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Diacylglycerol acyltransferase 1 (DGAT1) is known to play an important catalytic role in the final step of triglyceride biosynthesis. High fat diet fed DGAT1 knockout mice were resistant to weight gain and exhibited increased insulin and leptin sensitivity thereby indicating a plausible role for DGAT1 inhibitors in the treatment of obesity. 4-Phenylpiperidine-1-carbonyl cyclohexanecarboxylic acid (compound 6, DGAT1 IC50 = 57 nM) has been lately reported as a potent DGAT1 inhibitor. In our search for newer scaffolds possessing potent DGAT1 activity we undertook a systematic diversification of compound 6 to identify a 4-(5-phenylthiazole-2-carboxamido)cyclohexanecarboxylic acid scaffold. Further linker optimization of this scaffold identified compound 9e (DGAT1 IC50 = 14.8 nM) as a potent DGAT1 inhibitor. Coupled with its in vitro potency, compound 9e also exhibited 112 percent plasma triglyceride reduction at a 3 mpk dose in an oral fat tolerance test (FTT) when studied in Swiss mice., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

Purpose: To evaluate outcome of 6-strand triple Kessler repair for flexor tendon injuries, followed by early active motion rehabilitation., Methods: 25 men and one woman (36 fingers) underwent 6-strand triple Kessler repair for flexor tendon injuries in zones 2 to 5, followed by early active motion rehabilitation. Rehabilitation was started at days 3 to 5. Patients were instructed to passively flex all the fingers with the uninjured hand and to actively retain this position for 10 seconds. Active extension within the confines of the splint was allowed. At the end of week 8, strength training was commenced until a satisfactory range of motion was regained. Outcome measures included total active motion, grip strength, and the Disabilities of the Arm, Shoulder and Hand (DASH) score. Complications such as infection and wound dehiscence were recorded., Results: The mean follow-up was 1.2 (range, 1-2) years. Outcome was excellent in 24 digits, good in 4, and poor in 8. The mean grip strength was 80% (range, 60-100%) of normal in dominant hands and 60% (range, 50-65%) of normal in non-dominant hands. The mean DASH score was 15 (range, 0-52). One patient had wound dehiscence and superficial infection., Conclusion: Six-strand triple Kessler repair for flexor tendon injuries, followed by early active motion rehabilitation yields satisfactory results.

A new furanone metabolite of the rubrolide family, rubrolide R as diacetate (1), was isolated from a new species of the ascidian Synoicum, besides the known compounds rubrolide A (as diacetate), cadiolide B and prunolide A. The structure of the new rubrolide was elucidated by a study of spectral data. The crude extract and isolated compounds (prunolide A and cadiolide B) showed antiviral activity against the Japanese encephalitis virus. Prunolide A showed cytotoxic activity against breast cancer cell lines at a concentration of < 1 μM.

Thiazolidine-4-carboxylic acid derivatives were recognized recently for their potent antitubercular activity. A total of sixty four thiazolidine derivatives published in the recent times were collected and 3D QSAR models were developed, using CoMFA and COMSIA with high predictability. Later, we selected three new molecules, recently synthesized in our lab and evaluated them using the developed QSAR models. The in vitro antitubercular activity (MIC) obtained for these new molecules is in agreement with the predicted values (pMIC).

Airway obstruction in pregnancy is rare. We report the case of a 39-year-old nulliparous woman with a body mass index of 47 kg/m(2) and a large multinodular goitre causing tracheal compression with airway symptoms who declined thyroid surgery until after delivery. However, worsening hypertension precipitated an urgent caesarean section and thyroidectomy at 32 weeks of gestation. As general anaesthesia was required, an awake fibreoptic intubation via the oral route was felt to be the safest option. Caesarean section was performed and a healthy baby delivered followed by a total thyroidectomy. She was extubated, monitored closely for tracheomalacia and cared for postoperatively in the surgical high-dependency unit. This case highlighted a number of challenges managed successfully with a multidisciplinary team., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: Shortening tuberculosis (TB) treatment duration is a research priority. This paper presents data from a prematurely terminated randomized clinical trial, of 4-month moxifloxacin or gatifloxacin regimens, in South India., Methods: Newly diagnosed, sputum-positive HIV-negative pulmonary TB patients were randomly allocated to receive gatifloxacin or moxifloxacin, along with isoniazid and rifampicin for 4 months with pyrazinamide for first 2 months (G or M) or isoniazid and rifampicin for 6 months with ethambutol and pyrazinamide for first 2 months (C). All regimens were administered thrice-weekly. Clinical and bacteriological assessments were done monthly during treatment and for 24 months post-treatment. The Data and Safety Monitoring Board recommended termination of the trial due to high TB recurrence rates in the G and M regimens., Results: Of 416 patients in intent-to-treat analysis, 6 (5%) of 124, 2 (2%) of 110 and 2 (2%) of 137 patients with drug-susceptible TB in the G, M and C arms respectively had unfavorable response at the end of treatment; during the next 24 months, 17 (15%) of 115, 11 (11%) of 104 and 8 (6%) of 132 patients respectively, had TB recurrence. Of 38 drug-resistant patients 1 of 8 and 3 of 26 in the G and C arms respectively had unfavourable response at the end of treatment; and TB recurrence occurred in 2 of 7 and 2 of 23 patients, respectively. The differences in TB recurrence rates between the G and C arms was statistically significant (p = 0.02). Gastro-intestinal symptoms occurred in 23%, 22% and 9% of patients in the G, M and C arms respectively, but most reactions were mild and manageable with symptomatic measures; 1% required regimen modification., Conclusions: 4-month thrice-weekly regimens of gatifloxacin or moxifloxacin with isoniazid, rifampicin and pyrazinamide, were inferior to standard 6-month treatment, in patients with newly diagnosed sputum positive pulmonary TB., Trial Registration: Clinical Trials Registry of India CTRI/2012/10/003060.

