Antibiotic resistance to third generation cephalosporins due to CTX-M-type extended-spectrum beta-lactamases in clinical isolates of Escherichia coli

Organisms producing CTX-M-beta-lactamase are emerging around the world as a source of resistance to oxyiminocephalosporins such as cefotaxime. However, the laboratory detection of these strains is not well defined. The aim of this study was to determine the presence and prevalence of known CTX-M-beta-lactamases genes in clinical isolates of Escherichia coli from hospitals of Tehran. During six months [September to February, 2006], 160 clinical isolates of Escherichia coli collected from three university hospitals of Tehran. Phenotypic screening and confirmation tests for ESBL detection was according to CLSI advised. All of the ESBL-producing isolates were examined by PCR for presence of bla CTX-M genes. Primary phenptypic tests revealed that 56.69% [n=89] of E. coli isolates produced ESBLs. In confirmatory tests by use of clavulanic acid, ESBL production were confirmed [P+C+] in 96.7% [n=86] of isolates with primary positive test. The presence of an ESBL was not confirmed [P+C-] in 3.3% [n=3] of the screen positive. Of all screen positive isolates, 34 [35.78%] were positive for bla CTX-M genes from the CTX-M-I group, indicating CTX-M-1-like beta-lactamases and Two [2.1%] were positive for bla CTX-M genes from the CTX-M-III group, indicating CTX-M-3-like beta-lactamases. The remainder 59 [62.2%] were negative for bla CTX-M genes. The levels of resistance to ceftazidim were remarkably varible among CTX-M producers. This study provides futher evidence of the global dissemination of CTX-M type ESBLs and emphasize the need for their epidemiological monitoring

role of K-ATP channel in the preconditioning effect of magnesium in the rat isolated heart

There is growing interest for beneficial effect of Mg in the cardiovascular disorders. A number of cardiovascular disorders including myocardial infarction, arrhythmias and congestive heart failure have been associated with low extracellular or intracellular concentrations of Mg. The aim of present study was to investigate the preconditioning effects of magnesium [Mg] on cardiac function and infarct size in the globally ischemic-reperfusion in isolated rat heart. Rat hearts were Langendorff-perfused, subjected to 30 minutes of global ischemia and 90 minutes of reperfusion, and assigned to one of the following treatment groups with 7 hearts in each group: [1] control, [2] ischemic- reperfusion, [IR], [3] ischemic preconditioning, [IPC] of 5 minutes of global ischemia - reperfusion before lethal ischemia; or pretreatment with [4] 30 Mu mol/L of Diazoxide [Dia], [5] 8 mmol/L magnesium, [6] 10 Mu mol/L glibenclamid [Gli], [7] magnesium and Dia and [8] magnesium and Gli. Infarct size was measured by the triphenyltetrazolium chloride method. Left ventricular function was assessed by left ventricular developed pressure [LVDP], heart rate and coronary flow [CF]. Mg limited infarct size [9.76% vs 44.47% in IR, P< 0.001] as did Dia [10.2% vs 44.4% in IR P< 0.001] and IPC [8.69% vs 44.47% in IR, P< 0.001]. The protective effect of magnesium was abolished by Gli. Administration of Mg had an anti-infarct effect in ischemic-reperfusion isolated rat hearts and improved cardiac function. Blockade of K-ATP channel abolished the protective effects of magnesium and suggest that K-ATP channel has an important role in this effects

Determination of isosteviol by LC-MS/MS and its application forevaluation of pharmacokinetics of isosteviol in rat

Isosteviol has been found to have potential preventive or therapeutic effects against hypertension, ischemia reperfusion injury, diabetes and cancer, but little is known about the pharmacokinetics [PK] of the compound. The aim of this study was to develop a liquid chromatographic-tandem mass spectrometric [LC-MS/MS] method for determination of isosteviol in rat plasma and to assess in a preliminary manner the PK of isosteviol after intravenous bolus injection. Ions of analytes were generated using electro-spray ionization and detected in the positive-ion mode in LC-MS/MS. Multiple reaction monitoring was performed, using the precursor product ion combination for isosteviol m/z 319.4 - 273.4. Progesterone was used as an internal standard. Nitrogen was used as the nebulising gas and unit resolution was set for Q1 and Q3. Isosteviol solution was injected through the penile vein of rats at a dose of 8 mg/kg. Blood samples were collected from a jugular vein cannula. The PK parameters were calculated using a two - compartment PK model. The LC-MS/MS assay for isosteviol in rat plasma was linear over the range of 0.5-80 micro g/ml. The terminal half life of isosteviol [t [1/2]] was 406 +/- 31.7 min and clearance [CL] was 2.9 +/- 0.3 ml/min/kg. A sensitive LC-MS/MS assay for isosteviol in plasma has been successfully established and used in a preliminary PK evaluation of isosteviol in rats