\r\n\tTherefore, this book will investigate the dynamic oceanography and ship navigation impacts on marine oil pollution in addition to weather dynamic fluctuations too.
\r\n\tRounding out with practical simulation trajectory movements of oil spills using high-resolution models and remote sensing images, this book will bring an effective new source of technology and applications for today’s oil and marine pollution engineers.
Injury and infection, seemingly unrelated conditions, converge on a common process - inflammation, which is mediated partly by innate immune cells including macrophages and monocytes. These innate immune cells are equipped with pattern recognition receptors (such as TLR2, TLR4, and TLR9) (Brightbill et al. 1999; Poltorak et al. 1998; Hemmi et al. 2000), and can recognize both damage- and pathogen-associated molecular patterns (DAMPs, such as HMGB1; and PAMPs, such as endotoxin) (Andersson et al. 2000; Chen
Fetuin-A was first isolated by Pederson more than sixty years ago as a major plasma protein in the fetus (Pedersen 1944). During fetal development, it is expressed in most organs including the liver, kidney, gastrointestinal tract, skin and brain (Terkelsen et al. 1998; Kitchener et al. 1997; Dziegielewska et al. 2000; Kitchener et al. 1999). In adults however, fetuin-A is produced primarily by the liver, and its synthesis is divergently regulated during injury or infection, classifying it as a negative or positive APP.
\n\t\t\tAlthough fetuin-A is constitutively expressed in hepatocytes, its expression is negatively regulated by several proinflammatory cytokines. For instance, the fetuin-A expression levels in human HepG2 hepatoma cells were reduced by proinflammatory cytokines such as TNF, IL-1, IL-6, and IFN-γ (Daveau et al. 1988;Li et al. 2011a). IFN-γ, at concentrations as low as 10-50 ng/ml, reduced fetuin-A expression levels by as much as 50-70% (Li et al. 2011a). In contrast, HMGB1 (1 μg/ml), a late proinflammatory mediator of lethal systemic inflammation (Wang et al. 1999; Yang et al. 2004; Wang et al. 2008), elevated fetuin-A expression levels by 2-3 folds in HepG2 cells, suggesting that different cytokines divergently regulate hepatic fetuin-A expression.
\n\t\t\tIn patients with cerebral ischemic injury (stroke), plasma fetuin-A levels were paradoxically elevated (Weikert et al. 2008;Tuttolomondo et al. 2010). The elevation of circulating fetuin-A levels correlated with an increase not only in LDL-cholesterol levels (Tuttolomondo et al. 2010) but also in risk of cardiovascular disorders (Weikert et al. 2008). Similarly, serum fetuin-A levels were increased up to 10-fold in cattle following traumatic injury (Dziegielewska et al. 1992), suggesting fetuin-A as a positive APP during ischemic or traumatic injury. Notably, HMGB1 can be passively leaked from injured cells (Peltz et al. 2009), and functions as an early mediator of traumatic or ischemic injury (Zhu et al. 2010; Wu et al. 2007; Liu et al. 2007b; Tsung et al. 2005; Tsung et al. 2007; Watanabe et al. 2005). It is thus plausible that HMGB1 participates in the up-regulation of hepatic fetuin-A expression during injury.
\n\t\t\t\tIn an animal model of focal cerebral ischemia (i.e., permanent middle cerebral artery occlusion, MCAo), fetuin-A levels in the ischemic brain tissue were also elevated in a time-dependent manner, starting between 2-6 h, peaking around 24-48 h, and returning towards base-line at 72 h post MCAo (Wang et al. 2010). This time-dependent increase in cerebral fetuin-A levels parallels with the transient elevation of the blood-brain barrier (BBB) permeability (Belayev et al. 1996), suggesting that circulating fetuin-A can gain entry across the BBB into the ischemic brain tissue. This possibility was supported by the observation that peripherally (intravenously) administered FITC-labeled fetuin-A was found in the ischemic brain region at 24 h after MCAo (Wang et al. 2010).
\n\t\t\tIn animal models of endotoxemia and sepsis (induced by cecal ligation and puncture, CLP), circulating fetuin-A levels were decreased in a time-dependent fashion, starting between 2-6 h, reaching a nadir (with maximal reduction by 50-60%) around 24-48 h. Afterwards, fetuin-A levels started to increase, returning towards basal levels approximately 72 h post endotoxemia or sepsis, supporting fetuin-A as a negative APP in animal models of lethal endotoxemia and sepsis (Li et al. 2011a). Interestingly, disruption of expression of early proinflammatory cytokines (such as IFN-γ) impaired bacterial endotoxin-mediated down-regulation of fetuin-A expression (Li et al. 2011a). It thus appears that early proinflammatory cytokines (such as TNF and IFN-γ) function as negative regulators to reduce circulating fetuin-A levels during an early stage of endotoxemia or sepsis; whereas late-acting proinflammatory mediators (e.g., HMGB1) stimulate fetuin-A expression to restore its circulating levels at a late stage.
\n\t\t\t\tIn patients with other inflammatory diseases such as pancreatitis (Kusnierz-Cabala et al. 2010), chronic kidney diseases (Metry et al. 2008), and rheumatoid arthritis (Sato et al. 2007), serum fetuin A levels were also decreased by 20-30%. In these patients, circulating fetuin-A levels were not only inversely correlated with levels of inflammatory cytokines (such as IL-6) (Kusnierz-Cabala et al. 2010), but also associated with increased mortality rates (Metry et al. 2008). Collectively, these observations classify fetuin-A as a negative APP during infection or other inflammatory illness.
\n\t\t\tDespite its abundance, the functions of fetuin-A remain poorly understood. A wide range of biological functions have been proposed for fetuin-A based on its structural similarities to other proteins or physical interactions with biogenic molecules.
\n\t\t\tFetuin-A shares sequence similarity to type II TGF-β receptors (Demetriou et al. 1996) and insulin receptor tyrosine kinases (Mathews et al. 1997;Haasemann et al. 1991), and has thus been proposed as an inhibitor of the TGF-β or insulin signaling pathways. After binding to to TGF-β1, fetuin-A prevents TGF-β1 from binding to its receptors, thereby antagonizing TGF-β1-mediated antiproliferative effects (Demetriou et al. 1996). Similarly, fetuin-A can also bind to the insulin receptor, and consequently inactivate (rather than activate, as in the case for insulin) the receptor tyrosine kinase (Goustin & Abou-Samra 2010). This may partly explain why higher fetuin-A levels were associated with insulin resistance in some patients with type 2 diabetes (Ix et al. 2008).
\n\t\t\tAs a glycoprotein, fetuin-A carries two N-linked and three O-linked oligosaccharide chains that terminate with sialic acid residues, and can bind cationic Ca2+ ions. Accordingly, fetuin-A has been proposed as an endogenous inhibitor of pathological mineralization or calcification in soft tissues (Jahnen-Dechent et al. 2001;Schinke et al. 1996;Szweras et al. 2002;Schafer et al. 2003;Ketteler et al. 2003). Specifically, fetuin-A forms protein-mineral colloids with calcium and phosphate (Heiss et al. 2003;Wu et al. 2009), thereby preventing uncontrolled mineralization that may otherwise occur under pathological conditions (Rochette et al. 2009).
