Glycosides and amino acyl esters of carbohydrates as potent inhibitors of angiotensin converting enzyme

About 12 glycosides prepared through amyloglucosidase catalysis and 23 amino acyl esters of carbohydrates prepared through lipase catalysis in organic solvents showed angiotensin converting enzyme (ACE) inhibition activity. Both amino acyl esters of carbohydrates and glycosides exhibited IC50 values for ACE inhibition in the 0.5 mM to 15.7 mM range. Eugenyl-D-glucoside (IC50: 0.5+/-0.04 mM), L-isoleucyl-D-glucose (IC50: 0.7+/-0.067 mM), vanillyl-D-sorbitol (IC50: 0.8+/-0.09 mM), L-histidyl-D-fructose (IC50: 0.9+/-0.087 mM), L-tryptophanyl-D-fructose (IC50: 0.9+/-0.092 mM), octyl-D-glucoside (IC50: 1.0+/-0.093 mM), vanillyl-D-mannoside (IC50: 1.0+/-0.089 mM), L-valyl-D-mannitol (IC50: 1.0+/-0.092 mM) and L-phenylalanyl-D-glucose (IC50: 1.0+/-0.089 mM) were the compounds, which showed the best ACE inhibitory activities.     

Clinical profile and surgical outcome of Meckel's diverticulum

The aim of the study was to estimate the incidence and analyse the clinical profile and surgical outcome of the Meckel's diverticulum. This prospective study included 632 patients who were operated upon for acute abdomen during August 1999 to July 2004 in a single surgical unit. Pre-operative abdominal ultrasonography and plain x-ray abdomen erect were done depending on the necessity. These patients were subjected to laparotomy/appendicectomy depending on the case. A search for Meckel's diverticulum was done and if found, surgical resection and analysis by histopathological confirmation of the Meckel's diverticulum was performed. This study detected 9 patients (1.42%) with Meckel's diverticulum during the operation. In none of these cases pre-operative diagnosis of Meckel's diverticulitis was made. Out of 9 patients, 6 (66.6%) were males, 3 (33.4%) females. Four cases (44.4%) were symptomatic due to Meckel's diverticulum and 5 (55.6%) were asymptomatic. One patient presented with haematochezia, one with intestinal obstruction due to gangrene of the Meckel's diverticulum and one case of duplication of (double) Meckel's diverticulum. Histopathological examination of these specimens confirmed 2 cases with inflammation, one with gangrene and one ulcerated gastric mucosa in the Meckel's diverticulum. In 2 cases (22.2%) there was heterotopic epithelium (gastric-1, colonic-1). It is recommended that a search for Meckel's diverticulum in every case of appendicectomy, laparotomies for acute abdomen should be conducted and if found, Meckel's diverticulectomy/resection should be performed to avoid secondary complications arising from it.     

Young heroin users in Baltimore: a qualitative study

This study describes the characteristics of 67 young heroin users, interviewed using a semistructured qualitative questionnaire (QQ) as part of a larger study of 18- to 25-year-old heroin users seeking detoxification with buprenorphine at a drug treatment center in Baltimore. This new generation of heroin users has a different demographic profile compared to older heroin users in this area. Our data, supported by data from another clinic and from the Maryland State Alcohol and Drug Abuse Administration, seem to indicate that the younger heroin users in treatment settings are predominantly White, with a high proportion of women, often living in the suburbs. Based on responses to the QQ, all subjects initiated heroin use intranasally, usually in a group setting; 75% had subsequently gone on to use intravenously. The typical young heroin user in Baltimore Metropolitan area appears to be a young White man or woman from a middle/working-class background, with exposure to drug use among close contacts while growing up, experimenting with gateway drugs with peers before proceeding first to intranasal, and then intravenous heroin use, engaging in criminal activities to support the habit, repeatedly seeking help with assistance from family, but failing to sustain abstinence due to continued exposure to drug using peers and a poorly implemented plan of aftercare. Further research should focus on efforts to engage peer groups and families in order to improve treatment outcomes in young heroin users.     

In vivo antidiabetic activity and in silico studies on adenosine monophosphate-activated protein kinase (AMPK) of (2E,5E)-2,5-bis(4-hydroxy-3-methoxybenzylidene) cyclopentanone

Effect of bischalcone derivative (2E,5E)-2,5-bis(4-hydroxy-3-methoxybenzylidene) cyclopentanone (CA) on blood glucose level and lipid profile was investigated in normoglycemic and streptozotocin (STZ)-induced diabetic rats. In oral glucose and sucrose tolerance test, treatment with CA (25 mg/kg) and glidenclamide (10 mg/kg) significantly improved the glucose and sucrose tolerance in normal animals. In addition, respective treatment for 7-day resulted in significant percentage reduction in serum glucose (SG). In standardized STZ-induced diabetic rats, a single dose of CA treatment exhibited reduction in SG levels at different time intervals compared to basal levels. The lipid profile levels are restored to near-normal value of all tested parameters. The compound CA was docked into the active site of 5′-AMP (adenosine monophosphate)-activated protein kinase (PDB ID: 2OOX). The binding and docking energy were found to be ?6.9 and ?45.1 kcal/mol, respectively.     

Drug delivery from gold and titanium surfaces using self-assembled monolayers

Currently available drug-eluting stents (DES) use polymers for coating and releasing drugs. Increasing evidence suggests that inflammatory and hypersensitive reactions are caused by such polymer coatings. This study focused on developing new techniques for delivering drugs directly from metal implant surfaces. Hydroxyl-terminated self-assembled monolayers (SAMs) were coated on Au and Ti surfaces. Therapeutic self-assembled monolayers (TSAMs) were prepared by chemically attaching the model drug, flufenamic acid, to SAM coated metal surfaces. Three different methods of esterification (acid chloride esterification, dry heat esterification, and direct esterification) were explored to attach flufenamic acid to SAMs. TSAMs were characterized using X-ray photoelectron spectroscopy, fluorescence microscopy, atomic force microscopy, and contact angle goniometry. These techniques collectively confirmed the attachment of drug onto SAM coated metal surfaces. In vitro drug release was investigated by immersing TSAM coated metal specimens in tris-buffered saline (TBS) at 37 degrees C for 28 days. TBS was analyzed at 1, 3, 7, 14, 21, and 28 days for the amount of drug eluted using high performance liquid chromatography. Large data scatter was observed for the release profiles of TSAMs prepared by acid chloride esterification. TSAMs prepared by dry heat and direct esterification methods showed an initial burst release of the drug followed by a sustained slow release for up to 2 weeks. Thus, this study suggests the potential for using self-assembled monolayers as an alternate system for delivering drugs from coronary stents and other metal implants.