Enhanced spectrofluorimetric determination of esomeprazole and pantoprazole in dosage forms and spiked human plasma using organized media

A simple, sensitive and rapid spectrofluorimetric method was developed for the determination of esomeprazole (EMZ) and pantoprazole (PRZ) in their pharmaceutical formulations and human plasma. The proposed method is based on the fluorescence spectral behavior of EMZ in methanol in the presence of 0.1 m NaOH containing 0.5% methyl cellulose (MC) at 306/345 nm. The fluorescence intensity of EMZ was enhanced about 1.3‐fold and good linearity in the range 0.4–4.0 µg/mL with a lower detection limit of 0.04 µg/mL and lower quantification limit of 0.14 µg/mL. For PRZ, its methanolic solution exhibited marked native fluorescence at 290/325 nm after enhancement (about 2.1‐ or 1.4‐fold) using either 0.025% sodium dodecyl sulfate (SDS) or 0.05% MC in the presence of 0.2 m borate buffer of pH 9.5. The fluorescence–concentration plots of PRZ were rectilinear over the ranges 0.2–2.0 and 0.3–3.0 µg/mL with lower detection limits of 0.02 and 0.03 µg/mL and lower quantification limits of 0.07 and 0.09 µg/mL using sodium dodecyl sulfate and MC, respectively. The method was successfully applied to the analysis of EMZ and PRZ in their commercial dosage forms and the results were in good agreement with those obtained with the comparison method. Furthermore, in a preliminary investigation, the proposed method was extended to the in vitro determination of the two drugs in spiked human plasma and the results were satisfactory. Copyright © 2014 John Wiley & Sons, Ltd.     

Fast concurrent determination of guaifenesin and pholcodine in formulations and spiked plasma using first derivative synchronous spectrofluorimetric approach

Guaifenesin and pholcodine are frequently co-formulated in certain dosage forms. A new fast first derivative synchronous spectrofluorometric method has been used for their simultaneous analysis in mixtures. Here, first derivative synchronous spectrofluorometry enabled the successful simultaneous estimation of guaifenesin at 283 nm and pholcodine at 275 nm using a wavelength difference (Δλ) of 40 nm. The method was fully validated following International Council of Harmonization guidelines. For guaifenesin and pholcodine, linearity was determined within the corresponding ranges of 0.05–0.30 and 0.10–6.0 μg/ml. The two drugs were effectively analyzed using the developed approach in their respective formulations, and the results showed good agreement with those attained using reference methods. The method demonstrated excellent sensitivity, with detection limits down to 0.007 and 0.030 μg/ml and quantitation limits of 0.020 and 0.010 μg/ml for guaifenesin and pholcodine, respectively. Therefore, the procedure was successful in determining these drugs simultaneously in vitro in spiked plasma samples and syrup dosage form. The developed methodology also offered an environmentally friendly advantage by utilizing water as the optimal diluting solvent throughout the whole work. Different greenness approaches were investigated to ensure the method’s ecofriendly properties.     

Cardiac stem cells: Current knowledge and future prospects

Regenerative medicine is the field concerned with the repair and restoration of the integrity of damaged human tissues as well as whole organs.Since the inception of the field several decades ago,regenerative medicine therapies,namely stem cells,have received significant attention in preclinical studies and clinical trials.Apart from their known potential for differentiation into the various body cells,stem cells enhance the organ's intrinsic regenerative capacity by altering its environment,whether by exogenous injection or introducing their products that modulate endogenous stem cell function and fate for the sake of regeneration.Recently,research in cardiology has highlighted the evidence for the existence of cardiac stem and progenitor cells(CSCs/CPCs).The global burden of cardiovascular diseases’morbidity and mortality has demanded an in-depth understanding of the biology of CSCs/CPCs aiming at improving the outcome for an innovative therapeutic strategy.This review will discuss the nature of each of the CSCs/CPCs,their environment,their interplay with other cells,and their metabolism.In addition,important issues are tackled concerning the potency of CSCs/CPCs in relation to their secretome for mediating the ability to influence other cells.Moreover,the review will throw the light on the clinical trials and the preclinical studies using CSCs/CPCs and combined therapy for cardiac regeneration.Finally,the novel role of nanotechnology in cardiac regeneration will be explored.     

