Emerging pre-clinical safety assessments for potential probiotic strains: a review.

Probiotics are amply studied and applied dietary supplements of greater consumer acceptance. Nevertheless, the emerging evidence on probiotics-mediated potential risks, especially among immunocompromised individuals, necessitates careful and in-depth safety studies. The traditional probiotic safety evaluation methods investigate targeted phenotypic traits, such as virulence factors and antibiotic resistance. However, the rapid innovation in omics technologies has offered an impactful means to ultimately sequence and unknot safety-related genes or their gene products at preliminary levels. Further validating the genome features using an array of phenotypic tests would provide an absolute realization of gene expression dynamics. For safety studies in animal models, the in vivo toxicity evaluation guidelines of chemicals proposed by the Organization for Economic Co-operation and Development (OECD) have been meticulously adopted in probiotic research. Future research should also focus on coupling genome-scale safety analysis and establishing a link to its transcriptome, proteome, or metabolome for a fine selection of safe probiotic strains. Considering the studies published over the years, it can be inferred that the safety of probiotics is strain-host-dose-specific. Taken together, an amalgamation of in silico, in vitro, and in vivo approaches are necessary for a fine scale selection of risk-free probiotic strain for use in human applications.

Trend of Intravitreal Bevacizumab Dispensing Technique in Nepal.

INTRODUCTION: The main purpose of this survey was to find out what technique for bevacizumab injection is practiced by ophthalmologists in Nepal and to evaluate which is the best technique of drug dispensing and what possible hindrances are there in following it. MATERIALS AND METHODS: This was an online survey using google forms. RESULTS: There were a total of 34 participants in the survey. Most of the participants (58.8%) followed the same vial, multiple prick, multiple days method for giving intravitreal bevacizumab.. Majority of participants said they thought that aliquoting the drug and using it same day would be the best technique to prevent post injection endophthalmitis. Cost and unsuitability for small hospitals were the main factor preventing surgeons from practicing the best method. CONCLUSION: Risk of endophthalmitis can be reduced by following proper drug dispensing techniques. Aliquoting bevacizumab in smaller syringes under aseptic conditions can reduce the risk of endophthalmitis.

Probiotics for human health -new innovations and emerging trends.

The role of the gut microbiome in human health and disease with a particular emphasis on therapeutic use of probiotics under specific medical conditions was mainly highlighted in 1st Annual conference of Probiotic Association of India (PAi) and International Symposium on "Probiotics for Human Health - New Innovations and Emerging Trends" held on 27th-28th August, 2012 at New Delhi, India. There is increasing recognition of the fact that dysbiosis or alteration of this gut microbiome may be implicated in gastro-intestinal disorders including diarrheal diseases, ulcerative colitis, inflammatory bowel diseases, life style diseases viz. Diabetes Mellitus-2 and obesity etc. This report summarizes the proceedings of the conference and the symposium comprehensively. Although, research on probiotics has been continuing for the past few decades, the subject has been currently the major focus of attention across the world due to recent advances and new developments in genomics, transcriptomics, proteomics, metabolomics and emergence of new generation of high through put sequencing technologies that have immensely helped in understanding the probiotic functionality and mode of action from nutritional and health perspectives. There is now sufficient evidence backed up with good quality scientific clinical data to suggest that probiotic interventions could indeed be effective in various types of diarrheal diseases, other chronic gastrointestinal inflammatory disorders like pouchitis, necrotizing entero-colitis, allergic responses and lactose intolerance etc. This report makes a modest attempt to give all the stake holders involved in development of probiotic based functional/health foods an overview of the current status of probiotics research at the Global and National level. The most crucial issues that emerged from the lead talks delivered by the eminent speakers from India and abroad were the major focus of discussions in different plenary and technical sessions. By discussing some of these issues from scientific perspectives, the conference could achieve its prime objective of disseminating the current knowledge on the prospects of probiotics as potential biotherapeutics in the management of human health and diseases.

Haematological parameters as bioindicators of insecticide exposure in teleosts.