\n\t\t\tWhile investigating the mechanism underlying a cationic molecule spermine-mediated anti-inflammatory actions, we serendipitously discovered that macrophages lost their responsiveness to spermine when cultured under low serum conditions (Wang et al. 1997). That is, despite the addition of cytokine-suppressing concentrations of spermine, the bacterial lipopolysaccharide (LPS)-induced production of TNF by these serum-starved macrophages was uninhibited. Subsequently, we discovered that these serum-starved macrophages became deprived of fetuin-A that was required for spermine to inhibit TNF production (Wang et al. 1997). The involvement of fetuin-A in spermine-mediated immunosuppression was confirmed by adding highly purified fetuin-A or fetuin-specific antibodies, which respectively restored or impaired spermine-mediated TNF inhibition (Wang et al. 1997).
\n\t\t\t\tIt is plausible that fetuin-A functions as an opsonin for cationic spermine, and its availability to immune cells may be critical in regulating the innate immune response (Wang & Tracey 1999). Indeed, levels of fetuin-A in macrophage cultures could be altered by LPS stimulation or fetuin-A supplementation (Figure 1A). Intriguingly, the exogenously administered fetuin-A was predominantly localized in cytoplasmic punctate structures (Figure 1B), which co-localized with vesicles containing an autophagy marker (LC3) - possibly autophagosomes or amphisomes - in LPS-stimulated macrophages.
\n\t\t\t\tWhen given at higher concentrations (e.g., 3.5 mg/ml), crude fetuin-A (> 98%, Sigma-Aldrich) abrogated endotoxin-induced release of IL-1 and nitric oxide (Dziegielewska et al. 1998). Upon purification by gel filtration and ion-exchange chromatography, the highly purified intact fetuin-A could effectively inhibit IFN-γ- or LPS-induced release of HMGB1 (Li et al. 2011a), a newly identified late mediator of lethal endotoxemia and sepsis (Wang et al. 2008;Wang
Exogenous fetuin-A was internalized into cytoplasmic vesicles in macrophage cultures. A). Supplementation of exogenous fetuin-A prevented endotoxin-induced fetuin-A depletion. Murine macrophage-like RAW 264.7 cells were stimulated with LPS (100 ng/ml) in the absence or presence of fetuin-A (100 μg/ml) for 2 h, and cellular fetuin-A levels were determined by Western blotting. The relative fetuin-A levels, as a ratio to β-actin, were expressed as the mean ± SD of three independent experiments. *, p < 0.05 versus control (“+LPS”); #, p < 0.01 vs control (“+LPS”). B) Exogenous fetuin-A was internalized into LC3-containing cytoplasmic vesicles. GFP-LC3-transfected RAW 264.7 cells were stimulated with LPS (200 ng/ml) in the presence of fetuin-A (100 μg/ml) overnight, and immunostained with fetuin-A-specific antibodies.
In an animal model of carrageenan-induced inflammation, intraperitoneal administration of fetuin-A (5 to 500 mg/kg) dose-dependently attenuated the development of paw edema (Ombrellino et al. 2001). The sialic acid moieties of fetuin-A might be required for its anti-inflammatory activities. When these sialic acid residues were removed by neuraminidase, the resultant asialofetuin-A failed to potentiate the anti-inflammatory activities of spermine (Wang et al. 1997) and failed to attenuate carrageenan-induced TNF production
Cerebral ischemia is frequently caused by an obstruction of a cerebral artery. Despite advances in acute and prophylactic therapies, stroke represents the leading cause of long-term disability (500,000-700,000 cases per year), and the third most common cause of death (with a mortality rate of 20-25%) in the United States.
\n\t\t\t\tCerebral ischemic injury consists of two stages: primary tissue damage in the ischemic core and secondary tissue injury in the surrounding penumbra. The primary injury in the ischemic core is primarily mediated by tissue ion (Ca2+ and Na+) overload (Taylor & Meldrum 1995) and excitotoxicity (Lee et al. 1999); whereas the secondary injury in the surrounding penumbra is partly mediated by proinflammatory cytokines (Figure 2, Feuerstein et al. 1998).
\n\t\t\t\t\tCascade of events leading to primary injury in the ischemic core and secondary injury in the surrounding penumbra.
Within seconds to minutes after cerebral ischemia, decreased ATP production leads to failure of the Na+/K+-ATPase pump, disruption of membrane potentials, influx of sodium and calcium, and subsequent release of excitatory amino acids (such as glutamate, Figure 2). Engagement of glutamate with the ionotropic N-methyl-D-aspartate receptor (NMDA) leads to Ca2+ influx and activation of damaging proteases (e.g., phospholipase A2, nitric oxide synthase, endonucleases, and calpain) that compromise the functional and structural integrity of neuronal cells within 20-60 minutes (Figure 2). Early-stage therapeutics that block ion (Na+ and Ca2+) channels (Taylor & Meldrum 1995) and glutamate receptors (Meldrum 1990) fail in clinical trials, partly because of the impracticalities of administering such drugs at a time when those mechanisms are already activated. These failures have prompted the search for downstream targets that also mediate ischemic injury.
\n\t\t\t\t\tOutside of the ischemic core where cells are destined to die lies a penumbral zone where brain cell death continues slowly for hours and even days after the onset of ischemia (Figure 2). This progressive expansion of cell death in the penumbra (i.e., secondary injury) is mediated by ischemia-elicited inflammatory responses. Within a few hours, microglia and neurons become activated to produce TNF and other cytokines (Kato et al. 1996;Botchkina et al. 1997). Subsequently, polymorphonuclear cells infiltrate into the ischemic brain tissue within 12-48 hours (Akopov et al. 1996), followed by an influx of monocytes and macrophages over a period of one to several days. Together, these centrally- and peripherally-derived cells orchestrate a potentially injurious inflammatory response by overproducing various proinflammatory cytokines (Figure 2).
\n\t\t\t\t\t\tMany pro-inflammatory cytokines (e.g., TNF and IL-1) contribute to cerebral ischemic injury (Buttini et al. 1996;Zaremba & Losy 2001), because inhibition of their production (Meistrell et al. 1997;Bertorelli et al. 1998) or activity (Barone et al. 1997;Yang et al. 1999) confers protective effects. In addition, an ubiquitous nuclear protein, HMGB1, can be passively released from the ischemic core, and spilled into the surrounding periphery (Qiu et al. 2008). In the penumbra, it amplifies a potentially injurious inflammatory response by inducing various cytokines, chemokines, tissue factor and adhesion molecules (Andersson et al. 2000;Lv et al. 2009;Fiuza et al. 2003;Treutiger et al. 2003) (Figure 2). Indeed, HMGB1-specific neutralizing antibodies and antagonists (e.g., the A box) have been proven protective (Liu et al. 2007a;Muhammad et al. 2008), supporting a pathogenic role for HMGB1 in ischemic injury.
\n\t\t\t\t\tAnother abundant molecule, spermine, can also be passively released by injured cells (\n\t\t\t\t\t\t\tPaschen 1992\n\t\t\t\t\t\t). At higher (millimolar) concentrations, spermine could be neuroprotective by binding and blocking the NMDA receptor (Araneda et al. 1999;Ferchmin et al. 2000). In addition, it counter-regulates expression of inflammatory cytokines (Zhang et al. 2000;Zhang
During cerebral ischemia, brain spermine levels are decreased (Paschen et al. 1992), owing largely to an accompanying increase in the enzymatic activity of brain polyamine oxidase (Ivanova et al. 1998). The loss of spermine consequently tilts the balance towards neurotoxicity through activating the NMDA receptor, and increasing susceptibility to oxidative stress as well as excessive inflammatory response.
