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Biomedical subjects

A K Singla

Publications and source records attributed to A K Singla.

At least 19 recordsLinked to original sources

Inhibition of mutagenicity of food-derived heterocyclic amines by sulphoraphene--an isothiocyanate isolated from radish.

The naturally derived isothiocyanate, sulphoraphene [4-isothiocyanato-(1R)-(methylsulphinyl)-1-(E)-butene], isolated from seeds of radish ( Raphanus sativus L., Cruciferae) was investigated for its antigenotoxic effects against a battery of cooked food mutagens (heterocyclic amines) in the Ames Salmonella/reversion assay using Salmonella typhimurium TA98 (frame-shift mutation sensitive) and TA100 (base -pair mutation sensitive) bacterial strains in the presence of Aroclor 1254 induced rat liver S9. Results of the present in vitro anti-mutagenicity studies using the base-pair mutation sensitive strain TA100, strongly suggest that sulphoraphene is a potent inhibitor of the S9-mediated mutagenicity of all the tested heterocyclic amines (60 - 75 % inhibition at a dose of 500 nmol/plate).

Amines↗

Performance liquid chromatographic analysis of glipizide: application to in vitro and in vivo studies.

This paper describes the validation of a sensitive, accurate, and reproducible method for the determination of a release profile of glipizide from controlled-release dosage forms. In this method, an in vitro dissolution profile of commercial controlled-release dosage forms is determined using a reversed-phase C(18) column, mobile phase (acetonitrile-buffer, 0.05 M KH(2)PO(4) adjusted to pH 3.5 with orthophosphoric acid), and UV detection at a wavelength of 275 nm. The method is validated for linearity, accuracy, precision, and detection and quantitation limits. The same method can be exploited to determine the plasma concentration of glipizide. The peak area versus plasma concentration is linear over the range of 12.5-1000 ng/mL and the detection limit was 5 ng/mL in plasma. The average accuracy was 99.90% with a relative standard deviation (RSD) of not more than 3%. Repeatability and reproducibility were found to be good with an RSD of less than 3%.

Chromatography, Liquid↗

Liquid chromatographic method for determination of piperine in rat plasma: application to pharmacokinetics.

Piperine, a major alkaloid of Piper longum and Piper nigrum has been reported to have several pharmacological/toxicological effects. Though a number of methods for analysis of this omnipresent food component in pepper fruits are available, its analysis in body fluids has been largely neglected. A high-performance liquid chromatography method for the analysis of piperine in rat plasma is presented in this communication. Analysis was performed using a Symmetry C(18) column (250x4.6 mm) by isocratic elution with 25 mM KH(2)PO(4) (pH 4.5)-acetonitrile (35:65) and UV detection at 340 nm. The calibration plot was linear over the range studied (2-2000 ng) with correlation coefficient of 0.9984. Limit of detection and limit of quantitation were 1 ng/ml and 3 ng/ml, respectively. Good overall recovery (85.5+/-6%) was obtained with 4 ml ethyl acetate and extraction time of 3 min. Intra- and inter-assay coefficient of variation was found to be less than 7.5%. Plasma concentration-time profile of piperine in a conscious rat implanted with jugular vein cannula was obtained using this method. The method is simple, sensitive and reproducible.

Alkaloids↗

Inhibitory effect of curcumin and its natural analogues on genotoxicity of heterocyclic amines from cooked food.

Curcumin (C) and its natural analogues demethoxycurcumin (dmC) and bisdemethoxycurcumin (bdmC), known for their potent anti-inflammatory, antioxidant, antimutagenic and anticarcinogenic effects, were tested for their possible inhibitory effects against seven cooked food mutagens (heterocyclic amines): 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1), 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2), 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and 2-amino-6-methyldipyrido[1,2-a:3',2'-d]imidazole (Glu-P-1), in both TA98 and TA100 strains of Salmonella typhimurium using Ames Salmonella/reversion assay in the presence of Aroclor induced rat liver S9 homogenate. In the present investigations, curcumin as well as its two natural analogues i.e., dmC and bdmC were found to be highly effective in suppressing genotoxicity of all the tested cooked food mutagens in a dose-dependent manner, in both the frame shift (TA98) as well as base pair mutation sensitive (TA100) strains of S. typhimurium. However, bdmC appeared to be a relatively less active antimutagen compared to C and dmC. More than 80% inhibition of mutagenicity was observed at 200 microg/plate in case of C and dmC in both TA98 and TA100 against all tested cooked food mutagens. Where as, bdmC showed 39-79% inhibition in TA100 and 60-80% inhibition in TA98, at a dose of 200 microg/plate. These findings warrant further biochemical, enzymatic and in vivo investigations in animal models as well as in humans to establish the chemoprotective effect of these agents against mutagenic heterocyclic amines found in cooked food.

