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Biomedical subjects

M V Patel

Publications and source records attributed to M V Patel.

17 recordsLinked to original sources
PubMed2006

Simple liquid chromatography-tandem mass spectrometry method for determination of novel anti-methicillin-resistant Staphylococcus aureus fluoroquinolone WCK 771 in human serum.

A simple, rapid, specific, precise, accurate and sensitive method for determination of WCK 771 in human serum has been developed. The method uses high performance liquid chromatography with tandem mass spectrometric detection. Sample preparation involves protein precipitation method by addition of acetonitrile. Gatifloxacin was used as internal standard. The response was found to be linear from 0.312 to 40 microg/ml of serum with correlation coefficient greater than 0.99. Limit of detection and lower limit of quantification for WCK 771 was found to be 0.078 microg/ml and 0.312 microg/ml, respectively. The intra-day precision and accuracy from analysis of quality control (QC) samples at four concentrations was in the range of 2.36-2.58% and from 96.71 to 103.2%, respectively. The inter-day precision and accuracy from analysis of quality control samples at four concentrations was in the range of 3.14-6.82% and from 96.84 to 105.76%, respectively. WCK 771 was found to be stable for 24 h at auto-injector environment. WCK 771 was also found to be stable for 2h in serum at 25+/-3 degrees C and for 3 months at -20 degrees C. Mean absolute recovery at four different concentrations was 86.92% with standard deviation of 1.79. Throughput of the method is approximately one sample every 4 min. The method was also reproduced with monkey serum. The method was employed for estimation of drug serum levels during pre-clinical and clinical trials.

Animals↗
PubMed2006

Validated chiral high-performance liquid chromatography method for a novel anti-methicillin-resistant Staphylococcus aureus fluoroquinolone WCK 771.

A sensitive, simple, specific, precise, accurate and rugged method for the assay and determination of enantiomeric purity of S-(-)-9-fluoro-6,7-dihydro-8-(4-hydroxypiperidin-1-yl)-5-methyl-1-oxo-1H,5H-benzo[i,j]quinolizine-2-carboxylic acid L-arginine salt tetrahydrate (WCK 771) in bulk drug has been developed. The method is RP-HPLC using endcapped C-18 stationary phase and chiral mobile phase. Chirality to the mobile phase was imparted with addition of beta-cyclodextrin. The UV-vis detector was operated at 290 nm. The flow rate of mobile phase was 2 ml/min. The method offers excellent separation of two enantiomers with resolution more than 2 and tailing factor less than 1.5. The method was validated for the assay of WCK 771 and quantification of R-(+)-enantiomer impurity in bulk drug. The calibration curves showed excellent linearity over the concentration range of 0.05-0.15 mg/ml for WCK 771 and 0.5-7.5 microg/ml for R-(+)-enantiomer. The precision (RSD) of the assay was 0.23%. The limit of detection and limit of quantitation of the method for WCK 771 were 0.015 and 0.06 microg/ml, respectively. The limit of detection and limit of quantitation for R-(+)-enantiomer were 0.025 and 0.09 microg/ml, respectively. The average recovery of the R-(+)-enantiomer was 100.5%. Same method was applied for the assay and determination of enantiomeric purity of WCK 771 in the intravenous formulation.

Chromatography, High Pressure Liquid↗
PubMed2005

Activity of the new quinolone WCK 771 against pneumococci.

The activity of WCK 771, a new experimental quinolone being developed to overcome quinolone resistance in staphylococci, against quinolone-susceptible and -resistant pneumococci was determined. Comparative activities of ciprofloxacin, levofloxacin, gatifloxacin, moxifloxacin, clinafloxacin, vancomycin, linezolid, amoxycillin, cefuroxime, azithromycin and clarithromycin were determined with MIC and time-kill experiments. Animal experiments were also performed to test the in-vivo anti-pneumococcal activity of WCK 771 compared to levofloxacin. WCK 771 MIC50/90 values for 300 quinolone-susceptible Streptococcus pneumoniae isolates (108 penicillin-susceptible, 92 penicillin-intermediate and 100 penicillin-resistant) were 0.5/0.5 mg/L; the MICs of beta-lactams and macrolides rose with those of penicillin G, and all isolates were susceptible to vancomycin and linezolid. WCK 771 MIC50/90 values for 25 quinolone-resistant pneumococcal isolates were 4/8 mg/L, compared to 0.5/1 mg/L for clinafloxacin, 2/4 mg/L for gatifloxacin and moxifloxacin, 8/16 mg/L for levofloxacin, and 16/>32 mg/L for ciprofloxacin. Time-kill studies showed that WCK 771 was bactericidal against pneumococci after 24 h at 4 x MIC, as were the other quinolones tested. Animal model studies showed that WCK 771 had efficacy comparable to that of levofloxacin, by both the oral and subcutaneous routes, for systemic infection caused by three quinolone-susceptible isolates of pneumococci. Overall, WCK 771 was potent both in vivo and in vitro against quinolone-susceptible, but not quinolone-resistant, S. pneumoniae, regardless of penicillin susceptibility.

