Friedelin: Structure, Biosynthesis, Extraction, and Its Potential Health Impact.

Pharmaceutical companies are investigating more source matrices for natural bioactive chemicals. Friedelin (friedelan-3-one) is a pentacyclic triterpene isolated from various plant species from different families as well as mosses and lichen. The fundamental compounds of these friedelane triterpenoids are abundantly found in cork tissues and leaf materials of diverse plant genera such as Celastraceae, Asteraceae, Fabaceae, and Myrtaceae. They possess many pharmacological effects, including anti-inflammatory, antioxidant, anticancer, and antimicrobial activities. Friedelin also has an anti-insect effect and the ability to alter the soil microbial ecology, making it vital to agriculture. Ultrasound, microwave, supercritical fluid, ionic liquid, and acid hydrolysis extract friedelin with reduced environmental impact. Recently, the high demand for friedelin has led to the development of CRISPR/Cas9 technology and gene overexpression plasmids to produce friedelin using genetically engineered yeast. Friedelin with low cytotoxicity to normal cells can be the best phytochemical for the drug of choice. The review summarizes the structural interpretation, biosynthesis, physicochemical properties, quantification, and various forms of pharmacological significance.

N-glycosylation, a leading role in viral infection and immunity development.

N-linked protein glycosylation is an essential co-and posttranslational protein modification that occurs in all three domains of life; the assembly of N-glycans follows a complex sequence of events spanning the (Endoplasmic Reticulum) ER and the Golgi apparatus. It has a significant impact on both physicochemical properties and biological functions. It plays a significant role in protein folding and quality control, glycoprotein interaction, signal transduction, viral attachment, and immune response to infection. Glycoengineering of protein employed for improving protein properties and plays a vital role in the production of recombinant glycoproteins and struggles to humanize recombinant therapeutic proteins. It considers an alternative platform for biopharmaceuticals production. Many immune proteins and antibodies are glycosylated. Pathogen's glycoproteins play vital roles during the infection cycle and their expression of specific oligosaccharides via the N-glycosylation pathway to evade detection by the host immune system. This review focuses on the aspects of N-glycosylation processing, glycoengineering approaches, their role in viral attachment, and immune responses to infection.

Plasma neutrophil gelatinase-associated lipocalin and Interleukin-18 as predictors of acute kidney injury in renal transplant recipients: A pilot study.

Urine neutrophil gelatinase-associated lipocalin (NGAL) and interleukin-18 (IL- 18) have shown promise for predicting renal graft recovery. However, urinary flow rate variations may cause variable biomarker dilution. Plasma NGAL and IL-18 may form a biomarker panel that may help predict delayed graft function and slow graft function (SGF) in renal transplant recipients within the first two postoperative days earlier than serum creatinine. There are only a few studies in the literature using plasma NGAL for predicting renal graft recovery. Hence, we planned this study. This observational single-center, prospective cohort study was conducted in renal transplant recipients above 18 years of age. In 22 consecutive renal transplant recipients, we collected ethylenediaminetetraacetic acid-plasma samples 1 h before surgery and subsequently at 6 h, 24 h, and 48 h after surgery for NGAL and IL-18 by sandwich enzyme-linked immuno-sorbent assay technique. Serum creatinine was measured as a part of routine transplant protocol. In renal transplant recipients, neither serum levels of NGAL and IL-18 nor their trends could reliably predict SGF. The only significant correlation existed between serum creatinine at day 2 and IL-18 at day 2 with P = 0.023. Serum NGAL did not correlate with serum creatinine in this setting of renal transplantation. Patients with immediate graft function had a greater percentage decrease of creatinine at day 1 and day 2 (P = 0.002 and 0.001) The percentage change in IL-18 at 24 h and 48 h after transplant from baseline could predict the occurrence of early graft loss (EGL) (P = 0.05, 0.04). The cutoffs were -4.12% at day 1 and +3.39% at day 2 with area under receiver operator characteristics of 0.82 and 0.83, respectively. The percentage change in IL-18 may be a useful marker of EGL in renal transplant recipients. Serum NGAL and creatinine were not able to predict EGL.