\n\t\t\t\tDivergent roles of spermine in cerebral ischemic injury.
As mentioned earlier, when given peripherally, exogenous fetuin-A gains entry across the BBB into the ischemic brain tissue (Figure 4). The time-course of fetuin-A extravasation in the ischemic brain tissue parallels with the time-dependent alteration of the BBB permeability (Belayev et al. 1996), which was transiently elevated (5 -25 h post MCAo) followed by a return towards baseline at 72 h post MCAo (Belayev et al. 1996). It is possible that the temporal breakdown of the BBB is required for circulating fetuin-A to transiently gain entry into the brain. Consistently, peripheral administration of fetuin-A (50 mg/kg) promoted a dose-dependent protection against cerebral ischemic injury during an early stage of cerebral ischemia (i.e., 24 h post MCAo) (Wang et al. 2010). However, the fetuin-A-mediated protection was not long-lasting, and gradually diminished at a later stage (e.g., 7 days post MCAo). It is possible that the restore of BBB function at a late stage (3 days after MCAo) limits subsequent fetuin-A extravasation, thereby diminishing fetuin-A-mediated long-lasting protective effects.
\n\t\t\t\t\tGiven the aforementioned pathogenic roles of Ca2+ and spermine in cerebral ischemia (in section 4.2.1 and 4.2.2), as well as the capacity of fetuin-A in binding Ca2+ and spermine (in secton 3.2 and 3.3) (Suzuki et al. 1994;Wang et al. 1997), it is plausible that fetuin-A confers protection by caging these toxic cationic molecules (Lee et al. 1999;Ivanova et al. 1998), thereby depriving them from damaging enzymes (such as Ca2+ -dependent proteases and polyamine oxidase). Furthermore, the fetuin-A-mediated protection is associated with a reduction of ischemia-elicited HMGB1 leakage from the ischemic core, and an inhibition of expression of proinflammatory cytokines (e.g., TNF) in the penumbra (Wang et al. 2010) (Figure 4), suggesting that fetuin-A confers protection partly by attenuating early inflammatory responses.
\n\t\t\t\tProtective roles of fetuin-A in cerebral ischemic injury and sepsis.
Sepsis is the most common cause of death in intensive care units, claiming approximately 225,000 victims annually in the U.S. alone. The high mortality of sepsis is in part mediated by bacterial endotoxin, which activates macrophages and monocytes to sequentially release early (e.g., TNF and IL-1) (Dinarello 1996) and late (e.g., HMGB1) proinflammatory cytokines.
\n\t\t\t\tThe pathogenesis of sepsis is partly attributable to dysregulated systemic inflammatory responses that are initiated by early proinflammatory cytokines and sustained by late-acting proinflammatory mediators. For instance, excessive accumulation of early proinflammatory cytokines, including TNF (Tracey et al. 1987), interleukin (IL)-1 (Dinarello & Thompson 1991), interferon (IFN)-γ (Heinzel 1990), individually or in combination, contribute to the pathogenesis of lethal systemic inflammation. Because these early cytokines are difficult to target in clinical settings, we searched for other late proinflammatory mediators that may offer a wider therapeutic window.
\n\t\t\t\t\tAs aforementioned, HMGB1 is released from activated innate immune cells in response to microbial products (such as endotoxin or CpG-DNA) (Wang et al. 1999;Ivanov et al. 2007), or host cytokines (e.g., TNF or IFN-γ) (Wang et al. 1999;Rendon-Mitchell et al. 2003), and functions as a late mediator of endotoxemia and sepsis (Wang et al. 1999;Yang et al. 2004;Wang et al. 2008;Wang et al. 2009). In murine models of endotoxemia and sepsis, HMGB1 is first detectable in the circulation eight hours after the onset of diseases, subsequently increasing to plateau levels from 16 to 32 hours (Wang et al. 1999; Yang et al. 2004) (Figure 4). This late appearance of circulating HMGB1 parallels with the onset of animal lethality from endotoxemia or sepsis, and distinguishes itself from TNF and other early proinflammatory cytokines (Wang et al. 2001). Therefore, agents capable of selectively attenuating systemic HMGB1 accumulation at a late stage may hold potential in the treatment of lethal sepsis.
\n\t\t\t\tIn light of the anti-inflammatory activities of spermine
To understand the role of fetuin-A in systemic inflammatory diseases, we determined the influence of fetuin-A disruption on endotoxemic and septic lethality. Although fetuin-A-deficient C57BL/6J mice were not more susceptible to cerebral ischemic insult than sex- and body-matched (male, 27-29 g) wild-type C57BL/6J mice (Wang et al. 2010), they were more susceptible to lethal endotoxemic or septic insult (Li et al. 2011a). It suggests that endogenous fetuin-A occupies an integral role in host defense against lethal systemic inflammation.
\n\t\t\t\t\tThe protective role of fetuin-A was further supported by the observations that supplementation with exogenous fetuin-A (20-100 mg/kg) provided a dose-dependent protection against lethal endotoxemia (Li et al. 2011a). In an animal model of sepsis, delayed administration of fetuin-A (20 - 100 mg/kg), beginning 24 h
Supplementation of fetuin-A was associated with significant reduction of circulating HMGB1 levels, suggesting that fetuin-A confers protection by inhibiting late-acting proinflammatory mediators (Li et al. 2011a). The mechanisms underlying fetuin-A-mediated suppression of HMGB1 release may be complex. At the concentrations (100 μg/ml) that fetuin-A attenuated LPS-induced HMGB1 release in macrophage cultures, fetuin-A stimulated autophagy and impaired LPS-induced elevation of cytoplasmic and nuclear HMGB1 levels (Li et al. 2011a). It is presently unknown whether fetuin-A reduces cytoplasmic HMGB1 levels by stimulating its degradation in an autophagy-dependent fashion, as what has been shown for other HMGB1 inhibitors such as EGCG, the major catechin of Green tea (
Accumulating evidence has suggested the possibility that fetuin-A functions as a negative regulator of HMGB1 release during lethal systemic inflammation (Figure 4). First, the time-dependent decrease of circulating fetuin-A levels was accompanied by parallel but opposite changes – a time-dependent increase - of circulating HMGB1 levels in animal models of endotoxemia (Wang et al. 1999) or sepsis (Yang et al. 2004). Second, disruption of fetuin-A expression led to elevation of serum HMGB1 levels in endotoxemia and sepsis
Nevertheless, the current study can not exclude other alternative mechanisms by which fetuin-A confers these protective effects. For instance, fetuin-A may be capable of binding bacteria (Chmiela et al. 1997;Dubreuil et al. 2002), thereby affecting macrophage-mediated pathogen elimination. Furthermore, fetuin-A may facilitate macrophages-mediated ingestion and elimination of apoptotic neutrophils (Lord 2003;Jersmann et al. 2003), thereby preventing secondary necrosis and passive leakage of injurious molecules (e.g., proteases, reactive oxygen species, and HMGB1) (Bell et al. 2006).