Biphenyl carboxylic acids, exemplified by compound 5, are known potent inhibitors of diacylglycerol acyltransferase, DGAT1, an enzyme involved in the final committed step of triglyceride biosynthesis. We have synthesized and evaluated 2-phenylthiazole, 4-phenylthiazole, and 5-phenylthiazole analogs as DGAT1 inhibitors. The 5-phenylthiazole series exhibited potent DGAT1 inhibition when evaluated using an in vitro enzymatic assay and an in vivo fat tolerance test in mice. Compound 33 (IC50 = 23 nM) exhibiting promising oral pharmacokinetic parameters (AUCinf = 7058 ng h/ml, T1/2 = 0.83 h) coupled with 87 percent reduction of plasma triglycerides in vivo may serve as a lead for developing newer anti-obesity agents., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

Large cystic renal tumours can be confused with hepatic lesions even on crosssectional imaging. Careful clinical, sonographic and imaging analysis is needed for establishing correct diagnosis. We report a case of papillary cystic renal carcinoma in a 60 year old man, which was confused with amoebic liver abcess and was initially drained. Subsequent recurrence of symptoms prompted us to re-evaluate the case and repeat sonography confirmed the extrahepatic origin of mass based on simple observation that the liver and mass were moving separately on inspiration. Later guided aspiration from solid component of the mass confirmed the diagnosis as renal cell carcinoma. He was successfully treated with radical nephrectomy with uneventful post-operative recovery.

Severe flooding of the Brahmaputra River during the monsoon season and continuous rainfall in the northeast region (NER) of India cause an enormous loss of ginger crop every year. In this context, the present study investigates the variation in the essential oil composition and oleoresin and [6]-gingerol contents in 10 different fresh ginger cultivars harvested at 6- and 9-month maturity from five different states of NER. Monoterpenes, sesquiterpenes, and citral composition in the essential oil were evaluated to ascertain their dependence upon the maturity of ginger. Except Mizoram Thinglaidum, Mizoram Thingria, Nagaland Nadia, and Tripura I ginger cultivars, all other cultivars showed an increase in the citral content during the maturity that was observed for the first time. At 6-month maturity, a higher undecanone level was found in Nagaland Nadia (7.36 ± 0.61%), Tripura I (6.23 ± 0.61%), and Tripura III (9.17 ± 0.76%) cultivars, and these data can be used as a benchmark to identify those immature varieties. Interestingly, the Nagaland Nadia cultivar showed higher ar-curcumene (9.57 ± 0.58%) content than zingiberene (5.84 ± 0.24%), which was unique among all cultivars. Ginger harvested at 9-month maturity from the Tripura II cultivar had the highest citral content (22.03 ± 0.49%), and the Meghalaya Mahima cultivar had the highest zingiberene content (29.89 ± 2.92%). The oleoresin content was found to decrease with maturity in all cultivars, except Assam Fibreless and Manipur I. Moreover, the highest oleoresin (11.43 ± 0.58 and 9.42 ± 0.63%) and [6]-gingerol (1.67 ± 0.03 and 1.67 ± 0.05 g) contents were observed for Tripura II and Nagaland Nadia, respectively. This study suggests that Tripura and Nagaland are the most ideal locations in NER for ginger cultivation to obtain high yields of oleoresin and [6]-gingerol contents and harvesting at the 6-month maturation will compensate for the loss of ginger crop caused by the Brahmaputra River flooding in NER every year.

Osteochondromas are the most common benign bone tumours and account for 20 to 50% of benign bone tumours and 10 to 15% of all bone tumours. They usually occur in long bones; 40% occur around the knee joint, but in the hand they are uncommon and usually affect the proximal phalanx. The metacarpal is rarely involved. We report a 32-year-old man with a recurrent solitary osteochondroma of the metacarpal.

