40% of patients have experienced a cardiovascular event at 36 months after renal transplantation, with congestive heart failure and myocardial infarction being the most common events (22, 23)). The prevalence of cerebrovascular events, though less than dialysis patients, is still high in patients who have undergone renal transplantation, and the risk of cerebral hemorrhage is higher than in the general population (24, 25). Finally, incidence of peripheral arterial disease is lower in renal transplant recipients, though de novo peripheral arterial disease increases the relative risk for death by almost twofold (26).
There are also other risk factors that impact survival of transplant recipients. Survival is superior with an allograft from a living donor compared to those who receive a kidney from a deceased donor, including both standard criteria and extended criteria donors. Older patients who undergo renal transplantation have a higher mortality rate than younger recipients. The presence of systemic disorders, particularly vascular disease, is associated with poorer long-term patient survival after renal transplantation. Survival of diabetic patients after renal transplantation (75 to 80 percent at five years) is lower than that reported in nondiabetic patients. It is still better than diabetic patients on dialysis whose 5-year survival is estimated to be 30% (2).
Perhaps, the most important predictor of graft survival is renal function. 1-year creatinine of less than 1.5mg/dl and change of less than 0.3mg/dl portends excellent long-term graft survival (5). Higher creatinine values at one year signal poor long-term graft outcome.
Despite all of these, patient and graft survival has improved significantly in the recent decade, which likely reflects our improved ability to manage patient and graft related risk factors.
5. Management of medical co-morbidities
5.1. Hypertension
Immediate post transplant hypertension is common and most commonly reflects pain, although, could also reflect overzealous volume resuscitation (27). If patient is volume overloaded, he or she should be diuresed. Controlling pain likely needs to be done simultaneously as sometimes early-on it is difficult to determine the causative etiology of hypertension. Moderately elevated blood pressure should be tolerated as it will help to maintain adequate renal perfusion to the transplanted kidney. However, if blood pressure is greater than 180mm hg despite best pain control in euvolemic patient, a dihydropyridine calcium channel blocker such as nifedipine can be used (28). This will allow for dual benefit of ameliorating some of the afferent arteriolar vasoconstriction induced calcineurin inhibitors. Alternatively, an alpha blocker such as clonidine can be used if pain is difficult to control and blood pressure remains high, i.e., there is excessive sympathetic stimulation. Blood pressure should not be lowered below 110 mm hg. If patient is not taking medications orally, labetalol or hydralazine can be used for intravenous administrations.
Chronic hypertension is a risk factor for CVD and affects graft survival in the long-term (27). In the era of CNIs, roughly 60-90% of patients seem to be afflicted with hypertension (29). The etiology of hypertension is likely multifactorial and management needs to be more nuanced. Goal blood pressure as defined by KDOQI guidelines should be <130/80 mm Hg (30). The same medications used for hypertension control in general population may be beneficial in renal transplant population as well.
KDOQI establishes five points for the evaluation and management of hypertension in renal transplant patients (30). First, patients should be evaluated for chronic kidney disease, cardiovascular disease and any cardiovascular risk factors. Second, diet and lifestyle changes should be part of all therapy including sodium intake <2.4g/day, weight loss if BMI is >25kg/m2, exercise, moderate alcohol intake and smoking cessation. Third, risk factors for cardiovascular disease should be managed concurrently such as diabetes and hyperlipidemia. Fourth, systolic blood pressure should be managed to less than 130 mm Hg with anti-hypertensive medications. Fifth, for patients with spot urinary protein-to-creatinine ratio >500-1000mg/g a lower blood pressure goal may be advisable, an ACE inhibitor or ARB should be added or dose should be increased, ACE inhibitor or ARB may need to be used in combination and if still needed another antihypertensive medication should be added as needed to lower proteinuria.
Since calcium channel blockers are used early in transplant, they can be considered first-line therapy (29). ACE inhibitors are second line therapy and have been shown safe to use 6-12 weeks after transplant. For de novo initiation, it is recommended that therapy be started at least 6 weeks post-transplant (29). A recent randomized study comparing nifedipine and lisinopril demonstrated improved kidney outcomes (lower creatinine and improved GFR at 2 years) with the use of nifedipine (28). However, the study had limited follow-up, and it cannot be determined whether the improved GFR with calcium-channel blockers reflects the short-term hemodynamic effects of these agents or a long-term protective effect. Post transplant patients with hypertension and a compelling indication for an ACE inhibitor or an ARB should be restarted on therapy as soon as the graft is functional, the serum creatinine level is <2.5 mg/dL, and the potassium level is <5.5 mEq/L. If the patient has proteinuria, ACE inhibitor or ARB can be used as long as the reduction in GFR is less than 30% over 4 months. Since ACE inhibitor or ARB can potentiate hyperkalemia caused by CNIs, close attention should be paid to patient’s potassium. Finally, tailoring of therapy for hypertension should be ultimately based on patient’s risk factors as disucussed below.
Heart failure patients can be treated with thiazide diuretics (assuming adequate function of the transplant kidney), beta-blocker, ACE inhibitor or an ARB. Post-MI patients can be treated with beta-blocker and ACE inhibitor. Patients with cardiovascular risk factors can be treated with same anti-hypertensive medications as heart failure patients. Patient with diabetes may benefit from added anti-proteinuric effect of non-dihydropyridine calcium channel blocker such as verapamil. Verapamil can increase the levels of CNIs and levels need to monitored more closely. Patients with CKD, previous stroke and post transplanterythrocytosis may benefit from ACE inhibitor. ARB can be used as an alternative in cases of CKD and post-transplant erythrocytosis. All of the above indications for specific anti hypertensive regimens for various clinical entities have nicely been summarized by Dunn et al. as well (29).
Renal artery stenosis in allograft is a rare cause of hypertension and should be thought of when blood pressure is persistently elevated despite multiple pharmacologic interventions, patient has flash edema and/or sudden elevations in blood pressure. It usually occurs 3 months to 2 years after transplant, but early occurrences can happen post-transplant (31). Reported incidence is variable between 1 and 23%. Risk factors for renal artery stenosis include deceased donor kidney, delayed graft function, obese patients, severe atherosclerotic disease, CMV infection, difficulties with surgical technique when harvesting the graft or when transplanting the graft in the recipient (31). In this scenario, a Doppler renal ultrasound can be ordered which has 100% specificity and sensitivity when peak systolic velocity is greater than or equal to 2.5m/sec (2). MRI may be needed and should be pursued after discussing risks and benefits of nephrogenic systemic fibrosis with the patient. Stenting or surgery may be necessary if patient does have renal artery stenosis.
5.2. Diabetes
New-onset diabetes after transplant (NODAT) or pre-transplant diabetes is associated with increased CVD risk, especially NODAT. Diabetes is also associated with increased mortality (87% relative risk) and increased graft failure (63% relative risk) (35). Other complications seen in non-transplant patients such as retinopathy, nephropathy and infections especially in immunocompromised state as well as neuropathy resulting in diabetic ulcers can occur. It is estimated that about 30% of patients can have new diagnosis of diabetes post-transplant and another 1/3rd can have impaired glucose tolerance by 1 year post-transplant (32). Risk factors for NODAT are same those for developing diabetes in non-transplant patients including age, obesity, African American race and Hispanic ethnicity, family history and impaired glucose tolerance (2). Tacrolimus more than cyclosporine has been associated with NODAT, perhaps due to its higher toxicity to pancreatic islet cells (34). Furthermore, a strong association has been demonstrated between HCV status and the development of diabetes after kidney transplantation, particularly in patients receiving tacrolimus-based immunosuppression from the time of transplantation (33).
According to 2003 International Consensus Guidelines and subsequent updates, diabetes mellitus after transplantation may be diagnosed at any time after transplantation by any of the following (35, 36):
Symptoms of diabetes plus random plasma glucose ≥200 mg/dL(11.1 mmol/L). Symptoms include polyuria, polydipsia, and unexplained weight loss.
Fasting plasma glucose ≥126 mg/dL(7.0 mmol/L). Fasting is defined as no caloric intake for at least eight hours.
Two-hour plasma glucose ≥200 mg/dL(11.1 mmol/L) during an oral glucose tolerance test with 75g of anhydrous glucose dissolved in water according to WHO guidelines.
Impaired fasting glucose and/or impaired glucose tolerance is diagnosed by:
Fasting plasma glucose between 100 and 125 mg/dL (5.6 and 6.9 mmol/L) or a two-hour plasma glucose between 140 and 199 mg/dL (7.8 and 11.0 mmol/L) during an oral glucose tolerance test, respectively, according to ADA guidelines.
Management of diabetes includes screening for risk factors, monitoring for biochemical evidence of impaired glucose tolerance/NODAT, modifying immunosuppression as needed and treating diabetes mellitus aggressively.
Stepwise approach to evaluation and management is recommended by International Consensus Guidelines for renal transplant patients (35). Pre-Transplant patients should be screened for diabetes. Post-transplant HbA1c should be checked every 3 months for the 1st year and a HbA1c <7.0 should be targeted, even if insulin is required. Immunosuppresion modulation must be weighed against the risk of rejection and avoided if at all possible. If modulated, glucocorticoids dosage can be reduced first, followed by decreasing dosing of tacrolimus and switching to cyclosporine if still needed. Dietitian, ophthalmologist, endocrinologist and podiatrist should be involved early in management of diabetic patients. Microalbuminuria should be treated with ACEI or ARB. Non-pharmacologic management should be given a chance including diet, exercise before pharmacologic approach is accepted. Other risk factors including lipids should be managed appropriately as CVD risk factor.
Once decision has been made to initiate oral therapy, oral agent may be alpha-glucosidase inhibitor (e.g., acarbose), biguanide (metformin is the most commonly used biguanide), a meglitinide (e.g., repaglinide), a sulfonylurea, or a thiazolidinedione (e.g., rosiglitazone) (35). Metformin is contraindicated in women with cr>1.5mg/dl and in men with cr>1.4mg/dl for concern of lactic acidosis (23). Sulfonylureas are safe in general to use, but glyburide is should be avoided in patients with GFR <50ml/min/1.73m2 (23). Acarbose should be avoided with cr<2mg/dl (23). Repaglinide should be started at 0.5 mg with meals if GFR <40 mL/min/1.73 m2 and titrated carefully (23). Thiazolidinediones do not require any dose adjustment. Other medication such as exetanide, an incretin mimetic should be avoided if gfr<30ml/min/1.73m2 (23). Dipeptidyl Peptidase-4 inhibitor, sitagliptin needs to be dosed renally (23).
As a complication of pre-existing diabetes if patients do develop diabetic ketoacidosis, they should be managed in intensive care unit. Algorithm is available from American Diabetic Association for management and should be closely followed. Volume resuscitation and insulin drip should be initial treatment. Many liters of normal saline may be required especially in post-op setting. Close eye should be kept on magnesium, potassium and phosphorous and they should be repleted aggressively. Subcutaneous insulin can be switched to once anion gap closes with 3-4 hours overlap with insulin drip.
5.3. Dyslipidemia
Dyslipidemia is common after kidney transplant. Although causative association between kidney transplant and cardiovascular disease (CVD) remains unproven, kidney transplant is considered to be coronary heart disease equivalent risk (37). Accordingly, hyperlipidemia should be managed aggressively.
Elevations in total cholesterol with low-density lipoprotein (LDL) are common, and triglycerides can be elevated often as well (23, 37). High-density lipoprotein (HDL) is usually normal. Cyclosporine, rapamycin and steroids have the greatest effect on serum lipid levels in dose-related fashion (23, 37). Other traditional risk factors as diabetes, obesity, smoking, hypertension, genetic factors and physical inactivity are also of equivalent importance. KDOQI has published guidelines for management of dyslipidemia in CKD patients which should be followed for transplant patients as well. Given the benefits of lowering CVD risk in general population and high risk of CVD in transplant population, the same risk reduction steps in terms of managing dyslipidemia should be taken for the transplant population. Goal LDL should be less than 100mg/dl (38). Therapeutic lifestyle changes (TLC) should be applied above 100mg/dl of LDL which include goals for intervention to minimize traditional risk factors. Patients should be counseled in smoking cessation with any necessary pharmacotherapy and psychotherapy, controlling blood pressure as detailed previously, reducing saturated and trans fats, taking daily 81mg aspirin, at least 30minutes of walking at least 5 days a week or running 15 mins for 3 days a week, weight loss of at least 10% in 1st year and managing diabetes as discussed previously (23, 37). If TLC fails to lower LDL below in 100mg/dl, statins should be added to TLC. If the LDL level is 130mg/dl of more, TLC and statins should be initiated simultaneously. Careful attention should be paid to introduction of statins to cyclosporine-based medication regimen. Cyclosporine increases AUC of all statins and especially with fluvasatin can cause rhabodmyolysis (23, 38). A good rule of thumb is this scenario is to use half of the recommended dose of statins with cyclosporine and tacrolimus (23, 37). Bile acid sequestrants such as cholestyramine are not typically recommended because they interfere with absorption of immunosuppressive medications, unless patients have severe coronary disease, have failed maximal medical management and risk of mortality from ischemic heart disease outweighs risk of rejection.
Triglycerides (TGs) should be below 500mg/dl and may need pharmacotherapy above these levels to reduce the risk of pancreatitis in addition to TLC (37). Consideration should also be given, in cases where maximal medical management has failed to lower LDL below recommended levels, to changing the immunosuppressive protocol to one that is less likely to cause high LDL levels, if this can be done without causing undue risk to graft (37).
Non-HDL cholesterol, which is calculated as total cholesterol minus HDL cholesterol may be a better predictor of coronary mortality and may be a surrogate for the major atherogenic protein, apolipoprotein B (38). Lowering non-HDL cholesterol to less than 130mg/dl may ultimately require a combined approach to reduce LDL and TG. If LDL is less than 100mg/dl or more but TGs are 200mg/dl and non-HDL is 130mg/dl or more, treatment of non-HDL to levels below 130mg/dl should be pursued with statin and fibrate or nicotinic acid (37).
The overall prevalence of dyslipidemia during the first year after transplantation is >50% (23). This high prevalence of dyslipidemia justifies screening and monitoring. In all adults, complete lipid profile should be checked (23, 37):
2-3 months after transplantation, or
2-3 months after change in treatment, or other conditions known to cause dyslipidemias, and
At least, annually thereafter
5.4. Obesity
Obesity in adults is defined, as it is in major guidelines for the general population, as body mass index (BMI) ≥30 kg/m2 (23). Because some individuals may have BMI ≥30 kg/m2 that is not due to excess body fat, it is recommended that the definition of obesity in adults include waist circumference ≥102 cm (≥40 in.) in men and ≥88 cm (≥35 in.) in women (23).