\n\t\t\t\tA liver-derived acute phase protein, fetuin-A, appears to be distinctly regulated by different proinflammatory mediators. A previously under-appreciated protective role for fetuin-A in injury and infection has been suggested by recent studies. Fetuin-A is capable of crossing the blood-brain barrier, inhibiting early inflammatory response in animal models of cerebral ischemia, thereby conferring a short-term neuroprotection against ischemic injury. Disruption of fetuin-A expression renders mice significantly more susceptible to lethal endotoxemia or sepsis; whereas repetitive administration of fetuin-A confers a dose-dependent and long-lasting protection in animal models of lethal endotoxemia and sepsis. Thus, fetuin-A occupies protective roles against injury- or infection-elicited inflammation.
\n\t\tWe thank Arvin Jundoria for critical reading of the manuscript. Work in the author’s laboratory was supported by the National Institute of General Medical Sciences (R01GM063075 and R01GM070817 to HW) and the National Center of Complementary & Alternative Medicine (R01AT05076 to HW).
\n\t\tManagement of PCOS (polycystic ovary syndrome) related to infertility, includes lifestyle changes, ovulation induction by pharmaceuticals, or assisted reproductive technology (ART) as an
Hyperandrogenism, anovulation, and ovarian morphology are the basic determinants in the diagnosis of the polycystic ovarian syndrome (PCOS) according to international guidelines. Given the different clinical presentations in patients, the criteria for the diagnosis of this condition are still discussed, as well as whether the syndrome involves several different diseases with the same clinical picture, as well as discussions about what is really a clinical picture of the polycystic ovary. Therefore, different approaches in the diagnosis and treatment of patients, have been proposed for different phenotypes of PCOS. The criteria for pre-recognition of this condition have been adopted for years by various authoritative bodies at international meetings, such as the National Institute for Health (NIH), Rotterdam consensus, Androgen Excess, and PCO Society, but there has been a constant difference over the mandatory criteria for PCOS [1]. An important starting point in the diagnosis was to exclude diseases of other endocrine glands (pituitary gland, thyroid, and adrenal gland), which give a similar clinical picture and can be confused with PCOS.
Ovulation disorder in the general population of women is estimated at 15% (12–18%) [2]. Regular menstrual cycles are not the exclusive evidence of ovulation, since in some women there is a “subclinical disorder” of ovulation that is proven only by serum values of progesterone in the middle lutein phase of the cycle (21–24.d.c. which must be >5 ng/mL). In the case of PCOS, almost 80% of patients have ovulation disorder [3].
Hyperandrogenism (hyperandrogenemia) implies clinical and/or biochemical evidence of elevated serum androgens, but the incidence in the general population of women is unknown. Hirsutism, androgenic alopecia, and acne are clinical manifestations of hyperandrogenism. The intensity of hirsutism differs ethnically and geographically, and it is desirable to develop population-specific criteria for hirsutism. Almost 70% of women with hirsutism have PCOS, 40% have severely expressed acne, and only 22% have androgenic alopecia [4]. Hyperandogenemia (biochemical hyperandrogenism) is determined by free testosterone and free androgen index (FAI—free androgen index) [5]. A total of 78% of patients with PCOS have hyperandrogenism and 40% in an unselected population of patients with BMI >25 [6].
Polycystic ovary morphology (PCOM) is evaluated by ultrasound examination based on the number of antral follicles (> of 20 per ovary) and/or on the basis of total ovarian volume (> 10 mL), where the frequency of the ultrasonic probe is an extremely important parameter. Based on these international criteria, the prevalence of PCOM in the population is 12.5% [7, 8]. Ultrasonic examination of nonselective population, based only on PCOM, significantly increase the incidence of PCOS and vice versa.
Thus, on the basis of the described criteria, four PCOS phenotypes with different prevalence in the general and separate population are defined, which are as follows [5]:
Phenotype A (hyperandrogenism, anovulation, PCOM).
Phenotype B (hyperandrogenism, anovulation).
Phenotype C (hyperandrogenism, PCOM), ovulatory PCOS.
Phenotype D (anovulation, PCOM), non-hyperandrogenemic PCOS.
Compared to phenotype C and D, patients with phenotype A and B (classical phenotype) are more often obese, with hirsutism, more likely to have insulin resistance, dyslipidemia, fatty liver, and metabolic syndrome in later life. The frequency of individual phenotype differs significantly in different populations with symptoms of PCOS and also in the general population [9]. Each of the PCOS phenotypes has its own specifics in the treatment of impaired fertility.
The first line of treatment of patients with PCOS is the induction of ovulation with clomiphene citrate or letrozole.
Gonadotropin stimulation in patients with PCOS is associated with the development of a significantly higher number of follicles in the ovaries, as well as oocytes, a significantly higher number of developed embryos and embryos in excess for cryopreservation. Ovarian stimulation in these patients lasts longer and higher doses of gonadotropin are often required, which is associated with disorders of folliculogenesis caused by hyperandrogenism. Estimating the right dose of gonadotropin is the biggest challenge in the phase of ovarian stimulation and is often insufficient. The follicles do not grow, due to hyperandrogenism, and by increasing the dose, the ovary enters in hyperstimulation, which is an extreme of the ovarian response. A newer approach to ovarian stimulation with follitropin delta, based on the patient’s body mass and AMH value, proved to be the best, especially in the PCOS patient population and has a significant reduction in the risk of ovary hyperstimulation. Patients with hyperandrogenism and polycystic ovarian morphology (phenotype A and C) have the highest risk of ovary hyperstimulation [11].
Ovarian hyperstimulation syndrome (OHSS) is an iatrogenic complication of ovarian stimulation, and PCOS patients have the highest risk for complications during the IVF (
The protocol of choice for ovarian stimulation in patients with PCOS and risk for OHSS is an antagonistic protocol that can be fixed or flexible. In this stimulation, it is possible to achieve the final maturation of oocyte with GnRH (gonadotropin-releasing hormone) agonists, thereby avoiding the administration of hCG (human chorionic gonadotropin) injection, which is the basic molecule in the mechanism of development of OHSS in at-risk patients. In this way, the basic mechanism of vascular permeability and compromising circulation by leaking plasma from the vascular system into extracellular spaces are avoided. Those are signs of a more severe form of OHSS. Likewise, the stimulation cycle is abruptly “extinguished.” Menstrual bleeding occurs within a few days after the application of the GnRH agonist. Harvested oocytes are fertilized by IVF/ICSI procedure and developed embryos are cryopreserved, most often in the blastocyst stage, which represents the so-called “freeze-all” strategy that gives safety to the treatment of patients with PCOS. Embryo transfer is planned in the next cycle in which signs of hyperstimulation do not exist. Hormonal preparation of the endometrium, and ovarian stimulation, in this case, is not required.
Additional treatment of PCOS patients involves the use of various medications that have metabolic effects and that could significantly improve the treatment of these patients in IVF procedures by individualizing therapy. The fact is that within the PCOS population with the same PCOS phenotype, an individual woman may have a significantly different response to different types of treatments with respect to the unique hormonal/metabolic status associated with the PCOS phenotype as well. There is a large gap in the literature that indicates the need for new research and the need for an individual approach in the treatment of infertility of these patients.
