Effects of Cerastes cerastes (Egyptian sand viper) and Cerastes vipera (Sahara sand viper) snake venoms on blood coagulation: Separation of coagulant and anticoagulant factors and their correlation with arginine esterase and protease activities

Cerastes cerastes and Cerastes vipera venoms were anticoagulant at high concentrations and procoagulant at low concentrations. Ëach venom was fractionated by Sephadex G-100 gel filtration into 8 fractions. Arginine esterase activity in C. cerastes venom was found in three overlapping peaks of mol. wts 70,000, 54,000 and 39,000 and in two peaks of mol. wts 62,000 and 37,000 in the corresponding fractions of C. vipera venom. Two fractions were anticoagulant whereas three fractions were procoagulant in both species. The procoagulant fractions coincided with the arginine esterase activity, while the anticoagulant fractions had proteolytic activity. The anticoagulant activity, in both fractions, is due mainly to direct and/or indirect fibrinogenolysis. The procoagulant activity is probably due to activation at multiple sites in the blood coagulation cascade.     

Systemic treatment with n-6 polyunsaturated fatty acids attenuates EL4 thymoma growth and metastasis through enhancing specific and non-specific anti-tumor cytolytic activities and production of TH1 cytokines

Recently, there has been a great interest in the effects of different types of n-6 polyunsaturated acids (n-6 PUFAs) upon the immune system and cancer development. However, the effects of n-6 PUFAs are still controversial and as yet undefined. The present study aimed to investigate the anti-tumor effects of n-6 PUFAs against EL4 thymoma and the associated immune mechanisms. To this, sesame oil, a vegetable oil enriched with n-6 PUFAs, or free linoleic acid (LA) were administered intraperitoneally into C57BL/6 mice before and after challenge with EL4 lymphoma cells. Treatment with either sesame oil or LA attenuated the growth and metastasis of EL4 lymphoma. The anti-tumor effect of LA was superior to that of sesame oil, and associated with an increase in the survival rate of the tumor-bearing mice. In addition, both sesame oil and LA showed dose-dependent anti-lymphoma growth in vitro. Treatment with LA generated significant increases in the anti-lymphoma cytolytic and cytostatic activities of T cells and macrophages, respectively, and enhanced production of IL-2 and IFN-gamma while decreased production of IL-4, IL-6 and IL-10. In summation, the results suggest that n-6 PUFAs, represented by LA, can attenuate EL4 lymphoma growth and metastasis through enhancing the specific and non-specific anti-tumor cytolytic activities and production of TH1 cytokines. These findings might be of great importance for a proper design of systemic nourishment with PUFAs emulsions for cancer patients.     

An Unusual Case of Significant Weight Loss Following Malposition of a Laparoscopic Adjustable Gastric Band

Objective: Malposition or misplacement of gastric bands is a rare but recognised early complication of gastric band surgery. Malposition of the band would not normally result in significant weight loss after surgery. Case Report: To our knowledge, we report the first case in the English literature of a malpositioned gastric band encircling the pericardial fat pad only, who presented with delayed symptoms of dysphagia and gastro-oesophageal reflux resulting in significant weight loss (>60% of excess body weight) approximately 6 years after primary surgery. The patient underwent a water-soluble contrast study with antero-posterior views which was suggestive of a slipped band. However, on laparoscopy the band was found to be encircling the pericardial fat pad. Conclusion: We suggest that all contrast swallow studies for patients presenting with symptoms of gastric band slippage should include lateral views to exclude gastric band malposition, irrespective of the time of onset of symptoms after primary surgery. Copyright ? 2012 S. Karger GmbH, Freiburg.     

Novel compounds containing multiple guanide groups that bind the HIV coreceptor CXCR4

The G-protein-coupled receptor CXCR4 acts as a coreceptor for human immunodeficiency virus type 1 (HIV-1) infection, as well as being involved in signaling cell migration and proliferation. Compounds that block CXCR4 interactions have potential uses as HIV entry inhibitors to complement drugs such as maraviroc that block the alternate coreceptor CCR5 or in cancer therapy. The peptide T140, which contains five arginine residues, is the most potent antagonist of CXCR4 developed to date. In a search for nonpeptide CXCR4 ligands that could inhibit HIV entry, three series of compounds were synthesized from 12 linear and branched polyamines with 2, 3, 4, 6, or 8 amino groups, which were substituted to produce the corresponding guanidines, biguanides, or phenylguanides. The resulting compounds were tested for their ability to compete with T140 for binding to the human CXCR4 receptor expressed on mammalian cells. The most effective compounds bound CXCR4 with a 50% inhibitory concentration of 200 nM, and all of the compounds had very low cytotoxicity. Two series of compounds were then tested for their ability to inhibit the infection of TZM-bl cells with X4 and R5 strains of HIV-1. Spermine phenylguanide and spermidine phenylguanide inhibited infection by X4 strains, but not by R5 strains, at low micromolar concentrations. These results support further investigation and development of these compounds as HIV entry inhibitors.     

Gallstone disease. Management of common bile-duct stones and associated gallbladder stones: Surgical aspects

For many years, open exploration of the common bile duct has been the treatment of choice for patients with common bile-duct stones. During recent decades endoscopic sphincterotomy has gained wide acceptance as an effective and less invasive alternative. After sphincterotomy, subsequent (laparoscopic) cholecystectomy is warranted in patients with gallbladder stones. This chapter will discuss whether sphincterotomy should be performed prior to, during or after cholecystectomy, and will also address the question of whether single-stage treatment by laparoscopic cholecystectomy and laparoscopic bile-duct exploration is in fact preferable. The rate of recurrent choledocholithiasis after endoscopic biliary sphincterotomy can reach more than 20%. This review focuses on the risk factors--delayed bile-duct clearance and bactobilia--that may lead to recurrent primary bile-duct stone formation. Underlying altered bile composition (relative phospholipid deficiency) should be recognised in a subgroup of patients. Identification of these risk factors may significantly affect treatment policy.     

The diagnostic value of biomarkers (AshTest) for the prediction of alcoholic steato-hepatitis in patients with chronic alcoholic liver disease

BACKGROUND/AIMS: The aim was to identify a panel of biomarkers (AshTest) for the diagnosis of alcoholic steato-hepatitis (ASH), in patients with chronic alcoholic liver disease. METHODS: Biomarkers were assessed in patients with an alcohol intake>50 g/d, in a training group, and in two validation groups. Diagnosis of ASH (polymorphonuclear infiltrate and hepatocellular necrosis) and its histological severity (four classes: none, mild, moderate and severe) were assessed blindly. RESULTS: Two hundred and twenty-five patients were included, 70 in the training group, 155 in the validation groups, and 299 controls. AshTest was constructed using a combination of the six components of FibroTest-ActiTest plus aspartate aminotransferase. The AshTest area under the ROC curves for moderate-severe ASH was 0.90 in the training group, 0.88 and 0.89 in the validation groups. The median AshTest value was 0.005 in controls, 0.05 in patients without or with mild ASH, 0.64 in moderate, and 0.84 in severe ASH grade 3, (P<0.05 between all groups). At a 0.50 cut-off, the sensitivity of AshTest was 0.80 and the specificity was 0.84. CONCLUSIONS: In heavy drinkers, AshTest is a simple and non-invasive quantitative estimate of alcoholic hepatitis. The use of AshTest may reduce the need for liver biopsy, and therefore allow an earlier treatment of alcoholic hepatitis.