Assessment of the stability of novel antibacterial triazolyl oxazolidinones using a stability-indicating high-performance liquid chromatography method

To evaluate the stability of 12 triazolyl oxazolidinone [TOZ] derivatives in simulated gastric and intestinal fluids as well as in human plasma at 37 +/- 1°C. A stability-indicating high-performance liquid chromatography [HPLC] procedure with a C8 column [250 +/- 40 mm, 5 micro m particle size] and a mobile phase of acetonitrile/H2O [50/50 v/v] at 1.0 ml/min was used. Accelerated stability studies were conducted at 37 +/- 1°C in 0.1 M HCl solution as simulated gastric fluid and in phosphate buffer solution [pH about 7.4] as simulated intestinal fluid. The stability of TOZs in human plasma at a simulated biological temperature of 37 +/- 1°C was evaluated as well. The stability studies indicated that the examined TOZs were stable in the above media, with the exception of compounds 1a [tert- butyl 4-[4-[[R]-5-[[1H-1,2,3-triazol-1-yl]methyl]-2-oxooxazolidin-3-yl]-2-fluorophenyl]piperazine-1-carboxylate] and 1b [tert-butyl 4-[2-fluoro-4-[[R]-5-[[4-methyl-1H-1,2,3-triazol- 1-yl]methyl]-2-oxooxazolidin-3-yl]phenyl] piperazine-1-carboxylate], which underwent degradation in simulated gastric fluid. The degradation kinetics revealed degradation parameters [kdeg, t1/2, t90] of 0.180 h-1, 3.85 h, and 0.58 h for 1a and of 0.184 h-1, 3.76 h and 0.57 h for 1b, respectively. Furthermore, the degradation products were identified by mass-spectrometric analysis at mass-to-charge ratios 347.5 and 361.5, respectively, and proton nuclear magnetic resonance analysis. With the exception of compounds 1a and 1b, the TOZs are stable in simulated gastric and intestinal fluids as well as in human plasma. Being carbamate derivatives, compounds 1a and 1b underwent fast and complete degradation in simulated gastric fluid. The obtained results should be considered for future studies of formulation of structurally related TOZs in oral dosage forms

Antimicrobial resistant bacteria among health care workers in intensive care units at Ain Shams university hospitals

Fifty HCWs in ICUs of Internal medicine, Chest, Neonatology and Burn were included in prospective cohort study. Collection of nasal, hand and rectal swabs, proper biochemical identification, culture media and antibiotic sensitivity tests were used to detect Methicillin-resistant Staphylococcus aureus [MRSA]; vancomycin-resistant Enterococci [VRE] and extended spectrum beta-lactamase producing gram -ve bacilli [ESBLs]. S. aureus was isolated from 34% of HCWs; 28% were nasal carriers, 4% were hand carriers and 2% had S. aureus at both sites. Nasal and hand carriage rates of MRSA were 20% and 4% respectively, with an overall rate of 22%. Gram -ve bacilli were isolated from 8% of HCWs hand swabs and showed Citrobacter koseri, Escherichia coli, Kiebsiella pneumoniae and Pseudomonas aeruginosa. Hand carriage rate of ESBLs was 2%. Hand contamination with gram -ve bacilli and S. aureus was in 14% of HCWs. VRE carriage rate was 9.5%. ESBLs carriage rate in rectal swabs was 21.43%. K. pneumoniae was the most common ESBLs producing isolate [33.3%], followed by E. coli [18.75%]. In combined disc method, aztreonam was the most sensitive [90%] in detecting ESBLs. Burn ICU had highest% of MRSA and ESBLs carriage. Neonatal ICU showed highest% of VRE carriage. An insignificant association was between infection control training or antimicrobial intake and carriage of antimicrobial resistant bacteria

Corrosion inhibition of Cu in nitrate solution

The effect of ethylenediamine [ED] and acetic acid on the corrosion inhibition of copper in 0.1 M NaNO] was studied. The study involved electrochemical polarization methods, gravimetric measurements and scanning electron microscopy investigations [SEM]. Both of ED and concentrated solutions of acetic acid >/= 10[-3] M act as a promoter while diluted concentrations of acetic acid

