GUSB enzyme activity was increased >10-fold in brain, liver, spleen, lung, and kidney, but not in heart (Figure 3(b)). The expression pattern of GUSB gene among mouse

organs in vivo is consistent with the local expression of the TfR in the vascular barriers of these tissues. The liver and spleen are perfused with fenestrated capillaries that are highly porous, so the 100nm THLs can freely cross their vascular barrier [20]. Heart, lung, and kidney are perfused with capillaries with continuous endothelial barriers [38]. Thus, the observation that GUSB enzyme activity is increased in lung and kidney with TfRMAb-targeted THLs in vivo provides additional evidence for Inhibitors,research,lifescience,medical the expression of the TfR on the vascular barrier in these organs in the mouse [27]. Inhibitors,research,lifescience,medical Lack of expression in heart supports prior work with reporter genes showing that TfRMAb-targeted THLs are not delivered across the vascular barrier in heart [20, 21, 27]. The brain GUSB enzyme activity observed at 48h after a single THL administration approximated

2U/mg protein (Figure 3(b)), which represents 55% of the brain level in heterozygotes [39]. Since the replacement of just 1–5% of lysosomal enzyme activity in an organ may Inhibitors,research,lifescience,medical be sufficient to cause therapeutic effects and a reversal of lysosomal storage disease [37], the levels of GUSB enzyme activity generated in the brain of null mice with a single Inhibitors,research,lifescience,medical IV injection of THLs is Thiazovivin purchase within the therapeutic range. The plasmid DNA is expressed episomally in brain cells without integration into the host genome [33]. Therefore, long-term treatment of lysosomal storage disorders with intravenous administration of THLs will require repeat administration of the gene medicine at intervals that are determined by both the persistence of transgene expression and the turnover of the expressed protein in brain and peripheral organs. 5. Brain Expression of Therapeutic

Genes in a Model of Parkinson’s Disease The therapeutic efficacy of THLs was demonstrated in vivo in a model of Inhibitors,research,lifescience,medical Parkinson’s disease (PD), wherein the therapeutic gene encoded for tyrosine hydroxylase (TH) [30]. PD is associated with a loss of dopaminergic neurons in the substantia nigra, which terminate in the striatum [40, 41]. The rate limiting enzyme in the synthesis of dopamine is TH, and a potential treatment for PD is TH gene replacement therapy. Studies were performed in the rat 6-hydroxydopamine over (6-OHDA) model, and with THL packaged with a TH expression plasmid driven by the Gfap brain-specific promoter, designated clone 951 [30]. Gfap-TH-THLs were constructed with the OX26 MAb to target the rat TfR (Table 1). The intracerebral injection of 6-OHDA produced a 98% reduction in the levels of TH in the ipsilateral striatum as compared with the contralateral or nonlesioned control animals (Table 2).

Donepezil has the longest plasma half-life at about 70 hours compared with 6 hours for galantamine, 3 hours for tacrine, and 1.5 hours for rivastigmine (this has the practical advantage that it is excreted quickly from the body and so relief from side effects is much more speedy than with the longer-acting compounds). The half-life also

has implications for the daily dosing regimen: the advantage of donepezil is that it only needs to be given once a day. Tacrine This was the first drug to be introduced and, in many ways, was the gold standard by which the others were measured. The drug has positive Inhibitors,research,lifescience,medical effects on cognitive function at dosages of 160 mg/day, and benefits have been seen in terms of ADL and global function.18,19 Unfortunately, almost half of all patients experience liver side effects, usually a rise in transaminases, and so a search began for an agent as effective as tacrine, but without side effects. Donepezil As a piperidinc-based compound, the introduction of donepezil was important because of its lack of liver Inhibitors,research,lifescience,medical side effects and the convenience of once-daily dosing. One multinational study20 involved patients Inhibitors,research,lifescience,medical in Australia, Belgium, Canada, France, Germany, Ireland,

New Zealand, South Africa, and the UK. Fight hundred and eighteen (818) patients were randomized to receive placebo (n=274), 5 mg/day donepezil (n=271), or 10 mg/day donepezil (n=273).The mean age of patients was just over 70 and they all satisfied the NINCDS/ADRDA (National Institute of Neurological and Communicative Disorders and Stroke and Alzheimer