Spontaneous abortions in patients with PCOS are more common compared to the general population and they are associated with insulin resistance, hyperandrogenism, and obesity. These conditions are very often associated with PCOS, but they are also separate risks for the spontaneous loss of pregnancy. Studies link spontaneous abortion to impaired endometrial receptivity and to more frequent embryo aneuploidy of patients with PCOS. In the Asian population of women with PCOS phenotypes who have hyperandrogenism (A, B, C types), a higher risk for spontaneous miscarriage after IVF procedures was observed than in phenotype D [12]. Impaired glucose and insulin metabolism at the endometrial level and excessive expression of androgen receptors in the endometrium are associated with a signal transduction disorder during the implantation process in patients with PCOS [13]. The causes of more frequent embryo aneuploidy in PCOS patients have not yet been clarified. There are assumptions that impaired glucose metabolism and steroidogenesis lead to DNA molecule instability [14].
During the stimulated IVF cycle, various indicators of quality and success of treatment are monitored. Among other things, these are the total dose of gonadotropin used for stimulation, the number of aspirated oocytes, the number of oocytes in metaphase II, the percentage of fertilization, the number of developed embryos on the 3rd day, the number of developed blastocysts on the 5th day, the number of cryopreserved embryos, the proportion of conceived pregnancies, the number of born children, etc. Since PCOS phenotypes imply hormonal and metabolic differences, the question arises whether the indicators of the course of treatment are different in patients with different PCOS phenotypes.
The results of the studies so far indicate significant differences in treatment between PCOS patients and women who do not have this syndrome and who in studies represent the usual control group. Studies most often follow PCOS patients as a single group. Different criteria for defining PCOS phenotype are associated with problems of analysis and comparison of parameters that monitor the course and outcome of the IVF procedures in different studies [15]. There are two fundamental factors that are most often analyzed and compared in patients with PCOS—hyperandrogenism and PCO morphology of the ovaries, which are clinically very important factors in decision-making during the treatment of infertility by medically assisted fertilization procedures. The role of androgens in folliculogenesis is still unclear and there are conflicting results of studies dealing with this problem. The results of studies analyzing differences in treatment outcomes among defined PCOS phenotypes indicate a negative effect of hyperandrogenism in IVF procedures, and a higher incidence of complications later in pregnancy [16]. In patients with phenotype A and B, for every 1 pg./ml increase in free testosterone concentration, the proportion of clinically confirmed pregnancies decreases by 50–60% as well as the proportion of live births [17]. According to recent findings, the differences between PCOS phenotypes refer only to the number of good embryos for transfer, which is significantly higher in patients with hyperandrogenism and ovulation disorder, but without the typical PCO morphology of the ovaries (phenotype B). The proportion of biochemical and clinically confirmed pregnancies, as well as the number of couples with born children, do not differ significantly among phenotypically different PCOS patients [17, 18]. In addition, studies indicate that the proportion of clinically confirmed pregnancies, is significantly lower in women with PCOS phenotypes A, B and C compared to control patients [17]. The number of children born does not differ in different PCOS phenotypes. In some areas of the world, certain PCOS phenotypes have not been found at all, for example, there are no phenotypes B and C among Vietnamese women with PCOS [19]. Since the anti-Müller hormone (AMH) is often elevated in patients with PCOS, it has become a powerful factor that should have prognostic value in clinically assessing the outcome of treatment with medically assisted fertilization, however, it has been proven useful only in the group of patients with phenotype B. The proportion of clinically confirmed pregnancies and the proportion of babies born increases by 1.3 times for each 1 ng/ml serum AMH concentration increase [17].
PCOS patients’ oocytes quality can be associated with the hormonal and metabolic conditions, and therefore, consequently with the quality of the embryo. Poorer oocyte quality is part of the problem of subfertility in patients with PCOS. There is evidence that oocyte quality depends on PCOS phenotype and accompanying diseases and conditions that are more common in PCOS patients. Oocyte quality is defined by the morphology and morphology of associated structures, such as zona pellucida, cumulus oophorus, and corona radiata. An ovarian microenvironment in which follicles and oocytes grow and mature is exposed to multiple hormonal abnormalities in patients with PCOS. Well-known disruptive mechanisms include elevated concentrations of LH (luteinizing hormone) and FSH (follicle-stimulating hormone), impaired ratio of these hormones, elevated AMH values, impaired insulin-like growth factor secretion, and enzymes involved in the conversion of androgens to estrogens.
Hyperandrogenism interferes with the normal feedback loop between the ovaries, pituitary gland, and hypothalamus, which leads to an increased frequency of excretion of the releasing hormone for gonadotropins, and consecutively results in premature luteinization of granulose cells and abnormal maturation of the oocytes. There is also a direct effect of hyperandrogenism on the oocyte by activating its proapoptotic mechanism [20]. Hyperandogenic ovarium microenvironment interferes with the oocyte in the continuation of meiosis, promotes mitochondrial abnormalities and oxidative stress, and interferes with lipid metabolism in the oocyte [21].
High concentrations of AMH synthesized by granulosa cells, inhibit the recruitment of follicles, and therefore, the selection of follicles that will ovulate, leading to a vicious cycle of anovulation and hyperandrogenism. In addition, by blocking the action of FSH on follicle growth and blocking the action of aromatase in charge of converting androgens synthesized in theca cells to estrogens in granulosa cells, the chronic state of hyperandrogenism is again supported. There is evidence that in patients with PCOS an increased concentration of AMH in follicular fluid exists along with oocytes of low quality. Molecular mechanisms that lead to disruption in the growth and maturation of oocytes are not known [22]. Significantly lower follicular fluid AMH levels were observed in follicles of fertilized MII oocytes than in non-fertilized non-PCOS patients [23]. Also in our non-PCOS patients with sterility and impaired fertility, gene for the AMH and androgen receptor in human cumulus cells surrounding morphologically highly graded oocytes are underexpressed [24].
Hyperinsulinemia, insulin resistance, and obesity are metabolic disorders associated with PCOS that intertwine with hormonal disorders and further worsen the conditions of oocyte microenvironments. Hyperinsulinemia reduces the synthesis of binding globulin for sex hormones (SHBG), and insulin also competes with androgens for binding sites on this carrier, which means that it promotes hyperandrogenism and all its negative effects. The direct effect of hyperinsulinemia on oocytes has been proven to disrupt the expression of genes associated with the dynamics of the division spindle and the function of centrosomes. In the case of insulin resistance, there is a change in gene expression for glucose carriers in granulose cells, and therefore, a possible decrease in energy sources for the metabolism of the oocyte itself and the processes of meiosis [25].
Based on PCOS phenotype in the population of women being treated with medically assisted reproduction procedures, no difference has been found so far in the proportion of oocytes in metaphase II, percentage of fertilization, or the evaluation of quality embryos for transfer [17, 26]. According to available data to date, patients who have a classic PCOS phenotype (A and B) associated with insulin resistance and obesity also have the highest risk for low-quality oocytes [27].
