Effect of epidural volume extension with colloid on dose requirement for intrathecal spinal block: a double blind prospective study

Background: Epidural volume extension (EVE) is a modification of combined- spinal epidural anaesthesia (CSEA) in which fluid is injected in epidural space after the intrathecal block. Fluid in epidural space compress subarachnoid space and causes cephalic spread of intrathecal drug to increase block height. Purpose of study is to determine efficacy of EVE on dose requirement of intrathecal bupivacaine when colloid was used for EVE.Methods: Sixty patients of ASA physical status I or II, scheduled for elective caesarean sections were recruited and randomized into two groups (30 each group). Group 1: CSEA in which spinal block is followed by 10 ml Colloid (HES 6%) in epidural space; Group 2: CSEA but no fluid in epidural space. Onset of sensory block and hemodynamic variables were measured at 5 min. intervals up to 40 minutes then at 10 min. intervals till end of surgery. Ineffective block was top- up by epidural 0.5% bupivacaine in incremental doses.Results: Median effective dose of intrathecal bupivacaine was significantly lower, 4.0 mg (95% CI 4.40-5.60) in group 1 versus 7.0 mg (95% CI 6.93-7.61) in group 2. Only 11 patients required ephedrine in group 1 versus 20 in group 2. Requirement of ephedrine was significantly lower 2.20 (±2.94) mg in group 1 versus 4.0 (±2.88) mg groups 2. Changes in haemodynamic variables from baseline were significantly lower in group 1 than those in group 2.Conclusions: EVE with colloid was effective in lowering dose requirement of spinal bupivacaine while patients hemodynamically were more stable.

Antiangiogenic activity of zinc and zinc-sorafenib combination using the chick chorioallantoic membrane assay: a descriptive study

Background: Zinc, a trace element, is known for downregulating several proangiogenic growth factors and cytokines. However, its antiangiogenic activity is not adequately studied. The present study was aimed to evaluate the possible antiangiogenic activity of zinc via the chick chorioallantoic membrane (CAM) assay. Also, the antiangiogenic activity of the combination therapy of zinc with various doses of sorafenib, a tyrosine kinase inhibitor, was evaluated.Methods: A pilot study was initially conducted so as to select suitable doses of zinc and sorafenib. The antiangiogenic activity after combining zinc 2.5 μg/embryo with sorafenib 1, and 2 μg/embryo was also evaluated. The antiangiogenic activity was quantified in terms of total length of blood vessels, number of junctions, number of branching points, and mean length of the blood vessels.Results: Zinc 2.5 μg/embryo showed significant (p 0.05) to that of sorafenib 2 μg/embryo.Conclusions: Zinc caused significant antiangiogenic activity in the CAM assay. The lack of addition/synergism in the zinc-sorafenib combination could have been due to the variability in the dose/ratio selection. Addition of zinc to sorafenib therapy could improve treatment tolerability, reduce cost of therapy, and reduce the emergence of drug resistance. Future mechanistic studies could identify the exact pharmacodynamics of zinc as an angiogenesis inhibitor

Intravenous pharmacokinetics, oral bioavailability, dose proportionality and in situ permeability of anti-malarial lumefantrine in rats