Disease and Related Disorders Association)21 criteria for probable Alzheimer’s disease. Inhibitors,research,lifescience,medical Patients with mild-to-moderate impairment were included, as assessed by an MMSE score of between 10 and 26 and a CDR of 1 (mild) or 2 (moderate). The study lasted 30 weeks: 24 weeks with a double-blind, placebo-controlled phase followed by a single-blind placebo washout Inhibitors,research,lifescience,medical over 6 weeks. Patients started with 5 mg/day donepezil for 7 days followed by 10 mg/day. The positive effects on the ADAS-Cog arc shown in Figure 1. The percentage of patients rated as improved was 21 % for 5 mg/day, 25% for 10 mg/day, and 14% for placebo. The Autophagy animal study pattern of side effects (mostly related to the digestive system, Edoxaban eg, diarrhea, nausea, and vomiting, understandable in terms of the physiological effect of a cholinergic drug) was the same (10%) for placebo and 5 mg/day of the drug, and double that in those taking the higher dose. The IDDD was used to assess ADL and the drug showed a protective effect against the decline and activity that occurred with placebo. A similar USA-based study22 was in accordance with these findings and there was evidence that the 10 mg/day dosage was superior to the 5 mg/day dosage. Figure 1. Effect of donepezil, 5 and 10 mg/day, and placebo on Alzheimer’s Disease Assessment Schedule-Cognitive Section (ADAS-Cog) scores. Data are least square means±SE. *P<0.0001 ; **P=0.

In patients with GSD V, however, the test contractions always result in a large alkalinisation. Alkalinisation was caused by the significantly larger PCr consumption

than in controls and the absent increase of H+ by lactic acid formation. In most patients a distinct drop of ATP levels was found which in average resulted in significantly lower ATP concentrations at the end of contraction compared to the previous state at rest and to corresponding values of healthy controls (4). The decrease in ATP was mirrored by an increase in the phosphomonoester Inhibitors,research,lifescience,medical signal most likely indicating an increase in inosin-monophosphate by the degradation of the total adenosinephosphate pool. A further indication of a breakdown of adenine nucleotide

pool during exercise by deamination of AMP is the accumulation of ammonia in blood (8). Furthermore, during the recovery from each contraction period a significantly higher time constant of the pseudo-monoexponential Inhibitors,research,lifescience,medical time course of PCr recovery indicated a reduced rate of oxidative phosphorylation in GSD V (1, 4, 9). Inhibitors,research,lifescience,medical A further analysis of 31P-MRS data in terms of absolute concentration values seems to be forbidden in the case of GSD V patients. The best applicable method for such calibration described in literature uses the ATP concentration at initial rest as an internal standard (10). Since GSD V patients show higher PCr/ATP ratios in SKI 606 muscle than healthy controls and because ATP degeneration was found during moderate exercise the assumption of a given ATP level at the beginning of an examination does not seem

to be fair. Creatine treatment has beneficial effects in some hereditary Inhibitors,research,lifescience,medical myopathies. Six controlled randomized studies have recently appeared which show improvement in maximum voluntary contraction in patients with dystrophinopathies or myotonic dystrophies. Overall, a Cochrane meta-analysis favours creatine in these patients (11). Creatine is an amino acid formed from arginine and glycine in a two-step reaction in the kidneys and liver. After this, it traverses to the skeletal muscle were it is transported across the cell membrane via a sodium dependent Inhibitors,research,lifescience,medical creatine membrane transporter (12). Due to the equilibrium reaction of creatine kinase one has to expect that an uptake of creatine by the muscle fibres results in an elevation of intracellular phosphocreatine (PCr) levels. Transphosphorylation of ATP on creatine and subsequent rephosphorylation heptaminol of ADP by oxidative phosphorylation should result in elevated PCr/ATP ratios visible in 31PMR spectra of muscle. However, in patients with GSD V oral creatine supplementation in both, high (150 mg/kg daily) and low dose (60 mg/kg daily) application of creatine did not result in elevated PCr/ATP levels (6, 7). With low dose creatine working capacity for ischemic exercise improved and we found a higher consumption of PCr during aerobic and ischemic low-level exercise in McArdle patients.