Weight gain is common after renal transplant and can be associated with steroid usage (38). Hyperphagia as a side effect of steroid usage also contributes. Obesity contributes dyslipidemia, hypertension, CVD and diabetes mellitus in transplant patients. Risk factors for weight gain post-transplant include female gender, African American race and young age (38). Obesity is also a risk factor for DGF (See Delayed Graft Function) and obese renal transplant recipients suffers more surgical complications, including wound infections, delayed wound healing, lymphoceles and perinephric hematomas (1,38, 39). Longer surgical times and hospital stays are also reported in obese transplant recipients (38). Obesity is also a risk factor for decreased pancreas and kidney graft survival in combined pancreas-kidney transplant recipients (1).
Is it beneficial to lose weight before transplantation? DOPPS found that in dialytic population higher BMI (30-34.9 kg/m2) is associated with lower mortality (42); higher mortality is associated with malnutrition (38). Weight loss also remains a difficult goal to achieve in dialytic population. Should the obese patients be excluded from transplant? Evidence has shown that when obese patients are transplanted their mortality rate is lower than the dialytic population (38).
Obesity in transplant patients should be managed with diet, exercise and nutritional counseling. A nutritionist should be involved in management. Small, uncontrolled trials in KTRs suggest that diet and other behavior modifications are safe and help reduce weight over the short term (40, 41). There is no evidence that any one diet is more effective than any other. A reasonable goal is to create a caloric deficit of 500–1000 kcal/day (23). Diets of 1000–1200 kcal/day for women and 1200–1500 kcal/day for men can be effective with increased physical activity in maintaining sustained weight loss (23).Weight loss medications have not been studied in renal transplant patients and as such Orlistat should not be given with cyclosporine as it interferes with its bioavailability and absorption. In cases of morbid obesity, patients may choose to undergo gastric bypass. This procedure may be safe in transplant patients, though, experience is limited (38). Absorption and metabolism of immunosuppressive medications may be altered after gastric bypass. Cyclosporine, tacrolimus, sirolimus and mycophenolic acid levels have been noted to be altered in gastric bypass patients and requires specific levels for those medications to be followed up (43). Gastric bypass also increases risk for hyperoxaluria and oxalate nephropathy, and when undergoing gastric bypass patients should be advised against risks for oxalate nephrolithiasis and secondary CKD (38). When patients develop oxalate nephropathy, reversal of bypass needs to be considered (38).
5.5. Smoking
Given smoking’s pleotropic detrimental effects on almost every organ in our body and association with CVD as well as post-transplant cancer, intense efforts should be made to help patients quit smoking. This should include asking at each visit, advising to quit, providing psychiatric and non-psychiatric counseling as needed, initiating pharmacotherapy as needed and helping patients set up target dates to quit smoking. Studies have shown that the patients more likely to quit smoking have been more likely than not been counseled by their physicians. Even counseling for 3 min or less is effective (44). The ‘5 As’ of counseling include: (i) ask about tobacco use, (ii) advise to quit through clear and personalized messages, (iii) assess willingness to quit, (iv) assist quitting and (v) arrange follow-up and support (44). A number of pharmacological approaches are available to promote smoking abstinence. All nicotine replacement therapies such as lozenges, gum, inhaler, spray and patch are safe to use (23). Varenicline, a partial agonist of nicotinic receptor can also be used in transplant recipients (23). Bupropion increases cyclosporine levels and they should be monitored (23).
5.6. Cardiovascular disease
So far we have discussed the traditional risk factors of CVD. Non-traditional risk factors such as homocysteine, uremia, left ventricular hypertrophy and graft dysfunction also have a significant role to play (21).There is a complex interplay between traditional and non-traditional risk factors causing CVD in kidney transplant patients. The strongest risk factor for cardiac risk is pre-existing CVD prior to transplant. All risk factors as discussed thus far should be managed aggressively whether patient has pre-existing CVD or new-onset CVD. Allograft dysfunction also contributes to CVD risk, whether this is mediated to systemic inflammation or through secondary hypertension, hyperlipidemia and albuminuria is unclear. Homocysteine levels are known to be significantly high in patients who experience cardiovascular events and are associated with higher mortality (45, 46). However, the causal effect of high homocysteine levels on CVD has not been established. High dose folic acid as well as vitamin B6 and B12 can effectively reduce homocysteine levels. When this reduction was achieved using folic acid, vitamin b6 and vitamin b12 in a randomized control trial, it did not reduce the all-cause mortality, ESRD or composite outcome which included cardiovascular death and myocardial infarction among other things (47). Another risk factor that increases CVD risk is anemia and this will be discussed next.
5.7.Anemia
World Health Organization defined anemia in 1968 as <13g/dl for men and <12g/dl for women which was based on observations from international nutritional studies (48). Since then there have been multiple attempts at re-defining anemia. Dependent on cut-off level of hemoglobin used for defining anemia, prevalence in post-transplant population varies roughly between 10% and 40% (49-53). Anemia is associated with worse patient and graft survival, higher rates of acute rejection and may further exaggerate left ventricular hypertrophy which is associated with higher cardiovascular mortality.
The belief that enough erythropoietin production with new allograft will resolve any degree of anemia in patients with CKD is not always fully realized (49). There can be many reasons for this phenomenon. In the early-post transplant period, anemia can be related to blood loss from surgery. Later on though the anemia may be related to decline in kidney function and secondary loss of erythropoietin production or from bone marrow suppression from immunosuppressants (50-53). However, other traditional and non-traditional risk factors need such as iron deficiency anemia with or without gastrointestinal bleeding, folate or vitamin b12 deficiency, hemolysis, parvovirus or other viral infections and medications need to be investigated and treated appropriately (50-53). Iron deficiency anemia is under-recognized and under-treated in post-transplant patients. Up to 60% of patients without initial iron deficiency can become iron-deficiency by 6 months (2). Since iron deficiency is associated with cardiovascular mortality independent of anemia timely recognition and treatment is important. Iron repletion can be estimated by ferritin 200mg/dl and transferrin saturation above 20%. Parvovirus infection which can cause refractory anemia can be treated with intravenous immunoglobulin and by lowering immunosuppression (1). Azathioprine, mycophenolic acid and sirolimus can also cause anemia, and the doses of these medications may need to be reduced (1). Other medications such as ACEIs, ARBs, ganciclovir or trimethoprim-sulfamethoxazole also cause anemia and need to be kept in mind when cause is being investigated (1). When no cause is found, iron stores are adequate, allograft function is impaired and meets indications for treatment as they are stated by KDOQI guidelines for CKD patients, epoetinalfa and aranesp should be administered (1).
5.8. Thrombotic microangiopathy
As a related cause of anemia, thrombotic microangiopathy (TMA) needs to included in differential diagnosis for causes of hemolysis. TMA is a histology manifestation of several clinical conditions such as TTP-HUS, antibody-mediated rejection (AMR) or toxicity of CNI. TMA may manifest itself limited to allograft or there might be evidence of systemic hemolysis such as increased lactate dehydrogenase, positive direct COOMBs test, increase indirect bilirubin, low haptoglobin and increase reticulocyte index with evidence of fragmented RBCs on peripheral smear. Thrombocytopenia accompanies systemic evidence of TMA. 15% of transplant patients have evidence of TMA and 3% show evidence of TTP (1). Treatment includes substitution of the calcineurin inhibitor with an alternative agent; belatacept and plasmapheresis may be utilized for management. If AMR is suspected, it should be treated accordingly; steroids should be pulsed, rituximab or bortezomib may also be used along with IVIG. Use of bortezomib may be limited by degree of thrombocytopenia. Another potential treatment if all else fails is eculizumab, which remains experimental.
5.9. Erythrocytosis
Post-transplant erythrocytosis (PTE) occurs in 8-15% of recipients (2). It is defined as a hemoglobin concentration greater than 17 g/dL and/or hematocrit greater than 51 percent that occurs following transplantation, persists for more than 6 months and occurs in the absence of another underlying cause (2). Most often PTE occurs within the first 8-24 months after transplantation (2). PTE appears predominantly in patients without native kidney nephrectomy and in those, who had an adequate erythropoiesis prior to transplantation, as evidenced by no or limited use of ESA while on dialysis (54). The pathogenesis of PTE is not well understood and multiple hormonal systems as well as growth factors such as erythropoetin, Insulin-like growth factor-1, serum-soluble stem cell factor (sSCF), rennin-angiotensin system and endogenous androgens have been implicated (2, 55-59). Endogenous erythropoietin appears to play the central role. Persistent erythropoietin secretion from the diseased and chronically ischemic native kidneys does not conform to the normal feedback. However, erythropoietin levels in most PTE patients still remain within the "normal range," indicating that erythrocytosis finally ensues by the contributory action of additional growth factors on erythroid progenitors, such as angiotensin II, androgens, sSCF and insulin-like growth factor 1 (IGF-1) (55-57, 59). 25% of all patients with PTE may see resolution without any treatment. 60% of patients experience symptoms which can include lethargy, dizziness, plethora, headache among other things (2). 10% to 20% patients experience both venous and arterial thromboembolic events (2). Secondary causes should be excluded: pulmonary disease, erythroleukemia, renal cancer, and hepatitis B or C (2). It is recommended that the hemoglobin be maintained at <17.5 g/dl by ACE inhibitors or ARB even if the patient is normotensive (2, 60). Phlebotomy is used for patients with PTE who do not respond to treatment with an ARB or ACE inhibitor (60, 61). It is also used in conjunction with ACE inhibitors or ARBs for patients who present with hemoglobin greater than 18.5 gm/dL (60, 61). Relapse of PTE is common if therapy is discontinued (2, 60).
5.10. Reproductive Issues
5.10.1. Men
After renal transplantation about 2/3rd of men experience improved libido and sexual function. Males with CKD can experience hypogonadism (63). Balance is restored in hypothalamic-pituitary axis (HPA) after transplantation; however, the degree of pathologic injury to testis determines the reversibility of sexual function (1). Histologically, seminiferous tubular destruction and germinal cell aplasia can be seen (64). Consequently, sperm motility improves but not sperm count or morphology (65). Both sirolimus and cyclosporine can impair biosynthesis of testosterone (1, 66-67). Azathioprine doesn’t seem to alter male fertility. It should be kept in mind that beta-blockers and alpha-blockers can induce infertility in transplant patients and calcium channel blockers may cause reversible functional defects in sperm (62). Male patients should be asked about their sexual function and referred to urology as necessary. There are no contraindications to use of agents such as sildenafil for erectile dysfunction in kidney transplant recipients.
5.10.2. Women
Female infertility in CKD results from altered HPA axis with high FSH, LH and prolactin levels. The normal hormonal balance is restored within a year after transplantation (1). Since 1958 over 14000 pregnancies have been reported in renal transplant recipients (69).
5.10.3. Family planning
Pregnancy in transplant patients should be considered high-risk. It used to be that the patients were told to wait 2 yrs after transplant before planning pregnancy (1). Now, guidelines are provided by American Society of Transplantation to help counsel patient (69). Patients can safely plan pregnancy as long as the following conditions are met (68, 69).
Graft function is optimal, defined as a serum creatinine<1.5 mg/dL, (132 micromol/L) with <500 mg/24 h protein excretion
There are no concurrent fetotoxic infections, such as CMV
The patient is not on known teratogenic or fetotoxic medications
The immunosuppressive regimen is stable at maintenance levels
A recent meta-analysis covering 50 studies, 4706 pregnancies and 3570 kidney transplant patients, provides the proof as to why pregnancies in these patient population is deemed high-risk (71). According to that meta-analysis, complications of preeclampsia (27.0%), gestational diabetes (8.0%), Cesarean section (56.9%) and preterm delivery (45.6%) were higher than the general US population (3.8%, 3.9%, 31.9% and 12.5%, respectively). Pregnancy outcomes were more favorable in studies with lower mean maternal ages; obstetrical complications were higher in studies with shorter mean interval between kidney transplant and pregnancy. The overall post-transplant live birth rate was 73.5% compared to 66.7% for general US population; similarly, the overall post-transplant miscarriage rate of 14.0% was lower than 17.1%. Transplant recipients usually deliver late preterm (34-36 weeks), roughly 30-50% pregnancies experience intra-uterine growth restriction to some degree and on average give birth to low birth weight babies (~2.5 grams) (70-72). Pregnancy doesn’t increase the risk of rejection (71). In the above mentioned study rejection rate was 4.2% in over 2400 pregnant patients studied for rejection (72). Pregnancy also doesn’t increase the risk of graft loss (69, 71).
Patients can be counseled that there are no increase risks of birth defects from taking prednisone, azathioprine, and cyclosporine or tacrolimus during pregnancy (2). For azathioprine, no fetal anomalies have been noted at doses equal to or less than 2 mg/kg while in case of cyclosporine dose elevations may be required due to increase volume of distribution during pregnancy (1). Blood levels should be followed when CNIs are used. MMF and sirolimus should be discontinued 6 months before pregnancy, substituted with alternative agents and patients should be monitored closely for rejection during this time period (2). All pregnancies should be planned.
For the patients who are counseled contraception, barrier contraception is the best modality. The American Society of Transplantation Consensus conference suggested the use of progestin-only oral contraceptives and estrogen/progestin formulations providing blood pressure is adequately controlled (69). Also, for patients taking hormonal contraception, CNI levels should be monitored and patients should be advised on the risk of thromboembolism (2).
5.10.4. Pregnancy
The incidence of hypertension in pregnant kidney transplant patients is four-fold higher than uncomplicated pregnancies. About 30% of pregnancies experience pregnancy-induced hypertension (1). Cyclosporine may add to this burden of hypertension. Methyldopa, hydralazine and labetalol can be safely used to negotiate hypertension during pregnancy (1). ACEIs and ARBs are contraindicated during pregnancy and should be stopped as soon as the patient becomes pregnant (1).
Rejection can occur during pregnancy; given hyperfiltration during pregnancy, it can be difficult to diagnose based on creatinine. Once suspected, kidney allograft can be biopsied using real-time renal ultrasound. Rejection can be treated with steroids. Safety of antilymphocyte globulins or rituximab is unknown in pregnancy. IVIG has been used and has not reported to have adverse effects (2).
To decrease the risk of rejection during perinatal period from stress of labor, stress-dosing of hydrocortisone 100mg every 6-8 hours should be considered (1).
