Molecular fingerprint-derived similarity measures for toxicological read-across: Recommendations for optimal use.

Computational approaches are increasingly used to predict toxicity due, in part, to pressures to find alternatives to animal testing. Read-across is the "new paradigm" which aims to predict toxicity by identifying similar, data rich, source compounds. This assumes that similar molecules tend to exhibit similar activities i.e. molecular similarity is integral to read-across. Various of molecular fingerprints and similarity measures may be used to calculate molecular similarity. This study investigated the value and concordance of the Tanimoto similarity values calculated using six widely used fingerprints within six toxicological datasets. There was considerable variability in the similarity values calculated from the various molecular fingerprints for diverse compounds, although they were reasonably concordant for homologous series acting via a common mechanism. The results suggest generic fingerprint-derived similarities are likely to be optimally predictive for local datasets, i.e. following sub-categorisation. Thus, for read-across, generic fingerprint-derived similarities are likely to be most predictive after chemicals are placed into categories (or groups), then similarity is calculated within those categories, rather than for a whole chemically diverse dataset.

Studies on preparation of mixed toffee from guava and strawberry.

The present investigation was carried out to develop a technology for preparation of mixed toffee from guava and strawberry pulp and to study the changes in chemical composition and sensory properties of toffee during storage at ambient temperature as well as refrigerated condition. Preliminary experiments were conducted to find out optimum levels of guava and strawberry pulp. The toffees prepared were wrapped in metallic coated polythene wrapper, packed in 200 gauge polythene bags and stored at ambient (27 ± 2 oC) as well as refrigerated (5 ± 2 oC) condition for 90 days. The stored samples were drawn periodically at 30 days interval for organoleptic and chemical analysis. Preliminary studies were carried out to standardize the optimum levels of guava and strawberry pulp. Among various combinations of guava and strawberry pulp, 70 : 30 w/w (guava : strawberry) ratios toffee was found better than other combinations in respect to organoleptic properties and nutritional quality. The yield of fresh toffee was higher (868 g/kg of pulp) in toffee prepared from 100 % guava (control). The chemical composition indicated that the fresh toffees contained on an average moisture 8.73 %, TSS 83.21 oBrix, titrable acidity 0.3 %, total sugars 73.1 % and ascorbic acid 64.1 mg/100 g. The mean score of fresh toffees for colour and appearance was 8.29, texture 8.02, flavour 8.22, taste 8.32 and overall acceptability 8.16 on 9 point Hedonic scale. The cost of fresh toffee was Rs. 282/kg which was prepared from 70 : 30 guava and strawberry pulp level. The storage studies indicated that the TSS and total sugars increased with the advancement of storage period, while moisture content, ascorbic acid and acidity decreased. The rates of increase or decrease were relatively higher at ambient temperature than refrigerated temperature. The sensory quality of toffees also decreased at faster rate during 90 days storage period at ambient condition than the refrigerated condition. The toffee prepared from 70: 30 guava and strawberry pulp was found superior over other combinations in respect of organoleptic properties throughout storage period. However, toffees were found to be acceptable even after 90 days storage at ambient as well as refrigerated conditions.

Gastrointestinal amyloidosis in Australian indigenous patients.

This study documents the symptoms, racial distribution, pathological findings and outcomes of patients diagnosed with gastrointestinal amyloidosis in Alice Springs Hospital. In a 4 year retrospective survey. 9 patients, all indigenous, 7F/2M, had biopsy proven gastrointestinal amyloidosis. Four out of four patients tested were found to have AA amyloidosis. Presenting symptoms included diarrhoea, bloody in some, vomiting and abdominal pain. All but one had diabetes mellitus, type 2. Multiple infections were common and most patients had low serum albumin and transferrin concentrations but high serum ferritin concentrations. Five of the patients died, and the gastrointestinal symptoms of the remaining 4 remitted. Gastrointestinal amyloidosis should be included in the differential diagnosis of indigenous patients presenting with chronic diarrhoea, vomiting or abdominal pain. It carries a grave prognosis, is probably secondary to chronic infections but is potentially reversible.

Spectrum of acute viral hepatitis and its clinical outcome--a study from Ludhiana, Punjab.

This study was carried out to find the etiological spectrum and clinical profile of acute viral hepatitis in Ludhiana. Hepatitis E was encountered most frequently (44.56%) followed by hepatitis B (29.7%), whereas hepatitis D occurred least frequently (0.99%). The age group most commonly affected was 20-30 years(32,67%) followed by 30-40 years (23.76%). Males showed higher incidence as compared to females in the ratio of 62.4:37.6. The most frequent clinical features were anorexia and jaundice. The disease was found to be more common in urban set up(78.2%) than in rural regions (21.8%). Mortality was mainly because of fulminant hepatitic failure. In 1.98% of cases, etiology remained undecided. Total bilirubin and prothrombin time were found to be useful prognostic indicators.

Epidemiology of hepatitis E and A in Ludhiana.

AIM: To study the epidemiology of hepatitis E and A in Ludhiana. METHODS: A retrospective analysis of laboratory data of the year 2001 was done, to study the epidemiology of hepatitis E and A in Ludhiana in relation to prevalence, age, sex, area of residence and seasonal variation. RESULTS: Prevalence of HEV was 13.9%. Infection with it occurred through out the year with no preponderance of cases following the monsoons. Young male adults between 20-40 years of age were predominantly affected. Prevalence of HAV was 5.5% affecting mainly children below 14 years of age. Population of urban areas around "Gandha Naliash" (a large open sewer) was at high risk as there was clustering of HEV & HAV cases around that area.