Besides poor quality oocytes, PCOS patients can have larger numbers of germinal vesicle stages – metaphase I oocyte collected from IVF, due to their elevated antral follicles count. Those are commonly maturated with unsatisfactory results. When optimized maturation procedure will serve, not only for PCOS and infertile patients but also in cancer patients for the preservation of fertility and as a more patient-friendly alternative than standard controlled ovarian stimulation. PCOS patients are not the only ones that could benefit from
The definition of phenotypes of polycystic ovarian syndrome stemmed from a diverse and complex clinical picture of this endocrine disorder. Diagnostic criteria of individual phenotype, contribute to new concepts of research into the effects of obesity, hyperandrogenism, and metabolic disorders on reproduction in humans. According to the outcomes of the treatment of infertility of patients with this disorder, significant differences in the chances of conception compared to the population of infertile women who do not have polycystic ovary syndrome have been clearly proven. Less clear is the difference in infertility treatment outcomes between women with a defined polycystic ovarian syndrome phenotype, which is the area of new research. In cases of classical phenotype polycystic ovarian syndrome (A and B) associated with obesity and insulin resistance, negative effects of this disease on gametes and embryos are possible due to cellular process disorders related to glucose and androgen metabolism.
The publication is supported by H2020: MESOC – measuring the social dimension of culture; under Grant agreement no. 870935. Uniri-biomed-18-161 project: Extracellular vesicles in human follicular fluid: content and role in oocyte maturation and embryo quality.
Authors have no conflict of interest.
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Among them, a deep neuromuscular blockade (NMB) contributes to provide the surgeon with better operating conditions. This chapter discusses the interests and challenges of muscle relaxation during gynecological laparoscopy. The introduction of sugammadex into clinical practice provides the opportunity to modify the management of neuromuscular blockade to improve the surgical conditions during laparoscopy as well as the safety of the patients. The maintenance of a rocuronium-induced deep neuromuscular block from the trocar insertion until the end of laparoscopy is no longer incompatible with rapid recovery and awakening in optimal conditions. Neuromuscular transmission (NMT) monitoring is the key to adequate management and should be used in all cases. Objective measurements allow for excellent intubation and surgical conditions, the definition of thresholds and doses for the administration of reversal agents, and the exclusion of residual blockade prior to the patient extubation.",book:{id:"5409",slug:"fertility-oriented-female-reproductive-surgery",title:"Fertility-oriented Female Reproductive Surgery",fullTitle:"Fertility-oriented Female Reproductive Surgery"},signatures:"Christophe Dransart, Laurie Putz, Maria-Laura Marotta and Philippe\nE. Dubois",authors:[{id:"164978",title:"Prof.",name:"Philippe",middleName:"E",surname:"Dubois",slug:"philippe-dubois",fullName:"Philippe Dubois"},{id:"194443",title:"Dr.",name:"Christophe",middleName:null,surname:"Dransart",slug:"christophe-dransart",fullName:"Christophe Dransart"},{id:"194444",title:"Dr.",name:"Laurie",middleName:null,surname:"Putz",slug:"laurie-putz",fullName:"Laurie Putz"},{id:"194445",title:"Dr.",name:"Maria-Laura",middleName:null,surname:"Marotta",slug:"maria-laura-marotta",fullName:"Maria-Laura Marotta"}]},{id:"52300",doi:"10.5772/65296",title:"Endometriosis: When and How We Treat",slug:"endometriosis-when-and-how-we-treat",totalDownloads:1369,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Endometriosis is a chronic, nonmalignant and estrogen‐dependent disease in which endometrial glandular epithelium and stroma are outside the uterine cavity (ovaries, peritoneum, or rectovaginal septum). The prevalence is estimated from 2 to 10% in women of childbearing age and it rises up to 50% in women with infertility. Despite maximal efforts, the therapy of first choice in the management of endometriosis is still unclear. The aim of this chapter is to present an update of its management, emphasizing the benefits and disadvantages of surgical methods. We performed a systematic literature search on the PubMed database of English literature (search terms: endometrioma, surgery, ovarian reserve, assisted reproductive technologies) from 2010 to 2014. For endometrioma, operative laparoscopy proved to be the gold standard. Surgical procedures consist of partial excision of the cyst wall and electro‐coagulation of the rest. Stripping technique may be a better method for reducing the recurrence of pain symptoms, recurrence, and reoperation rates, but it raises concerns about ovarian reserve. For endometriosis, surgery often includes partial rectum or sacrouterine ligament resection. Hysterectomy is not obligatory and refused by the young patients. The approach should be laparoscopic and if necessary vaginal assisted. Good cooperation between various disciplines (gynecology, surgery, urology) is mandatory.",book:{id:"5409",slug:"fertility-oriented-female-reproductive-surgery",title:"Fertility-oriented Female Reproductive Surgery",fullTitle:"Fertility-oriented Female Reproductive Surgery"},signatures:"Sidonia Maria Saceanu, Stefan Patrascu, Anca Patrascu and Valeriu\nSurlin",authors:[{id:"158096",title:"Associate Prof.",name:"Valeriu",middleName:null,surname:"Surlin",slug:"valeriu-surlin",fullName:"Valeriu Surlin"},{id:"194539",title:"Dr.",name:"Stefan",middleName:null,surname:"Patrascu",slug:"stefan-patrascu",fullName:"Stefan Patrascu"},{id:"194540",title:"Dr.",name:"Sidonia Maria",middleName:null,surname:"Sandulescu",slug:"sidonia-maria-sandulescu",fullName:"Sidonia Maria Sandulescu"},{id:"194541",title:"Prof.",name:"Anca",middleName:null,surname:"Patrascu",slug:"anca-patrascu",fullName:"Anca Patrascu"}]},{id:"52615",doi:"10.5772/65769",title:"Bowel Dysfunction after Hysterectomy for Benign Conditions: Meta-Analysis and Systematic Review",slug:"bowel-dysfunction-after-hysterectomy-for-benign-conditions-meta-analysis-and-systematic-review",totalDownloads:1531,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"The aim of this study was to determine whether hysterectomy for a benign indication can cause functional gastrointestinal disorders (FGIDs). A systematic review was completed with the studies, which used a prospective design and validated quality of life questionnaires. A search strategy using Medline and Embase allowed the relevant studies published between 1950 and October 2010 to be found. Meta-analyses were also performed using the studies, which had similar research objectives. The search revealed 29 potentially suitable articles, of which 5 used a prospective design and validated quality of life questionnaires. The meta-analyses showed that the type of hysterectomy (total or subtotal) did not have an impact on whether a patient is likely to develop gastrointestinal symptoms post-surgery. The prospective studies did not show that hysterectomy for a benign indication causes FGIDs. The belief that hysterectomy can cause gastrointestinal dysfunction is based on the results of retrospective studies.",book:{id:"5409",slug:"fertility-oriented-female-reproductive-surgery",title:"Fertility-oriented Female Reproductive Surgery",fullTitle:"Fertility-oriented Female Reproductive Surgery"},signatures:"Constantina Pitsillides and Hany Lashen",authors:[{id:"191199",title:"Mr.",name:"Hany",middleName:null,surname:"Lashen",slug:"hany-lashen",fullName:"Hany