Haematological parameters, such as erythrocyte and leucocyte count, erythrocyte indices and thrombocyte number vis-a-vis coagulation of blood has been considered bioindicators of toxicosis in fish following exposure to organochlorine, organophosphate, carbamate and pyrethroid insecticides. This review deals with the effects of insecticides on the morphology of red blood cells, total erythrocyte count, haemoglobin content, haematocrit, mean corpuscular volume, mean corpuscular haemoglobin, mean corpuscular haemoglobin concentration, erythrocyte sedimentation rate, total and differential leucocyte counts, thrombocyte count and clotting time in the peripheral blood of a number of teleosts. The review also takes stock of knowledge of the subject and explores prospects of additional research in the related area.

In silico QSAR studies of anilinoquinolines as EGFR inhibitors.

Members of the epidermal growth factor receptor (EGFR) family of proteins are frequently overactive in solid tumors. A relatively new therapeutic approach to inhibit the kinase activity is the use of ATP-competitive small molecules. In silico techniques were employed to identify the key interactions between inhibitors and their protein receptors. A series of EGFR inhibitory anilinoquinolines was studied within the framework of hologram quantitative structure activity relationship (HQSAR), density functional theory (DFT)-based QSAR, and three-dimensional (3D) QSAR (CoMFA/CoMSIA). The HQSAR analysis implied that substitutions at certain sites on the inhibitors play an important role in EGFR inhibition. DFT-based QSAR results suggested that steric and electronic interactions contributed significantly to the activity. Ligand-based 3D-QSAR and receptor-guided 3D-QSAR analyses such as CoMFA and CoMSIA techniques were carried out, and the results corroborated the previous two approaches. The 3D QSAR models indicated that steric and hydrophobic interactions are dominant, and that substitution patterns are an important factor in determining activity. Molecular docking was helpful in identifying a bioactive conformer as well as a plausible binding mode. The docked geometry-based CoMFA model with steric and electrostatic fields effect gave q(2) = 0.66, r(2) = 0.94 with r(2) (predictive) = 0.72. Similarly, CoMSIA with hydrophobic field gave q(2) = 0.59, r(2) = 0.85 with r(2) (predictive) = 0.63. Bulky groups around site 3 of ring "C", and hydrophilic and bulky groups at position 6 of ring "A" are desirable, with a hydrophobic and electron-donating group at site 7 of ring "A" being helpful. Accordingly, potential EGFR inhibitors may be designed by modification of known inhibitors.

Alterations in electrocardiographic parameters after subacute exposure of fluoride and ameliorative action of aluminium sulphate in goats.

Fluorosis or crippling disease is one of the existing environmental challenges for animal and human beings in most parts of the globe. In the present study, sodium fluoride alone and with aluminium sulphate (ameliorative agent) was administered orally daily for 30 days in healthy goats of group 1 and 2, respectively, to access the effect on the electrocardiogram. All waves of Lead I, Lead II, Lead III, aVR, aVL and aVF in electrocardiographs were recorded before and after 30 days exposure of fluoride. A significant (P < 0.05) increase in P-R, Q-T and S-T intervals were observed in goats of group 1 as compared to their pre treatment values. The T wave duration was also significantly (P < 0.05) prolonged and as a result, bradycardia was observed after subacute exposure of fluoride for 30 days in group 1. But, in group 2, no such changes were observed. On the basis of results, it may be concluded that subacute toxicity of fluoride produces significant changes in different waves of electrocardiogram and aluminium sulphate has ameliorative efficacy.

Alterations in biochemical parameters during subacute toxicity of fluoride alone and in conjunction with aluminum sulfate in goats.

Fluoride toxicity is a serious health problem in many parts of the globe. In present study, sodium fluoride at 20 mg/kg alone and in conjunction with aluminum sulfate at 150 mg/kg was administered orally daily for 30 days in healthy goats of group 1 and 2, respectively, to access the alterations in the various biochemical parameters during subacute toxicity of fluoride alone and in conjunction with aluminum sulfate. In Group 1, significant alterations in plasma glucose, blood urea nitrogen (BUN), creatinine, total protein, albumin, globulin, albumin/globulin ratio, magnesium, and sodium were observed on different days of exposure from their pre-exposure values. However, no significant changes were observed in plasma calcium, phosphorus, and potassium on different days of exposure of sodium fluoride. Similar type of biochemical alterations were noticed in the goats of Group 2 except BUN, total protein magnesium, and sodium. On the basis of results, it could be concluded that sodium fluoride alone and in conjunction with aluminum sulfate produced significant alterations in the various biochemical parameters of the body.

Disposition kinetics and urinary excretion of levofloxacin on concomitant administration with meloxicam in cross-bred calves.