Background: Formal sexual education is a mandatory component of the high school curriculum in most Canadian provinces. The present study was a preliminary assessment of sexual knowledge among a sample of Ontario adolescents who had completed their high school sexual education requirements., Methods: A questionnaire, testing understanding of the learning objectives of Ontario's minimally required high school sexual education course, was distributed in a paediatric emergency department to 200 adolescent patients who had completed the course., Results: Respondents demonstrated good understanding of pregnancy physiology and sexually transmitted infections, but poor understanding of concepts related to reproductive physiology, contraception, HIV/AIDS and sexual assault. Most respondents could not identify Canada's age of sexual consent., Conclusions: Respondents demonstrated concerning gaps in sexual knowledge despite completion of their sexual education requirements. Further studies must determine whether a representative, population-based student sample would exhibit similar findings. Sexual education currently offered in Ontario may require investigation.

Objective: Human papillomavirus oncoproteins E6 and E7 down modulate Toll-like receptor (TLR) 9 expression in infected keratinocytes. We explored the status of expression and function of TLR7, TLR8, and TLR9 in primary human Langerhans cells (LCs) isolated from cervical tumors., Methodology: Single-cell suspensions were made from fresh tissues of squamous cell carcinoma (International Federation of Gynecology and Obstetrics stage IB2); myeloid dendritic cells were purified using CD1c magnetic activated cell separation kits. Langerhans cells were further flow sorted into CD1a*CD207* cells. Acute monocytic leukemia cell line THP-1-derived LCs (moLCs) formed the controls. mRNA from flow-sorted LCs was reverse transcribed to cDNA and TLR7, TLR8, and TLR9 amplified. Monocyte-derived Langerhans cells and cervical tumor LCs were stimulated with TLR7, TLR8, and TLR9 ligands. Culture supernatants were assayed for interleukin (IL) 1β, IL-6, IL-10, IL-12p70, interferon (IFN) α, interferon γ, and tumor necrosis factor (TNF) α by Luminex multiplex bead array. Human papillomavirus was genotyped., Results: We have for the first time demonstrated that the acute monocytic leukemia cell line THP-1 can be differentiated into LCs in vitro. Although these moLCs expressed all the 3 TLRs, tumor LCs expressed TLR7 and TLR8, but uniformly lacked TLR9. Also, moLCs secreted IL-6, IL-1β, and tumor necrosis factor α to TLR8 ligand and interferon α in response to TLR9 ligand; in contrast, tumor LCs did not express any cytokine to any of the 3 TLR ligands. Human papillomavirus type 16 was one of the common human papillomavirus types in all cases., Conclusions: Cervical tumor LCs lacked TLR9 expression and were functionally anergic to all the 3: TLR7, TLR8, and TLR9 ligands, which may play a crucial role in immune tolerance. The exact location of block(s) in TLR7 and TLR8 signaling needs to be investigated, which would have important immunotherapeutic implications.

Hyponatremia is a common electrolyte abnormality among children and adults. Visual disturbance associated with hyponatremia has been described in the past; however, all of these cases presented primarily with other classical signs and symptoms of hyponatremia, such as seizures, gastrointestinal upset, lethargy, or headache. We present a child who developed blindness on post-operative day #6 after resection of a brain tumour. Computed tomography of the head showed no new bleed, mass lesion, edema, or occipital lobe pathology. Laboratory evaluation revealed acute hyponatremia (115 mmol/L). No other obvious symptoms of hyponatremia were present prior to its identification. As her hyponatremia was gradually corrected, her blindness completely resolved. This is the first reported patient with acute hyponatremia to present primarily with blindness; a "precondition" of chronically increased intracranial pressure (first hit) compounded by acute hyponatremia (second hit) may have induced reversible visual loss. Checking electrolytes should be the standard of care for neurosurgical patients with acute visual disturbance or other unexplained symptoms. It is a simple measure that quickly identifies a dangerous but reversible condition.

Diacylglycerol acyltransferase, DGAT1, is a promising target enzyme for obesity due to its involvement in the committed step of triglyceride biosynthesis. Amino biphenyl carboxylic acids, exemplified by compound 4, are known potent inhibitors of hDGAT1. However the high cLogP and poor solubility of these biphenyl analogs might tend to limit their development. We have synthesized and evaluated compounds containing 3-phenylisoxazole, 5-phenyloxazole, and 3-phenyl-1,2,4-oxadiazole biaryl units for their hDGAT1 inhibition. Our aim in synthesizing such heterocyclic analogs was to improve the cLogP and solubility of these molecules while retaining hDGAT1 potency. Several compounds within the 3-phenylisoxazole series exhibited potent hDGAT1 inhibition when evaluated using an in vitro enzymatic assay. Certain promising compounds were studied for their potential to reduce triglyceride levels using an in vivo fat tolerance test in mice and were also evaluated for any possible improvement to their solubility. Compound 40a (IC(50) = 64 nM) with an in vivo plasma triglyceride reduction of 90 percent, and a solubility of 0.43 mg/ml at pH 7.4 may serve as a new lead for developing newer anti-obesity agents., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