Transabdominal gastroesophageal devascularization without esophageal transection for emergency treatment of variceal hemorrhage.

BACKGROUND: The Suguira procedure is an effective non-shunting operation to treat life-threatening hemorrhage from esophageal or gastric varices. The goal of esophageal transection is interruption of submucosal varices, but this leads to high morbidity and mortality rates from esophageal fistulization. AIM: To evaluate a variant of this procedure in which the esophagus is not transected, but the varices are underrun from outside the lumen. METHODS: During the last four and a half years, we performed this modified gastroesophageal devascularization with or without splenectomy in 18 patients as emergency treatment of bleeding esophageal and gastric varices. The data were analyzed retrospectively. RESULTS: Bleeding was controlled in all patients. Three patients with Child's class C disease undergoing emergency surgery died during the early postoperative period. Rebleeding rate was 17% (3 patients). The overall survival was 72.2% (13 of 18). No patient had encephalopathy over a mean follow up of 30 months. CONCLUSION: Gastroesophageal devascularization with variceal under-running without esophageal transection is an effective and safe alternative to shunt surgery in the emergency situation.

Hepatic artery pseudoaneurysm and hemobilia following laparoscopic cholecystectomy.

Iatrogenic or accidental injury to the right hepatic artery or its branches can result in formation of pseudoaneurysm, which may rupture into the biliary system, leading to life-threatening hemobilia. We describe one such case following laparoscopic cholecystectomy and discuss its management.

Serum zinc levels in hepatic encephalopathy.

BACKGROUND: Zinc is essential for various metabolic processes of the body. Since serum zinc levels are lowered in liver diseases, it has been postulated to be a precipitating factor for hepatic encephalopathy. METHODS: We prospectively studied serum zinc levels in consecutive patients with fulminant hepatic failure, subacute hepatic failure and chronic liver disease with encephalopathy. Serum zinc levels were correlated with various clinical and biochemical parameters and final outcome of patients. Serum zinc levels were estimated by atomic absorption spectrometry at admission and also 24 hours after recovery in survivors. RESULTS: Of the 55 patients (age 17-65 years, 35 men) studied, 30 had acute, 5 subacute and 20 chronic liver disease. Patients with hepatic encephalopathy had significantly lower serum zinc levels as compared to 20 age and sex matched controls. High serum bilirubin levels and prothrombin time showed inverse relationship with serum zinc levels. There was no relationship of serum zinc levels with age, sex, grade and duration of encephalopathy, liver size, ascites or splenomegaly. CONCLUSIONS: Hepatic encephalopathy is associated with low serum zinc levels. Recovery occurred in 17 patients despite persisting low serum zinc levels. Serum bilirubin > 23 mg/dL and prothrombin time prolongation > 12 seconds above control have inverse correlation with serum zinc level.

Widespread and lateralization effects of acute traumatic brain injury on norepinephrine turnover in the rat brain.

Norepinephrine (NE) has been implicated in recovery of function following traumatic brain injury (TBI). While bilateral decrease in brain NE turnover occur at 6-24 h after TBI, it is unknown what effects unilateral TBI might have on brain NE turnover the first few minutes after injury. Her male Sprague-Dawley rats had unilateral confusions of either the right or left somatosensory cortex produced by an air between piston. At 30 min after TBI, brain NE turnover was assessed by measuring the ratio of 3-methoxy-4 hydroxyphenylglycol (MHPG) to NE levels in various brain regions. Both right and left TBI produced 32-103% increases in NE turnover at the injury site and in the ipsilateral cerebral cortex surrounding, rostral and caudal to the injury as compared to the contralateral, uninjured site or to the homologous sites in uninjured controls. NE turnover was also altered selectively in some brain areas not affected by right TBI. Left TBI decreased NE turnover by 29% in the frontal cortex contralateral to the injury and by 24% bilaterally in the hypothalamus while increasing locus coeruleus NE turnover by 72% compared to uninjured controls. Thus, unilateral cortical TBI produced predominantly ipsilateral increases in cortical NE turnover but variable, bilateral changes in NE turnover in subcortical areas which were dependent upon the side of injury. These subcortical differences may explain some of the lateralized effects of cortical injury on post-injury behavior.

Evaluation of culture techniques for detection of spontaneous bacterial peritonitis in cirrhotic ascites.

This prospective study was done in cirrhotic patients to evaluate ascitic fluid culture techniques by the conventional method and by an alternate method of bedside ascitic fluid inoculation into blood culture bottles, with an aim to improve bacteriological diagnosis of spontaneous bacterial peritonitis (SBP). Of the 300 patients who were evaluated, 43 who had a total leukocyte count greater than 500/mm3 or a polymorphonuclear cell count greater than 250/mm3 in ascitic fluid were included. There were 30 episodes of SBP in 28 patients and another 15 patients had culture-negative neutrocytic ascites (CNNA). Escherichia coli was the commonest organism cultured, being found in 60%. There was significantly greater (p < 0.001) ascitic fluid culture positivity with direct inoculation into blood culture bottles, i.e. 66.7% compared to 31.1% by conventional method at 48 hours, and this was evident even 24 hours after inoculation i.e. 33.3% positivity compared to 4.4%. Bacteremia was present in 53.3% of patients with SBP and 33.3% with CNNA. Ascitic fluid inoculation directly into blood culture bottles leads to a significantly increased percentage of culture positivity and reduces the time needed for detection of SBP from 48 to 24 hours.