Impact of Functional Hepatic Venous Outflow Obstruction on Perioperative Outcome After Living-Donor Liver Transplant.

OBJECTIVES: An optimal initial graft function after living-donor liver transplant depends on optimal graft hemodynamics. Nonmechanical impediments to free hepatic venous outflow, due to elevated central venous pressure, may obstruct the "functional" hepatic venous outflow. Here, we evaluated whether central venous pressure affected early graft function and outcomes in adult living-donor liver transplant recipients. MATERIALS AND METHODS: This prospective observational study included 61 living-donor liver transplant recipients without technical complications who received transplants from August 2013 to November 2014. Hemodynamic variables were measured preoperatively, at anhepatic phase, 30 minutes postreperfusion, at end of surgery, and during postoperative days 1-5. RESULTS: Patients with high central venous pressure showed functional hepatic venous outflow obstruction, which caused delayed recovery of graft function. Although postoperative central venous pressure was the only identified independent risk factor for mortality, all 5 deaths in our study group occurred in those who had high central venous pressure at the anhepatic, postreperfusion, end of surgery, and postoperative phases. A postoperative central venous pressure value of ~11 mm Hg was determined to be the cutoff for high-risk mortality, with area under the curve of 0.859 (sensitivity of 80%, specificity of 68%). Increased central venous pressure was associated with increased portal venous pressure (increase of 45%, range, 28%-89%; P = .001). Central venous pressure at end of surgery (r = 0.45, P ≤ .001) and at posttransplant time points (r = 0.29, P = .02) correlated well with portal venous pressure at end of surgery. Other risk factors for early allograft dysfunction were Model for End-Stage Liver Disease and cardiac output posttransplant. CONCLUSIONS: High central venous pressure, modulating portal venous pressure, can result in functional hepatic venous outflow obstruction, causing delayed graft function recovery and increased risk of mortality. Maintaining a central venous pressure below 11 mm Hg is beneficial.

Post-operative hypertension, a surrogate marker of the graft function and predictor of survival in living donor liver transplant recipients: A retrospective study.

BACKGROUND AND AIMS: De novo hypertension (HTN) in liver transplantation recipients is a known entity. We investigated haemodynamic behaviour after a liver transplant to see if it can predict survival to discharge from the hospital. METHODS: electronic records of Haemodynamic parameters and laboratory investigations of 95 patients of living donor liver transplant (LDLT) were retrospectively analysed. RESULTS: Twenty-three patients were operated for acute liver failure (ALF) and 72 patients for chronic liver disease (CLD). Eight patients of CLD and four of ALF did not survive. CLD patients had statistically significant rise in systolic blood pressure from the post-operative day (POD) 1 to POD 4 and diastolic blood pressure (DBP) from POD 3 to POD 6. Heart rate (HR) significantly decreased from POD 3 to POD 5. Haemodynamic parameters returned to baseline values within 20 days. Diastolic HTN had a positive predictive value of 100% for survival with 100% sensitivity and specificity. Systolic HTN had a positive predictive value of 100% for survival (sensitivity-89%, specificity-100%). ALF patients had a significant decrease in HR from POD 2 to POD 10. Bradycardia (HR ≤60/min) had a positive predictive value of 100% for survival with a sensitivity of 45% and 58% in CLD and ALF, respectively, with a specificity of 100% in both the groups. Non-survivors had no significant change in haemodynamics. In CLD group, International Normalised Ratio had statistically significant, strong negative correlation with DBP. CONCLUSION: Haemodynamic pattern of recovery may be used for predicting survival to discharge after LDLT.

Intraoperative blood loss in orthotopic liver transplantation: The predictive factors.

Liver transplantation has been associated with massive blood loss and considerable transfusion requirements. Bleeding in orthotopic liver transplantation is multifactorial. Technical difficulties inherent to this complex surgical procedure and pre operative derangements of the primary and secondary coagulation system are thought to be the principal causes of perioperative hemorrhage. Intraoperative practices such as massive fluid resuscitation and resulting hypothermia and hypocalcemia secondary to citrate toxicity further aggravate the preexisting coagulopathy and worsen the perioperative bleeding. Excessive blood loss and transfusion during orthotopic liver transplant are correlated with diminished graft survival and increased septic episodes and prolonged ICU stay. With improvements in surgical skills, anesthetic technique, graft preservation, use of intraoperative cell savers and overall perioperative management, orthotopic liver transplant is now associated with decreased intra operative blood losses. The purpose of this review is to discuss the risk factors predictive of increased intra operative bleeding in patients undergoing orthotopic liver transplant.