Investigation of many bacterial and viral infections circulating in pigeons showing nervous symptoms

Pigeon’s flocks have shown several neurological symptoms including circling, torticollis, tremors, paralysis, which caused suspicion for viral or bacterial natural infections. Pigeon paramyxovirus type-1 (PPMV-1) is a notifiable disease-causing high morbidity and mortality with severe nervous symptoms. Clinical represented tissue specimens were collected from 50 infected pigeon flocks in eight governorates. All samples were examined bacteriologically (isolation, identification and serotyping) for E. coli, Salmonella spp., S. aureus and pseudomonas aeruginosa. Antimicrobial susceptibility test (AST) was accomplished for all isolates using a disk-diffusion test. For viral identification, RT-PCR specific oligonucleotide primers were used for distinguishing of Avian influenza virus, PPMV-1 and PPMV-3. Neurological manifestations were observed in pigeon’s flocks mainly in winter and autumn. The mortality rate in eight governorates was about 50% in 10 flocks and other houses mortality rate was ranged from 10 to 20%. Post mortem examination have shown hemorrhagic enteritis, soft and friable brain tissues and/or hemorrhages. The percentage of isolated bacteria E. coli, Salmonella spp., S. aureus and Pseudomonas aeruginosa were 75%, 75%, 50% and 18.75%; respectively. The antibiotic resistance pattern for bacterial isolates showed resist to ampicillin, amoxicillin- clavulinic acid, teteracyclin, ceftriaxone, doxycycline, sulfamethoxazole-trimethoprim and ceftazidine with different result for each type of bacteria, while Salmonella spp., isolates showed only a highly intermediate result for ciprofloxacin. Eight samples are positive with 16% to PPMV-1. Also, sample No.5,6,9 was co-infected with different types of bacterial isolates in addition to NDV. In conclusion, we reported several neurological symptoms in pigeon’s flocks mainly of bacterial infections (E. coli, Salmonella spp., S. aureus and Pseudomonas aeruginosa).     

Efficient Bayesian inference for mechanistic modelling with high-throughput data

Bayesian methods are routinely used to combine experimental data with detailed mathematical models to obtain insights into physical phenomena. However, the computational cost of Bayesian computation with detailed models has been a notorious problem. Moreover, while high-throughput data presents opportunities to calibrate sophisticated models, comparing large amounts of data with model simulations quickly becomes computationally prohibitive. Inspired by the method of Stochastic Gradient Descent, we propose a minibatch approach to approximate Bayesian computation. Through a case study of a high-throughput imaging scratch assay experiment, we show that reliable inference can be performed at a fraction of the computational cost of a traditional Bayesian inference scheme. By applying a detailed mathematical model of single cell motility, proliferation and death to a data set of 118 gene knockdowns, we characterise functional subgroups of gene knockdowns, each displaying its own typical combination of local cell density-dependent and -independent motility and proliferation patterns. By comparing these patterns to experimental measurements of cell counts and wound closure, we find that density-dependent interactions play a crucial role in the process of wound healing.     

Evaluation of cefquinome's efficacy in controlling avian colibacillosis and detection of its residues using high performance liquid chromatography (HPLC)

This study aimed to evaluate the efficacy of cefquinome in treatment and controlling of Escherichia coli experimentally infected broiler chickens, in addition of detection of its residues using High performance liquid chromatography (HPLC). In this study, 150 one-day old Cobb broiler chicks were used. On the 14^th day chicks experimentally infected and divided into 3 equal groups (50 each); control group (G1) non-infected, non-treated, (G2) infected with E. coli O₇₈ non treated, (G3) infected with E. coli O₇₈, cefquinome treated. Cefquinome was administrated 5^th day post infection, intramuscularly by a dose of (2 mg/ kg b w.t) for 3 consecutive days. Experimental E. coli infection in broilers induced weakness, loss of appetite, depression, cough and watery diarrhea in addition to a recorded mortality (30%) with reduction in growth performance, erythrogram, total proteins, albumin, antioxidants and haemagglutination inhibition (HI) titers. In addition, a significant increase in feed conversion rate (FCR), leukocytic count, liver enzymes, kidney functions, total globulins, malondialdehyde, nitric oxide and lysozyme activity. Treatment with cefquinome led to decreased mortality rate, improvement in clinical signs, growth performance and modulated most of these altered parameters. Cefquinome's residues was not detected in breast muscles 3^rd day and liver and kidneys 7^th days post treatment. Therefore, it's recommended that cefquinome is a good choice for controlling of colibacillosis in broilers and its withdrawal time 3 days in breast muscles and 7 days in liver and kidney post treatment.     