Background: Existing methods for the preparation of panel slides necessitate handling high-grade acid-fast bacilli positive sputum samples., Objective: To compare panel slides prepared using the phenol ammonium sulphate sediment (PhAS) method with those prepared using the N-acetyl-L-cysteine (NALC) method in proficiency testing., Methods: Pooled sputum specimens of known smear-positives and -negatives were divided into two parts: one part was used for preparing panel slides using the NALC method and the other using PhAS, a non-hazardous method. Respectively 413 and 384 smears of different grades were prepared in three batches using the PhAS and NALC methods. Smear grade and quality were recorded by 121 microscopists during proficiency testing in different states. Agreement between reference and reported results was analysed using the kappa test., Results: The overall agreement was 96% for the PhAS method and 91% for the NALC method. There were 37 errors using the NALC method compared to 21 for the PhAS method (P < 0.223). Smear quality was equally good in both methods; however, the cell count was significantly higher in the PhAS than in the NALC method., Conclusion: The PhAS method, a non-hazardous procedure with good-quality smears, may be further explored for the preparation of panel slides.

Background: AUTODOCK Vina is an open-source program which is steadfast and authentic to perform docking simulations. Though, Auto Dock Tools can help perform docking simulations with Vina, it largely remains as a platform for docking single molecule at a time., Findings: "AUDocker LE" is designed with an aim to develop a software tool as a front end graphical interface with C# language to perform docking experiments in Windows based computers. It helps users to perform automated continuous docking of large ligand databases into a set of predefined protein targets. It will also help the user to analyze the results to select promising lead molecules., Conclusion: AUDocker LE provides a straight forward graphical interface which can be used in a standard personal computer with Microsoft Windows XP or Windows 7 as the operating system where Autodock Vina, Python 2.5 and .net frame work are preinstalled.

A series of 2-{4-[4-(2,5-disubstituted thiazolyl)phenylethyl] piperazin-1-yl}-1,8-naphthyridine-3-carbonitriles were synthesized in an effort to prepare novel atypical antipsychotic agents. The compounds were synthesized either by microwave irradiation technique or by conventional synthesis and were characterized by spectral data (IR, (1)H NMR, and MS) and the purity was ascertained by microanalysis. The D(2) and 5-HT(2A) affinity of the synthesized compounds was screened in vitro by radioligand displacement assays on membrane homogenates isolated from rat striatum and rat cortex, respectively. Furthermore, all the synthesized compounds were screened for their in vivo pharmacological activity in Swiss albino mice. The D(2) antagonism studies were performed using climbing mouse assay model and 5-HT(2A) antagonism studies were performed using quipazine-induced head twitches in mice. It was observed that none of the new chemical entities exhibited catalepsy and 10f is the most active among the synthesized compounds with 5-HT(2A)/D(2) ratio of 1.1286 although the standard drug risperidone exhibited 5-HT(2A)/D(2) ratio of 1.0989.

Yellow fever is among one of the most lethal viral diseases for which approved antiviral therapies were yet to be discovered. Herein, functional assignment of complete YFV proteome was done through support vector machine. Major envelope (E) protein that mediates entry of YFV into host cell was selected as a potent molecular target. Three dimensional structure of the molecular target was predicted using Modeller9v7. The model was optimized in Maestro9.0 applying OPLS AA force field and was evaluated using PROCHECK, ProSA, ProQ and Profile 3D. The BOG pocket residues Val48, Glu197, Thr200, Ile204, Thr265, Thr268 and Gly278 were located in YFV E protein using SiteMap2.3. More than one million compounds of Ligandinfo Meta database were explored using a computational virtual screening protocol targeting BOG pocket of the E protein. Finally, ten top ranked lead molecules with strong binding affinity to BOG pocket of YFV E protein were identified based on XP Gscore. Drug likeliness and comparative bioactivity analysis for these leads using QikProp3.2 had shown that these molecules would have the potential to act as better drug. Thus, the 10 lead molecules suggested in the present study would be of interest as promising starting point for designing antiviral compound against yellow fever.

Some novel substituted pyramidinopyrazoles and pyrimidinotriazoles have been synthesized by using 6-anisyl-5-cyan-2-hydrazine-3-N-methyl-3, 4-dihydropyrimidine-4-one as the starting material. Structures of these compounds have been established by IR, (1)H NMR, Mass and elemental analysis data and have been evaluated for their antimicrobial activity. Significant antimi.crobial activity was observed for some members of these series.

A series of N-2-(4-(4-(2-substitutedthiazol-4-yl) piperazin-1-yl)-2-oxoethyl)acetamides were synthesized in an effort to prepare novel atypical antipsychotic agents. The compounds were synthesized by either microwave irradiation technique or by conventional synthesis and were characterized by spectral data (IR, (1)H NMR, and MS) and the purity was ascertained by microanalysis. All the synthesized compounds were screened for their in vivo pharmacological activity in Swiss albino mice. D(2) antagonism studies were performed using climbing mouse assay model and 5-HT(2A) antagonism studies were performed using quipazine induced head twitches in mice. It was observed that none of the new chemical entities exhibited catalepsy. AG 3 was found to be the most active compound.