Acute liver failure in pregnancy: Challenges and management.

Acute liver failure (ALF) in pregnancy negatively affects both maternal and foetal outcome. The spectrum of liver disease in pregnancy may range from mild asymptomatic transaminitis to fatal and irreversible deterioration in liver functions leading to significant morbidity and even mortality. In this comprehensive review, we searched articles published as review articles, clinical trials, and case series in the Medline from 1970 to 2012. The overall outcome of ALF in pregnancy depends on the aetiology, timely diagnosis, prompt management, and early referral to a centre equipped in managing medical or obstetric complication. The foetal outcome is affected by the stage of pregnancy in which the mother has a deterioration of the liver function, with a worst prognosis associated with first or second-trimester liver failure. When ALF complicates pregnancy, liver transplantation is the one of the viable options. Management protocols need to be individualised for each case keeping in mind the risk versus benefit to both the mother and the foetus.

Addition of sub-anaesthetic dose of ketamine reduces gag reflex during propofol based sedation for upper gastrointestinal endoscopy: A prospective randomised double-blind study.

BACKGROUND AND AIMS: Gag reflex is unwanted during upper gastrointestinal endoscopy (UGIE). Experimental studies have demonstrated that N-methyl-D-aspartate receptor antagonism prevents gag reflex. We conducted a study to determine if sub-anaesthetic doses of ketamine, added to propofol, reduce the incidence of gag reflex. METHODS: This prospective, randomised, double-blind and placebo-controlled study was done in a tertiary care hospital. A total of 270 patients undergoing UGIE, were randomised to propofol (P) group (n = 135) or propofol plus ketamine (PK) group (n = 135). All patients received propofol boluses titrated to Ramsay sedation score of not <4. Patients in PK group in addition received ketamine, 0.15 mg/kg immediately before the first-propofol dose. Top-up doses of propofol were given as required. Stata 11 software (StataCorp.) was used to calculate the proportion of patients with gag reflex and the corresponding relative risk. Propofol consumed and time to recovery in the two groups was compared using Student's t-test and Cox proportional hazards regression respectively. RESULTS: Significantly, fewer patients in the PK group had gag reflex compared to the P group (3 vs. 23, risk ratio = 0.214, 95% confidence interval [CI], 0.07-0.62; P = 0.005). The incidence of hypotension (6 vs. 16, risk ratio = 0.519, 95% CI = 0.25-1.038; P = 0.06), number of required airway manoeuvres (4 vs. 19, risk ratio = 0.32, 95% CI = 0.13-0.74; P = 0.014), median time to recovery (4 min vs. 5 min, hazard ratio = 1.311, 95% CI = 1.029-1.671; P = 0.028) and propofol dose administered (152 mg vs. 167 mg, 95% CI = 4.74-24.55; P = 0.004) was also less in the PK group compared to the P group. CONCLUSION: Ketamine in sub-anaesthetic dose decreases gag reflex during UGIE.

Perioperative risk factors in patients with liver disease undergoing non-hepatic surgery.

The patients with liver disease present for various surgical interventions. Surgery may lead to complications in a significant proportion of these patients. These complications may result in considerable morbidity and mortality. Preoperative assessment can predict survival to some extent in patients with liver disease undergoing surgical procedures. A review of literature suggests nature and the type of surgery in these patients determines the peri-operative morbidity and mortality. Optimization of premorbid factors may help to reduce perioperative mortality and morbidity. The purpose of this review is to discuss the effect of liver disease on perioperative outcome; to understand various risk scoring systems and their prognostic significance; to delineate different preoperative variables implicated in postoperative complications and morbidity; to establish the effect of nature and type of surgery on postoperative outcome in patients with liver disease and to discuss optimal anaesthesia strategy in patients with liver disease.