The disposition kinetics and urinary excretion study of levofloxacin was conducted in 5 male cross-bred calves following its single intravenous administration (4mgkg(-1)) concurrently with meloxicam (0.5mgkg(-1)). Levofloxacin was estimated by microbiological assay. The drug levels above MIC(90) in plasma, were detected up to 10h. Disposition kinetic parameters were calculated by two-compartment open model. Rapid distribution of levofloxacin was evidenced by a small distribution half-life (0.13±0.01h) and high K(12)/K(21) ratio (2.21±0.15). High ratio of AUC/MIC (90.2±3.41) indicated good antibacterial activity of levofloxacin. The AUC, Vd(area), elimination half-life, MRT and total body clearance were 9.02±0.34µgml(-1)h, 1.38±0.05lkg(-)1, 2.16±0.08h, 2.58±0.11h and 0.45±0.02lkg(-1)h(-1), respectively. About 38.4% of the administered dose of levofloxacin was excreted in urine within 24h. A suitable intravenous dosage regimen for levofloxacin would be 1.8mgkg(-1) repeated at 8h intervals when prescribed with meloxicam in calves.

Subcutaneous pharmacokinetics and dosage regimen of cefotaxime in buffalo calves (Bubalus bubalis).

The pharmacokinetics and dosage regimen of cefotaxime following its single subcutaneous administration (10 mg/kg) were investigated in buffalo calves. Plasma and urine samples were collected over 10 and 24 h post administration, respectively. Cefotaxime in plasma and urine was estimated by microbiological assay technique using E. coli as test organism. The pharmacokinetic profiles fitted one-compartment open model. The peak plasma levels of cefotaxime were 6.48 +/- 0.52 microgram/ml at 30 min and the drug was detected upto 10 h. The absorption half-life and elimination halflife were 0.173 +/- 0.033 h and 1.77 +/- 0.02 h, respectively. The apparent volume of distribution and total body clearance were 1.17 +/- 0.10 l/kg and 0.45 +/- 0.03 l/kg/h, respectively. The urinary excretion of cefotaxime in 24 h, was 5.36 +/- 1.19 percent of total administrated dose. A satisfactory subcutaneous dosage regimen for cefotaxime in buffalo calves would be 13 mg/kg repeated at 12 h intervals.

Effect of reduced glutathione treatment on selenosis, blood selenium concentration and glutathione peroxidase activity after repeated short-term selenium exposure in buffalo calves.

Effects of repeated feeding of selenium, when given alone or along with reduced glutathione, on whole blood selenium levels, selenosis and glutathione peroxidase activity, was studied in buffalo calves. After feeding 2.5 mg/kg of BW sodium selenite, good correlation was found between the onset of selenosis and whole blood selenium concentrations. Adverse effects appeared when the whole blood selenium concentrations increased above 2 microg/ml and mortality occurred when they exceeded 3.4 microg/ml. Reduced glutathione, given i.v. at 5 mg/kg of BW arrested the progress of selenosis and prevented mortality which was 100% in the sodium selenite supplemented group; also a reduced whole blood selenium concentration was noted. Whole blood selenium concentrations were a better and more sensitive indicator of selenium status than glutathione peroxidase activity alone.

Pharmacokinetics and dosage regimen of ceftriaxone in E. coli lipopolysaccharide induced fever in buffalo calves.

The present study was planned to investigate the pharmacokinetics of ceftriaxone in experimentally induced febrile buffalo calves (n=5). The fever was induced by intravenous injection of E.coli lipopolysaccaride (1 microgram/kg). To study the pharmacokinetics, ceftriaxone was administered at the dose rate of 10 mg/kg body wt. in all animals. At 1 min, the peak concentration of ceftriaxone was 79.4+/-2.37 microgram/ml and the drug was detected up to 6 h. The elimination rate constant was 0.35+/-0.02 /h and elimination half-life was 2.04+/-0.14 h. The apparent volume of distribution (Vd(area)) and total body clearance (Cl(B)) were 1.21+/-0.15 l/kg and 0.41+/-0.03 l/kg/h, respectively. To maintain a minimum therapeutic concentration of 1 microgram/kg, a satisfactory dosage regimen of cefriaxone in febrile buffalo calves is 19 mg/kg followed by 18 mg/kg at 8 h intervals.