We investigated the effect of anesthesia on serum lipid parameters in adult bonnet macaques (Macaca radiata). We treated 10 animals with ketamine hydrochloride (15 mg/kg intramuscularly) and, on the next day, thiopentone sodium (25 mg/kg intravenously). Blood samples were obtained before and after anesthetic treatment. Serum cholesterol, triglycerides, very low-density lipoprotein (VLDL), and high-density lipoprotein (HDL) were measured by autoanalyzer. Ketamine anesthesia significantly decreased serum cholesterol and HDL levels, whereas thiopentone significantly reduced triglycerides and VLDL and increased HDL values. Although the effects of ketamine hydrochloride and thiopentone sodium on serum biochemical values have been reported, no literature addressing the effect of anesthesia on lipid parameters in bonnet macaques is available. These findings will be useful in designing experiments assessing pathologic and toxicologic changes in serum lipid parameters and interpreting data obtained from adult bonnet monkeys.

Eugenia jambolana (Jamun) fruit has been reported to give soothing effect on human digestive system. Present study includes the effect of ethanolic extract of seeds of E. jambolana (EJE) against gastric ulcers induced by 2 h cold restraint stress (CRS), aspirin (ASP, 200 mg/kg, 4 h), 95% ethanol (EtOH, 1 ml/200 g, 1 h) and 4 h pylorus ligation (PL) in rats. To ascertain the mechanism of action of EJE, its effect was studied on mucosal offensive acid-pepsin secretion, lipid peroxidation (LPO, free radical) and defensive mucin secretion, cell proliferation, glycoprotein and glutathione (GSH, an antioxidant). Acute and subacute toxicity studies were also conducted for the safety profile of Eugenia jambolana. EJE 200 mg/kg, when administered orally for 10 days in rats was found to reduce the ulcer index in all gastric ulcer models. It tended to decrease acid-pepsin secretion, enhanced mucin and mucosal glycoprotein and decreased cell shedding but had no effect on cell proliferation. It showed antioxidant properties indicated by decrease in LPO and increase in GSH levels in the gastric mucosa of rats. Acute toxicity study indicated LD50 to be more than 10 times (>2000 mg/kg) of the effective ulcer protective dose while subactue toxicity study (>1000 mg/kg) indicated no significant change in the general physiological and haematological parameters, liver and renal function tests. The result of the present study indicates that E. jambolana seed has gastro-protective properties mainly through promotion of mucosal defensive factors and antioxidant status and decreasing lipid peroxidation.

The objective of this study was to quantify end-organ damage caused by bacteremic sepsis. Twelve adult swine were divided into two groups. The anesthesia control group (n = 6) received general anesthesia for 4 hours. The septic shock group (n = 6) received an infusion of Aeromonas hydrophila under general anesthesia for 4 hours. Swine were sacrificed at the end of the 4-hour procedure. Tissues from lungs, kidneys, livers, and hearts were stained with hematoxylin and eosin. Images of tissues were studied with digital image analysis. In lungs, cytoplasmic area (CA), nuclear area (NA), intra-alveolar hemorrhage (IAH), total airspace (TAS), and alveolar septum thickness (ST) were measured. Nuclear and cytoplasmic intensities (NI and CI) were measured in integrated optical density units (IOD). In kidneys, livers, and hearts, CA, CI, NA, and NI were measured similarly. Sinusoidal blood in the liver and vacuolization (VAC) in the kidney were also measured. In septic lungs, CI, NA, NI, ST, IAH, TAS, and ratios of NA/CA, NI/CI, and IAH/TAS were significantly increased compared with the control (P < 0.02). In septic kidneys, CI, NA, VAC, NA/CA, and NI/CI were significantly increased (P < 0.0005). In livers, CA, CI, and NI/CI were significantly increased (P < 0.005). In hearts, the ratios of NA/CA and NI/CI were statistically significant. End organs from septic swine, with exception of the heart, showed significantly higher levels of cellular damage. Digital image analysis provides an objective, precise, and accurate method of quantifying image characteristics. Automating these tasks is a high priority in the research and clinical community in providing a reproducible method for longitudinal analysis of various biological studies.

We report two patients who presented to our obstetric unit with a diagnosis of neurocardiogenic syncope. The first patient presented to the obstetricians in the second trimester having had two episodes of syncope during her pregnancy. The second patient had a pacemaker fitted prior to conceiving. We present the peri-partum management of both these patients.

Asparagus racemosus (AR) is a herb used as a rasayana in Ayurveda and is considered both general and female reproductive tonic. Methanolic extract of A. racemosus roots (ARM; 100 mg/kg/day for 60 days) showed teratological disorders in terms of increased resorption of fetuses, gross malformations e.g. swelling in legs and intrauterine growth retardation with a small placental size in Charles Foster rats. Pups born to mother exposed to ARM for full duration of gestation showed evidence of higher rate of resorption and therefore smaller litter size. The live pup showed significant decrease in body weight and length and delay of various developmental parameters when compared to respective control groups. AR therefore, should be used in pregnancy cautiously as its exposure during that period may cause damage to the offspring.