Herpes Simplex Virus 1 Upregulates p35, Alters CDK-5 Localization,and Stimulates CDK-5 Kinase Activity during Acute Infection in Neurons

The cyclin-dependent kinase 5 (CDK-5) activating protein, p35, is important for acute herpes simplex virus 1 (HSV-1) replication in mice. This report shows that HSV-1 increases p35 levels, changes the primary localization of CDK-5 from the nucleus to the cytoplasm, and enhances CDK-5 activity during lytic or acute infection. Infected neurons also stained positive for the DNA damage response (DDR) marker γH2AX. We propose that CDK-5 is activated by the DDR to protect infected neurons from apoptosis.     

Fluvastatin Interferes with Hepatitis C Virus Replication via Microtubule Bundling and a Doublecortin-like Kinase-Mediated Mechanism

Hepatitis C virus (HCV)-induced alterations in lipid metabolism and cellular protein expression contribute to viral pathogenesis. The mechanism of pleiotropic actions of cholesterol-lowering drugs, statins, against HCV and multiple cancers are not well understood. We investigated effects of fluvastatin (FLV) on microtubule-associated and cancer stem cell marker (CSC), doublecortin-like kinase 1 (DCLK1) during HCV-induced hepatocarcinogenesis. HCV replication models, cancer cell lines and normal human hepatocytes were used to investigate the antiviral and antitumor effects of statins. FLV treatment resulted in induction of microtubule bundling, cell-cycle arrest and alterations in cellular DCLK1 distribution in HCV-expressing hepatoma cells. These events adversely affected the survival of liver-derived tumor cells without affecting normal human hepatocytes. FLV downregulated HCV replication in cell culture where the ATP pool and cell viability were not compromised. Pravastatin did not exhibit these effects on HCV replication, microtubules and cancer cells. The levels of miR-122 that regulates liver homeostasis and provides HCV genomic stability remained at steady state whereas DCLK1 mRNA levels were considerably reduced during FLV treatment. We further demonstrated that HCV replication was increased with DCLK1 overexpression. In conclusion, unique effects of FLV on microtubules and their binding partner DCLK1 are likely to contribute to its anti-HCV and antitumor activities in addition to its known inhibitory effects on 3-hydroxy-3-methylglutary-CoA reductase (HMGCR).     

Conversion of oil waste to valuable fatty acids using Oleaginous yeast

Oil waste poses a highly dangerous threat to the environment, mainly because it is considered a high energy demanding degradation process. Oleaginous yeast utilizing oil waste to produce microbial fatty acids is considered an innovative method for oil waste elimination. In the present study, fifteen yeast isolates were screened for their lipid content, three of which were chosen for their high lipid content as compared to the standard strain Phaffia rhodozyma NRRL-Y-10921. The three selected isolates were further screened for their fatty acid profile. Yeast isolate (NC-I), identified as Yarrowia lipolytica, was chosen because it exceeded the lipid production of the standard strain by 21%, it also produced the highest C 14:0 (myristic acid), C 18:1 (oleic acid) and C18:2 (linoleic acid), compared to the other two isolates. Growth on different oil wastes resulted in an increase in total lipid content which reached its maximum when oil waste of frying vegetables was added to the media (57.89%). A variation in the fatty acid profile was detected when different types of oil waste were used before and after fermentation. The addition of different glucose concentrations to the vegetable oil waste media resulted in the appearance of C 22:0 (behenic acid) which was not present when the basal medium was used. Scanning Electron Microscopy indicated morphologic changes when the yeast was grown in high glucose concentration as compared to those grown in oil waste media. The activity of malate dehydrogenase (MDH) enzyme exhibited a correlative relationship with the lipid content under various glucose concentrations. The obtained results indicate that vegetable oil waste is suitable for microbial fatty acid production and that the fatty acid profile could be maneuvered through the manipulation of the fermentation media.