<p>Abstract</p> <p>Background</p> <p>Despite the wide spread use of lumefantrine, there is no study reporting the detailed preclinical pharmacokinetics of lumefantrine. For the development of newer anti-malarial combination(s) and selection of better partner drugs, it is long felt need to understand the detailed preclinical pharmacokinetics of lumefantrine in preclinical experimental animal species. The focus of present study is to report bioavailability, pharmacokinetics, dose linearity and permeability of lumefantrine in rats.</p> <p>Methods</p> <p>A single dose of 10, 20 or 40 mg/kg of lumefantrine was given orally to male rats (N = 5 per dose level) to evaluate dose proportionality. In another study, a single intravenous bolus dose of lumefantrine was given to rats (N = 4) at 0.5 mg/kg dose following administration through the lateral tail vein in order to obtain the absolute oral bioavailability and clearance parameters. Blood samples were drawn at predetermined intervals and the concentration of lumefantrine and its metabolite desbutyl-lumefantrine in plasma were determined by partially validated LC-MS/MS method. <it>In-situ </it>permeability study was carried in anaesthetized rats. The concentration of lumefantrine in permeability samples was determined using RP-HPLC.</p> <p>Results</p> <p>For nominal doses increasing in a 1:2:4 proportion, the C_maxand AUC_0-∞values increased in the proportions of 1:0.6:1.5 and 1:0.8:1.8, respectively. For lumefantrine nominal doses increasing in a 1:2:4 proportion, the C_maxand the AUC_0-tvalues for desbutyl-lumefantrine increased in the proportions of 1:1.45:2.57 and 1:1.08:1.87, respectively. After intravenous administration the clearance (Cl) and volume of distribution (Vd) of lumefantrine in rats were 0.03 (± 0.02) L/h/kg and 2.40 (± 0.67) L/kg, respectively. Absolute oral bioavailability of lumefantrine across the tested doses ranged between 4.97% and 11.98%. Lumefantrine showed high permeability (4.37 × 10^-5cm/s) in permeability study.</p> <p>Conclusions</p> <p>The pharmacokinetic parameters of lumefantrine and its metabolite desbutyl-lumefantrine were successfully determined in rats for the first time. Lumefantrine displayed similar pharmacokinetics in the rat as in humans, with multiphasic disposition, low clearance, and a large volume of distribution resulting in a long terminal elimination half-life. The absolute oral bioavailability of lumefantrine was found to be dose dependent. Lumefantrine displayed high permeability in the <it>in-situ </it>permeability study.</p

The impact of different fertiliser management options and cultivars on nitrogen use efficiency and yield for rice cropping in the Indo-Gangetic Plain: two seasons of methane, nitrous oxide and ammonia emissions

This study presents detailed crop and gas flux data from two years of rice production at the experimental farm of the ICAR-Indian Agricultural Research Institute, New Delhi, India. In comparing 4 nitrogen (N) fertiliser regimes across 4 rice cultivars (CRD 310, IR-64, MTU 1010, P-44), we have added to growing evidence of the environmental costs of rice production in the region. The study shows that rice cultivar can impact yields of both grain, and total biomass produced in given circumstances, with the CRD 310 cultivar showing consistently high nitrogen use efficiency (NUE) for total biomass compared with other tested varieties, but not necessarily with the highest grain yield, which was P-44 in this experiment. While NUE of the rice did vary depending on experimental treatments (ranging from 41% to 73%), 73%), this did not translate directly into the reduction of emissions of ammonia (NH3) and nitrous oxide (N2O). Emissions were relatively similar across the different rice cultivars regardless of NUE. Conversely, agronomic practices that reduced total N losses were associated with higher yield. In terms of fertiliser application, the outstanding impact was of the very high methane (CH4) emissions as a result of incorporating farmyard manure (FYM) into rice paddies, which dominated the overall effect on global warming potential. While the use of nitrification and urease inhibiting substances decreased N2O emissions overall, NH3 emissions were relatively unaffected (or slightly higher). Overall, the greatest reduction in greenhouse gas (GHG) emissions came from reducing irrigation water added to the fields, resulting in higher N2O, but significantly less CH4 emissions, reducing net GHG emission compared with continuous flooding. Overall, genetic differences generated more variation in yield and NUE than agronomic management (excluding controls), whereas agronomy generated larger differences than genetics concerning gaseous losses. This study suggests that a mixed approach needs to be applied when attempting to reduce pollution and global warming potential from rice production and potential pollution swapping and synergies need to be considered. Finding the right balance of rice cultivar, irrigation technique and fertiliser type could significantly reduce emissions, while getting it wrong can result in considerably poorer yields and higher pollution

Clinically Actionable Hypercholesterolemia and Hypertriglyceridemia in Children with Nonalcoholic Fatty Liver Disease