Standardized aqueous extract of Neem (Azadirachta indica) leaves (AIE) has been reported to show both ulcer protective and ulcer healing effects in normal as well as in diabetic rats. To study the mechanism of its ulcer protective/healing actions, effects of AIE (500 mg/ kg) was studied on various parameters of offensive acid-pepsin secretion in 4 hr pylorus ligation, pentagastrin (PENTA, 5 microg/kg/hr)-stimulated acid secretion and gastric mucosal proton pump activity and defensive mucin secretion including life span of gastric mucosal cells in rats. AIE was found to inhibit acid-pepsin secretion in 4 hr pylorus ligated rats. Continuous infusion of PENTA significantly increased the acid secretion after 30 to 180 min or in the total 3 hr acid secretion in rat stomach perfusate while, AIE pretreatment significantly decreased them. AIE inhibited the rat gastric mucosal proton pump activity and the effect was comparable with that of omeprazole (OMZ). Further, AIE did not show any effect on mucin secretion though it enhanced life span of mucosal cells as evidenced by a decrease in cell shedding in the gastric juice. Thus, our present data suggest that the ulcer protective activity of AIE may be due to its anti-secretary and proton pump inhibitory activity rather than on defensive mucin secretion. Further, acute as well as sub acute toxicity studies have indicated no mortality with 2.5 g/kg dose of AIE in mice and no significant alterations in body or tissues weight, food and water intake, haematological profile and various liver and kidney function tests in rats when treated for 28 days with 1 g/kg dose of AIE.

Background: The use of low flow circle systems necessitates a 'leak free' breathing system which is commonly achieved by using a cuffed tracheal tube (TT). We hypothesized that low flow circle system anesthesia can equally effectively be achieved by using the LMA in pediatric anesthesia., Methods: Following local ethics committee approval we randomly recruited 45 patients scheduled for elective surgery and requiring mechanical ventilation into three groups (cuffed TT, uncuffed TT and LMA group, n = 15). The size of the TT was determined by means of the formula (age/4) + 4.5 for uncuffed and (age/4) + 4 for cuffed TT whereas the size of the LMA size was dependent on weight. Following induction of anesthesia and muscle paralysis patients were ventilated with pressure controlled ventilation through a pediatric circle system and the lowest fresh gas flow (FGF) determined., Results: The FGF achieved were (median and range) 0.20 (0.2-0.25) l.min(-1) for the LMA group, 0.20 (0.2-0.4) l.min(-1) for the cuffed TT group and 1.15 (0.2-4.75) l.min(-1) for the uncuffed group. The differences between the LMA and cuffed TT compared with the uncuffed TT were significant (P < 0.0001 and P = 0.0002, respectively). The difference in FGF between LMA and cuffed TT was not significant., Conclusion: We conclude that pressure controlled ventilation using an LMA is an alternative to a cuffed TT during low flow circle system anesthesia in children. Low FGF is unlikely to be achieved consistently using an uncuffed TT because of a substantial leak.

Background: Leptospirosis, a zoonosis, is a re-emerging disease, affecting populations across the globe. However, the current methods of diagnosis are time- consuming, cumbersome, imprecise or expensive., Aim: To develop an assay for differential and early diagnosis of Leptospirosis., Methods and Material: IgG based ELISA for evaluation of three antigens, namely, a gel-purified recombinant protein (rLipL32), secreted proteins and whole organism sonicates of Leptospira spp. The antigens were evaluated using, rabbit polyclonal antiserum and human sera samples., Results: Studies with a rabbit polyclonal antiserum indicated the utility of these antigens in differentiating Leptospira from other common pathogenic organisms. Evaluation of these antigens with fifteen representative human serum samples indicated gel-purified rLipL32 to be a potentially useful antigen for detection of leptospirosis. The results obtained with IgG ELISA were correlated with the results of microscopic agglutination test (MAT)., Conclusion: Gel-purified rLipL32 is a valuable antigen for early and accurate diagnosis of leptospirosis. Further evaluation of this assay in field conditions and larger sera samples will indicate its suitability in case of an epidemic.