All immunosuppressive medications enter maternal-fetal circulation to varying degrees. There is lack of data on pharmacokinetics and pharmacodynamics for various immunosuppressants making it difficult to predict about intra utero medication exposure. The placenta metabolizes prednisone to prednisolone; therefore, only low levels have been detected in the fetal circulation (1). Azathioprine is a prodrug that is rapidly metabolized to 6-mercaptopurine. This moiety does pass into the fetus and a relative fetal lack of the enzyme inosinepyrophosphorylase prevents it from being transformed into its active form thioinosinic acid (72). CNI readily cross the placenta and enter the fetal circulation (1, 73). In one study, it was found that cyclosporine in fetal blood was able to inhibit T cell function to the same degree as that found in maternal serum (73). Much less is known about the maternal–fetal transport of MMF and sirolimus. Although there appear to be no obvious congenital abnormalities associated with in utero exposure to conventional immunosuppressive agents, long-term follow-up of exposed children is needed.
During breast feeding this exposure may continue to the infant. It is not known whether this exposure constitutes a risk to the infant. Currently according to the consensus from American Society of Transplantation, breast feeding is not contraindicated. The American Academy of Pediatrics supports breastfeeding for mothers who are taking prednisone and advises against it for those who are taking cyclosporine (74). There are no specific American Academy of Pediatrics recommendations for mothers who are taking azathioprine or tacrolimus (74)
5. 11. Adherence
Nonadherence is associated with high risk of rejection and allograft loss (23). Kidney transplant recipients show most nonadherence with regards to their immunosuppression, as compared to recipients of other organs (23).
Adherence can be defined as ‘the extent to which the patient’s behavior matches the agreed-upon prescriber’s recommendations’(23). Non adherence is defined by KDIGO as deviation from the prescribed medication regimen sufficient to adversely influence the regimen’s intended effect’ (23). These definitions are derived from a consensus conference on adherence (75). Non adherence can be at the time of transplant or subsequently. It can be complete or partial and encompasses non compliance with timing of medications (23). It is estimated that non adherence to long-term medication is as high as 50% in developed countries and higher in developing countries (76). Risk factors for nonadherence include nonadherencebehavior prior to transplantation, psychiatric illness, personality disorders, poor social support, substance abuse and other high-risk behavior, adolescence, high education level, time since transplantation, lack of adequate follow-up with transplant specialists, inadequate pretransplant education, multiple adverse effects from medications, complex medication regimens, expensive medications and poor access to healthcare (23, 75, 77).
Ongoing patient education and psychosocial support remains two important cornerstones for treating patient nonadherence. The following are some approaches that are more likely to promote adherence and have been divided into two arms: A) education and medical interventions and behavioral and B) psychosocial approaches. Combination of these interventions produces the best results (79-80).
Examples of education and medical interventions (23, 77):
Ensure that patients know their medications by name, dosage and reason for prescription; reinforce these points during every clinic visit.
Inform patients about the adverse effects of drugs.
Provide written instructions for each change in medication dose or frequency.
Reduce the number and frequency of medications. If possible, medications should be given once daily
Ensure the patients understand that they need to continue taking immunosuppressive agents even if the transplanted organ is functioning well.
Help establish a system to remind patients to take their medications such as pill boxes or electronic devices that help remind the patient when to take their medications
Inquire about problems during every clinic visit, and address specific patient concerns.
Monitor compliance with laboratory work, clinic visit and prescription refills.
Monitor patients with highest risk of nonadherence (i.e., poorly educated, low family income, patients with history of nonadherence) and provide all possible interventions available
Concomittantly, behavioral strategies and psychosocial approaches also need to be part of the interventions as education and medical interventional strategies are unlikely to suffice on their own.
Examples of behavioral and psychosocial approaches (23, 77):
Provide positive support feedback for adherence
Encourage patient to demonstrate a track record of medication adherence and knowledge.
Encourage individual team members to develop rapport with patient.
Identify and involve a backup support system (family or friends).
Treat depression, anxiety or other psychological issues.
Ultimately there is no single strategy that works for all patients and all of the above approaches need to be individualized to the patient at hand (23). A transplant pharmacist involvement can also improve adherence at 1-year with medication regimens (80, 81)
Zoster: Recommended only before, but not after transplant
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Introduction",level:"1"},{id:"sec_2",title:"2. Early post operative management",level:"1"},{id:"sec_2_2",title:"2.1. Assessing fluid status",level:"2"},{id:"sec_3_2",title:"2.2. Delayed & slow graft function",level:"2"},{id:"sec_4_2",title:"2.3. Immunosuppression",level:"2"},{id:"sec_5_2",title:"2.4. Infection prophylaxis",level:"2"},{id:"sec_7",title:"3. Early post-transplant follow-up: First three months",level:"1"},{id:"sec_7_2",title:"3.1. Immunosuppression",level:"2"},{id:"sec_9",title:"4. Long-term follow-up",level:"1"},{id:"sec_9_2",title:"4.1. Immunosuppression",level:"2"},{id:"sec_10_2",title:"4.2. Patient and graft survival",level:"2"},{id:"sec_12",title:"5. Management of medical co-morbidities",level:"1"},{id:"sec_12_2",title:"5.1. Hypertension",level:"2"},{id:"sec_13_2",title:"5.2. Diabetes",level:"2"},{id:"sec_14_2",title:"5.3. Dyslipidemia",level:"2"},{id:"sec_15_2",title:"5.4. Obesity",level:"2"},{id:"sec_16_2",title:"5.5. Smoking",level:"2"},{id:"sec_17_2",title:"5.6. Cardiovascular disease",level:"2"},{id:"sec_18_2",title:"5.7.Anemia",level:"2"},{id:"sec_19_2",title:"5.8. Thrombotic microangiopathy",level:"2"},{id:"sec_20_2",title:"5.9. Erythrocytosis",level:"2"},{id:"sec_21_2",title:"5.10. Reproductive Issues",level:"2"},{id:"sec_21_3",title:"5.10.1. Men",level:"3"},{id:"sec_22_3",title:"5.10.2. Women",level:"3"},{id:"sec_23_3",title:"5.10.3. Family planning",level:"3"},{id:"sec_24_3",title:"5.10.4. Pregnancy",level:"3"},{id:"sec_27",title:"5. 11. Adherence",level:"1"}],chapterReferences:[{id:"B1",body:'DanovitchGHandbook of Kidney Transplantationth edition. Philadelphia: Lippincott Williams & Wilkins. 2009'},{id:"B2",body:'UptodateInc. https://www.uptodate.com.Accessed July 20, 2012'},{id:"B3",body:'FugeW. WHoggB. MThe Insensible Losses In Surgical Patients. Ann. Surg. 1938108114'},{id:"B4",body:'YarlagaddaS. GCocaS. GFormica RN Jr, Poggio ED, Parikh CR. Association between delayed graft function and allograft and patient survival: A systematic review and meta-analysisNephrol Dial Transplant 20092410391047\n\t\t\t'},{id:"B5",body:'HariharanSMcbrideM. ACherikhW. STollerisC. BBresnahanB. AJohnsonC. PPost-transplant renal function in the first year predicts long-term kidney transplant survivalKidney Int 200262311318'},{id:"B6",body:'United Network of Organ Sharing Databasehttps://www.unos.org.Accessed July 21, 2012\n\t\t\t'},{id:"B7",body:'SiedleckiAIrishWBrennanD. CDelayed Graft Function in Kidney Transplant. Am.J. Transplant. 20111122792296\n\t\t\t'},{id:"B8",body:'PretagostiniRLaiQPoliLLevi Sandri GB, Travaglia D, Rossi M. Predicitive Characteristics of Delayed Graft Function After Expanded And Standard Criteria Donor Kidney Transplantations. Transplant Proc. 200941114951\n\t\t\t'},{id:"B9",body:'OjoA. OWolfeR. AHeldP. JPortF. KSchmouderR. LDelayed Graft function: Risk factors and implications for renal allograft survival.Transplantation199763968974'},{id:"B10",body:'KoningO. HPloegR. JVan BockelJ. HGroenewegenMVan Der WoudeF. JPersijnG. Get alRisk factors for delayed graft function in cadaveric kidney transplantation: A prospective study of renal function and graft survival after preservation with University of Wisconsin solution in multi-organ donors. European Multicenter Study Group. Transplantation 19976316201628'},{id:"B11",body:'ShoskesD. ACeckaJ. MDeleterious effects of delayed graft function in cadaveric renal transplant recipients independent of acute rejection.Transplantation19986616971701'},{id:"B12",body:'ShoskesD. ACeckaJ. MEffect of delayed graft function on short and long-term kidney graft survival.Clin Transplant 1997297303'},{id:"B13",body:'MclarenA. JJassemWGrayD. WFuggleS. VWelshK. IMorrisP. JDelayed graft function: Risk factors and the relative effects of early function and acute rejection on long-term survival in cadaveric renal transplantationClin Transplant 199913266272'},{id:"B14",body:'GiralMBertolaJ. PFoucherYVillersDBironneauEBlanloeilYet alEffect of brain-dead donor resuscitation on delayed graft function: Results of a monocentric analysis.Transplantation20078311741181'},{id:"B15",body:'DoshiM. DGargNReeseP. PParikhC. RRecipient risk factors associated with delayed graft function: A paired kidney analysisTransplantation201191666671'},{id:"B16",body:'Meier-kriescheH. UArndorferJ. AKaplanBThe impact of body mass index on renal transplant outcomes: A significant independent risk factor for graft failure and patient death.Transplantation2002737074'},{id:"B17",body:'ParekhJBostromAFengSDiabetes mellitus: A risk factor for delayed graft function after deceased donor kidney transplantationAm J Transplant 201010298303'},{id:"B18",body:'JohnstonOOKellyPSpencerSDonohoeJWalsheJ. JLittleDM, et al. Reduced graft function (with or without dialysis) vs immediate graft function-a comparison of long-term renal allograft survivalNeph. Dial. Transplant. 20062122702274\n\t\t\t'},{id:"B19",body:'SRTR-Scientific Registry of Transplant Recipientshttp://www.srtr.org/annual_reports/2010.Accessed July 27, 2012'},{id:"B20",body:'BriggsJ. DCauses of death after renal transplantation.Nephrol Dial Transplant 20011545 EOF9 EOF'},{id:"B21",body:'LiefeldtLBuddeKRisk factors for cardiovascular disease in renal transplant recipients and strategies to minimize risk.Transpl International 20102311911204\n\t\t\t'},{id:"B22",body:'ShiraliA. CBiaM. JManagement of cardiovascular disease in renal transplant recipientsClin J Am SocNephrol 20083491504'},{id:"B23",body:'Kidney Disease: Improving Global Outcomes (KDIGO) Transplant Work GroupKDIGO clinical practice guideline for the care of kidney transplant recipients. Am J Transplant 2009Suppl. 3): S1155'},{id:"B24",body:'LentineK. LRocca Rey LA, Kolli S, Bacchi G, Schnitzler MA, Abbott KC, et al. Variations in the risk for cerebrovascular events after kidney transplant compared with experience on the waiting list and after graft failureClin J Am SocNephrol 200831090101'},{id:"B25",body:'AbediniSHolmeIFellströmBJardineAColeEMaesBet alCerebrovascular events in renal transplant recipients. Transplantation 2009871127'},{id:"B26",body:'SnyderJ. JKasiskeB. LMacleanRPeripheral arterial disease and renal transplantation.J Am SocNephrol 200617205668'},{id:"B27",body:'OpelzGWujciakTRitzEAssociation of chronic kidney graft failure with recipient blood pressure: collaborative transplant study.Kidney Int 19985321722\n\t\t\t'},{id:"B28",body:'MidtvedtKHartmannAFossAFauchaldPNordalK. PRootweltKet alSustained improvement of renal graft function for two years in hypertensive renal transplant recipients treated with nifedipine as compared to lisinopril. Transplantation 20017217871792\n\t\t\t'},{id:"B29",body:'DunnB. LTeusinkA. CTaberD. JHemstreetB. AUberL. AWeimertN. AManagement of Hypertension in Renal Transplant Patients: A Comprehensive Review of Nonpharmacologic and Pharmacologic Treatment Strategies.Ann Pharmacother July/August 20104412591270\n\t\t\t'},{id:"B30",body:'K/DOQI Clinical Practice Guidelines on Hypertension and Antihypertensive Agents in Chronic Kidney Disease. http://www.kidney.org. (Accessed on July 31, 2012).'},{id:"B31",body:'BrunoSRemuzziGRuggenentiPTransplant Renal Artery Stenosis.J.Am.Soc.Neph, 200415134141\n\t\t\t'},{id:"B32",body:'2011 USRDS Annual Reporthttp://www.USRDS.org.Accessed August 14, 2012'},{id:"B33",body:'BloomR. DRaoVWengFGrossmanR. ACohenDMangeK. CAssociation of hepatitis C with post transplant diabetes in renal transplant patients on tacrolimus. J Am SocNephrol 200213137480'},{id:"B34",body:'KasiskeB. LSnyderJ. JGilbertsonDMatasA. JDiabetes Mellitus After Kidney Transplantation In The United StatesAm. J. 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Gastric bypass in morbidly obese patients with chronic renal failure and kidney transplant.Transplantation200478469474'},{id:"B44",body:'Counseling to prevent tobacco use and tobacco-caused diseaseIn, Rockville,MD, US Preventive Services Task Force. Agency forHealthcare Research and Quality. 200315\n\t\t\t'},{id:"B45",body:'Ducloux\n\t\t\t\t\t\tD, Motte\n\t\t\t\t\t\tG, Challier\n\t\t\t\t\t\tB, Gibey\n\t\t\t\t\t\tR, ChalopinJM.. Serum total homocysteine and cardiovascular disease occurrence in chronic, stable renal transplant recipients: a prospective study. J Am SocNephrol 2000; 11:134-7.'},{id:"B46",body:'WinkelmayerW. CKramarRCurhanG. CChandrakerAEndlerGFödingerMet alFasting plasma total homocysteine levels and mortality and allograft loss in kidney transplant recipients: a prospective study. J Am SocNephrol 20051625560'},{id:"B47",body:'BostomA. GCarpenterM. AKusekJ. WLeveyA. SHunsickerLPfefferM. 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Nephrol Dial Transplant 2006; 21:3559. '},{id:"B52",body:'Molnar\n\t\t\t\t\t\tMZ,MucsiI, Macdougall IC, MarshJE, Yaqoob M, Main J,et al. Prevalence and management of anaemia in renal transplant recipients: data from ten European centres. Nephron ClinPract 2010; 117: c127-134. '},{id:"B53",body:'\n\t\t\t\t\tMooreL. WSmithS. OWinsettR. PAcchiardoS. RGaberA. OFactors affecting erythropoietin production and correction of anemia in kidney transplant recipientsClin Transplant 1994835864\n\t\t\t'},{id:"B54",body:'FreiDGuttmannR. DGormanPA matched-pair control study of postrenal transplant polycythemia.Am J Kidney Dis 198236 EOF42 EOF\n\t\t\t'},{id:"B55",body:'GastonR. SJulianB. ACurtisJ. JPost-transplant erythrocytosis: an enigma revisited. Am J Kidney Dis 1994\n\t\t\t'},{id:"B56",body:'KesslerMHestinDMayeuxDMertesP. MRenoultEFactors predisposing to post-renal transplant erythrocytosis. A prospective matched-pair control study.ClinNephrol 199683 EOF9 EOF\n\t\t\t'},{id:"B57",body:'VlahakosD. 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JSexual function in chronic kidney disease.Adv Chronic Kidney Dis. 200714119125'},{id:"B64",body:'ZeynelogluH. BOktemMDurakTMale infertility after renal transplantation: Achievement of pregnancy after intracytoplasmic sperm injection.Transplant Proc. 20053730813084'},{id:"B65",body:'AkbariFAlaviMEsteghamatiAMehrsaiADjaladatHZohrevandRet alEffect of renal transplantation on sperm quality and sex hormone levels. BJU Int. 2003Aug; 922813'},{id:"B66",body:'TondoloVCitterioFPanocchiaNNanniGFaviEBresciaAet alGonadal function and immunosuppressive therapy after renal transplantation.Transplant Proc. 2005May;3719157'},{id:"B67",body:'KaczmarekIGroetznerJAdamidisILandwehrPMuellerMVogeserMSirolimus impairs gonadal function in heart transplant recipientsAm J Transplant. 2004Jul;410848'},{id:"B68",body:'MckayD. BJosephsonM. APregnancy after Kidney Transplantation CJASN 2008Mar;3Suppl 2: S11725'},{id:"B69",body:'MckayD. BJosephsonM. AArmentiV. TAugustPCosciaL. ADavisC. 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1. Introduction
Solid acids are the most important solid catalysts nowadays, considering not only the total amount used but also the final economic impact. Solid catalysts have a great advantage over liquid catalysts. They are, in fact, generally almost fully recovered from reaction products without any operation or with quite easy procedures.