The advantage of postoperative therapy is the knowledge of the pathological stage to appropriately select patients for therapy. The pros and cons of preoperative versus postoperative therapy are further discussed in Table 1. Table 1 Pros and Cons of preoperative versus postoperative therapy for esophageal cancer ((5)) With preoperative therapy, optimal tumor downstaging can result in complete pathological response of the tumor, portending improved survival outcomes for esophageal carcinoma. Pathological complete response (pCR) has often been used as a surrogate #Ceritinib manufacturer keyword# for efficacy of therapy and a measure by which various neoadjuvant therapies in esophageal

cancer can be compared. Rohatgi et al retrospectively analyzed 235 patients who underwent preoperative CRT for adenocarcinoma (82%) or squamous cell (18%) carcinoma of the esophagus and found that patients who experienced pCR had longer overall and disease free survival rates, fewer distant metastases, and less disease recurrences Inhibitors,research,lifescience,medical (6). At 37-month follow-up, patients with pCR had a 74% overall survival, compared to 65% for those with <50% residual disease after CRT, and 40%

for those with >50% residual disease after CRT. In addition, pCR may be more predictive of survival for patients with adenocarcinoma than squamous Inhibitors,research,lifescience,medical cell carcinoma in those Inhibitors,research,lifescience,medical receiving preoperative CRT (7). Preoperative chemotherapy Investigators have evaluated multiple neoadjuvant regimens consisting of preoperative chemotherapy or perioperative chemotherapy. Despite the available studies, biases may still remain

about the benefit of perioperative chemotherapy versus CRT. RTOG 8911 compared surgery alone with chemotherapy followed by surgery, revealing no overall survival difference between the two arms. Patients who underwent less than an R0 resection had an ominous prognosis (5-year overall survival for R0 resection 32%, and R1 resection 5%) (8). Inhibitors,research,lifescience,medical Cunningham et al evaluated surgery alone compared to a regimen consisting of 3 cycles of both preoperative and postoperative epirubicin, cisplatin, and 5-fluorouracil (ECF) for resectable gastroesophageal cancer and showed significant downstaging, but pathological complete and response rates were zero. With the addition of chemotherapy, 5-year survival was improved from 23% to 36% with chemotherapy and progression free survival was also significantly improved (9). The Medical Research Council also demonstrated a significant 2-year overall survival benefit from 34% to 43% with the addition of 2 cycles of preoperative cisplatin and 5-FU (p=0.004) (10). A meta-analysis by Urschel et al evaluated 11 randomized clinical trials including nearly 2,000 patients treated with neoadjuvant chemotherapy compared to surgery alone (11).

After a myocardial infarction, the ventricle undergoes a progressive pathological and anatomical transformation resulting in a vicious cycle of left ventricular dilation, eccentric hypertrophy, and reduced function. Macroscopically these see more changes manifest as thinning of the infarct scar

and, ultimately, an alteration of the left ventricular geometry to a spherical globe. These changes are collectively termed cardiac remodeling.3 Although the term cardiac remodeling was initially coined to describe the changes that transpire following myocardial infarction,4,5 it is clear that very similar Inhibitors,research,lifescience,medical processes are taking place following other types of injury such as occur Inhibitors,research,lifescience,medical with pressure overload (aortic valve stenosis, hypertension), volume overload (valvular regurgitation), inflammatory disease (myocarditis), and idiopathic dilated cardiomyopathy.6 Although the etiologies of these diseases are different, they share molecular, biochemical, and cellular processes to collectively change the shape and function of the myocardium. Therefore, therapies that target the remodeling process itself are important for

all of these conditions. Currently the pharmaceutical therapy of heart failure is based on inhibition of the neurohumoral pathways that are activated secondary to the deterioration of cardiac function, diuretics to alleviate the salt Inhibitors,research,lifescience,medical and water overload, Inhibitors,research,lifescience,medical and other strategies to mitigate predisposing, aggravating, or triggering factors. With our increasing understanding of the pathophysiology of heart failure, it is now clear that the changes in size, shape, and function of the heart that occur following injury result from remodeling at the cellular, interstitial, and molecular levels.7 Therefore, emerging therapies propose to intervene directly in the remodeling process at the cellular and the molecular levels.

Several pathophysiological phenomena characterize heart failure and appear to contribute to the progression of the disease. These include alterations in Inhibitors,research,lifescience,medical β-adrenergic receptor signaling due to desensitization, impaired calcium homeostasis, until reduced excitation–contraction coupling, and altered energetics. Examples for future possible interventions in these processes that can ameliorate heart failure will be given here. This short review does not aim to discuss tried and tested approaches for the treatment of heart failure, nor can it give a comprehensive list of all possible approaches for heart failure. Rather, examples for future and emerging therapies targeting several pathophysiological pathways will be highlighted. BEYOND G-PROTEIN-COUPLED RECEPTOR (GPCR) BLOCKADE Currently, the most effective treatments for heart failure are blockade of the β-adrenergic β1 receptors (β1AR) and angiotensin II type 1A receptors (AT1aR), which are both G-protein-coupled receptors (GPCRs).