OBJECTIVE: To determine the percentage of children with nonalcoholic fatty liver disease (NAFLD) in whom intervention for low-density lipoprotein cholesterol or triglycerides was indicated based on National Heart, Lung, and Blood Institute guidelines. STUDY DESIGN: This multicenter, longitudinal cohort study included children with NAFLD enrolled in the National Institute of Diabetes and Digestive and Kidney Diseases Nonalcoholic Steatohepatitis Clinical Research Network. Fasting lipid profiles were obtained at diagnosis. Standardized dietary recommendations were provided. After 1 year, lipid profiles were repeated and interpreted according to National Heart, Lung, and Blood Institute Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction. Main outcomes were meeting criteria for clinically actionable dyslipidemia at baseline, and either achieving lipid goal at follow-up or meeting criteria for ongoing intervention. RESULTS: There were 585 participants, with a mean age of 12.8 years. The prevalence of children warranting intervention for low-density lipoprotein cholesterol at baseline was 14%. After 1 year of recommended dietary changes, 51% achieved goal low-density lipoprotein cholesterol, 27% qualified for enhanced dietary and lifestyle modifications, and 22% met criteria for pharmacologic intervention. Elevated triglycerides were more prevalent, with 51% meeting criteria for intervention. At 1 year, 25% achieved goal triglycerides with diet and lifestyle changes, 38% met criteria for advanced dietary modifications, and 37% qualified for antihyperlipidemic medications. CONCLUSIONS: More than one-half of children with NAFLD met intervention thresholds for dyslipidemia. Based on the burden of clinically relevant dyslipidemia, lipid screening in children with NAFLD is warranted. Clinicians caring for children with NAFLD should be familiar with lipid management

Traumatic Aorto-Mesenteric-Portal Fistula: Percutaneous management: Case Report

Two months after a stab injury to the abdomen, a 35-year-old male presented at the All India Institute of Medical Sciences with haematemesis, shock and portal hypertension. Computed tomography of the abdomen and abdominal angiography revealed a large fistulous communication between an abdominal aortic pseudoaneurysm and a branch of the superior mesenteric vein. The fistula was occluded percutaneously, which allowed the patient to stabilise haemodynamically and, finally, to undergo a definitive surgical excision of the pseudoaneurysm and repair of the aortic defect

Traumatic Aorto-Mesenteric-Portal Fistula Percutaneous management : Case Report

Two months after a stab injury to the abdomen, a 35-year-old male presented at the All India Institute of Medical Sciences with haematemesis, shock and portal hypertension. Computed tomography of the abdomen and abdominal angiography revealed a large fistulous communication between an abdominal aortic pseudoaneurysm and a branch of the superior mesenteric vein. The fistula was occluded percutaneously, which allowed the patient to stabilise haemodynamically and, finally, to undergo a definitive surgical excision of the pseudoaneurysm and repair of the aortic defect

(Impact Factor: 1.479) www.ijreat.org www.ijreat.org Effect Of Natural Asphalt On Performance Characteristics Of Bitumen And Its Mixes

Trinidad Lake Asphalt (TLA) is natural bitumen. The soluble bitumen in Trinidad Lake Asphalt has a high viscosity and if this is blended with paving grade bitumen, it can produce a material with high resistance to deformation and with suitable weathering properties. In this study TLA pellets have been used as a modifier to modify VG-30 grade paving bitumen, and it was found that it improved the properties of the VG 30 grade binder. Various binder properties were checked like softening point, penetration value, viscosity indices, and properties of modified and unmodified binder after short term aging were studied, and Rheology of binders was also studied. After witnessing the improved properties of binder, bituminous (asphalt) mixes were prepared to check the performance characteristics of TLA modified asphalt mixes. Results of wheel tracking test, beam fatigue test, and tensile strength ratios indicate that a worthwhile improvement in resistance to deformation, comparable to conventional asphalt mix, can be obtained by the addition of 2% of TLA by weight of VG 30 grade bitumen