Amines↗

Chemistry and pharmacology of the Citrus bioflavonoid hesperidin.

Hesperidin, a bioflavonoid, is an abundant and inexpensive by-product of Citrus cultivation. A deficiency of this substance in the diet has been linked with abnormal capillary leakiness as well as pain in the extremities causing aches, weakness and night leg cramps. No signs of toxicity have been observed with the normal intake of hesperidin or related compounds. Both hesperidin and its aglycone hesperetin have been reported to possess a wide range of pharmacological properties. This paper reviews various aspects of hesperidin and its related compounds, including their occurrence, physical and chemical properties, analysis, pharmacokinetics, safety and toxicity and the marketed products available. A special emphasis has been laid on the pharmacological properties and medicinal uses of these compounds.

Citrus↗

Piperine inhibits gastric emptying and gastrointestinal transit in rats and mice.

Piperine (1), an alkaloid of black and long peppers, inhibited gastric emptying (GE) of solids/liquids in rats and gastrointestinal transit (GT) in mice in a dose and time dependent manner. Compound 1 significantly inhibited GE of solids and GT at the doses extrapolated from humans (1 mg/kg and 1.3 mg/kg p.o. in rats and mice, respectively). However, at the same dose the effect was insignificant for GE of liquids. One week oral treatment of 1 mg/kg and 1.3 mg/kg in rats and mice, respectively, did not produce a significant change in activity as compared to single dose administration. GE inhibitory activity of 1 is independent of gastric acid and pepsin secretion.

Alkaloids↗

Antidiarrhoeal activity of piperine in mice.

Peppers are common food ingredients used worldwide. They are also added in traditional antidiarrhoeal formulations of different herbs. Piperine (1) is an alkaloidal constituent of black and long peppers recently established as a bioavailability enhancer of drugs and other substances. As a part of efforts to study its effects on the gastrointestinal tract, the experiments were performed to determine the rationale, if any, for its use in traditional antidiarrhoeal formulations. Antidiarrhoeal activity of 1 against castor oil, MgSO4 and arachidonic acid was studied in mice. It significantly inhibited diarrhoea produced by these cathartics at 8 and 32 mg/kg p.o. dose. Inhibition of castor oil induced enteropooling by 1 suggests its inhibitory effect on prostaglandins. The results validate the rationale for its use in traditional antidiarrhoeal formulations.

Alkaloids↗

Are women who are Jehovah's Witnesses at risk of maternal death?

OBJECTIVE: The purpose of this study was to determine the rates of obstetric hemorrhage and maternal mortality in women who are Jehovah's Witnesses and to evaluate a protocol that uses erythropoietin to optimize the red blood cell mass before delivery. STUDY DESIGN: Obstetric outcomes were described for all of the women who were Jehovah's Witnesses and who delivered at Mount Sinai Medical Center during an 11-year period. The risk of maternal death was compared with our general obstetric population during this interval. RESULTS: A total of 332 women who were Jehovah's Witnesses had 391 deliveries. An obstetric hemorrhage was experienced in 6% of this population. There were 2 maternal deaths among the women who were Jehovah's Witnesses, for a rate of 512 maternal deaths per 100,000 live births versus 12 maternal deaths per 100,000 live births (risk ratio, 44; 95% CI, 9-211). Erythropoietin was associated with a nonsignificant increase in hematocrit level. CONCLUSION: Women who are Jehovah's Witnesses are at a 44-fold increased risk of maternal death, which is due to obstetric hemorrhage. Patients should be counseled about this risk of death, and obstetric hemorrhage should be aggressively treated, including a rapid decision to proceed to hysterectomy when indicated.

Adult↗

Chitosan: some pharmaceutical and biological aspects--an update.