We studied the relationship between the timing of discontinuing chronic angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II receptor subtype 1 antagonists (ARA) and hypotension after the induction of general anesthesia in a general surgical population. We retrospectively studied 267 hypertensive patients receiving chronic ACEI/ARA therapy undergoing elective noncardiac surgery under general anesthesia. During preoperative visits, patients were asked to either take their last ACEI/ARA therapy on the morning of surgery or withhold it up to 24 h before surgery. The number of hours from the last ACEI/ARA dose to surgery was recorded during the preoperative interview. Electronic medical and anesthesia records were reviewed for comorbidities, type and dose of anesthetics used, intraoperative hemodynamics, IV fluids, perioperative vasopressor administration, and rate of severe postoperative complications. Arterial blood pressure (BP) and heart rate were recorded during the 60-min postinduction period, and hypotension was classified as moderate (systolic BP or=10 h before surgery. During the first 30 min after anesthetic induction, moderate hypotension was more frequent in patients whose most recent ACEI/ARA therapy was taken <10 h (60%) compared with those who stopped it >or=10 h (46%) before induction (P = 0.02). The adjusted odds ratio for moderate hypotension was 1.74 (95% confidence interval, 1.03-2.93) for those who took their ACEI/ARA therapy <10 h before surgery (P = 0.04). There were no differences between groups in the incidence of severe hypotension, nor was there a difference in the use of vasopressors. During the 31-60 min after induction, the incidence of either moderate (P = 0.43) or severe (P = 0.97) hypotension was similar in the two groups. No differences in postoperative complications were found between groups. In conclusion, discontinuation of ACEI/ARA therapy at least 10 h before anesthesia was associated with a reduced risk of immediate postinduction hypotension.

Chemical investigation of a soft coral species of the genus Lobophytum has resulted in the isolation of three new sphingolipids--(2S,3S,4R)-2-nonadecanoylamino-octadecane-1,3,4-triol (1), (2S,3R,4E,8E)-[(2'R)-2'-hydroxyheptadecanoylamino]-4,8-octadecadiene-1,3-diol (2), 1-O-(beta-D-glucopyranosyl)-(2S,3R,4E,8E)-2-[(2'R)-2'-hydroxynonadecanoylamino]-9-methyl-4,8-octadecadiene-1,3-diol (3) and a sterol--(24S)-ergost-5-en-3beta,7beta-diol (4) along with the known sphingolipid--(2S,3R,4E,8E)-2-hexadecanoylamino-4,8-octadecadien-1,3-diol (5) which showed cytotoxicity against human peripheral blood mononuclear cells (PBMC).

Various 6-substituted benzothiazolyl-2-thiosemicarbazones were synthesized and screened for anticonvulsant activity in maximal electroshock induced seizure (MES) and subcutaneous pentylenetetrazole (scPTZ) induced seizure models in mice. The neurotoxicity was assessed using the rotorod method. The 6-methyl benzothiazolyl-2-thiosemicarbazones showed anticonvulsant activity in both mice i.p. and rat oral MES screen. The 6-nitro benzothiazolyl thiosemicarbazone derivative 1a emerged as the most promising one with anti-MES activity in mice i.p., rat i.p. and rat p.o. evaluations. All the compounds exhibited lesser or no neurotoxicity compared to phenytoin. The isatinimino derivatives had shown better activity when compared to the benzylidene or acetophenone derivatives.

A new sphingolipid, (2S,3R,4E)-1,3-dihydroxy-2-[(nonadecanoyl) amino]-octadec-4-ene (1) along with ubiquitous batyl alcohol is isolated from the gorgonian, Junceella juncea Pallas (Gorgonaceae) of the Indian Ocean. The structure of 1 is determined on the basis of 1H- and 13C-NMR, COSY, FABMS, and GC-EIMS experiments.

Two new sphingosines, (2S,3R)-2-(docosanoyl amino)nonadecane-1,3-diol (1) and (2S,3S,4R)-2-[(2'R)-2'-hydroxynonadecanoylamino]nonadecane-1,3,4-triol (3), along with the known (2S,3R,4E)-2-(heptadecanoylamino)octadec-4-ene-1,3-diol, have been isolated from Pseudopterogorgia australiensis, of the Indian Ocean. The structures were deduced from spectral and chemical methods. Compounds 1-3 showed moderate antibacterial activity.

A classical live attenuated sheep pox vaccine was prepared using the Ranipet strain of sheep pox virus (SPV) at the 50th passage in a secondary lamb testicular cell system. The TCID50 and RD50 were 10(9.63)/ml and 10(9.51)/ml. respectively. The SID50 of SPV challenge virus was 10(5)/ml. The vaccine was found to have no adverse effects in laboratory animals, and was safe and effective in SPV seronegative lambs. In the field, 660 sheep were vaccinated with an immunizing dose containing 1 x 10(2) TCID50. Randomly selected vaccinated sheep mounted good cell-mediated immunity and humoral responses as measured by glucose utilization test and serum neutralization test, respectively, for the study period of 6 months.

The phenyl (thio) semicarbazide derivatives of phthalimido pharmacophore were synthesized and evaluated for their anticonvulsant and neurotoxic properties. Initial anticonvulsant screening was performed using intraperitoneal (i.p.), maximal electroshock-induced seizure (MES), subcutaneous pentylenetetrazole (scPTZ) and subcutaneous strychnine (sc STY)-induced seizure threshold tests in mice. Compound 2c afforded protection in all the three screens. Compounds except 1d, 2a and 2d showed no neurotoxicity up to 300 mg/kg. Compounds 1a, 1b, 2c, 2d, 2g and 2i were found to show oral MES activity. The compounds exhibited CNS depression and behavioral despair side effects, lesser than the conventional antiepileptic drugs.