Some toxic effects of molybdenum in adult male albino rats

Ammonium molybdate is an essential trace element in plants, animals and humans, as it is present as a cofactor for some enzymes; also, it is an environmental pollutant. Thirty adult male albino rats were used to investigate the adverse effects of ammonium molybdate on the liver, kidneys, spleen and lungs of adult male albino rats. Therty adult male rats were equally divided into 3 groups. The rats of the 1[st] group were left without treatment and used as a negative control group for measuring the basic parameters. The rats of the 2[nd] group were daily intragastrically administered 2 ml normal saline [vehicle of molybdenum] for each rat for 30 days and were used as a positive control group. The rats of the 3rd group were daily intragastrically administered ammonium molybdate in a dose of 136 mg /kg body weight in 2 ml of normal saline [1/5 of the LD50] for each rat for 30 days. At the end of the study, blood samples were collected from the retro-orbital plexus of each anethetized rat in all groups for measuring levels of liver enzymes [ALT, AST, Aikaline phosphatase], total bilirubin, urea and createnine; then the rats were sacrificed, and specimens from the livers kidneys, spleens and lungs of all rats were collected for histopathological examination. The levels of liver enzymes, bilirubin, urea and createnine of the rats of the 3[rd] group [ammonium molybdate group] were statistically significantly elevated compared to those of the negative control group [P <0.001]. Histopathological examination of the rats of the 3rd group showed, moderate liver damage consisting of scattered necrotic areas, inflammatory infiltrates and congested central vein, In the Kidneys, there were degeneration of the epithelium of the convoluted tubules appeared as cloudy swelling and congestion. There were also cellular infiltrates. Histopathological examination of the spleen showed reactive follicular hyperplasia with areas of necrosis and congestion reflecting congested splenomegally. The lungs revealed diffuse haemorrhage and mononuclear inflammatory cellular infiltration in the interstitial tissue with congested dilated vessels. It can be concluded that ammonium molybdate could produce toxic effects on the liver, kidneys, spleen and lungs of adult male albino rats

Nephrotoxic effects of celecoxib on adult male albino rats

Nonsteroidal anti-inflammatory drugs are widely used for a variety of indications, including acute pain, arthritic pain, and headache. The long-term use of these agents is often limited by unwanted adverse effects, such as gastritis and renal dysfunction. In an effort to decrease the adverse effects while retaining pain-relieving properties, the selective cyclo-oxygenase [COX]-2 inhibitors were developed. The aim of the present study was to evaluate the nephrotoxic hazards of celecoxib and also to evaluate the extent of recovery that occur after discontinuation of this drug during a follow up period .The study was conducted on 50 adult male albino rats weighing approximately [150-200 gm] and divided into 3 groups; group I [negative control group]: consisted of 15 rats, each rat was given no medications to evaluate the basic parameters; group II [positive control group [Gum acacia group]]: consisted of 15 rats, each rat was gavaged with 2 mL of Gum acacia suspension once daily for 6 weeks and group III [celecoxib group]: consisted of 20 rats, each rat was gavaged with 14,4 mg celecoxib/rat once daily for 6 weeks. Twenty four hours after the last dose of celecoxib, 15 rats from each control group and 10 rats from the celecoxib group were used. The kidneys of the rats of these groups were investigated histopathologically by light microscope and biochemically by measuring blood urea nitrogen and serum creatinine, sodium and potassium levels. The remaining rats of celecoxib group were left for another 6 weeks without drug, administration for follow up. At the end of this period the. rats were examined as mentioned above. The main findings of the present study were as follow: group 1 [negative control group], and group II [positive control group], showed no abnormal findings without a statistically significant difference between them so we used the results of the negative control group to compare it with those of celecoxib group. As regard biochemical changes, there was an increase in blood urea nitrogen and serum creatinine, sodium and potassium levels in the rats of celecoxib group with a statistically significant difference when compared with the negative control group [P<0.001]. Six weeks after discontinuation of celecoxib administration, the above mentioned biochemical changes improved and showed a statistically significant difference when compared with the results obtained 24 hours after the last dose of celecoxib, but the level of improvement didn't reach to the control level and gave a significant difference when compared with the negative control group. This means that, these parameters improved but didn't return to the level' of the control, which was supported by the histopathological results. As regard histopathological study of celecoxib group, microscopical examination of the kidneys showed severe affection of the kidneys in the form of renal papillary necrosis and acute and chronic tubulo-interstitial nephritis with interstitial oedema and inflammatory cell infiltrate. After 6 weeks of follow-up, histopathological examination of the kidney in the celecoxib group showed incomplete recovery. It could, be concluded that celecoxib is nephrotoxic and its toxic effects were partially reversible after its discontinuation