Animals↗
PubMed2001

Discovery of inhibitors of cell adhesion molecule expression in human endothelial cells. 1. Selective inhibition of ICAM-1 and E-selectin expression.

A critical early event in the inflammatory cascade is the induced expression of cell adhesion molecules on the lumenal surface of vascular endothelial cells. These adhesion molecules include E-selectin, ICAM-1, and VCAM-1, which serve to recruit circulating leukocytes to the site of the inflammation. These adhesive interactions allow the leukocytes to firmly adhere to and cross the vascular endothelium and migrate to the site of tissue injury. Pharmaceutical agents which would prevent the induced expression of one or more of the cell adhesion molecules on the endothelium might be expected to provide a novel mechanism to attenuate the inflammatory responses associated with chronic inflammatory diseases. A thieno[2,3-d]pyrimidine, A-155918, was identified from a whole-cell high-throughput assay for compounds which inhibited the tumor necrosis factor-alpha (TNFalpha)-induced expression of E-selectin, ICAM-1, or VCAM-1 on human vascular endothelial cells. Traditional medicinal chemistry methods were applied to this low-micromolar inhibitor, resulting in the 2,4-disubstituted thieno[2,3-c]pyridine A-205804, a potent and selective lead inhibitor of E-selectin and ICAM-1 expression (IC(50) = 20 and 25 nM, respectively). The relative position of the nitrogen atom in the thienopyridine isomer was shown to be critical for activity, as was a small amide 2-substituent.

Administration, Oral↗
PubMed2001

Transcriptional regulators of steroidogenesis, DAX-1 and SF-1, are expressed in human skin.

DAX-1 and SF-1 are members of the orphan nuclear receptor superfamily that are critical regulatory components of the hypothalamic-pituitary-adrenal-gonadal axis. In adrenal and gonadal tissues they regulate the expression of the cytochrome P450 steroid hydroxylase genes, key mediators of steroidogenesis. The identification of a number of steroid hydroxylases in human skin prompted us to investigate the presence of DAX-1 and SF-1. Immuno histochemical analysis of human skin revealed a distinctive staining pattern for DAX-1 and SF-1 in skin and its appendages. Prominent staining for DAX-1 was confined to the epidermis, sebaceous glands, sweat glands, and outer root sheath of the hair follicle with weaker expression in the inner root sheath, matrix cells, and dermal papilla cells. Similarly, SF-1 was also detected in the epidermis but displayed a scattered nuclear pattern across all layers. SF-1 immunoreactivity was also detected in the exocrine glands and was stronger than DAX-1 in the inner root sheath, matrix cells, and dermal papilla cells. Co-localization of DAX-1 and SF-1 was demonstrated by immunocytochemistry in the HaCaT keratinocyte cell line, primary keratinocytes, preadipocytes, and dermal papilla cells. Reverse transcriptase-polymerase chain reaction analysis demonstrated the expression of DAX-1 and SF-1 mRNA in whole human skin and Western analysis also confirmed the presence of DAX-1 protein in skin-derived cells. Our investigations demonstrate that two important regulators of steroidogeneisis are present in human skin and its appendages. These transcription factors may have a role in cutaneous steroidogenesis and thus be involved in hair follicle cycling or pathologies associated with steroids. Further studies are needed to determine the functional roles of DAX-1 and SF-1 in human skin.

3T3 Cells↗
PubMed1999

Effect of surface charge on the stability of oil/water emulsions during steam sterilization.

Intravenous lipid emulsions are used for total parenteral nutrition and as carriers for lipophilic drugs. Exposure to the high temperature (121 degrees C) required for steam sterilization may cause coalescence and an increase in droplet size. The purpose of this study was to investigate whether an increase in the electrostatic repulsive force between oil droplets produced by formulation modification improves the thermal stability of lipid emulsions during autoclaving. The addition of a small amount, 0.66 or 1.32 mmol/kg (mm), of purified anionic phospholipid fractions (phosphatidic acid, phosphatidylglycerol, or phosphatidylinositol) to the standard formula increased the zeta potential from its normal value of -11 mV to -39 mV. Emulsions with the larger negative zeta potential did not exhibit any change in oil droplet size or distribution during steam sterilization at 121 degrees C for 15 min. The autoclaved emulsions having the larger negative zeta potential did not exhibit any evidence of coalescence when samples were stored for 1 month at 4 degrees C, room temperature, or 40 degrees C. Reduction of the negative surface charge of the oil droplets by the addition of stearylamine confirmed that the surface charge was an important factor, as emulsions having a reduced negative surface charge separated into two phases during autoclaving.