Chitosan, a natural polysaccharide, is being widely used as a pharmaceutical excipient. It is obtained by the partial deacetylation of chitin, the second most abundant natural polymer. Chitosan comprises a series of polymers varying in their degree of deacetylation, molecular weight, viscosity, pKa etc. The presence of a number of amino groups permit chitosan to chemically react with anionic systems, thereby resulting in alteration of physicochemical characteristics of such combinations. Chitosan has found wide applicability in conventional pharmaceutical devices as a potential formulation excipient, some of which include binding, disintegrating and tablet coating properties. The polymer has also been investigated as a potential adjuvant for swellable controlled drug delivery systems. Use of chitosan in novel drug delivery as mucoadhesive, gene and peptide drug administration via the oral route as well as its absorption enhancing effects have been explored by a number of researchers. Chitosan exhibits myriad biological actions, namely hypocholesterolemic, antimicrobial and wound healing properties. Low toxicity coupled with wide applicability makes it a promising candidate not only for the purpose of drug delivery for a host of drug moieties (antiinflammatories, peptides etc.) but also as a biologically active agent. It is the endeavour of the present review to provide an insight into the biological and pharmaceutical profile of chitosan. Various investigations carried out recently are reported, although references to research performed on chitosan prior to the recent reviews have also been included, where appropriate.

Animals↗

Nifedipine loaded chitosan microspheres: characterization of internal structure.

In the present investigation, a simple technique was employed to obtain cross-sections of unloaded and nifedipine loaded chitosan microspheres. Microspheres, adhering to a polymerized resin block, were cut with an ultramicrotome and viewed with a scanning electron microscope. Unloaded microspheres exhibited a uniform dense matrix structure while crystals of nifedipine were clearly visible in the drug-loaded microspheres. At 2% drug loading, however, no crystals could be seen in the microspheres indicating that either the drug was molecularly dispersed or dissolved in the matrix at this concentration. This was confirmed by powder X-ray diffractometry studies where no peak due to crystalline nifedipine was observed. At high Span 85 concentration (1.5% w/v), the external surface of the microspheres collapsed, but the internal structure remained dense. When the drug was dispersed in the chitosan solution with stirring during preparation, the entrapment was good and the shape of the crystals was changed. The internal structure of the microspheres following dissolution exhibited the presence of pores.

Chitin↗

Potential applications of carbomer in oral mucoadhesive controlled drug delivery system: a review.

Carbomers are extensively being used in controlled drug delivery systems (CDDS). They are also finding numerous applications in oral mucoadhesive drug delivery because of their ability to interact with the mucus glycoprotein and to remain localized to a specific site. The present review aims at giving an insight into the potential application of carbomers in mucoadhesive CDDS. This review deals with the physicochemical properties of carbomers and various mechanisms of mucoadhesion. The mechanism for the release of the drug, both water soluble and water insoluble, is discussed. The use of carbomers in oral delivery of peptides or protein-based drugs is also covered.

Acrylic Resins↗

Nimesulide: some pharmaceutical and pharmacological aspects--an update.

Nimesulide, a non-steroidal anti-inflammatory drug (NSAID), is administered orally or rectally twice daily for a variety of inflammation and pain states. This is a unique NSAID, not only because of its chemical structure but also because of its specific affinity to inhibit cyclooxygenase-2 (COX-2), thus exerting milder effects on the gastrointestinal mucosa. Current data on selective COX-2 inhibitors suggest that they may have an efficacy similar to that of standard NSAIDs. Initial general clinical experience with selective COX-2 inhibitors appears to show that they are particularly promising in individuals at risk because of renal diseases, hypertension or congestive heart failure. Various experimental models and clinical studies have demonstrated the anti-inflammatory efficacy of nimesulide. Nimesulide is superior, or at least comparable in efficacy, to other NSAIDs, but is better tolerated and has less potential for adverse reactions. Thus, selective COX-2 inhibitors should have anti-inflammatory effects devoid of side effects on the kidney and stomach. They may also demonstrate new important therapeutic benefits as anticancer agents as well as help prevention of premature labour and even retard the progression of Alzheimer's disease. No clinically significant drug interactions have been reported for nimesulide. Not much has been reported about the pharmaceutical aspects of nimesulide. Its poor aqueous solubility poses bioavailability problems in-vivo. This could be overcome by the formation of inclusion complexes with beta-cyclodextrin, as has been reported by various researchers. However, absence of any in-vivo data regarding the relative absorption of nimesulide from beta-cyclodextrin complex compared with that from conventional formulations of the drug makes the use of such fast-releasing complexes rather questionable. Only a limited number of assay procedures (HPLC, spectrophotometric, spectrofluorimetric) for the determination of nimesulide and its metabolite in plasma/urine samples or in dosage forms have been reported in the literature. The purpose of this review is to provide a concise overview of the pharmacological and pharmaceutical profile of nimesulide. Various investigations carried out recently are reported, although older references to research performed on nimesulide have also been included, where appropriate.