9,10 However,

adverse toxicity of the ARV drugs has been reported to also impart negatively on adherence to treatment.9–11 It is, therefore, necessary that clinicians have a clear understanding of the potential adverse effects of the ARV drugs. In addition, they should be able to readily recognise adverse effects in patients and manage them effectively. The risk of specific adverse effects varies from one ARV drug to another, from one drug class to another, and from one patient to another.12 The spectrum of adverse effects associated with ARVs may also vary between progestogen antagonist developed and developing countries.13 The nucleoside reverse transcriptase inhibitors (NRTIs) are associated with lactic acidosis, lipodystrophy, and hyperlipidemia9,11, while the non-nucleoside reverse transcriptase inhibitors (NNRTIs) are associated with neuropsychiatric symptoms, rash, liver toxicity, and lipid abnormalities.11 Protease inhibitors (PIs) are associated with gastrointestinal intolerance and glucose and lipid abnormalities9.

The entry inhibitor (maraviroc) and the integrase inhibitor (raltegravir) are new drugs used for treatment-naive and treatment-experienced patients. Maraviroc is associated with bronchitis, nasopharyngitis, and esophageal candidiasis, while raltegravir is associated with increased risk of myopathy and rhabdomyolysis.14 selleck chemicals There have been reports of adverse events to specific ARV drugs which include peripheral neuropathy and lipodystrophy associated with stavudine10, 15, anaemia associated with zidovudine16, 17, and nevirapine based hepatotoxicity and rash9, 18–20. The incidence of hepatotoxicity has been reported as 8% and 16% for patients on efavirenz (EFV) and nevirapine (NVP), respectively20, while the incidence of anaemia

associated with zidovudine ranged from 3– 12% in developing countries.13 As a means of improving adherence to ARV drugs, newer ones are available as fixed- dose combination21. Despite the decreased pill counts and frequency of dosing per day for usual starting regimens, ART continue to have significant adverse effects that others require monitoring for drug interactions and long-term morbidity related to cardiovascular, dermatological, bone, musculoskeletal and kidney disease.22 Most clinical trials have a relatively short follow-up duration and can underestimate longer term complications of therapy. A six years follow-up of patients in a Swiss Cohort study showed the presence of laboratory adverse events that was associated with higher rates of mortality, highlighting the importance of adverse events in overall patient management.23 Several factors may predispose individuals to adverse effects of ARV drugs. Females appear to have a higher risk than male to develop Stevens-Johnson syndrome, rashes, and hepatotoxicity from NVP.24,25 Females are also at higher risk than males to develop lactic acidosis from NRTIs.

2 and MI but no association with CAD. This was replicated in an independent population. Epidemiologists have claimed for decades that blood group O offers protection from MI. Blood groups A, B, and O are different forms of the same gene at 9q34.2. The A and B genes encode for a protein (alpha 1, 3N-acetylgalactosaminyltransferase) that transfers a carbohydrate moiety onto von Wille-brand Factor (vWF). This prolongs the life of vWF and predisposes to coronary thrombosis and MI. The blood group O gene codes for a protein that has been mutated and lacks any biochemical

activity Inhibitors,research,lifescience,medical and thus does not transfer the carbohydrate moiety onto vWF. As a result, individuals with blood group O show no increased risk for MI. The frequency of the gene that encodes for A or B blood group occurs in about 57% of Caucasians. The average relative increased risk for MI is about 20% depending on the genotype. In the recent Nurses’ Health Study and Health Professionals Follow-up Study of more Inhibitors,research,lifescience,medical than 90,000 individuals,

4,070 developed heart disease. In this 20-year follow-up study, having blood group A or B alone was associated with an increased risk of MI of about 10%; Selisistat however, the combination of A and B blood groups increased the risk to 20%.31 It also has been shown that plasma levels of vWF complex are approximately 25% higher in individuals with A, B, or AB blood groups as opposed to blood Inhibitors,research,lifescience,medical group O.32 These results Inhibitors,research,lifescience,medical have important implications for people undergoing angioplasty, bypass surgery, and other such procedures. For example, should individuals of blood group A or B receive some form of antiplatelet therapy such as aspirin? 9p21

