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Biomedical subjects

S Patil

Publications and source records attributed to S Patil.

At least 19 recordsLinked to original sources
PubMed1999

Efflux of rhodamine from CD56+ cells as a surrogate marker for reversal of P-glycoprotein-mediated drug efflux by PSC 833.

The expression of high levels of P-glycoprotein (Pgp) in circulating mononuclear cells allowed us to use an ex vivo assay as a surrogate measure of Pgp antagonism. Efflux of rhodamine from CD56(+) cells was measured before the start of PSC 833 and at varying times thereafter. Patients receiving PSC 833 had decreased rhodamine efflux from their circulating CD56(+) cells. Time course studies showed that following a single oral dose of PSC 833, decreased rhodamine efflux was found in some patients within 15 minutes of treatment. Maximal inhibition was observed at times ranging from 45 minutes to 60 minutes. A dose-response relationship was shown between the concentration of PSC 833 in the blood and the inhibition of rhodamine efflux, with an apparent plateau of the inhibition of rhodamine efflux at approximately 1,000 ng/mL. The Ki, defined as the concentration required for half-maximal inhibition of Pgp-mediated rhodamine efflux, was determined to be in the range of 29 to 181 ng/mL; although results in two patients were distinctly different, with Ki values of 914 and 916 ng/mL. MRK-16 staining was similar among all patients. We conclude that measurement of rhodamine efflux from CD56(+) cells provides a surrogate assay with the potential for monitoring Pgp antagonism in clinical trials.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1998

Isocratic, simultaneous reversed-phase high-performance liquid chromatographic estimation of six drugs for combined hypertension therapy.

We report an isocratic, HPLC procedure for assay of the orally administered hypertension drugs [atenolol, amlodipine, nifedipine, nitrendipine, nimodipine and felodipine given in retention order] of which atenolol, an aryloxypropanolamine beta-blocker is administered with anyone of the other five dihydropyridine calcium channel blockers in combined hypertension therapy. The drugs were dissolved in methanol and 20 microliters of a mix of the drugs was injected onto a reverse phase JASCO-metaphase ODS (250 x 4.0 mm) 5 mu column. Any one of the six drugs could be used as the internal standard. The drugs were resolved by elution with a pH 4.5 equivolume mobile phase of acetonitrile-0.01 M KH2PO4, with pH adjustments done with H3PO4 (flow-rate 1.5 ml min-1). The column effluent was monitored at 250 nm. The detector response (peak height ratio) was linear in the dynamic range of 25-3200 ng ml-1 of these drugs, with the detection limits at approximately 15 ng ml-1. Full statistical evaluation of the data including linear regression (least-square fit) analysis was performed. The suggested procedure has the advantage that all the five dihydropyridine derivatives can be quantified alone or in formulation with atenolol.

Antihypertensive Agents↗
PubMed1998

Alteration of the fatty acid substrate specificity of lysophosphatidate acyltransferase by site-directed mutagenesis.

The JC201 strain of Eschericia coli contains a temperature-sensitive lesion in lysophosphatidate acyltransferase (LPAT) activity. The LPAT gene from JC201 was isolated by PCR and a single mutant nucleotide, adenine-440, was identified by DNA sequence analysis. Site-directed mutagenesis converted the mutant adenine-440 back to the native guanine-440 nucleotide. The restored LPAT gene rescued JC201 cells at the non-permissive temperature. The fatty acid substrate specificity of LPAT from Eschericia coli was altered by site-directed mutagenesis of a single amino acid in the restored LPAT gene. Threonine-122 of LPAT was changed to alanine or leucine. A change from threonine-122 to alanine increased the substrate specificity in vitro for oleoyl-CoA and linoleoyl-CoA; whereas a change to leucine increased the substrate specificity for lignoceroyl-CoA.

1-Acylglycerol-3-Phosphate O-Acyltransferase↗
PubMed1998

The role of intracellular alkalinization in the establishment of anterior neural fate in Xenopus.