Chemical examination of the marine sponge Iotrochota baculifera of the Indian Ocean furnished a sphingolipid (1), a new glycosphingolipid (iotroridoside-B, 2) and a four-component mixture of sphingolipids (3a-d) with two new components. Structure elucidation was carried out by spectral and chemical methods.

A patient with spondylometaphyseal dysplasia, an extremely rare form of dwarfism, presented for elective caesarean section. We report the successful management under regional anaesthesia, using a combined spinal epidural technique. There seem to be only two previous reports of spinal anaesthesia and there are no previous reports of the use of combined spinal epidural in a pregnant dwarf. Regional anaesthesia is thought to be complex in these dwarfs due to vertebral malformation and unpredictable anatomy of the spinal canal. They may present difficulties with intubation as well. Spondylometaphyseal dysplasia is reviewed and its anaesthetic implications discussed.

The 50% ethanol extract of the whole plant of Solanum nigrum was tested in vitro for its cytoprotection against gentamicin-induced toxicity on Vero cells. Cytotoxicity was significantly inhibited as assessed by the Trypan blue exclusion assay and mitochondrial dehydrogenase activity (MTT) assay. The test extract also exhibited significant hydroxyl radical scavenging potential, thus suggesting its probable mechanism of cytoprotection.

The dried alcoholic (50%) extract of the plant Luffa echinata was investigated for inhibition of lipid peroxidation, for hydroxyl radical scavenging activity and interaction with 1,1-diphenyl-2-picrylhydrazyl stable free radical (DPPH). It was found that the test extract exhibited a considerable inhibition of lipid peroxidation and possessed hydroxyl radical scavenging activity. Evaluation of antiradical scavenging activity showed significant interaction with DPPH. These properties could be considered as a useful and exploitable combination for justifying the reported activity.

We have investigated the effect of phenolic antioxidants on cisplatin-induced cytotoxicity in vero (African Green Monkey Kidney) cells and in rat renal cortical slices in vitro, and on cisplatin-induced nephrotoxicity in rats in vivo. Incubation of cisplatin with vero cells resulted in time- and concentration-dependent cytotoxicity, as characterized by decreased tryphan blue exclusion (TBE) and increased release of lactate dehydrogenase (LDH) into the medium. Cisplatin also caused reduction of glutathione (GSH) in a concentration-dependent manner. In the rat renal cortical slices model, incubation of cisplatin for 120 min caused an increase in malondialdehyde (MDA), a decrease in GSH and inhibited p-aminohippurate (PAH) uptake in a concentration-dependent manner. Among phenolic antioxidants, isoeugenol (IG) was found to be more active against cisplatin-induced cytotoxicity in vero cells as well as in rat renal cortical slices than eugenol (EG) and dehydrozingerone (DZ). However none of the test compounds were able to arrest the reduction of the GSH content induced by cisplatin in either the vero cells or the renal cortical slice model. Administration of cisplatin (3 mg/kg) i.p. to rats resulted in significant reduction of body weight, and elevation of blood urea nitrogen (BUN) and serum creatinine. Treatment with IG 10 mg/kg i.p. 1 h before cisplatin resulted in partial but significant protection against the cisplatin-induced reduction of body weight, and elevation of BUN and serum creatinine, the protection being 34, 46, and 62%, respectively. EG and DZ (10 mg/kg, i.p.) were found to be inactive in vivo. Because IG is a potent free radical scavenger and protects against cisplatin-induced toxicitiy, the present results have many clinical implications in chemotherapy and thus warrants further investigation.

Osteotomy has been used in treatment of unstable intertrochanteric hip fractures in an attempt to increase the stability of the fracture fragments. We have assessed this stability in a randomised prospective study on 138 patients, all having been fixed by dynamic hip screen, comparing anatomical reduction with medialisation osteotomy. The groups were similar in terms of age, gender and fracture configuration. There was no difference in final results in both groups except that operation time was longer in osteotomy group and the blood loss was more. We found no clear benefit from osteotomy and therefore recommend anatomical reduction and fixation by a sliding hip screw in most cases. Rarely, a fracture configuration which does not allow anatomical reduction may benefit from an osteotomy.

A simple rapid method for isolation of genomic DNA from cervical scrape cells has been standardized. Sufficient amount of good quality genomic DNA was isolated from each cervical scrape specimen. Total 120 cervical scrape specimens from wide spectrum of cervical lesions were analysed for the presence of HPV 16 DNA by Southern hybridization using 32P labelled HPV 16 DNA as probe under stringent conditions. Viral DNA sequences were detected in 78 of the specimens. About 36% (5 out of 14) of normal cervical smears and 59% (46 out of 78) of inflammatory cervical smears had the viral DNA sequences. Except a lone sample, the rest 27 samples of different grades of dysplasia specimens and squamous cell carcinoma samples had viral DNA sequences. Due to development of sensitive Southern hybridization method, the presence of HPV 16 DNA could be detected in high percentage of specimens belonging to the inflammatory cervical specimens.