Plasma levels of soluble CD14 and endothelin-1 in infants with respiratory syncytial virus-induced bronchiolitis as predictors of subsequent recurrent wheezing in a two years follow-up study

Respiratory syncytial virus [RSV] infections have been demonstrated to be associated with subsequent recurrent wheezing episodes and the development of childhood asthma. The CD14 receptor responds to the microbial burden in the environment and modulates the development of the allergic phenotype. Endothelin-1 is a potent bronchoconstrictor involved in many diseases including respiratory tract infections. Plasma levels of soluble CD14 [SCD14] and endothelin-1 [ET-1] were measured by a commercially available enzyme-linked immunosorbent assay [ELISA] in 32 infants who were hospitalized with RSV bronchiolitis to investigate their relation to the subsequent development of recurrent wheezing during a two years follow-up period. Thirty healthy infants were served as a control group. The results proved that the mean level of plasma sCD14 was significantly lower in infants with acute RSV bronchiolitis compared to control group [22.01 +/- 6.27 vs 817.50 +/- 247.52 ng/ml, p<0.001]. The mean sCD14 plasma level of 18.52 +/- 5.24 ng/ml in the group of 19 children who exhibited recurrent wheezing was significantly lower than the level of 27.11 +/- 3.57ng/ml in the group of 13 children who did not exhibit recurrent wheezing [P<0.001]. the mean plasma level of ET-1 was significantly increased in infants with RSV bronchiolitis compared to the controls [3.86 +/- 1.44 vs 0.71 +/- 0.18 pg/ml, p<0.001] and the mean plasma ET-1 level of 4.60 +/- 1.17 pg/ml in the group of children who exhibited recurrent wheezing was significantly higher than level of 2.78 +/- 1.11 pg/ml in the group of children who did not exhibit recurrent wheezing [P<0.001]. the risk for subsequent development of recurrent wheezing was not influenced by age at hospitalization, sex, breast-feeding, positive family history of atopy, or passive smoking. The results of this study showed that plasma level of sCD14 was decreased and plasma endothelin-1 was increased in infants during acute RSV bronchiolitis and their levels were significantly different in infants who had experienced subsequent wheezing than in infants who not and that reduced plasma sCD14 and increased ET-1 levels in infants with RSV bronchiolitis are useful in predicting the risk to develop subsequent recurrent wheezing. From the results of this study, it can be recommended that CD14 may be a potential target for preventive measures against atopic diseases. This study also encourage further studies on the value of ET-1 antagonism among alternative therapeutic modalities of childhood asthma

Serum protein S-100 and serum ionized calcium as early prognostic markers for the severity of hypoxic - ischemic encephalopathy after birth asphyxia

This study was performed at Al Ansar Hospital in Jeddah during the period from September 2004 to September 2005. Our objective was to identify whether moderate or severe hypoxic-ischemic encephalopathy [HIE] after birth asphyxia can be predicted by measuring serum protein S-100 or serum ionized calcium concentrations soon after birth. The study included two groups, asphyxia group and control group. The asphyxiated group included 21 full term asphyxiated newborn infants, who were subdivided clinically into: 10 asphyxiated newborns with no HIE, 5 asphyxiated newborns with mild HIE, 3 asphyxiated newborns with moderate HIE, and 3 newborns with severe HIE. The control group included 10 full term healthy normal newborn infants. Neurological examinations were performed during the first 3 days after birth, and Apgar score was estimated at 1 and 5 min after birth. Blood samples were collected from cord blood and 4 h after birth to estimate serum protein S-100, serum ionized calcium, pH, and base deficit. At 4 h after birth, there was a significant increase in serum protein S-100 and a significant decrease in serum ionized calcium in asphyxiated newborns compared with controls, and also a significant difference between asphyxiated newborns with moderate or severe HIE and asphyxiated newborns with no or mild HIE. Both markers had a high positive predictive value and a high specificity, which in case of serum protein S-100 became more higher when combined with serum ionized calcium, cord blood pH, cord blood base deficit, and Apgar score at 1 min. We concluded that serum protein S-100 and serum ionized calcium are early markers for moderate or severe HIE after asphyxia, which help us to initiate and continue or stop the neuroprotective therapy. We concluded also that these markers are of high positive predictive value and of high specificity