Our previous work demonstrated that Xenopus ectoderm cells undergo an alkalinization in response to planar inductive signals during neural induction in explants. We have examined the role of intracellular alkalinization in the establishment of anterior neural fate. First, RT-PCR was used to examine neural-specific gene expression in planar explants in which the alkalinization is prevented by treatment with 4,4'-dihydrodiisothiocyanatostilbene-2,2'-disulfonate (H2DIDS). In explants cultured in the presence of H2DIDS, expression of NCAM and the anterior neural gene otx2 is greatly reduced or absent. Second, neural-specific gene expression was examined in isolates of uninduced animal cap ectoderm cultured in the presence of either methylamine or ammonium chloride. NCAM, otx2, and the anterior neural inducer noggin were expressed in alkalinized ectoderm, while the more posterior neural markers krox-20 and Hox B9 were undetectable. Expression of NCAM, otx2, and noggin was observed at stage 11 in both alkalinized ectoderm and the newly induced neural plate, suggesting that intracellular alkalinization could contribute to propagation of noggin signaling through the dorsal ectoderm. Alkalinization of uninduced ectoderm at stage 10.5 led to an upregulation of otx2 within 15 min. Activation of NCAM expression in alkalinized dissociated cells was identical to that observed in intact animal caps, indicating that alkalinization-mediated changes in gene expression do not require cell-cell contact. Finally, the effects of intracellular alkalinization on protein tyrosine phosphorylation were investigated using 2D gel electrophoresis and immunoblots probed with an antiphosphotyrosine antibody. Several phosphorylated protein detected in induced and alkalinized ectoderm were greatly reduced or absent in uninduced ectoderm, indicating that alkalinization elicits alterations in tyrosine phosphorylation similar to some of those observed during neural induction in vivo. Our results indicate that intracellular alkalinization plays a critical role in the activation of anterior neural-specific gene expression and that alkalinization may act by regulating the activity of a tyrosine kinase or phosphatase.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1998

Molecular motion and orientation distributions in melt-processed, fully aromatic liquid crystalline polyesters from 1H NMR.

Fully-aromatic thermotropic liquid crystalline polymers (LCP) containing 4-hydroxybenzoic acid (HBA) and 6-hydroxy-2-naphthoic acid (HNA) were studied with 1H NMR. A two- or three-parameter nematic director distribution in molten or nearly molten samples was obtained via rigorous simulation of wideline spectral lineshapes. This methodology was further employed to yield the chain director distribution in macroscopic sections derived from a frozen contraction flow. In addition, the dynamic conformation of polymer chains through the melting transition was monitored via lineshape analysis of samples having (bulk) isotropic director distributions. Extension of rigorous 1H NMR spectral deconvolution to recently developed solid-state NMR imaging sequences is discussed.

Crystallization↗
PubMed1998

Prescribing patterns among medical practitioners in Pune, India.

In 1975 the World Health Assembly requested the Director-General to advise Member States on the selection and procurement of essential drugs corresponding to their national health needs. We report here the results of a study of the prescribing patterns and rational drug utilization of medical practitioners of Pune, an industrial city in the west of India, which was undertaken by analysing their prescriptions. The results indicated a lack of rational prescribing practices by a significant number of practitioners. Fixed-dose formulations dominated the prescribing pattern and generic prescriptions were negligible, with prescriptions for essential drugs accounting for less than 60% of the total number of drugs prescribed. More than 30% of prescriptions were irrational, with the probability of such prescriptions increasing significantly with the number of drugs per prescription. A study of sources of drug formulations available for prescription revealed significantly more fixed-dose combinations, many of which were irrational. These results call for intervention strategies to promote rational drug therapy in India.

Anti-Bacterial Agents↗
PubMed1998

Caspase inhibitor BD-fmk distinguishes transforming growth factor beta-induced apoptosis from growth inhibition.

Transforming growth factor beta (TGFbeta) is essential for immune regulation and growth control. TGFbeta has previously been shown to inhibit cell growth as well as induce cell death in lymphocytes, although the mechanisms controlling these processes are not well understood. The mouse pre-B lymphoma cell line WEHI 231 was used to examine the mechanisms of TGFbeta-mediated growth inhibition and apoptosis. TGFbeta inhibits the growth of WEHI 231 cells in a dose-dependent manner; however, a decrease in viability is also observed, which is indicative of increased cell death. TGFbeta induces oligonucleosomal DNA ladder formation in a dose-dependent manner, indicating the mechanism of cell death is via apoptosis. The broad spectrum caspase inhibitor BD-fmk, but not tetrapeptide inhibitors of specific caspases, completely blocks TGFbeta-induced apoptosis while maintaining cellular viability. BD-fmk, however, has no effect on TGFbeta-induced growth inhibition. The ability of TGFbeta to down-regulate cyclin A-associated kinase activity, postulated to mediate TGFbeta growth inhibition, is not affected by the caspase inhibitor BD-fmk. These results suggest that caspases do not regulate cell cycle mediators of growth and provide the first demonstration that a pharmacological inhibitor of TGFbeta-induced apoptosis is capable of distinguishing growth inhibitory from apoptotic pathways.