Lashen"}]},{id:"52626",doi:"10.5772/65544",title:"Laparoscopic Surgery in the Treatment of Endometriosis",slug:"laparoscopic-surgery-in-the-treatment-of-endometriosis",totalDownloads:1380,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Endometriosis is a benign disease, which affects about 10% of reproductive age women and almost 50% of infertile women. Although every year at least 300 new articles deal with this topic, endometriosis is still a enigmatic disease starting with theories of etiopathogenesis where there is still no consensus about the major cause of endometriosis. Also there is still no consensus about the management of the disease, mainly when there is an infertile patient who is preparing for in vitro fertilization procedure.",book:{id:"5409",slug:"fertility-oriented-female-reproductive-surgery",title:"Fertility-oriented Female Reproductive Surgery",fullTitle:"Fertility-oriented Female Reproductive Surgery"},signatures:"Sonja Pop-Trajkovic Dinic, Jasmina Popovic, Radomir Zivadinovic,\nDejan Mitic, Vladimir Antic and Milan Trenkic",authors:[{id:"69225",title:"Dr.",name:"Sonja",middleName:null,surname:"Pop-Trajkovic",slug:"sonja-pop-trajkovic",fullName:"Sonja Pop-Trajkovic"},{id:"194904",title:"Dr.",name:"Vladimir",middleName:null,surname:"Antic",slug:"vladimir-antic",fullName:"Vladimir Antic"},{id:"194905",title:"Prof.",name:"Jasmina",middleName:null,surname:"Popovic",slug:"jasmina-popovic",fullName:"Jasmina Popovic"},{id:"194906",title:"Dr.",name:"Milan",middleName:null,surname:"Trenkic",slug:"milan-trenkic",fullName:"Milan Trenkic"}]}],mostDownloadedChaptersLast30Days:[{id:"53784",title:"Microsurgical Cesarean Section",slug:"microsurgical-cesarean-section",totalDownloads:2355,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Worldwide, not only is cesarean section (CS) the most commonly performed major surgery, but it is also the commonest obstetric operation. CD is associated with some chronic maternal morbidities including pelvic pain, adhesions and adverse reproductive effects. CS carries long‐term sequele which can adversely affect subsequent pregnancies. Why do some women develop bad sequele of CS‐like adhesions, and infertility is well demonstrated in this chapter. Fertility‐oriented step‐by‐step description of CS techniques is extensively described. Some recent controversial issues related to CS like the development of uterine nitche (isthmocele) at the CS scar site, placenta accrete and the role of cesarean myomectomy are discussed in details. At the end of this chapter, the reader will conceive enjoy fertility‐oriented concept of CS.",book:{id:"5409",slug:"fertility-oriented-female-reproductive-surgery",title:"Fertility-oriented Female Reproductive Surgery",fullTitle:"Fertility-oriented Female Reproductive Surgery"},signatures:"Atef Darwish",authors:[{id:"29304",title:"Prof.",name:"Atef",middleName:"M.M.",surname:"Darwish",slug:"atef-darwish",fullName:"Atef Darwish"}]},{id:"52615",title:"Bowel Dysfunction after Hysterectomy for Benign Conditions: Meta-Analysis and Systematic Review",slug:"bowel-dysfunction-after-hysterectomy-for-benign-conditions-meta-analysis-and-systematic-review",totalDownloads:1531,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"The aim of this study was to determine whether hysterectomy for a benign indication can cause functional gastrointestinal disorders (FGIDs). A systematic review was completed with the studies, which used a prospective design and validated quality of life questionnaires. A search strategy using Medline and Embase allowed the relevant studies published between 1950 and October 2010 to be found. Meta-analyses were also performed using the studies, which had similar research objectives. The search revealed 29 potentially suitable articles, of which 5 used a prospective design and validated quality of life questionnaires. The meta-analyses showed that the type of hysterectomy (total or subtotal) did not have an impact on whether a patient is likely to develop gastrointestinal symptoms post-surgery. The prospective studies did not show that hysterectomy for a benign indication causes FGIDs. The belief that hysterectomy can cause gastrointestinal dysfunction is based on the results of retrospective studies.",book:{id:"5409",slug:"fertility-oriented-female-reproductive-surgery",title:"Fertility-oriented Female Reproductive Surgery",fullTitle:"Fertility-oriented Female Reproductive Surgery"},signatures:"Constantina Pitsillides and Hany Lashen",authors:[{id:"191199",title:"Mr.",name:"Hany",middleName:null,surname:"Lashen",slug:"hany-lashen",fullName:"Hany Lashen"}]},{id:"51944",title:"Hysteroscopic Surgery for Submucosal Fibroids",slug:"hysteroscopic-surgery-for-submucosal-fibroids",totalDownloads:17730,totalCrossrefCites:0,totalDimensionsCites:1,abstract:"This chapter presents a contemporary summary of the evidence of the clinical impact of submucosal fibroids and discusses the methods used to investigate and surgically manage this common gynaecological condition.",book:{id:"5409",slug:"fertility-oriented-female-reproductive-surgery",title:"Fertility-oriented Female Reproductive Surgery",fullTitle:"Fertility-oriented Female Reproductive Surgery"},signatures:"Rashi Kalra and Roger J Hart",authors:[{id:"187858",title:"Prof.",name:"Roger",middleName:null,surname:"Hart",slug:"roger-hart",fullName:"Roger Hart"},{id:"187861",title:"Dr.",name:"Rashi",middleName:null,surname:"Kalra",slug:"rashi-kalra",fullName:"Rashi Kalra"}]},{id:"52626",title:"Laparoscopic Surgery in the Treatment of Endometriosis",slug:"laparoscopic-surgery-in-the-treatment-of-endometriosis",totalDownloads:1380,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Endometriosis is a benign disease, which affects about 10% of reproductive age women and almost 50% of infertile women. Although every year at least 300 new articles deal with this topic, endometriosis is still a enigmatic disease starting with theories of etiopathogenesis where there is still no consensus about the major cause of endometriosis. Also there is still no consensus about the management of the disease, mainly when there is an infertile patient who is preparing for in vitro fertilization procedure.",book:{id:"5409",slug:"fertility-oriented-female-reproductive-surgery",title:"Fertility-oriented Female Reproductive Surgery",fullTitle:"Fertility-oriented Female Reproductive Surgery"},signatures:"Sonja Pop-Trajkovic Dinic, Jasmina Popovic, Radomir Zivadinovic,\nDejan Mitic, Vladimir Antic and Milan Trenkic",authors:[{id:"69225",title:"Dr.",name:"Sonja",middleName:null,surname:"Pop-Trajkovic",slug:"sonja-pop-trajkovic",fullName:"Sonja Pop-Trajkovic"},{id:"194904",title:"Dr.",name:"Vladimir",middleName:null,surname:"Antic",slug:"vladimir-antic",fullName:"Vladimir Antic"},{id:"194905",title:"Prof.",name:"Jasmina",middleName:null,surname:"Popovic",slug:"jasmina-popovic",fullName:"Jasmina Popovic"},{id:"194906",title:"Dr.",name:"Milan",middleName:null,surname:"Trenkic",slug:"milan-trenkic",fullName:"Milan Trenkic"}]},{id:"52107",title:"Deep Neuromuscular Blockade Improves Surgical Conditions During Gynecological Laparoscopy",slug:"deep-neuromuscular-blockade-improves-surgical-conditions-during-gynecological-laparoscopy",totalDownloads:1510,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Obtaining an appropriate laparoscopic workspace depends on several factors related to the patient (i.e., weight and abdominal compliance) and the procedure (i.e., body’s position, depth of anesthesia and intra-abdominal (IA) pressure). Among them, a deep neuromuscular blockade (NMB) contributes to provide the surgeon with better operating conditions. This chapter discusses the interests and challenges of muscle relaxation during gynecological laparoscopy. The introduction of sugammadex into clinical practice provides the opportunity to modify the management of neuromuscular blockade to improve the surgical conditions during laparoscopy as well as the safety of the patients. The maintenance of a rocuronium-induced deep neuromuscular block from the trocar insertion until the end of laparoscopy is no longer incompatible with rapid recovery and awakening in optimal conditions. Neuromuscular transmission (NMT) monitoring is the key to adequate management and should be used in all cases. Objective measurements allow for excellent intubation and surgical conditions, the definition of thresholds and doses for the administration of reversal agents, and the exclusion of residual blockade prior to the patient extubation.",book:{id:"5409",slug:"fertility-oriented-female-reproductive-surgery",title:"Fertility-oriented Female Reproductive Surgery",fullTitle:"Fertility-oriented Female Reproductive Surgery"},signatures:"Christophe Dransart, Laurie Putz, Maria-Laura Marotta and Philippe\nE. 