Predisposes to Coronary Atherosclerosis and not Myocardial Infarction The 9p21 risk variant for CAD is perhaps the most robust genetic variant and the most studied of those risk variants with unknown function. This risk variant is contained in a long non-protein coding RNA (LncRNA) of 126,000 bps referred to as Anril, which remains of unknown function. The 9p21 risk variant was not introduced into the genome until Inhibitors,research,lifescience,medical the arrival of higher primates and is Oxygenase highly conserved in the human genome. The 9p21 risk allele occurs in 75% of humans except for Africans (50% heterozygous, 25% homozygous). Each risk variant is associated with an increased relative risk for CAD of about 25%. The risk of 9p21 is consistently observed by investigators throughout the world to be independent of conventional risk factors such as cholesterol, diabetes, or hypertension. In individuals with premature CAD, 9p21 homozygosity is associated with a 2-fold increased risk for CAD. The 9p21 risk variant also contributes to increased risk for intracranial and abdominal aortic aneurysms33 and Alzheimer’s disease34 and has recently been associated with periodontitis35 and gout,36 diseases with a marked inflammatory component.

Adherence was considered good when it was 95% and above or poor when it was below 95%. The adherence levels were correlated with therapeutic outcome through laboratory measurement of CD4+ cell count and viral load. Therapeutic outcome was good when the CD4+ cell count increased by at least 50 to 100 cells/dL and the viral load was reduced to undetectable level within 3 to 6 months of commencing ARV therapy34. Virological failure occurred when

the viral load failed to reduce to undetectable level within 3 to 6 months of commencement of HAART and when the CD4+ cell count did not increase by at least 50 GSK J4 supplier cells /dL within same period this was considered immunological failure. Data analysis The major outcomes measured were the types and frequency of ART regimens prescribed, adherence to treatments, and the types and frequency of adverse events to the ARV drugs experienced by the patients. Birinapant concentration Data were analyzed using simple descriptive statistics. A Chi-square test with Yates correction was used to determine an association between adherence and therapeutic outcome at a 5% level of significance. Ethical considerations The research protocol was reviewed and approved by

the Research and Ethics Committee of LUTH.. Results Socio-demographic characteristics The records of 390 eligible patients were reviewed in this study. The median age of the patients was 32 (range 13–67) years, while the mean age was 35years (sd 9.67). The socio-demographics of the patients are as presented in Table 1. Table 1 Socio-demographic characteristics of participants Prescribed ART regimes A total of 2944 prescriptions were reviewed and 23 different ARV drug combinations were prescribed. The patterns of ART regimens prescribed at the clinic are presented in Table 2. The most frequently prescribed regimen was AZT-3TC-NVP, followed by D4T-3TC-NVP Table 2 Different Antiretroviral Drug Combinations and their Frequency of Prescription Adherence and therapeutic outcome The majority of DNA ligase the patients (75%) with good adherence had good therapeutic outcome and almost all (95%) of those who adhered poorly had therapeutic failure. Subjecting this to chi square analysis showed

that drug adherence was associated with good therapeutic outcome (χ2 = 115.60, p<0.0001). Table 3 shows the association between adherence and therapeutic outcome. Table 3 Relationship between Adherence and Therapeutic outcome Adverse events associated with ARV drugs The adverse events associated with the use of the various ARV drugs are summarized in Table 4. Table 4 Adverse Drug Events of Antiretroviral Drug Combinations at LUTH PEPFAR Clinic. Only complaints or ailments that developed or were observed in each of the patients after the commencement of therapy of a particular combination of antiretroviral drugs were included. A total of 90 different adverse events were recorded ranging from minor symptoms such as rash and catarrh to serious ones such as hepatomegaly and death.