Probably infrared spectroscopy is the most largely used spectroscopy technique to study the adsorption of molecules on solid surfaces. Other techniques need an ultra-high vacuum, while IR spectroscopy can be investigated over a wide range of temperatures and pressures. However, most of the materials used as adsorbents, for instance, semiconductor and insulator surfaces, have strong IR signals, so the spectrum is predominantly that of the adsorbent, which is a disadvantage [1].
Compared to infrared absorption spectroscopy, Raman scattering has an inherently low sensitivity. But this limitation was largely surpassed by the development of high-performance single-stage spectrometers combined with notch filters and CCD cameras. Moreover, the sensitivity of Raman spectroscopy can be increased by taking advantage of resonance effects, for example in resonance Raman spectroscopy, coherent anti-Stokes Raman spectroscopy (CARS), surface-enhanced Raman spectroscopy (SERS), or tip-enhanced Raman spectroscopy (TERS) [2].
The interaction of molecules adsorbed on solid acids can be weak or strong, but in solids with higher acidity, the interaction is often so strong that electron abstraction may occur, occurring in fact a redox reaction. It depends not only on the acidity of the solid acid but also on the ionization potential of the adsorbed molecule. Organic molecules with relatively low ionization potential can be ionized giving rise to radical cations. However, depending on some conditions, a charge transfer complex is observed. Radical cations of molecules with extended conjugation, as polyenes and some aromatic molecules, have electronic absorption shifted to the visible region of the spectrum, opening the possibility of exploring the Resonance Raman effect with the enhancement of the chromophore responsible for the electronic transition.
The theory behind the resonance Raman Effect will not be presented here, but for whoever is interested, the excellent article by Clark and Dines is recommended [3].
In the present review the interaction of organic molecules with high acidity solids and the species resulting from the interaction, observed through Resonance Raman spectroscopy (RRS), is presented. Three types of solid acids, zeolites, clays, and sulfated metallic oxides, are chosen because of the greater number of RRS studies with these solid acids.
2. Zeolites
Zeolites are crystalline aluminosilicates with general chemical composition Mx/nx+[AlxSiyO2(x + y)]zH2O. Its lattice consists of a network of SiO44− and AlO44− tetrahedra with Si or Al atoms at the centers and oxygen atoms in each corner. The presence of aluminum atoms replacing silicon atoms in the zeolite network creates an excess negative charge. Charge-compensating cations (M+) are introduced into the structure to compensate for the negative charge. These readily exchangeable cations are not covalently bound to the zeolite framework [4].
The Si/Al ratio may vary from Si/Al = 1 (faujasite X) to Si/Al = ∞ (silicalite). The number of cations in the framework and the zeolite properties as the thermal and chemical stability or the polarity of the internal surfaces are determined by the Al content.
Electron transfer processes at interfaces are central to many important chemical processes and are vital to energy conversion and storage technologies. Investigations of the mechanism of electron transfer reactions at interfaces are often difficult to perform because of the heterogeneity of the surfaces and because the reaction intermediates, often radicals, are generally highly reactive and difficult to isolate for extended periods of time to allow detailed characterization [5].
A common way to stabilize these intermediates is their isolation in frozen rare gas or halocarbon matrices.
Zeolites and other porous solids are an alternative to the study of electron-transfer processes, allowing the stabilization of radical cations for longer periods of time [6]. Garcia and Roth had made an extensive review about the generation and reaction of organic radical cation in zeolites [7].
Some acid zeolites have the ability to generate spontaneously organic radical cations upon adsorption of organic electron donors or the radical cations can be generated by the action of radiation or light. The restricted mobility within zeolite pores limits the tendency of free radicals or radical cations to dimerize and prevents access to reagents that typically would cause their decay in solution.
The spontaneous ionization depends on the ionization potential of the guest as well as on the ionizing capacity of the host, which is directly related to the Si/Al ratio and to the nature of the charge balancing cation. The highest yield was found from H+. Ramamurthy et al. showed that an increasing Al content enhanced the electron acceptor ability [4]. They reported the generation of stable radical cations from α,ω-diphenyl polyenes (trans-stilbene, trans, trans-1,4-diphenyl butadiene, all-trans- 1,6-diphenylhexatriene, and all-trans-1,8-diphenyl-1,3,5,7- octatetraene upon inclusion in the channels of pentasil zeolites.
A systematic spectroscopic investigation of radical species of several organic molecules formed upon the interaction with zeolites was done by Moissette in the 2000s and 2010s. Most of the investigated molecules are aromatic, as trans-stilbene anthracene and other ones. UV–visible, ESR, and Raman spectra were obtained with excitation in and off-resonance, but in the present review, only the resonance Raman results of Moissette are presented. Only the Moissette results with t-stilbene and N, N, N′, N′ -tetramethyl-p-phenylenediamine (TMPD) and N, N, N′, N′ -tetramethylbenzidine (TMB) are included in this review, but Moissette investigated a larger number of molecules, as can be found in the literature.
2.1 Trans-stilbene
Many Moissette studies were done with trans-stilbene, a molecule considered as a prototype system for the photoisomerization reaction and as a model for photosensitized electron-donor structure [8]. Trans-Stilbene (E-1,2-diphenylethene, t-St) has a relatively low ionization potential value (Ig = 7.65 eV in the gas phase) and has the appropriate dimensions to enter the channels of medium-pore zeolites [9]. Moissette et al. investigated the formation of t-stilbene radicals in HZSM-5 and HFER zeolites, that differ in their pore size [10]. As HFER has a narrower pore size the radical cation is the only stable species while in the larger pore diameter HZSM-5, the electron transfers are faster and the radical cation (RC) evolves after several minutes/hours to a charge transfer complex (CTC). Three exciting laser lines, at 473, 515, and 633 nm, have been used to take advantage of the RR effect. The wavelengths have been chosen to correspond to the absorptions of the charge separated states and could give rise to resonance Raman enhancement of the specific vibrational modes of the radical cation or the charge transfer complex. The RC has a characteristic band at 475 nm, while the bands at 565 and 625 nm are characteristic of CTC 1 and the bands at 375 and 700 nm are characteristic of CTC 2. Exciting with 473 nm Raman bands at 1285 and 1605 cm−1 and a weak band at about 1565 cm−1 were observed. The spectrum excited with 515 nm presents the same main Raman bands characteristic of RC at 1290 and 1609 cm−1 as well as the contributions at 1560 and 1550 cm−1. The resonance effect of the RC species is not as marked as at 473 nm given that the excitation is in the lower energy side of the absorption band. A broadening is observed especially at about 1600 cm−1 corresponding to the position of CTC contribution. Exciting with 633 nm broad and intense bands centered at 1596 cm−1 and 1192 cm−1 containing several contributions are observed. Several bands of lower intensity are also observed around 1320 cm−1. These features were assigned to the resonance-enhanced bands of the CTC 1 species. The authors do not assign Raman bands to CTC 2 species, but the broadening of the Raman bands exciting with 633 nm may be a sign of the presence of another species.
When t-St was adsorbed in the medium size channel of nonacidic NaZSM-5 zeolite, the interaction between Na+ cation and t-St occurred through one phenyl group coordinated to the Na+ cation [11]. The similarity between Raman spectra of t-St in solution and occluded in NaZSM-5 led the authors to conclude that the interaction was weak, with no radical formation. Only with laser UV (266 nm) photoionization t-St•+ was generated. Exciting with 4880 nm resonance Raman bands of the radical cation was observed. With 632 nm excitation, a different spectrum was observed, assigned to a primary t-St•+-electron pair. Contrary to Moissette that did not observe spontaneous ionization of t-stilbene in NaZSM-5 zeolite, Ramamurthy [4] reported the formation of radical cation species upon adsorption of t-stilbene on the zeolite. Ramamurthy made the adsorption of t-stilbene diluted in a trimethylpentane solution. As Moissette did the adsorption experiments in the solid-state, this fact may have led to differences in the adsorption behavior.
2.2 N, N, N′, N′ -tetramethyl-p-phenylenediamine (TMPD) and N, N, N′, N′ -tetramethylbenzidine (TMB)
N, N, N′, N′ -tetramethyl-p-phenylenediamine (TMPD) and N, N, N′, N′-tetramethylbenzidine (TMB) were used as probes to characterize the nature of active sites in acid zeolite HZSM-5 [12]. These two amines are strong electron donors and are known to have low ionization potentials in the gas phase and to exhibit proton affinity. The rod-shaped N, N, N′, N′ - tetramethyl-p-phenylenediamine (TMPD) and N, N, N′, N′ - tetramethylbenzidine (TMB) molecules can penetrate within the porous void of ZSM-5 zeolites.
After several days of the mixing of TMPD and HZSM-5 powders, an intense UV–visible spectrum with the vibronic structure of TMPD•+ between 500 and 650 nm is observed. The vibrational progression of the TMPD•+ band (with peaks separated by ~1500 cm−1) is assigned to the stretching mode of the aromatic ring. RR and off-resonance Ramana spectra of the mixed TMPD and H6ZSM-5 powders were obtained with 514.4 and 632.0 nm excitation and 1064 nm, respectively. All the spectra are very similar, with wavenumbers and intensities characteristic of the TMPD•+ species in solution. Raman bands assignable to neutral TMPD or protonated H2TMPD are absent, which provided evidence of complete ionization of TMPD upon sorption in the experimental conditions.
Exposure of HZSM-5 to TMB for several days led to an intense absorption around 465 and 900 nm with the vibronic structure of TMB•+ between 400 and 500 nm. After several weeks a shoulder around 500 nm is induced in the spectra. This last feature was previously assigned to the TMB2+ dication [13]. Raman spectra of TMB adsorbed on HZSM-5 after several days of exposure were obtained with excitation at 514.5, 488.9, and 1064 nm. Exciting at 5145 nm within the electronic absorption of TMB2+ the resonance Raman spectrum of the dication is observed predominantly, compared with the bands of the TMB2+ in solution as charge-transfer bromide salt. The Raman spectrum obtained with 4880 nm excitation shows the simultaneous presence of TMB•+ and TMB2+ in the porous void of the zeolite. However, it is not possible to give a quantitative estimation of the amount of dication. Nonetheless, the dication is probably a minor species as the FT-Raman spectrum displays only the radical cation. It should be noted that TMB2+ decomposes quickly in neutral organic solutions, but it can be stabilized in acid solution. The acidic property of HZSM-5 appears suitable to stabilize the dication. After 15 days of interaction between TMB and the zeolite the absence of a Raman band assignable to neutral TMB or protonated H2TMB provided evidence of complete ionization of TMB upon sorption under the experimental conditions.
2.3 Phenothiazine
Phenothiazines represent an important class of bioactive molecules. The photochemistry of phenothiazine (PTZ) (Figure 1) and its derivatives have been extensively studied because of its pharmacological interest [14]. Due to the low oxidation potential of PTZ, it is proposed that its role is to donate electrons or to transfer charge to the drug’s receptor sites. This idea was corroborated by the discovery of many phenothiazine charge-transfer complexes. There has been an extensive study of the formation and reactivity of PTZ’s stable radical cations [15], which are involved in an alternative to the biological activity mechanism [16].
Figure 1.
Phenothiazine and its radical cation PTZ⋅•+.
As reported by Hester et al., the most intense electronic transition of PTZ radical cation (PTZ•+) in the visible region can be found at 513 nm [17]. A resonance Raman investigation of PTZ•+ in an aqueous solution was carried out by the authors, following the contour of the band. An enhancement was observed in several Raman bands, with the most intensified one being the one at 476 cm−1. This band was tentatively assigned to a CNC angular deformation mode. A band at 644 cm−1, assigned to the C-N stretching mode was also enhanced. Both bands have frequencies shifted to higher values compared to the ground state of the parent compounds which led them to suggest that the electron density in the radical cation of phenothiazine is localized on the N atom.
An RRS of PTZ•+ obtained from the interaction of the neutral molecules with the mordenite zeolite, which has strong oxidizing sites was performed [18]. Phenothiazine is adsorbed in larger amounts in the acid sites of mordenite due to its larger pores. The observation of a pink color soon after PTZ was adsorbed on the mordenite is indicative of the formation of the radical cation PTZ•+. Figure 2 shows the strongest band in the PTZ visible spectrum, located at 516 nm, which was attributed by Hester et al. to the radical cation PTZ•+ [17]. The electronic spectrum calculated by the TDDFT method for PTZ•+ is also displayed (Figure 3).
Figure 2.
(a) Diffuse reflectance spectrum of PTZ adsorbed on mordenite; (b) TDDFT (time-dependent density functional theory) calculated electronic spectrum of PTZ•+ [18].