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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. 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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. 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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. This topic will closely deal with all emerging trends in this discipline.",annualVolume:11411,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/15.jpg",editor:{id:"441442",title:"Dr.",name:"Şükrü",middleName:null,surname:"Beydemir",fullName:"Şükrü Beydemir",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003GsUoIQAV/Profile_Picture_1634557147521",institutionString:null,institution:{name:"Anadolu University",institutionURL:null,country:{name:"Turkey"}}},editorTwo:{id:"13652",title:"Prof.",name:"Deniz",middleName:null,surname:"Ekinci",fullName:"Deniz Ekinci",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYLT1QAO/Profile_Picture_1634557223079",institutionString:null,institution:{name:"Ondokuz Mayıs University",institutionURL:null,country:{name:"Turkey"}}},editorThree:null,editorialBoard:[{id:"219081",title:"Dr.",name:"Abdulsamed",middleName:null,surname:"Kükürt",fullName:"Abdulsamed Kükürt",profilePictureURL:"https://mts.intechopen.com/storage/users/219081/images/system/219081.png",institutionString:null,institution:{name:"Kafkas University",institutionURL:null,country:{name:"Turkey"}}},{id:"241413",title:"Dr.",name:"Azhar",middleName:null,surname:"Rasul",fullName:"Azhar Rasul",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRT1oQAG/Profile_Picture_1635251978933",institutionString:null,institution:{name:"Government College University, Faisalabad",institutionURL:null,country:{name:"Pakistan"}}},{id:"178316",title:"Ph.D.",name:"Sergey",middleName:null,surname:"Sedykh",fullName:"Sergey Sedykh",profilePictureURL:"https://mts.intechopen.com/storage/users/178316/images/system/178316.jfif",institutionString:null,institution:{name:"Novosibirsk State University",institutionURL:null,country:{name:"Russia"}}}]},{id:"17",title:"Metabolism",keywords:"Biomolecules Metabolism, Energy Metabolism, Metabolic Pathways, Key Metabolic Enzymes, Metabolic Adaptation",scope:"Metabolism is frequently defined in biochemistry textbooks as the overall process that allows living systems to acquire and use the free energy they need for their vital functions or the chemical processes that occur within a living organism to maintain life. 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. Thus all studies on metabolism will be considered for publication.",annualVolume:11413,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/17.jpg",editor:{id:"138626",title:"Dr.",name:"Yannis",middleName:null,surname:"Karamanos",fullName:"Yannis Karamanos",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002g6Jv2QAE/Profile_Picture_1629356660984",institutionString:null,institution:{name:"Artois University",institutionURL:null,country:{name:"France"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"243049",title:"Dr.",name:"Anca",middleName:null,surname:"Pantea Stoian",fullName:"Anca Pantea Stoian",profilePictureURL:"https://mts.intechopen.com/storage/users/243049/images/system/243049.jpg",institutionString:null,institution:{name:"Carol Davila University of Medicine and Pharmacy",institutionURL:null,country:{name:"Romania"}}},{id:"203824",title:"Dr.",name:"Attilio",middleName:null,surname:"Rigotti",fullName:"Attilio Rigotti",profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institutionString:null,institution:{name:"Pontifical Catholic University of Chile",institutionURL:null,country:{name:"Chile"}}},{id:"300470",title:"Dr.",name:"Yanfei (Jacob)",middleName:null,surname:"Qi",fullName:"Yanfei (Jacob) Qi",profilePictureURL:"https://mts.intechopen.com/storage/users/300470/images/system/300470.jpg",institutionString:null,institution:{name:"Centenary Institute of Cancer Medicine and Cell Biology",institutionURL:null,country:{name:"Australia"}}}]},{id:"18",title:"Proteomics",keywords:"Mono- and Two-Dimensional Gel Electrophoresis (1-and 2-DE), Liquid Chromatography (LC), Mass Spectrometry/Tandem Mass Spectrometry (MS; MS/MS), Proteins",scope:"With the recognition that the human genome cannot provide answers to the etiology of a disorder, changes in the proteins expressed by a genome became a focus in research. 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. The Proteomics topic aims to attract contributions on all aspects of MS-based proteomics that, by pushing the boundaries of MS capabilities, may address biological problems that have not been resolved yet.",annualVolume:11414,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/18.jpg",editor:{id:"200689",title:"Prof.",name:"Paolo",middleName:null,surname:"Iadarola",fullName:"Paolo Iadarola",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSCl8QAG/Profile_Picture_1623568118342",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorTwo:{id:"201414",title:"Dr.",name:"Simona",middleName:null,surname:"Viglio",fullName:"Simona Viglio",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRKDHQA4/Profile_Picture_1630402531487",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorThree:null,editorialBoard:[{id:"72288",title:"Dr.",name:"Arli Aditya",middleName:null,surname:"Parikesit",fullName:"Arli Aditya Parikesit",profilePictureURL:"https://mts.intechopen.com/storage/users/72288/images/system/72288.jpg",institutionString:null,institution:{name:"Indonesia International Institute for Life Sciences",institutionURL:null,country:{name:"Indonesia"}}},{id:"40928",title:"Dr.",name:"Cesar",middleName:null,surname:"Lopez-Camarillo",fullName:"Cesar Lopez-Camarillo",profilePictureURL:"https://mts.intechopen.com/storage/users/40928/images/3884_n.png",institutionString:null,institution:{name:"Universidad Autónoma de la Ciudad de México",institutionURL:null,country:{name:"Mexico"}}},{id:"81926",title:"Dr.",name:"Shymaa",middleName:null,surname:"Enany",fullName:"Shymaa Enany",profilePictureURL:"https://mts.intechopen.com/storage/users/81926/images/system/81926.png",institutionString:"Suez Canal University",institution:{name:"Suez Canal University",institutionURL:null,country:{name:"Egypt"}}}]}]}},libraryRecommendation:{success:null,errors:{},institutions:[]},route:{name:"profile.detail",path:"/profiles/317085",hash:"",query:{},params:{id:"317085"},fullPath:"/profiles/317085",meta:{},from:{name:null,path:"/",hash:"",query:{},params:{},fullPath:"/",meta:{}}}},function(){var t;(t=document.currentScript||document.scripts[document.scripts.length-1]).parentNode.removeChild(t)}()