Immunomodulatory effects of Bifidobacterium bifidum 231 on trinitrobenzenesulfonic acid-induced ulcerative colitis in rats.

AIM: Ulcerative colitis and Crohn's disease are two important chronic Inflammatory bowel diseases (IBD) characterized by prominent intestinal inflammation. Probiotics are the bacteria that promote the host health by its immunomodulatory activity. The present study investigated the correlation between in vitro adhesion and immunomodulatory properties, and to assess the therapeutic potential of Bifidobacterium bifidum 231 (BIF 231), a new strain of probiotic in ulcerative colitis in rats. METHODS: In vitro adhesion assays and immunomodulatory effect of BIF 231 on interleukins (IL-1ß and IL-10) in IEC-6 cell lines were quantified by gram staining, scanning electron microscopy and q-PCR respectively. Colitis was induced by intra-rectal instillation of trinitrobenzenesulfonic acid. Colitis was evaluated by alterations in colon gross morphology, histologically and biochemically. Colonic interleukin-1ß (IL-1ß) and interleukin-10 (IL-10) mRNA and protein expression were assessed by q-PCR, ELISA and western blot. RESULTS: BIF 231 showed better adhesion and immunomodulation by up-regulating IL-10 levels in IEC-6 cell lines. In vivo studies with treatment of BIF 231 (1.4×1011 CFU/rat/day) revealed anti-inflammatory effects both macroscopically and histologically. BIF 231 lowered TBARS, nitric oxide and augmented GSH levels. BIF 231 treatment to colitic rats down regulated IL-1ß levels with concurrent increase in IL-10 levels. CONCLUSIONS: BIF 231 exerted beneficial in vitro adhesion and immunomodulatory properties which facilitated the recovery of the damaged tissue in TNBS-induced colitis.

Impact of aflatoxin B1 on the pharmacokinetic disposition of enrofloxacin in broiler chickens.

The potential impact of subchronic exposure of aflatoxin B1 was investigated on the pharmacokinetic disposition of enrofloxacin in broiler chickens. Broiler chickens given either normal or aflatoxin B1 (750µg/kg diet) supplemented diet for 6 weeks received a single oral dose of enrofloxacin (10mg/kg body wt). Blood samples were drawn from the brachial vein at predetermined time intervals after drug administration. Enrofloxacin plasma concentrations analyzed by RP-HPLC were significantly lower in aflatoxin B1-exposed broiler chickens at 0.167, 0.5 and 1.0h after drug administration. In aflatoxin B1-exposed broiler chickens, the absorption rate constant (ka) of enrofloxacin (0.20±0.05h(-1)) was significantly decreased as compared to the unexposed birds (0.98±0.31h(-1)). The values of [Formula: see text] , tmax and AUC0-∞ of enrofloxacin were nonsignificantly increased by 17%, 26% and 17% in aflatoxin-exposed broiler chickens, respectively. Subchronic aflatoxin B1 exposure markedly decreased the initial absorption of enrofloxacin without significantly influencing other pharmacokinetic parameters in broiler chickens.

Effects of aflatoxin B1 on tissue residues of enrofloxacin and its metabolite ciprofloxacin in broiler chickens.

The impact of subchronic exposure of aflatoxin B1 on the tissue residues of enrofloxacin and its metabolite ciprofloxacin was examined in broiler chickens. Broiler chickens given either normal or aflatoxin B1 (750 µg/kg diet) supplemented diets for 6 weeks received enrofloxacin (10 mg/kg/day, p.o.) for 4 days and thereafter, residue levels were determined. Aflatoxin B1 induced alterations in serum marker enzymes. As compared to unexposed broiler chickens, enrofloxacin concentrations in aflatoxin B1-exposed broiler chickens were significantly higher in all tissues (0.62-4.53 µg/g) analyzed except muscle 24h after termination of enrofloxacin administration. Ciprofloxacin was detectable in tissues of only mycotoxin-exposed broiler chickens. Enrofloxacin residues in liver, kidney and skin plus fat persisted for 10 days in mycotoxin-exposed broiler chickens whereas it was detectable only in liver of unexposed broiler chickens. Our results indicate that subchronic aflatoxin B1 exposure markedly influences the residue levels of enrofloxacin and ciprofloxacin in tissues of broiler chickens.