Figure 3.
RR spectra of PTZ adsorbed on mordenite zeolite at the exciting wavelengths: a) 457.9 nm; b) 488.0 nm; c) 496.5 nm; d) 514.5 nm; e) calculated. Arrows indicate the corresponding bands. Asterisk indicates a plasma line [18].
The RR spectra were excited with laser lines close to the most intense electronic transition of PTZ•+ located at 516 nm.
Exciting with 457.9 nm radiation gives rise to the weakest Raman spectrum. Raman excitation with radiations near 514.5 nm (488.0 and 496.5 nm).
It was noticed that excitation with 457.9 nm radiation gave the weaker Raman signal, while other wavelengths led to the increase of the Raman signal, with characteristic PTZ•+ Raman bands showing up. Raman spectra excited near 514.5 nm (488.0 and 496.5 nm) also show enhancement of several vibrational modes, involving ring, CNC, and CSC vibrations, while with excitation at 514.5 nm there is a striking difference, giving the highest RR intensity and the best signal/noise ratio together with significative enhancement of the band at 476 cm−1. This fact can be explained by the resonance with the electronic transition band at ca. 516 nm.
The most intensified Raman band at 476 cm−1 was assigned to a CSC bending mode, according to DFT (density functional theory) B3LYP/6- 31G(d,p) and TDDFT (time-dependent DFT) calculations, distinct from the previous assignment of Hester et al. Luchez et al. [19] also have obtained the PTZ•+ radicals in mordenite, HZSM-5, and H-FER zeolites, following the reaction by UV–visible and Raman spectra. Two wavelengths, 1064 nm and 6328 nm, were used to excite the Raman spectra, but none of them reached the energy of the main electronic transition of PTZ•+, so in this condition, it is not possible to obtain the RR spectrum of this species.
3. Clays
Clay minerals are aluminosilicates, most of them of layered structures with tetrahedral silicate and octahedral aluminate sheets. The tetrahedral cation, Si4+, can be replaced by Al3+` or Fe3+ cations, and the octahedral cations normally are Al3+, Mg2+, Fe2+, and Fe3+ [20].
Smectite clays, (which have been most often used in organic reactions), have a 2:1 layer type, where one octahedral sheet is sandwiched by two tetrahedral sheets. If in the 2:1 layer-type aluminosilicate, the Al3+ is substituted by divalent cations, as Mg2+ (montmorillonite) in an octahedral sheet, results in a negative charge [21]. To balance the layer charge, cations are introduced between the layers. These cations are hydrated and exchangeable. In natural clays they are typically Na+, K+ Ca2+, and Mg2+; similar ions can be exchanged with these ions. Smectite clays have the unique properties of cation exchange capacity, intercalation, and swelling ability, which are important factors in their activity for various reactions involving organic molecules. Clays dried to low water content can behave as acids [22, 23]. Cation-exchanged montmorillonites act as strong Brönsted acids, where the reactive protons are derived from the dissociation of hydrated water molecules because of polarization by exchangeable cations. This situation may be represented by the following equilibrium reaction (Eq. 1):
MH2Oxn+⇌MOHH2Ox−1n−1++H+E1
Equilibrium reaction between [M(H2O)x}n+ and the respective species following dissociation of hydrated water molecule and H+.
Brönsted acidity results from the terminal hydroxy groups on the external surface and the hydrated cations in the space between the layers of the clay. Lewis acidity is due to central metal ions such as Al3+, Mg2+, and Fe3+ in the lattice and also from other metallic cations in the interlamellar space. Often the central metal ions are fully bonded to adjacent oxygen atoms in an octahedral site; so, these intact octahedra within the crystal arrays are unable of originating much Lewis acidity. Nevertheless, in the case of zeolites with small particle size, for instance, MMT K10 (typically 5–10 μm), what happens is that the sandwich layers are squashed to a remarkable extent, generating many broken edges of stacked layers, which contribute to Brønsted as well as Lewis acidity
The Lewis acid sites interaction between the metal cation and adsorbed organic molecules, especially with electron-donating character, results in electron transfer from the organic molecule to metal cation [24] with the consequent formation of radical cations and the reduction of metal ions to lower valency.
Mortland and Pinnavaia reported the interaction of some aromatic organic molecules with transition metal ions (Cu2+, Fe3+) exchanged montmorillonite. They observed the formation of colored adsorption complexes, which was explained due to the electron transfer from the aromatic molecule to the metal ion [25, 26].
The formation of aromatic radical cations was also observed by Pinnavaia et al. upon the adsorption of aromatic molecules on Cu2+, Fe3+ and VO2+ cation exchanged layered silicates (hectorite). Electron spin resonance spectra were useful to identify the radical cations while UV absorption spectra showed the presence of two species. Besides the radical cation, a charge transfer complex between the metal cation and the aromatic molecule was also observed. Infrared spectra of the adsorbed samples also showed that after some days oligomers and polymers of benzene, toluene, and anisole were formed [27].
3.1 p-dimethoxy benzene
Y. Soma, M. Soma, and I. Harada investigated the interaction of several aromatic molecules with clays, mainly transition metal exchanged montmorillonites using Raman spectroscopy in order to characterize the chromophore responsible for the absorption in the UV–visible region. P-dimethoxy benzene was the first one chosen by the authors [28] because the RR spectra of the radical cation of this molecule in solution had already been investigated by Ernstbrunner et al. [29]. The Raman spectra of p-dimethoxy benzene adsorbed on Cu2+- and Ru3+- montmorillonite were similar to the respective spectrum of p-dimethoxy benzene radical cation reported by Ernstbrunner et al. for the species in solution. RR enhancement in the blue region (maximum with excitation at 457.9 nm) was observed in agreement with the absorption band maxima at 435 and 450 nm. The most intensified band was the ring stretching at 1622 cm−1. It is also noticeable that the ring breathing band at 820 cm−1 which is the strongest band in the neutral molecule, is very weak in the cation. The enhancement of the ring stretching mode and the weakness of the ring breathing mode are also observed in the adsorbed samples on Cu2+- and Ru3+-montmorillonite.
3.2 Anisole
When anisole is adsorbed on Cu(II)-montmorillonite, the interaction between the adsorbate and the clay gives rise to several species, depending on the presence of water [30]. In a dry atmosphere, the sample has a green-blue color. In the UV visible spectrum, a broadband from ~550 nm to ~850 nm and other bands with the maximum at ca. 470 nm are observed. The RR spectra with excitation wavelengths of 6100 nm and 4570 nm are shown in Figure 4(b) and (c), respectively, along with the Raman spectrum of liquid anisole. The RR spectrum excited with 6100 nm has bands at 995, 1208, 1325, 1528, and 1618 cm−1, that resembles the spectrum of 4,4′-dimethoxybiphenyl but the inter ring CC stretching at 1325 cm−1 is upshifted, indicating the formation of a radical cation species of this molecule, similar to observed in the spectrum of 4,4′-dimethoxybiphenyl on Cu2+- and Ru3+- montmorillonite, reported in the same article [30]. Exciting with 457.9 nm a more complex spectrum is observed, as can be seen in Figure 4(c). The authors made a deconvolution of the spectrum, which allowed the distinction of two spectra, the one in black is similar to the spectrum observed with 610.0 nm excitation, due to 4,4′-dimethoxybiphenyl radical cation, and the other in white has a resemblance with the spectrum of liquid anisole, but with shifts in some bands, as the ring breathing mode (925 cm−1 compared to 995 cm−1 in the liquid anisole spectrum). Another difference is the intensification of the ring stretching band at around 1600 cm−1, which is a signal of radical cation formation.
Figure 4.
(a) Raman spectrum of liquid anisole with 524.5 nm exciting wavelength and RR spectra of anisole adsorbed on Cu(II)- montmorillonite with (b) 610.0 nm and c) 457.9 nm exciting wavelengths. Adapted from Soma et al. [30].
The authors proposed the following reactions to take place with anisole in the interlayer of the Cu(II)-montmorillonite (Figure 5).
Figure 5.
Reactions occurring with anisole in Cu (II)-montmorillonite. Adapted from [30].
The first reaction, a redox reaction forming Cu+ and the radical cation of anisole is favored in a dry atmosphere. In the second one anisole, radical cation reacts with neutral anisole, forming 4,4′-dimethoxybiphenyl radical cation.
3.3 Benzene
Soma et al. studied benzene adsorbed on Cu2+-montmorillonite by RR spectroscopy [31]. Two species were observed: type II (red form), formed upon adsorption in an exhaustively dried atmosphere, and type I (yellow form) when exposed to humid air. Type I has a band with an absorption maximum at 380 nm while type II has an absorption maximum at 520 nm, besides a strong broad absorption that begins at 800 nm and extends into the near-infrared region.
The RR spectra of benzene adsorbed on Cu2+− montmorillonite with excitation at 4579 and 5145 nm are very different from the Raman spectra of liquid benzene, resembling the spectra of p-phenylene molecules, e.g. p-terphenyl or p-quaterphenyl, indicating that oligomerization occurred on the clay surface. The presence of the inter ring C-C stretching at 1324 cm−1 (type II) or 1240 cm−1 (type I) is strong evidence of oligomerization. Type I and Type II are assigned to poly p-phenylene and poly p-phenylene radical cation, respectively, based on the results of RR spectra of poly p-phenylene (PPP) and AsF5-PPP complex reported by Tzinis [32]. He observed a shift to a higher frequency of the inter ring C-C stretching in the complex compared to the bulk PPP. Based on the results of RR spectra and absorption spectra, it was concluded that benzene adsorbed on Cu2+-montmorillonite is polymerized to PPP cation (type II) and reversibly reduced to PPP in humid air (type I) as follows (Figure 6).
Figure 6.
Reactions of benzene with Cu(II)-montmorillonite. Adapted from [31].
(C6H6)phys means physically adsorbed benzene, (C6H4)n and (C6H4)nk+, PPP and its cation, respectively.
Benzene adsorbed on Fe3+- and Ru3+- montmorillonite was also investigated by RR spectroscopy and showed a similar behavior; two species being formed, type I in humid air and type II in the dry atmosphere [33]. The authors noted, however, a difference between benzene /Fe3+- and benzene/Cu2+- montmorillonite: for the first one the transformation of type II to type I in humid air did not occur easily mainly after repeating the reaction, in contrast to what was observed with Cu2+- montmorillonite complex.
3.4 Benzidine
Aqueous suspensions of benzidine and montmorillonite clay (BZ-MMT system) give rise to samples with blue, yellow, purple, and orange-brown colors, depending on the pH of the suspension. In order to assign the species formed in these samples, in situ RR spectroscopy investigation was performed [34].
From pH 3 to 9, the main species responsible for the blue color is the radical cation of BZ (BZ(+center dot)) which has λ(max) at 600 nm. At pH lower than 3, the major species that gives rise to the yellow color is the dication, BZ(2+) with λ(max) at 440 nm. Following the dehydration of the blue BZ-MMT slurry, a yellow color appears, which was assigned to BZ(+center dot) and BZ(2+) species, according to its RR spectrum. At pH higher than 9, the orange-brown colored sample was characterized as poly(benzidine) (PBZ). When the blue BZ-MMT aqueous suspension was left standing for 3 weeks a purple color appeared and it was found to be from a mixture of BZ(+center dot) and BZ(2+) species together with PBZ. Synthetic Syn1 and pillared MMT clays in aqueous suspensions at different pHs were also tested to investigate the possibility of BZ oxidation. In these acidic clays, only the BZ(+center dot) was identified, BZ(2+) species was not observed probably due to the majority presence of the less reactive BZ(+center dot). At pHs above 9, the benzidine polymerization through the reaction between unprotonated BZ(+center dot) radical cations is catalyzed by the clay.
4. Sulfated metal oxides
The preparation and the highly acid properties of sulfated metal oxide were reported for the first time by Hino and Arata [35] and Hino et al. [36], who investigated the catalytic properties of sulfated TiO2 and ZrO2. These metal oxides were able to catalyze the isomerization of n-butane at room temperature, which only very strong acid catalysts are able to do. Thereafter they have been considered by some authors as superacids. In sulfated metal oxides, there are Lewis acid sites and Brönsted acid sites. The super acidity of these materials is attributed to the Brönsted and Lewis acid sites that have increased acidity due to the inductive effect of sulfate, which is coordinately bound to the Ti4+. The sulfate group act as an electron-withdrawing group, making Ti4+ more electron-deficient, that is, a strong Lewis acid site, which in turn also withdraws electron density from the -OH group, creating or increasing the Bronsted acid site, as can be seen in Figure 7.
Figure 7.
Ilustrative structure of sulfated titania, representing the sulfate linked to the metal on the chelate form and indicating the Lewis and Brönsted acid sites. [37].
The unusual catalytic properties of these materials are attributed to the presence of very strong Lewis or Brönsted acid sites or both types of sites or to their oxidative ability. The oxidative ability was postulated by Ghenciu and Farcasiu [38], who observed that benzene was oxidized when adsorbed on sulfated ZrO2 and heated at 373 K. Several oxidation products, such as phenyl esters and phenols were formed, which were evidence of the presence of oxidizing sites [38].
The strong ionizing properties of sulfated ZrO2 and its relation to the catalytic activity were investigated by Chen et al. [39]. Benzene was used as a probe to study to evaluate the strong ionizing properties of sulfated ZrO2 due to its high ionizing potential value (9.24 eV). In the ESR spectrum, a hyperfine structured peak was observed and attributed to a biphenyl cation. They proposed the following explanation: a two-step process took place as a consequence of the interaction of benzene with sulfated ZrO2. A CT complex between sulfated ZrO2 and benzene was formed in the first step. Then a complete electron transfer from benzene to the ZrO2 occurred, originating a benzene radical cation, this, in turn, reacted with a benzene molecule, forming the biphenyl radical cation.
As with sulfated ZrO2, sulfated TiO2 (a solid acid) also may have the ability to interact with aromatic compounds and form CT complexes and may oxidize aromatic molecules with the formation of radical cations.