Mortality, morbidity, and survivals are similar (19),(20). The learning curve in pancreatic surgery suggested that after 60 PD’s, there are improved outcomes of estimated blood loss, operative time, length of stay, and margin status— factors

which have been associated with overall outcome (21). The results presented in this study are consistent with the conclusions presented by published literature. The benefits of regionalization of complex surgery were Inhibitors,research,lifescience,medical demonstrated in a number of studies. Benefits of a high volume center include a decrease in mortality and cost and the ability to perform prospective randomized trials and to provide surgical training (22),(23). Figure 3 Survival analyzed with respect to ASA score One of the goals of this study is to determine if we can provide excellent care to patients diagnosed with periampullary Inhibitors,research,lifescience,medical tumors. The closest medical center with pancreaticobiliary service to our center is approximately 90 miles. Given the choice for location of service, an overwhelming majority of patients preferred not to travel long distances. Having a pancreaticobiliary service in our encatchment area serves to facilitate treatment

as well as to allow patient’s family members easier Inhibitors,research,lifescience,medical access to the treating medical center. There has been a dramatic improvement of surgical care in treating periampullary tumors over the last two decades. Anesthetic and CCI-779 perioperative care during Inhibitors,research,lifescience,medical the duration of our study have made the greatest contribution to decreasing perioperative mortality. The development of clinical pathways also has contributed to optimizing the outcome (24). There are limitations to a single institutional series such as ours. Patient

population is not large. Because of the small number of patients, meaningful statistical analysis is difficult to derive. Morbidity, mortality, and long term outcomes (cancer specific survival, overall survival) nevertheless have utility in assessing a cancer program. The data Inhibitors,research,lifescience,medical presented here gives support to continuing the pancreaticobiliary program at our institution. Our results reflect the dedication of specialists with interest in treating pancreaticobiliary disorders. We assert that hospital volume alone cannot be the sole determinant of outcome. It is our belief that surgeon volume combined with a multidisciplinary approach and excellent Olopatadine ancillary support provide an excellent prediction of survival as demonstrated in this study of patients with pancreatic and biliary malignancies. The factors contributing to improved survival for patients diagnosed with periampullary tumors are numerous. Improved perioperative critical care and improved surgical care decrease operating time. Advances in adjunctive therapies contribute to improved survival. It is through these novel therapies that we will see further improvement in survival rates (25).

0 g/dL (maximum of 3 L removed) and infused with a combination of albumin and crystalloid to restore isovolemia. Prospective randomized controlled studies demonstrate that it is safe and that ANH protected against allogeneic transfusions (22,28). As compared with standard volume management, Jarnagin et al. demonstrated that ANH resulted in fewer intraoperative transfusions (1.6% versus Inhibitors,research,lifescience,medical 10.4%, P=0.04). While interesting in concept, ANH is not routinely used in many centers at this time. We have not adopted

this strategy yet in our own practice. Blood loss-limiting surgical techniques Surgeons can take measures during hepatic parenchymal transection to further limit hemorrhage. These include temporary hepatic inflow occlusion (Pringle maneuver) and total vascular exclusion (TVE). These techniques are designed to isolate hepatic circulation (inflow and/or outflow) from the systemic circulation and minimize blood loss during dissection and Inhibitors,research,lifescience,medical transection of the hepatic parenchyma (Figure 1). A central Inhibitors,research,lifescience,medical tenet to the success of vascular exclusion is based on the premise that the liver (and

patient) is more tolerant to warm ischemia with reperfusion than to bleeding and the consequences of bleeding (e.g. transfusions.). Figure 1 Demonstration of potential sites of vascular occlusion. Pringle find more maneuver Originally performed for hepatic trauma, the Pringle maneuver is a straightforward way to minimizing blood loss during hepatectomy (47). A noncrushing clamp or a rumel tourniquet is placed around the structures in the porta hepatis to occlude

hepatic Inhibitors,research,lifescience,medical venous and arterial inflow during parenchymal transection. This can be performed in an intermittent or continuous manner with similar outcomes. It is recommended that the occlusion time be limited to an hour or less, as the ischemic insult will ultimately result in further hepatic parenchymal loss. After hepatic pedicle clamping with the Pringle, there is a 10% decrease in the cardiac index with a 40% increase in SVR and a 40% increase in mean arterial pressure (48-51). Inhibitors,research,lifescience,medical As compared with the previously mentioned occlusion techniques, the Pringle maneuver is relatively well-tolerated, but the anesthesiology staff should be continuously informed when it is applied because of the possibility of cardiac dysfunction and of air embolism, particularly if the hepatectomy is being done under low CVP. The potential sequela Endonuclease of air emboli, in the patient with a low CVP who may have an open hepatic vein, can be minimized by placing the patient in 15 degree Trendelenberg (24,25,52). The Pringle maneuver can be applied in a continuous or intermittent fashion. Many retrospective studies and prospective clinical trials have been performed examining the role and type of the Pringle maneuver, and its relationship to blood loss and reperfusion injury. Belghiti et al.