Animals↗

Mucin production in the middle ear in response to lipopolysaccharides.

OBJECTIVE: This study examined the response of middle ear tissue to establish the lowest dose of lipopolysaccharide to induce mucin production in a rat otitis media model. METHODS: Twenty-six male Sprague-Dawley rats' eustachian tubes were obstructed before transtympanic inoculation of the bulla tympanica with 35 microL of Krebs Ringer or 1, 10, 100, or 1000 microgram/mL lipopolysaccharide. After 7 days the effusion and a lavage were collected for mucin ELISA measurement, and tissue was collected for histologic evaluation. RESULTS: Mucin secretion was significantly increased in the 100 microgram/mL 51.20 +/- 13.6 microgram/mL (SE) and 1000 microgram/mL 69.42 +/- 8.57 microgram/mL groups when compared with the Krebs Ringer control group 1.84 +/- 0.28 microgram/mL (P < 0.05). Histologic evaluation shows goblet cell metaplasia and hyperplasia in the middle ear epithelium in the 1000 and 100 microgram/mL groups. CONCLUSIONS: The histology and ELISA results suggest that a middle ear effusion is generated with a dose of lipopolysaccharide as low as 100 microgram/mL.

Animals↗

Aggressive surgical treatment of digital papillary adenocarcinoma.

The case of a 38-year-old white man with digital papillary adenocarcinoma is presented. It is a lesion of the skin often occurring in the digits of the hand or of the feet. This disease is rare and has not been reported in the plastic surgical or orthopedic literature to date. A case report is presented here along with our rationale for aggressive surgical treatment consisting of amputation.

Adenocarcinoma, Papillary↗

Dissolution test method for rifampicin-isoniazid fixed dose formulations.

A dissolution procedure for a rifampicin-isoniazid combination formulation was evaluated using 0.1 N hydrochloric acid solution and 0.4% (w/v) sodium lauryl sulphate solution as dissolution media. Rifampicin and isoniazid along with degradation components were chromatographed using reversed-phase liquid chromatography on a 10 microns octadecylsilica column using methanol-0.01 M disodium hydrogen phosphate (70:30, v/v; pH 4.6 +/- 0.1) as mobile phase. The detection was carried out at 254 nm. The data obtained indicate that the dissolution medium consisting of 0.4% (w/v) sodium lauryl sulphate solution is suitable for such a combination. The degradation observed in dissolution medium consisting of 0.1 N hydrochloric acid was 10-23%.

Capsules↗

The gastric augment single pedicle tube catheterizable stoma: a useful adjunct to reconstruction of the urinary tract.

Since 1990 we have used stomach for bladder augmentation and continent urinary diversions in 73 patients, of whom 15 received a gastric tube catheterizable stoma and are the subject of this report. The gastric tube receives its blood supply from the same vascular pedicle as the gastric patch and, therefore, it can be moved anywhere along with the patch. The tube is then reimplanted in the reservoir or bladder following the Mitrofanoff principle and brought to the skin as a catheterizable stoma. Patient age ranged from 12 to 60 years. Three patients underwent augmentation cystoplasty and 12 received a composite gastrointestinal continent reservoir (in 10 a prior bowel conduit was detubularized and used as part of the reservoir). The appendix was either previously removed (10 patients) or not suitable as a catheterizable limb (4). All patients are continent. Catheters used to empty the reservoir varied from 12F to 18F. Complications included an early traumatic perforation of the tube in 1 patient, distal stenosis in 1 and mucosal redundancy in 1. Of these patients 2 required revision. Two patients had mild peristomal skin irritation without ulceration. Anatomical and technical aspects of this procedure are presented. In summary, we believe the gastric augment single pedicle tube to be a useful tool for the reconstructive urologist, which in select cases may obviate the need for additional bowel anastomosis to create a tapered intestinal catheterizable limb.

Adolescent↗