Differential effects of vitamin E supplementation on cardiovascular risk factors and on cardiac vulnerability to ischemia and reperfusion in rats

The present study was performed to examine the effects of vitamin E on hemodynamics, electrocardiogram [ECG] pattern, plasma levels of lipid profile, enzymes reflecting myocardial cell integrity creatine kinase [CK] and lactate dehydrogenase [LDH] and rate of lipid peroxidation as well as on myocardial performance after ischemia-reperfusion injury in isolated rat hearts. Vitamin E-treated rats were injected with vitamin E in a dose of 4 mg/100g body weight [b.w.] daily, for 6 consecutive days. Control rats were treated with vitamin E-solvent, daily, for the same duration. Then, rats were sacrificed, and the isolated heart were subjected to 30 min. ischemia followed by 30 min period of reperfusion. The present study demonstrated that administration of vitamin E in normal rats did not produce any appreciable hemodynamic effects as regards heart rate [HR], mean arterial pressure [MAP,], and pressure rate product[PRP]. The ECG pattern showed no arrhythmias or ischemic changes compared to control group. Concerning changes in plasma lipid profile, vitamin E-treated rats showed significant reduction in both total cholesterol [TC], and low density lipoprotein-cholesterol [LDL-C] Moreover, high density lipoprotein-cholesterol / total cholesterol [HDL-C/TC] was significantly elevated, in contrast to a non significant decrease in both low density lipoprotein-cholesterol/ total cholesterol [LDL-C /TC] and LDL-C /HDL-C ratios, when compared with controls. Myocardial cellular integrity, estimated by the plasma level of CK and LDH, was preserved by the administration of vitamin E, revealed evidently by the significant decrease in CK and LDH release in plasma of rats treated with vitamin E as compared to control rats. Moreover, the plasma level of malondialdehyde, as an index for the degree of lipid peroxidation, was significantly reduced. The preischemic, baseline activity of the isolated hearts obtained from rats treated with vitamin E, revealed non significant changes in myocardial inotropy except for prolongation of half relaxation time. Also there was a significant reduction in both heart rate and LDH release in the coronary effluent, while there was a non significant change in tile coronary flow rate. The results of the isolated hearts subjected to reperfusion following 30 minutes ischemic period, showed that vitamin E decreased the detrimental effect of reperfusion on the inotropic activity observed in the control group, evident by superior recovery of postischemic reperfusion myocardial functions. Manifested by elevated peak developed tension, and tension generation per unit time, concomitant with shortening of time to peak tension, and half relaxation time, along the reperfusion period. In addition, the percentage recovery of the heart rate was better during the whole reperfusion period but the difference was statistically significant only at 15-minute of reperfusion, and as well myocardial flow rate percentage .showed significant superior recovery in vitamin E-treated rat hearts. Moreover, there was a significant reduction in both CK and LDH release in the coronary effluent of vitamin E treated rat hearts, compared to control hearts. It could be concluded that vitamin E administration has a favorable potential against the risk of atherosclerosis and lipid peroxidation and as well it may attenuate the detrimental effects of postischemic reperfusion on the myocardial contractility

Spiral CT detection of coronary artery calcification and increased carotid intimal-medial thickness by carotid ultrasonography: valuable non invasive methods for detecting early coronary artery diseases and atherosclerosis