Biopharmaceutical and pharmacodynamic studies on topically applied diclofenac gel available in Indian market.

In the present investigation, an attempt was made to study and compare, analgesic and anti-inflammatory activity produced by four marketed topical diclofenac formulations in order to justify their usefulness in the treatment of pain and inflammation. By using a diffusion cell, in vitro percutaneous permeation studies were carried out to correlate in vivo activity. The in vivo analgesic activity study was performed by tail flick method on Wistar albino rats. The anti-inflammatory activity was performed on rats by carrageenan induced inflammation. It was evident from the study that three among tested three gels; diclofenac permeated effectively through the skin and was able to elicit analgesic and anti-inflammatory responses. The study also indicated the presence of therapeutic inequivalence among the marketed topical formulation and the need of bio equivalency and therapeutic equivalency testing of marketed topical applications meant for therapeutic use.

Ibuprofen-loaded ethylcellulose/polystyrene microspheres: an approach to get prolonged drug release with reduced burst effect and low ethylcellulose content.

The aim of this study was to develop ethylcellulose microspheres for prolonged drug delivery with reduced burst effect. Ethylcellulose microspheres loaded with ibuprofen were prepared with and without polystyrene, which was used to retard drug release from ethylcellulose microspheres. Ibuprofen-loaded ethylcellulose microspheres with a polystyrene content of 0-25% were prepared by the solvent evaporation technique and characterized by drug loading, infrared spectroscopy, differential scanning calorimetry and scanning electron microscopy. The in vitro release studies were performed to study the influence of polystyrene on ibuprofen release from ethylcellulose microspheres. The microspheres showed 28-46% of drug loading and 80-92% of entrapment, depending on polymer/drug ratio. The infrared spectrum and thermogram showed stable character of ibuprofen in the microspheres and revealed an absence of drug polymer interaction. The prepared microspheres were spherical in shape and had a size range of 0.1-4 microm. Ethylcellulose/polystyrene microspheres showed prolonged drug release and less burst effect when compared to microspheres prepared with ethylcellulose alone. Microspheres prepared with an ethylcellulose/polystyrene ratio of 80:20 gave a required release pattern for oral drug delivery. The presence of polystyrene above this ratio gave release over 24 h. To find out the mechanism of drug release from ethylcellulose/polystyrene microspheres, the data obtained from in vitro release were fitted in various kinetic models. High correlation was obtained in Higuchi and Korsmeyer-Peppas models. The drug release from ethylcellulose/polystyrene microspheres was found to be diffusion controlled.

Design and in vitro evaluation of oral colon targeted drug delivery systems for tinidazole.

The aim of the present investigation is to develop colon targeted drag delivery sytems for tinidazole using guar gum as a carrier in the treatment of amoebiasis. Fast-disintegrating tinidazole core tablets were compression-coated with 55, 65 and 75% of guar gum. All the formulations were evaluated for the hardness, drug content uniformity, and subjected to in vitro drug release studies. The amount of tinidazole released from tablets at different time intervals was estimated by HPLC method. The compression-coated formulations released < 0.5% of tinidazole in the physiological environment of stomach and small intestine. When the dissolution study was continued in simulated colonic fluids, the compression coated tablet with 55% of guar gum coat released 99% of tinidazole after degradation by colonic bacteria at the end of 24 h of the dissolution study. The compression coated tablets with 65 and 75% of guar gum coat released about 67 and 20% of tinidazole, respectively in simulated colonic fluids indicating the susceptibility of the guar gum formulations to the rat caecal contents. The results of the study show that compression coated tinidazole tablets with either 55 or 65% of guar gum coat is most likely to provide targeting of tinidazole for local action in the colon owing to its minimal release of the drug in the first 5 h of physiological environment of stomach and small intestine. The tinidazole compression coated tablets showed no change either in physical appearance, drug content or in dissolution pattern after storage at 40 degrees C/75% RH for 6 months.