4.1 Benzene
A RR spectroscopy study using a commercial sulfated TiO2, following its interaction with benzene was reported by our group [40]. Besides the remarkable enhancement of ν(CC) ring modes, the appearance of non-totally symmetric vibrations was observed in the Raman spectra. The presence of benzene was confirmed by the characteristic benzene ring breathing mode. The preferential enhancement of the ν(CC) ring modes and the appearance of non-totally symmetric vibrations were explained by the RR enhancement due to benzene to Ti(IV) CT transition [41]. Negligible amounts of radicals were detected in the ESR spectrum, because of the moderate strength of the acid sites of the sulfated TiO2 used in the study. The RR spectra of benzene on sulfated TiO2 with 457.9 and 476.5 nm exciting wavelengths are shown in Figure 8. The bands of anatase TiO2 (marked with asterisks) acts as an internal standard to measure the Raman signal intensification. It is noteworthy the striking enhancement of the band at ca. 1600 cm−1, due to benzene ring CC stretching mode exciting with 476.5 nm. This wavelength corresponds to an absorption band in this energy range, assigned to a charge transfer transition. This sulfated TiO2 was not able to oxidize benzene, a molecule with relatively high ionization potential, but a strong interaction occurred, as can be seen in the RR spectra.
Figure 8.
RR spectra of benzene on sulfated TiO2 with two exciting wavelengths: (a) 457.9 nm and (b) 476.5 nm. On the left: The 100–1700 cm−1 spectral region and on the right: The 900–1700 cm−1 region. *TiO2 bands, +plasma lines of the 457.9 argon-ion laser, Hg lamp line.
The experimental Raman spectrum of the benzene radical cation is unknown. However, the Raman spectra of the phenylene oligomeric radical cations such as biphenyl [42] and p-terphenyl that are formed after adsorption on zeolites [43] have been reported in the literature. These species present the RR effect as reported in the literature for some radical cations.
We have performed an investigation of benzene adsorbed on a very highly acid sulfated TiO2, synthesized by sol–gel method [44] at room temperature. A tentative assignment of the species formed from the interaction was done with Raman and electron spin resonance (ESR) spectroscopy [45]. From the absorption spectra in the visible and near-infrared (NIR), it was possible to identify these species as phenylene oligomer radical cations. The UV–visible-near IR spectrum of benzene/sulfated TiO2 sample shows two maxima, one between 400 and 500 nm and the other in the NIR region that begins at ca. 1100 nm and increases towards the infrared. An explanation to this spectrum is based on the RR spectroscopy study of the interaction of benzene with Fe(III)-doped montmorillonite, reported by Soma et al. [31]. They observed two kinds of spectra. The dried sample had an absorption band at 510 nm and was named Type I. When moisture was allowed to contact the dried sample, the band at 510 nm shifted to 380 nm and the spectrum was named Type II. Both types have an absorption that begins at 660 nm and extends to the NIR region. Type I and Type II are assigned to PPP and PPP radical cation, respectively. The Raman spectra of benzene with sulfated TiO2, excited with several excitation wavelengths are seen in Figure 9. It is evident that the spectra do not resemble the spectrum of liquid benzene, mainly because of the absence of the ring breathing mode at 998 cm−1, the most intense band of neat benzene. It is noteworthy the intensification of some bands, notably the one at ca. 1600 cm−1, with the maximum of intensification using exciting wavelengths of 514.5 nm and 1064 nm. These two wavelengths correspond to the two absorptions in the visible-near IR regions of the benzene/sulfated TiO2 sample. The behavior is similar to that observed by Soma et al. RR spectra were observed and the species that gave rise to these spectra are phenylene oligomers or phenylene oligomer radical cations.
Figure 9.
RR spectra of benzene/sulfated TiO2* sample and liquid benzene at the indicated exciting wavelengths [45]. * = sulfated TiO2 prepared by sol–gel method.
5. Conclusions
Several examples of the use of RR spectroscopy as a tool to identify species formed from the interaction of solid acids with several aromatic molecules were presented. The solid acids have strong acid sites, which can oxidize molecules adsorbed on them or originate charge-transfer complexes. The solid acids were zeolites, clays, and sulfated metal oxides, because of their strong acid sites. Selected works from the literature that report spontaneous ionization of molecules adsorbed on the solid acids and the follow-up of the intermediate species by RR spectroscopy were reported. The intermediate species are radical cations or charge transfer complexes that have absorptions in the visible and in some cases near the IR region. The RR spectra were able to characterize the intermediate species and also to provide information of the chromophore responsible for the electronic transition, because of the preferential RR enhancement of its vibrational modes.
Acknowledgments
The author is grateful to Molecular Spectroscopy Laboratory (Institute of Chemistry, São Paulo University, São Paulo) for the Raman spectra on Jobin-Yvon U-1000 spectrometer and to FAPESP (process 2017/06194-2) for the financial support.
\n',keywords:"resonance Raman spectroscopy, solid acids, radical cation, charge transfer complex",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/79545.pdf",chapterXML:"https://mts.intechopen.com/source/xml/79545.xml",downloadPdfUrl:"/chapter/pdf-download/79545",previewPdfUrl:"/chapter/pdf-preview/79545",totalDownloads:132,totalViews:0,totalCrossrefCites:0,dateSubmitted:"June 27th 2021",dateReviewed:"October 14th 2021",datePrePublished:"December 3rd 2021",datePublished:"January 7th 2022",dateFinished:"December 3rd 2021",readingETA:"0",abstract:"Many solid acids with very strong acid sites, as some zeolites, transition metal exchanged montmorillonites, sulfated metallic oxides, are known to have the oxidizing ability, which can be related to the catalytic activity of these materials. The interaction of these solid acids with aromatic molecules can give rise to several oxidation products. Intermediate species of aromatic molecules formed by interaction with strong solid acids had been reported, as radical cations, proving the oxidizing ability of the solids. Besides radical cations, charge transfer complexes between the solid acids and aromatic molecules can be formed. These radical cations and charge transfer complexes usually show absorption bands in the visible region, opening the possibility of studying these species by Resonance Raman Spectroscopy (RRS). Benzene and substituted benzenes, phenothiazine, t-stilbene, adsorbed on solid acids, are examples of molecules that had been investigated by RRS. Exciting the spectrum with suitable radiation makes it possible to observe the RRS of the species of interest even when its concentration is low, because of the preferential enhancement of the vibrational modes of the chromophore. A review of RRS studies of molecules adsorbed on solid acids is presented. RRS proved valuable in characterizing intermediate species as radical cations or charge transfer complexes formed on the solid acids.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/79545",risUrl:"/chapter/ris/79545",signatures:"Lucia Kiyomi Noda",book:{id:"10644",type:"book",title:"Recent Developments in Atomic Force Microscopy and Raman Spectroscopy for Materials Characterization",subtitle:null,fullTitle:"Recent Developments in Atomic Force Microscopy and Raman Spectroscopy for Materials Characterization",slug:"recent-developments-in-atomic-force-microscopy-and-raman-spectroscopy-for-materials-characterization",publishedDate:"January 7th 2022",bookSignature:"Chandra Shakher Pathak and Samir Kumar",coverURL:"https://cdn.intechopen.com/books/images_new/10644.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",isbn:"978-1-83968-230-8",printIsbn:"978-1-83968-229-2",pdfIsbn:"978-1-83968-231-5",isAvailableForWebshopOrdering:!0,editors:[{id:"318029",title:"Dr.",name:"Chandra Shakher",middleName:null,surname:"Pathak",slug:"chandra-shakher-pathak",fullName:"Chandra Shakher Pathak"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:[{id:"350159",title:"Associate Prof.",name:"Lucia",middleName:null,surname:"Kiyomi Noda",fullName:"Lucia Kiyomi Noda",slug:"lucia-kiyomi-noda",email:"lucia.noda@unifesp.br",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Zeolites",level:"1"},{id:"sec_2_2",title:"2.1 Trans-stilbene",level:"2"},{id:"sec_3_2",title:"2.2 N, N, N′, N′ -tetramethyl-p-phenylenediamine (TMPD) and N, N, N′, N′ -tetramethylbenzidine (TMB)",level:"2"},{id:"sec_4_2",title:"2.3 Phenothiazine",level:"2"},{id:"sec_6",title:"3. Clays",level:"1"},{id:"sec_6_2",title:"3.1 p-dimethoxy benzene",level:"2"},{id:"sec_7_2",title:"3.2 Anisole",level:"2"},{id:"sec_8_2",title:"3.3 Benzene",level:"2"},{id:"sec_9_2",title:"3.4 Benzidine",level:"2"},{id:"sec_11",title:"4. Sulfated metal oxides",level:"1"},{id:"sec_11_2",title:"4.1 Benzene",level:"2"},{id:"sec_13",title:"5. Conclusions",level:"1"},{id:"sec_14",title:"Acknowledgments",level:"1"}],chapterReferences:[{id:"B1",body:'Hendra PJ, Passingham G, Warnes GM, Burch R, Rawlence DJ. Fourier transform Raman spectroscopy in the study of species adsorbed on catalyst surfaces. Chemical Physics Letters. 1989;164(2,3):178-184. 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Free radical studies by resonance Raman spectroscopy: Phenothiazine, 10-methylphenothiazine and phenoxazine radical cations. Journal of the Chemical Society, Perkin Transactions 2. 1981;77:852-859. DOI: 10.1039/P29810000852'},{id:"B18",body:'Noda LK, Gonçalves NS. Assignment of the electronic transition of phenothiazine radical cation in the visible region - a resonance Raman spectroscopy and theoretical calculation investigation. Journal of Molecular Structure. 2019;1191:253-258. DOI: 10.1016/j.molstruc.2019.04.053'},{id:"B19",body:'Luchez F, Carre´ S, Moissette A, Poizat O. Sorption and spontaneous ionization of phenothiazine within channel type zeolites: Effect of the confinement on the electron transfers. RSC Advances. 2011;1:341-350. DOI: 10.1039/c1ra00220a'},{id:"B20",body:'Soma Y, Soma M. Chemical reactions of organic compounds on clay surfaces. Environmental Health Perspectives. 1989;83:205-214. DOI: 10.2307/3430656'},{id:"B21",body:'Brindley GW, Brown G. Crystal Structures of Clay Minerals and Their X-ray Identification. London: Mineralogical Society of Great Britain; 1980. p. 518'},{id:"B22",body:'Laszlo P. Chemical reactions on clays. Science. 1987;235:1473-1477. DOI: 10.1126/science.235.4795.1473'},{id:"B23",body:'Pinnavaia TJ. Intercalated clay catalysts. Science. 1983;220:365-371. DOI: 10.1126/science.220.4595.365'},{id:"B24",body:'Theng BKG. Clay-activated organic reactions. In: Developments in Sedimentology (H. Van Olphen and F. Vaniale, Eds.)vol. 35. Elsevier:Amsterdam; 1982. pp. 197-238'},{id:"B25",body:'Mortland MM, Pinnavaia TJ. Formation of copper(II) arene complexes on the interlamellar surfaces of montmorillonite. Nature. 1971;229:75-77. DOI: 10.1038/physci229075a0'},{id:"B26",body:'Pinnavaia TJ, Mortland MM. Interlamellar metal complexes on layer silicate. I. Copper(II)-arene complexes on montmorillonite. The Journal of Physical Chemistry. 1971;75:3957-3962. DOI: 10.1021/j100695a007'},{id:"B27",body:'Pinnavaia TJ, Hall PL, Cady SS, Mortland MM. Aromatic radical cation formation on the intracrystal surfaces of transition metal layer lattice silicates. The Journal of Physical Chemistry. 1974;78:994-999. DOI: 10.1021/j100603a010'},{id:"B28",body:'Soma Y, Soma M, Harada I. Raman spectroscopic evidence of formation of p-dimethoxybenzene cation on Cu- and Ru- montmorillonites. Chemical Physics Letters. 1983;94(5):475-478. DOI: 10.1016/0009-2614(83)85035-0'},{id:"B29",body:'Ernstbrunner E, Girling RB, Grossman WEL, Hester RE. Free radical studies by resonance Raman spectroscopy. 1. 1,4-dimethoxybenzene radical cation. Journal of the Chemical Society, Perkin Transactions 2. 1978;2:177-184. DOI: 10.1039/p29780000177'},{id:"B30",body:'Soma Y, Soma M, Harada I. Reactions of aromatic molecules in the interlayer of transition-metal ion exchanged montmorillonite studied by Resonance Raman Spectroscopy. 2. Monosubstituted benzenes and 4,4′-disbstituted biphenyls. The Journal of Physical Chemistry. 1985;89(5):738-742. DOI: 10.1021/j150658a021'},{id:"B31",body:'Soma Y, Soma M. Resonance Raman spectra of benzene adsorbed on Cu2+- montmorillonite. Formation of poly(p-phenylene) cations in the interlayer of the clay mineral. Chemical Physics Letters. 1983;99(2):153-156. DOI: 10.1016/0009-2614(83)80549-1'},{id:"B32",body:'Tzinis C-H, Baughman RH, Risen WM Jr. Raman Spectra of Highly Conducting Poly-p-phenylene Complexes. Office of Naval Research; 1980. Providence, Rhode Island: Technical Report No. TR-80-01'},{id:"B33",body:'Soma Y, Soma M, Harada I. The reaction of aromatic molecules in the interlayer of transition-metal ion-exchanged montmorillonite studied by resonance Raman spectroscopy. 1. Benzene and p –Phenylenes. The Journal of Physical Chemistry. 1984;88:3034-3038. DOI: 10.1021/j150658a021'},{id:"B34",body:'Nascimento GM, Barbosa PSM, Constantino VRL, Temperini MLA. Benzidine oxidation on cationic clay surfaces in aqueous suspension monitored by in situ resonance Raman spectroscopy. Colloids and Surfaces A: Physicochemical and Engineering Aspects. 2006;289:39-46. DOI: 10.1016/j.colsurfa.2006.04.005'},{id:"B35",body:'Hino M, Arata K. Reactions of butane and isobutane catalysed by titanium oxide treated with sulphate ion. Solid superacid catalyst. Journal of the Chemical Society, Chemical Communications. 1979;24:1148-1149. DOI: 10.1039/C39790001148'},{id:"B36",body:'Hino M, Kobayashi S, Arata K. Solid catalyst treated with anion. 2. Reactions of butane and isobutane catalyzed by zirconium oxide treated with sulfate ion. Solid superacid catalyst. Journal of the American Chemical Society. 1979;101:6439-6441. DOI: 10.1021/ja00515a051'},{id:"B37",body:'Almeida RM, Noda LK, Gonçalves NS, Meneghetti SMP, Meneghetti MR. Transesterification reaction of vegetable oils, using superacid sulfated TiO2–base catalysts. Applied Catalysis A. 2008;347:100-105. DOI: 10.1016/j.apcata.2008.06.006'},{id:"B38",body:'Ghenciu A, Farcasiu D. Oxidizing ability as the defining factor of reactivity of sulfated zirconia. Chemical Communications. 1996;2:169-170. DOI: 10.1039/CC9960000169'},{id:"B39",body:'Chen FR, Coudurier G, Joly JF, Vedrine JC. Superacid and catalytic properties of sulfated zirconia. Journal of Catalysis. 1993;143(2):616-626. DOI: 10.1006/jcat.1993.1304'},{id:"B40",body:'Noda LK, Rosales R, Gonçalves NS, Sala O. Evidences for charge-transfer complex formation in the benzene adsorption on sulfated TiO2 – a resonance Raman spectroscopy investigation. Journal of Raman Specroscopy. 2008;39(3):415-420. DOI: 10.1002/jrs.1843'},{id:"B41",body:'Gonçalves NS, Noda LK. Spectroscopic study of the charge-transfer complexes TiCl4/styrene and TiCl4/polystyrene. Journal of Molecular Structure. 2017;1146:750-754. DOI: 10.1016/j.molstruc.2017.06.029'},{id:"B42",body:'Buntinx G, Poizat O. Triplet (T1) state and radical cation resonance Raman investigation of biphenyl derivatives. The Journal of Chemical Physics. 1989;91:2153-2162. DOI: 10.1063/1.457023'},{id:"B43",body:'Belhadj F, Moissette A, Bernard C, Hureau M, Derriche Z. Effects of spatial constraints and Brönsted acid site locations on para-terphenyl ionization and charge transfer in zeolites. ChemPhysChem. 2011;12:1378-1388. DOI: 10.1002/cphc.201000825'},{id:"B44",body:'Noda LK, Almeida RM, Probst LFD, Gonçalves NS. Characterization of sulfated TiO2 prepared by the sol–gel method and its catalytic activity in the n-hexane isomerization reaction. Journal of Molecular Catalysis A. 2005;225(1):39-46. DOI: 10.1016/j.molcata.2004.08.025'},{id:"B45",body:'Gonçalves NS, Rettori D, Silva GMG, Noda LK. Spectroscopic study of radical cation species formed on sulfated TiO2 upon benzene adsorption. Vibrational Spectroscopy. 2018;99:80-85. DOI: 10.1016/j.vibspec.2018.08.012'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Lucia Kiyomi Noda",address:"lucia.noda@unifesp.br",affiliation:'