Currently available non invasive techniques can identify only patients with advanced coronary artery disease [CAD] who manifest myocardial ischemia. Also, the gold standard invasive coronary angiography provides no information on plaque burden other than the extent of luminal obstruction and vascular remodeling phenomenon results in disparity between plaque burden and angiographic stenosis. To evaluate detection of coronary artery calcification [CAC] by spiral CT and increased carotid intimal-medial thickness [IMT] by B-mode ultrasound as non-invasive tools for detection of early atherosclerotic process, so that preventive measures may be instituted before occlusive vascular diseases occurs. 70 subjects with their age 51.68 +/- 10.1 years, divided into: group A include 31 patients with CAD 12 patients have already done coronary angiography, and group B include 39 subjects without evidence of CAD, were subjected to clinical evaluation, some laboratory investigations. E.C.G., X-ray chest, echocardiography, carotid ultrasonography for measurement of carotid IMT and spiral CT scan of heart for coronary calcium scorings [CCS]. Both increased carotid IMT and CAC were detected in 55.7% of total 70 individuals, 83.9% of group A and 33.3% of group B. Significant increase of Carotid IMT and high CCS was detected in patients with angiographyically documented CAD than those with normal coronary angiography. There was a significant positive association between both increased carotid IMT and CAC and some risk factors for CAD e.g. age, male sex, smoking, diabetes mellitus, hypertension, serum cholesterol level and also with ECG evidence of CAD. Detection of coronary artery calcification by spiral CT and increased carotid intima media thickness by ultrasound may represent a valuable non invasive methods for identification of early atherosclerotic process. Spiral CT scan has on advantage over invasive coronary angiography via giving information about plaque burden and vascular remodeling phenomen that does not affect its specificity

Plasma Endothelin 1 [ET-1] in Type 2 [non-insulin-dependent] Diabetes Mellitus

To evaluate the level of plasma endothelin-1 in NIDDM with and without hypertension. Plasma ET-1 levels were evaluated [by enzyme immunoassay] in 50 subjects. Thirty patients with NIDDM [15 nor-motensive and 15 hypertensive] and twenty subjects serving as controls [10 hypertensive and 10 healthy normotensive]. Circulating ET-1 levels are significantly higher in normotensive NIDDM [2.41 +/- 0.36 ng/mL] and hypertensive NIDDM [2.63 +/- 0.44 ng/ml] when compared with healthy controls [0.73 +/- 0.14 ng/ml] and hypertensive controls [0.84 +/- 0.13 ng/ml] [P<0.001]. Also there are no significant correlations between plasma ET-1 levels and fasting blood glucose [r = 0.188. P>0.05], mean blood pressure [r = 0.129, P>0.05], duration of diabetes [r = 0.137, P>0.05] and age of subjects [r = 0.099. P>0.05] Significant plasma endothelin-1 elevation in diabetic subjects may relate to diabetic endothelial cell damage and in turn be an important background factor in diabetic vascular complications and endothelin-1 receptor antagonists may have a role in ameliorating this dysfunction

Determination of cephalexin and cepheadine mixture using full spectrum Quantitation [FSQ] method for multicomponent analysis

A rapid and highly precise spectrophotometric full spectrum quantitation [FSQ] was described for multicomponent analysis of cephalexin and cephradine in mixture. The proposed method avoids the spectral overlap between individual antibiotic concentrations. Analysis of mixtures containing variable concentrations of the examined compounds using FSQ showed a st and ard error of estimate [SEE] of 0.097 for cephalexin and 0.101 for cephradine. The validity of FSQ technique was evaluated and the assay results showed insignificant difference with those of HPLC procedure. The utility of the proposed FSQ in stability studies of cephradine in 0.01 M arginine solution indicated that hydrolysis of the drug followed first order kinetics with a degradation rate constant of 0.104 hr-1 and degradation half- life of 6.7 hours

Comparison of the efficacy and safety of intranasal midazolam [Dormicum] and sufentanil for pre induction of anaethesia in pediatric patients

Behavioral and physiologic responses to sedation with either sufentanil or midazolam administered nasally for preinduction of anesthesia were evaluated in eighty pediatric patients aged 0.5-10 years, ASA I or II. Patients were randomly assigned into 4 groups: midazolam with inhalation induction [n= 19], midazolam with I.V. induction [n= 20], sufentanil with inhalation induction [n= 21] and sufentanil with I.V. induction [n= 20]. Patients given sufentanil were more likely to separate willingly from their parents compared with patients given midazolam. Patients given sufentanil and midazolam respond similarly to the anesthesia face mask. Sufentanil was associated with mild decrease ventilatory responses. Time from end of surgery to tracheal extubation and time in the recovery room were similar sufentanil was more effective than midazolam in facilitation of intravenous catheter and separation of preschool children from parents and result in a pleasant postoperative course