Drug Stability↗
PubMed1997

Diffusion coefficients of polymer chains in the diffusion layer adjacent to a swollen hydrophilic matrix.

A semiempirical formula was developed for the diffusion coefficient, Dp, of polymer within the diffusion layer adjacent to a matrix undergoing swelling and dissolution. This formula of Dp was a key element in a comprehensive mathematical model that described the swelling and dissolution of polymer and the release of drug. For hydroxypropyl methylcellulose (HPMC), Dp can be related to molecular weight (M) and concentration (Cp) of HPMC as Dp approximately 7.24 x 10(-5) M-0.6 [1+ 700(M/ 96000)0.7Cp/8]-2. Consistent with literature results, this formula yields Dp infinity M-0.64 under a dilute condition and Dp infinity Cp-7/4M-2 under a semidilute condition. Accordingly, the average Dp within the diffusion layer, was determined as infinity M-0.53, suggesting that the average mobility of HPMC within the diffusion layer decreases with M. This scaling law, combined with the relationship of Cp.dis infinity M-0.8, led to an important scaling law for matrix dissolution flux, Jp infinity M-1.15. The parameter Cp.dis, defined as the polymer disentanglement concentration or the polymer concentration at the tablet-diffusion layer interface, was a key parameter in that mathematical-model. The scaling law of Jp infinity M-1.15 indicates that the matrix dissolution rate decrease sharply with M at low M and gradually approaches a plateau as M becomes large. The plateau characteristics of Jp with M is consistent with the limiting drug release rate observed for HPMC-containing matrices, suggesting the critical role matrix dissolution plays in drug release.

Diffusion↗
PubMed1995

Drug release from hydrophilic matrices. 1. New scaling laws for predicting polymer and drug release based on the polymer disentanglement concentration and the diffusion layer.

Two scaling laws for predicting polymer and drug release profiles from hydrophilic matrices were developed. They were developed on the basis of the diffusion layer and the polymer disentanglement concentration, rho p,dis, the critical polymer concentration below which polymer chains detach off a gelled matrix that is undergoing simultaneous swelling and dissolution. The relation between rho p,dis and molecular weight, M1 for (hydroxypropyl)methylcellulose (HPMC) in water was established as rho p,dis (g/mL) varies M-0.8. This power-law relationship for rho p,dis, along with the diffusion layer adjacent to the gelled matrix, leads to the scaling law of mp(t)/mp(infinity) varies Meq-1.15, where mp(t)/mp(infinity) is the fractional HPMC release. The scaling law explains the observation that polymer and drug release rates decreased sharply with M at low M and approach limiting values at high M. Experimentally, mp(t)/mp(infinity) was found to scale with Meq as mp(t)/mp(infinity) varies Meq-0.93, where Meq is the equivalent matrix molecular weight. Moreover, fractional drug release, md(t)/md(infinity), followed Meq as md(t)/md(infinity) varies Meq-0.48. These two scaling laws imply that, if the release profiles are known for one composition, release profiles for other compositions can be predicted. The above two power laws lead to two master curves for mp(t)/mp(infinity) and md(t)/md(infinity), suggesting that the release mechanism for soluble drugs from HPMC matrices is independent of matrix compositions, presumably via a diffusion-controlled process. Limitations of the power laws are discussed.

Benzodiazepines↗
PubMed1995

Drug release from hydrophilic matrices. 2. A mathematical model based on the polymer disentanglement concentration and the diffusion layer.