Federal University of São Paulo, Diadema, Brazil
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It is may be of interest to note that this chapter is suitable for undergraduate level students in the fields of HVAC and R, mechanical, and construction engineering.",book:{id:"8394",slug:"low-temperature-technologies",title:"Low-temperature Technologies",fullTitle:"Low-temperature Technologies"},signatures:"Mohamed Elnaggar and Mohammed Alnahhal",authors:[{id:"178453",title:"Dr.",name:"Mohamed",middleName:null,surname:"Elnaggar",slug:"mohamed-elnaggar",fullName:"Mohamed Elnaggar"},{id:"308344",title:"Dr.",name:"Mohammed",middleName:null,surname:"Alnahhal",slug:"mohammed-alnahhal",fullName:"Mohammed Alnahhal"}]},{id:"69746",title:"Energy and Exergy Analysis of Refrigeration Systems",slug:"energy-and-exergy-analysis-of-refrigeration-systems",totalDownloads:1538,totalCrossrefCites:0,totalDimensionsCites:5,abstract:"Refrigeration systems have the priority in design for residential and industrial applications. The chapter includes five major refrigeration systems: vapor-compression refrigeration; ammonia-water absorption refrigeration; gas refrigeration where standard air is the most popular refrigerant; multi-pressure refrigeration including multistage, cascade, and multipurpose refrigeration system; and heat pump systems. Energy and exergy analysis has been presented for most of the systems. The energetic and the exergetic COP for each system are presented. Renewable energy sources are also discussed including geothermal, solar, and wind energy, a with combination with refrigeration systems in different industrial and residential applications. 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Exergy analysis involves the application of exergy concepts, balances, and efficiencies to evaluate and improve energy and other systems. Many scientists suggest that processes or sytems can be well evaluated and improved using exergy analysis in addition to or in place of energy analysis. Application of exergy analysis has given us more beneficial opportunities through a big part of a wide range of processes and systems particularly for the evaluation of energy systems and technologies as well as an environmental impact in all existing thermal and nuclear power plants. Conventional energy technologies, especially for power generation plants, have made numerous energy and exergy analyses and have produced beneficial results. Also, the use of energy and exergy analyses for advanced nuclear energy technologies can be expected to provide meaningful insights into performance that can assist in achieving optimal design concepts. 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Dr. Summers is a systems ecologist and began his career at the EPA in 1989 and has worked in various programs and capacities. This includes leading the National Coastal Assessment in collaboration with the Office of Water which culminated in the award-winning National Coastal Condition Report series (four volumes between 2001 and 2012), and which integrates water quality, sediment quality, habitat, and biological data to assess the ecosystem condition of the United States estuaries. He was acting National Program Director for Ecology for the EPA between 2004 and 2006. He has authored approximately 150 peer-reviewed journal articles, book chapters, and reports and has received many awards for technical accomplishments from the EPA and from outside of the agency. 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He also has an honorary appointment to serve as a Collaborative Professor at Kanazawa University, Japan, from Mar 2015 to the present. \nFormerly, Dr. Rahman was a faculty member of the University of Chittagong, Bangladesh, affiliated with the Department of Chemistry (Oct 2002 to Mar 2012) and the Department of Applied Chemistry and Chemical Engineering (Mar 2012 to Sep 2015). Dr. Rahman was also adjunctly attached with Kanazawa University, Japan (Visiting Research Professor, Dec 2014 to Mar 2015; JSPS Postdoctoral Research Fellow, Apr 2012 to Mar 2014), and Tokyo Institute of Technology, Japan (TokyoTech-UNESCO Research Fellow, Oct 2004–Sep 2005). \nHe received his Ph.D. degree in Environmental Analytical Chemistry from Kanazawa University, Japan (2011). He also achieved a Diploma in Environment from the Tokyo Institute of Technology, Japan (2005). Besides, he has an M.Sc. degree in Applied Chemistry and a B.Sc. degree in Chemistry, all from the University of Chittagong, Bangladesh. \nDr. Rahman’s research interest includes the study of the fate and behavior of environmental pollutants in the biosphere; design of low energy and low burden environmental improvement (remediation) technology; implementation of sustainable waste management practices for treatment, handling, reuse, and ultimate residual disposition of solid wastes; nature and type of interactions in organic liquid mixtures for process engineering design applications.",institutionString:null,institution:{name:"Fukushima University",institutionURL:null,country:{name:"Japan"}}},editorTwo:{id:"201020",title:"Dr.",name:"Zinnat Ara",middleName:null,surname:"Begum",slug:"zinnat-ara-begum",fullName:"Zinnat Ara Begum",profilePictureURL:"https://mts.intechopen.com/storage/users/201020/images/system/201020.jpeg",biography:"Zinnat A. Begum received her Ph.D. in Environmental Analytical Chemistry from Kanazawa University in 2012. She achieved her Master of Science (M.Sc.) degree with a major in Applied Chemistry and a Bachelor of Science (B.Sc.) in Chemistry, all from the University of Chittagong, Bangladesh. Her work affiliations include Fukushima University, Japan (Visiting Research Fellow, Institute of Environmental Radioactivity: Mar 2016 to present), Southern University Bangladesh (Assistant Professor, Department of Civil Engineering: Jan 2015 to present), and Kanazawa University, Japan (Postdoctoral Fellow, Institute of Science and Engineering: Oct 2012 to Mar 2014; Research fellow, Venture Business Laboratory, Advanced Science and Social Co-Creation Promotion Organization: Apr 2018 to Mar 2021). 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He also obtained an MSc in Molecular and Genetic Medicine, and a Ph.D. in Clinical Immunology and Human Genetics from the University of Sheffield, UK. He also completed a short-term fellowship in Pediatric Clinical Immunology and Bone Marrow Transplantation at Newcastle General Hospital, England. Dr. Rezaei is a Full Professor of Immunology and Vice Dean of International Affairs and Research, at the School of Medicine, Tehran University of Medical Sciences, and the co-founder and head of the Research Center for Immunodeficiencies. He is also the founding president of the Universal Scientific Education and Research Network (USERN). Dr. Rezaei has directed more than 100 research projects and has designed and participated in several international collaborative projects. He is an editor, editorial assistant, or editorial board member of more than forty international journals. He has edited more than 50 international books, presented more than 500 lectures/posters in congresses/meetings, and published more than 1,100 scientific papers in international journals.",institutionString:"Tehran University of Medical Sciences",institution:{name:"Tehran University of Medical Sciences",country:{name:"Iran"}}},{id:"180733",title:"Dr.",name:"Jean",middleName:null,surname:"Engohang-Ndong",slug:"jean-engohang-ndong",fullName:"Jean Engohang-Ndong",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/180733/images/system/180733.png",biography:"Dr. Jean Engohang-Ndong was born and raised in Gabon. After obtaining his Associate Degree of Science at the University of Science and Technology of Masuku, Gabon, he continued his education in France where he obtained his BS, MS, and Ph.D. in Medical Microbiology. He worked as a post-doctoral fellow at the Public Health Research Institute (PHRI), Newark, NJ for four years before accepting a three-year faculty position at Brigham Young University-Hawaii. Dr. Engohang-Ndong is a tenured faculty member with the academic rank of Full Professor at Kent State University, Ohio, where he teaches a wide range of biological science courses and pursues his research in medical and environmental microbiology. Recently, he expanded his research interest to epidemiology and biostatistics of chronic diseases in Gabon.",institutionString:"Kent State University",institution:{name:"Kent State University",country:{name:"United States of America"}}},{id:"188773",title:"Prof.",name:"Emmanuel",middleName:null,surname:"Drouet",slug:"emmanuel-drouet",fullName:"Emmanuel Drouet",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/188773/images/system/188773.png",biography:"Emmanuel Drouet, PharmD, is a Professor of Virology at the Faculty of Pharmacy, the University Grenoble-Alpes, France. As a head scientist at the Institute of Structural Biology in Grenoble, Dr. Drouet’s research investigates persisting viruses in humans (RNA and DNA viruses) and the balance with our host immune system. He focuses on these viruses’ effects on humans (both their impact on pathology and their symbiotic relationships in humans). He has an excellent track record in the herpesvirus field, and his group is engaged in clinical research in the field of Epstein-Barr virus diseases. He is the editor of the online Encyclopedia of Environment and he coordinates the Universal Health Coverage education program for the BioHealth Computing Schools of the European Institute of Science.",institutionString:null,institution:{name:"Grenoble Alpes University",country:{name:"France"}}},{id:"131400",title:"Prof.",name:"Alfonso J.",middleName:null,surname:"Rodriguez-Morales",slug:"alfonso-j.-rodriguez-morales",fullName:"Alfonso J. Rodriguez-Morales",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/131400/images/system/131400.png",biography:"Dr. Rodriguez-Morales is an expert in tropical and emerging diseases, particularly zoonotic and vector-borne diseases (especially arboviral diseases). He is the president of the Travel Medicine Committee of the Pan-American Infectious Diseases Association (API), as well as the president of the Colombian Association of Infectious Diseases (ACIN). He is a member of the Committee on Tropical Medicine, Zoonoses, and Travel Medicine of ACIN. He is a vice-president of the Latin American Society for Travel Medicine (SLAMVI) and a Member of the Council of the International Society for Infectious Diseases (ISID). Since 2014, he has been recognized as a Senior Researcher, at the Ministry of Science of Colombia. He is a professor at the Faculty of Medicine of the Fundacion Universitaria Autonoma de las Americas, in Pereira, Risaralda, Colombia. He is an External Professor, Master in Research on Tropical Medicine and International Health, Universitat de Barcelona, Spain. He is also a professor at the Master in Clinical Epidemiology and Biostatistics, Universidad Científica del Sur, Lima, Peru. In 2021 he has been awarded the “Raul Isturiz Award” Medal of the API. Also, in 2021, he was awarded with the “Jose Felix Patiño” Asclepius Staff Medal of the Colombian Medical College, due to his scientific contributions to COVID-19 during the pandemic. He is currently the Editor in Chief of the journal Travel Medicine and Infectious Diseases. His Scopus H index is 47 (Google Scholar H index, 68).",institutionString:"Institución Universitaria Visión de las Américas, Colombia",institution:null},{id:"332819",title:"Dr.",name:"Chukwudi Michael",middleName:"Michael",surname:"Egbuche",slug:"chukwudi-michael-egbuche",fullName:"Chukwudi Michael Egbuche",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/332819/images/14624_n.jpg",biography:"I an Dr. Chukwudi Michael Egbuche. I am a Senior Lecturer in the Department of Parasitology and Entomology, Nnamdi Azikiwe University, Awka.",institutionString:null,institution:{name:"Nnamdi Azikiwe University",country:{name:"Nigeria"}}},{id:"284232",title:"Mr.",name:"Nikunj",middleName:"U",surname:"Tandel",slug:"nikunj-tandel",fullName:"Nikunj Tandel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/284232/images/8275_n.jpg",biography:'Mr. Nikunj Tandel has completed his Master\'s degree in Biotechnology from VIT University, India in the year of 2012. He is having 8 years of research experience especially in the field of malaria epidemiology, immunology, and nanoparticle-based drug delivery system against the infectious diseases, autoimmune disorders and cancer. He has worked for the NIH funded-International Center of Excellence in Malaria Research project "Center for the study of complex malaria in India (CSCMi)" in collaboration with New York University. The preliminary objectives of the study are to understand and develop the evidence-based tools and interventions for the control and prevention of malaria in different sites of the INDIA. Alongside, with the help of next-generation genomics study, the team has studied the antimalarial drug resistance in India. Further, he has extended his research in the development of Humanized mice for the study of liver-stage malaria and identification of molecular marker(s) for the Artemisinin resistance. At present, his research focuses on understanding the role of B cells in the activation of CD8+ T cells in malaria. Received the CSIR-SRF (Senior Research Fellow) award-2018, FIMSA (Federation of Immunological Societies of Asia-Oceania) Travel Bursary award to attend the IUIS-IIS-FIMSA Immunology course-2019',institutionString:"Nirma University",institution:{name:"Nirma University",country:{name:"India"}}},{id:"334383",title:"Ph.D.",name:"Simone",middleName:"Ulrich",surname:"Ulrich Picoli",slug:"simone-ulrich-picoli",fullName:"Simone Ulrich Picoli",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/334383/images/15919_n.jpg",biography:"Graduated in Pharmacy from Universidade Luterana do Brasil (1999), Master in Agricultural and Environmental Microbiology from Federal University of Rio Grande do Sul (2002), Specialization in Clinical Microbiology from Universidade de São Paulo, USP (2007) and PhD in Sciences in Gastroenterology and Hepatology (2012). She is currently an Adjunct Professor at Feevale University in Medicine and Biomedicine courses and a permanent professor of the Academic Master\\'s Degree in Virology. She has experience in the field of Microbiology, with an emphasis on Bacteriology, working mainly on the following topics: bacteriophages, bacterial resistance, clinical microbiology and food microbiology.",institutionString:null,institution:{name:"Universidade Feevale",country:{name:"Brazil"}}},{id:"229220",title:"Dr.",name:"Amjad",middleName:"Islam",surname:"Aqib",slug:"amjad-aqib",fullName:"Amjad Aqib",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229220/images/system/229220.png",biography:"Dr. Amjad Islam Aqib obtained a DVM and MSc (Hons) from University of Agriculture Faisalabad (UAF), Pakistan, and a PhD from the University of Veterinary and Animal Sciences Lahore, Pakistan. Dr. Aqib joined the Department of Clinical Medicine and Surgery at UAF for one year as an assistant professor where he developed a research laboratory designated for pathogenic bacteria. Since 2018, he has been Assistant Professor/Officer in-charge, Department of Medicine, Manager Research Operations and Development-ORIC, and President One Health Club at Cholistan University of Veterinary and Animal Sciences, Bahawalpur, Pakistan. He has nearly 100 publications to his credit. His research interests include epidemiological patterns and molecular analysis of antimicrobial resistance and modulation and vaccine development against animal pathogens of public health concern.",institutionString:"Cholistan University of Veterinary and Animal Sciences",institution:null},{id:"62900",title:"Prof.",name:"Fethi",middleName:null,surname:"Derbel",slug:"fethi-derbel",fullName:"Fethi Derbel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/62900/images/system/62900.jpeg",biography:"Professor Fethi Derbel was born in 1960 in Tunisia. He received his medical degree from the Sousse Faculty of Medicine at Sousse, University of Sousse, Tunisia. He completed his surgical residency in General Surgery at the University Hospital Farhat Hached of Sousse and was a member of the Unit of Liver Transplantation in the University of Rennes, France. He then worked in the Department of Surgery at the Sahloul University Hospital in Sousse. Professor Derbel is presently working at the Clinique les Oliviers, Sousse, Tunisia. His hospital activities are mostly concerned with laparoscopic, colorectal, pancreatic, hepatobiliary, and gastric surgery. He is also very interested in hernia surgery and performs ventral hernia repairs and inguinal hernia repairs. He has been a member of the GREPA and Tunisian Hernia Society (THS). During his residency, he managed patients suffering from diabetic foot, and he was very interested in this pathology. For this reason, he decided to coordinate a book project dealing with the diabetic foot. Professor Derbel has published many articles in journals and collaborates intensively with IntechOpen Access Publisher as an editor.",institutionString:"Clinique les Oliviers",institution:null},{id:"300144",title:"Dr.",name:"Meriem",middleName:null,surname:"Braiki",slug:"meriem-braiki",fullName:"Meriem Braiki",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/300144/images/system/300144.jpg",biography:"Dr. Meriem Braiki is a specialist in pediatric surgeon from Tunisia. She was born in 1985. She received her medical degree from the University of Medicine at Sousse, Tunisia. She achieved her surgical residency training periods in Pediatric Surgery departments at University Hospitals in Monastir, Tunis and France.