A comprehensive model is developed to describe the swelling/dissolution behaviors and drug release from hydrophilic matrices. The major thrust of this model is to employ an important physical property of the polymer, the polymer disentanglement concentration, rho p,dis, the polymer concentration below which polymer chains detach off the gelled matrix. For (hydroxypropyl)methylcellulose (HPMC) in water, we estimate that rho p,dis scales with HPMC molecular weight, M, as rho p,dis varies M-0.8. Further, matrix dissolution is considered similar to the dissolution of an object immersed in a fluid. As a result, a diffusion layer separating the matrix from the bulk solution is incorporated into the transport regime. An anisotropic expansion model is also introduced to account for the anisotropic expansion of the matrix where surface area in the radial direction dominates over the axial surface area. The model predicts that the overall tablet size and the characteristic swelling time correlate with rho p,dis qualitatively. Two scaling laws are established for fractional polymer (mp(t)/mp(infinity)) and drug (md(t)/md(infinity)) released as mp(t)/mp(infinity) varies M-1.05 and md(t)/md(infinity) varies M-0.24, consistent with the limiting polymer molecular weight effect on drug release. Model predictions for polymer and drug release agree well with observations, within 15% error. Evolution of water concentration profiles and the detailed structure of a swollen matrix are discussed.

Benzodiazepines↗
PubMed1994

Balhimycin, a new glycopeptide antibiotic produced by Amycolatopsis sp. Y-86,21022. Taxonomy, production, isolation and biological activity.

A new glycopeptide antibiotic, balhimycin, has been isolated from the fermentation broth of a Amycolatopsis sp. Y-86,21022. Balhimycin belongs to the vancomycin class of glycopeptides and contains a dehydrovancosamine sugar. The biological activity of balhimycin has been compared extensively with that of vancomycin against methicillin resistant staphylococci and also against anaerobes. Balhimycin is marginally superior to vancomycin in its in vitro activity against anaerobes and in its bactericidal properties.

Actinobacteria↗
PubMed1991

Traumatic ischaemic optic neuropathy (a case report).

A 22-year-old patient presented with a clinical picture of unilateral optic neuropathy following blunt trauma to the orbit. Clinical findings, fundus fluorescein angiography and neurophysiological studies were suggestive of an ischaemia, a rare etiology.

Adult↗
PubMed1987

Physical model for non-steady-state dissolution of dental enamel.

The purpose of this study was to provide a rigorous theoretical understanding of the dissolution behavior of dental enamel over the entire time-course of demineralization and to simulate by computer an erosion-type caries lesion according to the physical "hydroxyapatite model". The appropriate diffusion equations which account for simultaneous diffusion and equilibrium of all species in enamel pores, boundary layer, and bulk solution, and which also take into consideration surface reaction kinetics, were employed to allow for calculation of the micro-environmental solution concentration and changes in the mineral density as a function of time and distance within the enamel. This comprehensive physical model for non-steady-state enamel dissolution also explicitly takes into account changes in the diffusivity and the dissolution rate constant as a function of mineral density. Demineralization experiments were conducted in 0.1 mol/L sink acetate buffer (pH = 4.50, mu = 0.50), with ground bovine dental enamel blocks of known surface area mounted (with beeswax) in a rotating disk apparatus. Mineral density profiles were quantified by means of contact x-ray microradiography. The physical model was used to predict mineral density profiles for given demineralization treatments. The experimental profiles agreed quite well with the predicted profiles, when the effective diffusivity of the enamel was assumed to be a function of porosity and when changes in surface area of the crystallites were taken into consideration.

Animals↗
PubMed1987

Effect of acid type on kinetics and mechanism of dental enamel demineralization.

The influence of acid type (pKa effects) of weak organic acid buffers on dissolution kinetics of dental enamel was critically examined for rigorous testing of the behavioral validity of the physical model of Patel et al. (1987). Quantitative evaluation of this model indicated that monitoring initial dissolution rates was a viable approach to critical testing of the model. Initial dissolution rates were determined in 0.1 mol/L acetate (pKa = 4.77), benzoate (pKa = 4.20), and salicylate (pKa = 2.98) buffers (pH = 4.50, mu = 0.50), with ground bovine enamel blocks of known surface area mounted in a rotating disk apparatus. The Levich theory was used to study dependence of dissolution rates on stirring rates in these buffers. The experimental data were analyzed by the physical model which includes pKa effects, complexation of the buffer anion with the other ions, surface kinetics, simultaneous diffusion and equilibrium of all species in enamel pores, diffusion layer thickness, and bulk solution composition. The KIAP (formula: see text) governing the dissolution reaction and the surface resistance factor were deduced from the model. Dissolution kinetics was also followed in these buffers in the presence of calcium or phosphate common ions. In effect, by conducting both the stirring rate studies and common ion experiments, we derived the driving force function independently by these two techniques. The results obtained in this study were consistent with the model, indicating that pKa effects on the dissolution of dental enamel can be accounted for quantitatively by the model, and it was found that weak acids do not influence either the apparent solubility or the surface reaction process of bovine dental enamel.

Acetates↗