\r\nShe is currently working at the Pediatric surgery department, Sidi Bouzid Hospital, Tunisia. Her hospital activities are mostly concerned with laparoscopic, parietal, urological and digestive surgery. She has published several articles in diffrent journals.",institutionString:"Sidi Bouzid Regional Hospital",institution:null},{id:"229481",title:"Dr.",name:"Erika M.",middleName:"Martins",surname:"de Carvalho",slug:"erika-m.-de-carvalho",fullName:"Erika M. de Carvalho",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229481/images/6397_n.jpg",biography:null,institutionString:null,institution:{name:"Oswaldo Cruz Foundation",country:{name:"Brazil"}}},{id:"186537",title:"Prof.",name:"Tonay",middleName:null,surname:"Inceboz",slug:"tonay-inceboz",fullName:"Tonay Inceboz",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/186537/images/system/186537.jfif",biography:"I was graduated from Ege University of Medical Faculty (Turkey) in 1988 and completed his Med. PhD degree in Medical Parasitology at the same university. I became an Associate Professor in 2008 and Professor in 2014. I am currently working as a Professor at the Department of Medical Parasitology at Dokuz Eylul University, Izmir, Turkey.\n\nI have given many lectures, presentations in different academic meetings. I have more than 60 articles in peer-reviewed journals, 18 book chapters, 1 book editorship.\n\nMy research interests are Echinococcus granulosus, Echinococcus multilocularis (diagnosis, life cycle, in vitro and in vivo cultivation), and Trichomonas vaginalis (diagnosis, PCR, and in vitro cultivation).",institutionString:"Dokuz Eylül University",institution:{name:"Dokuz Eylül University",country:{name:"Turkey"}}},{id:"71812",title:"Prof.",name:"Hanem Fathy",middleName:"Fathy",surname:"Khater",slug:"hanem-fathy-khater",fullName:"Hanem Fathy Khater",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/71812/images/1167_n.jpg",biography:"Prof. Khater is a Professor of Parasitology at Benha University, Egypt. She studied for her doctoral degree, at the Department of Entomology, College of Agriculture, Food and Natural Resources, University of Missouri, Columbia, USA. She has completed her Ph.D. degrees in Parasitology in Egypt, from where she got the award for “the best scientific Ph.D. dissertation”. She worked at the School of Biological Sciences, Bristol, England, the UK in controlling insects of medical and veterinary importance as a grant from Newton Mosharafa, the British Council. Her research is focused on searching of pesticides against mosquitoes, house flies, lice, green bottle fly, camel nasal botfly, soft and hard ticks, mites, and the diamondback moth as well as control of several parasites using safe and natural materials to avoid drug resistances and environmental contamination.",institutionString:null,institution:{name:"Banha University",country:{name:"Egypt"}}},{id:"99780",title:"Prof.",name:"Omolade",middleName:"Olayinka",surname:"Okwa",slug:"omolade-okwa",fullName:"Omolade Okwa",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/99780/images/system/99780.jpg",biography:"Omolade Olayinka Okwa is presently a Professor of Parasitology at Lagos State University, Nigeria. She has a PhD in Parasitology (1997), an MSc in Cellular Parasitology (1992), and a BSc (Hons) Zoology (1990) all from the University of Ibadan, Nigeria. She teaches parasitology at the undergraduate and postgraduate levels. She was a recipient of a Commonwealth fellowship supported by British Council tenable at the Centre for Entomology and Parasitology (CAEP), Keele University, United Kingdom between 2004 and 2005. She was awarded an Honorary Visiting Research Fellow at the same university from 2005 to 2007. \nShe has been an external examiner to the Department of Veterinary Microbiology and Parasitology, University of Ibadan, MSc programme between 2010 and 2012. She is a member of the Nigerian Society of Experimental Biology (NISEB), Parasitology and Public Health Society of Nigeria (PPSN), Science Association of Nigeria (SAN), Zoological Society of Nigeria (ZSN), and is Vice Chairperson of the Organisation of Women in Science (OWSG), LASU chapter. She served as Head of Department of Zoology and Environmental Biology, Lagos State University from 2007 to 2010 and 2014 to 2016. She is a reviewer for several local and international journals such as Unilag Journal of Science, Libyan Journal of Medicine, Journal of Medicine and Medical Sciences, and Annual Research and Review in Science. \nShe has authored 45 scientific research publications in local and international journals, 8 scientific reviews, 4 books, and 3 book chapters, which includes the books “Malaria Parasites” and “Malaria” which are IntechOpen access publications.",institutionString:"Lagos State University",institution:{name:"Lagos State University",country:{name:"Nigeria"}}},{id:"273100",title:"Dr.",name:"Vijay",middleName:null,surname:"Gayam",slug:"vijay-gayam",fullName:"Vijay Gayam",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/273100/images/system/273100.jpeg",biography:"Dr. Vijay Bhaskar Reddy Gayam is currently practicing as an internist at Interfaith Medical Center in Brooklyn, New York, USA. He is also a Clinical Assistant Professor at the SUNY Downstate University Hospital and Adjunct Professor of Medicine at the American University of Antigua. He is a holder of an M.B.B.S. degree bestowed to him by Osmania Medical College and received his M.D. at Interfaith Medical Center. His career goals thus far have heavily focused on direct patient care, medical education, and clinical research. He currently serves in two leadership capacities; Assistant Program Director of Medicine at Interfaith Medical Center and as a Councilor for the American\r\nFederation for Medical Research. As a true academician and researcher, he has more than 50 papers indexed in international peer-reviewed journals. He has also presented numerous papers in multiple national and international scientific conferences. His areas of research interest include general internal medicine, gastroenterology and hepatology. He serves as an editor, editorial board member and reviewer for multiple international journals. His research on Hepatitis C has been very successful and has led to multiple research awards, including the 'Equity in Prevention and Treatment Award” from the New York Department of Health Viral Hepatitis Symposium (2018) and the 'Presidential Poster Award” awarded to him by the American College of Gastroenterology (2018). He was also awarded 'Outstanding Clinician in General Medicine” by Venus International Foundation for his extensive research expertise and services, perform over and above the standard expected in the advancement of healthcare, patient safety and quality of care.",institutionString:"Interfaith Medical Center",institution:{name:"Interfaith Medical Center",country:{name:"United States of America"}}},{id:"93517",title:"Dr.",name:"Clement",middleName:"Adebajo",surname:"Meseko",slug:"clement-meseko",fullName:"Clement Meseko",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/93517/images/system/93517.jpg",biography:"Dr. Clement Meseko obtained DVM and PhD degree in Veterinary Medicine and Virology respectively. He has worked for over 20 years in both private and public sectors including the academia, contributing to knowledge and control of infectious disease. Through the application of epidemiological skill, classical and molecular virological skills, he investigates viruses of economic and public health importance for the mitigation of the negative impact on people, animal and the environment in the context of Onehealth. \r\nDr. Meseko’s field experience on animal and zoonotic diseases and pathogen dynamics at the human-animal interface over the years shaped his carrier in research and scientific inquiries. He has been part of the investigation of Highly Pathogenic Avian Influenza incursions in sub Saharan Africa and monitors swine Influenza (Pandemic influenza Virus) agro-ecology and potential for interspecies transmission. He has authored and reviewed a number of journal articles and book chapters.",institutionString:"National Veterinary Research Institute",institution:{name:"National Veterinary Research Institute",country:{name:"Nigeria"}}},{id:"158026",title:"Prof.",name:"Shailendra K.",middleName:null,surname:"Saxena",slug:"shailendra-k.-saxena",fullName:"Shailendra K. Saxena",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRET3QAO/Profile_Picture_2022-05-10T10:10:26.jpeg",biography:"Professor Dr. Shailendra K. Saxena is a vice dean and professor at King George's Medical University, Lucknow, India. His research interests involve understanding the molecular mechanisms of host defense during human viral infections and developing new predictive, preventive, and therapeutic strategies for them using Japanese encephalitis virus (JEV), HIV, and emerging viruses as a model via stem cell and cell culture technologies. His research work has been published in various high-impact factor journals (Science, PNAS, Nature Medicine) with a high number of citations. He has received many awards and honors in India and abroad including various Young Scientist Awards, BBSRC India Partnering Award, and Dr. JC Bose National Award of Department of Biotechnology, Min. of Science and Technology, Govt. of India. Dr. Saxena is a fellow of various international societies/academies including the Royal College of Pathologists, United Kingdom; Royal Society of Medicine, London; Royal Society of Biology, United Kingdom; Royal Society of Chemistry, London; and Academy of Translational Medicine Professionals, Austria. He was named a Global Leader in Science by The Scientist. He is also an international opinion leader/expert in vaccination for Japanese encephalitis by IPIC (UK).",institutionString:"King George's Medical University",institution:{name:"King George's Medical University",country:{name:"India"}}},{id:"94928",title:"Dr.",name:"Takuo",middleName:null,surname:"Mizukami",slug:"takuo-mizukami",fullName:"Takuo Mizukami",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/94928/images/6402_n.jpg",biography:null,institutionString:null,institution:{name:"National Institute of Infectious Diseases",country:{name:"Japan"}}},{id:"233433",title:"Dr.",name:"Yulia",middleName:null,surname:"Desheva",slug:"yulia-desheva",fullName:"Yulia Desheva",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/233433/images/system/233433.png",biography:"Dr. Yulia Desheva is a leading researcher at the Institute of Experimental Medicine, St. Petersburg, Russia. 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Much of biochemistry is devoted to enzymes, proteins that catalyze chemical reactions, enzyme structures, mechanisms of action and their roles within cells. Biochemistry also studies small signaling molecules, coenzymes, inhibitors, vitamins, and hormones, which play roles in life processes. Biochemical experimentation, besides coopting classical chemistry methods, e.g., chromatography, adopted new techniques, e.g., X-ray diffraction, electron microscopy, NMR, radioisotopes, and developed sophisticated microbial genetic tools, e.g., auxotroph mutants and their revertants, fermentation, etc. More recently, biochemistry embraced the ‘big data’ omics systems. 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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. 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In recent years, the application of chemistry to biological molecules has gained significant interest in medicinal and pharmacological studies. This topic will be devoted to understanding the interplay between biomolecules and chemical compounds, their structure and function, and their potential applications in related fields. Being a part of the biochemistry discipline, the ideas and concepts that have emerged from Chemical Biology have affected other related areas. 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Behind these definitions are hidden all the aspects of normal and pathological functioning of all processes that the topic ‘Metabolism’ will cover within the Biochemistry Series. 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Thus proteomics, an area of research that detects all protein forms expressed in an organism, including splice isoforms and post-translational modifications, is more suitable than genomics for a comprehensive understanding of the biochemical processes that govern life. The most common proteomics applications are currently in the clinical field for the identification, in a variety of biological matrices, of biomarkers for diagnosis and therapeutic intervention of disorders. From the comparison of proteomic profiles of control and disease or different physiological states, which may emerge, changes in protein expression can provide new insights into the roles played by some proteins in human pathologies. Understanding how proteins function and interact with each other is another goal of proteomics that makes this approach even more intriguing. Specialized technology and expertise are required to assess the proteome of any biological sample. Currently, proteomics relies mainly on mass spectrometry (MS) combined with electrophoretic (1 or 2-DE-MS) and/or chromatographic techniques (LC-MS/MS). MS is an excellent tool that has gained popularity in proteomics because of its ability to gather a complex body of information such as cataloging protein expression, identifying protein modification sites, and defining protein interactions. 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