Animals↗
PubMed1997

Risk of preeclampsia in second-trimester triploid pregnancies.

OBJECTIVE: To determine the magnitude of the risk and the predictive clinical characteristics for development of preeclampsia when triploidy is diagnosed in the second trimester. METHODS: A retrospective analysis of databases maintained by the cytogenetics laboratories at the University of Iowa and University of North Carolina was performed to identify all cases of triploidy. We examined the karyotype, maternal serum screening (particularly the hCG level), ultrasound results, and evidence of maternal hypertensive disease. RESULTS: Seventeen cases of triploidy were identified between 1987 and 1996. Preeclampsia or hypertension complicated six of these cases with onset between 15 and 22.5 weeks' gestation. In these six cases, the serum hCG level was extremely high. Serum screening results were available in seven cases in which preeclampsia did not develop, and the hCG levels were under 0.09 multiples of the median in five of the seven cases. In all six cases in which preeclampsia or hypertension developed, there was sonographic evidence of placentomegaly. Sonographic findings in 16 of 17 cases revealed fetal growth restriction, oligohydramnios, fetal anomalies, placentomegaly, or a combination of these. CONCLUSION: In our series of pregnancies complicated by triploidy, the risk of developing preeclampsia or hypertension in the second trimester was 35%. It appears that elevated serum hCG levels and placentomegaly are associated with a higher risk of preeclampsia but low hCG levels are not. This information is important in counseling patients who are hesitant to terminate a pregnancy purely for a fetal abnormality, even if the anomaly is lethal.

Adolescent↗
PubMed1997

Familial hypomagnesemia maps to chromosome 9q, not to the X chromosome: genetic linkage mapping and analysis of a balanced translocation breakpoint.

Familial hypomagnesemia with secondary hypocalcemia (HSH) (MIM 307600) was studied in three inbred Bedouin kindreds from Israel. The three kindreds, one extended and two nuclear families, contained 13 affected individuals, 11 males and two females. Assuming that the individuals affected with hypomagnesemia shared a chromosomal region inherited from a common ancestor, we used a DNA pooling strategy in a genome-wide search for loci which show homozygosity for shared alleles in affected individuals. DNA samples from affected individuals within a single kindred were pooled and used as the template for PCR amplification of short tandem repeat polymorphic markers (STRPs). Pooled DNA from unaffected siblings and parents were used as controls. A shift towards homozygosity was observed in the affected DNA pool compared with the control pools with D9S301 (GATA7D12). Genotyping of individual DNA samples with D9S301 and several flanking markers confirmed linkage to chromosome 9 with maximum LOD scores of 3.4 (theta = 0.05), 3.7 (theta = 0) and 2.3 (theta = 0) for the three families. We have identified a 14 cM interval on chromosome 9 (9q12-9q22.2), flanked by proximal marker D9S1874 and distal marker D9S1807, within which all affected individuals from the three kindreds are homozygous for a shared haplotype. The disease segregates with a common affected haplotype in the three families, suggesting that hypomagnesemia is caused by a common ancestral mutation in these families. Although HSH has been previously reported to be X linked, these linkage data demonstrate that the disorder is an autosomal recessive disease in these kindreds. Mapping of a chromosomal breakpoint in a somatic cell line established from a patient with HSH and a balanced X;9 translocation placed the chromosomal breakpoint in a 500 kb region flanked by D9S1844 and D9S273. Identification of the gene responsible for hypomagnesemia will provide insight into the regulation of this essential cation.

Arabs↗
PubMed1997

Responsiveness of human male volunteers to immunization with ovine follicle stimulating hormone vaccine: results of a pilot study.

A study of 140 days duration was performed to examine if human male volunteers (n = 5) respond to ovine follicle stimulating hormone (oFSH) immunization (administered adsorbed on Alugel on days 1, 20, 40 and 70) by producing antibodies capable of both binding and neutralizing bioactivity of human FSH. The kinetics of antibody production for both the immunogen (oFSH) and the cross-reactive antigen (hFSH) were essentially similar. The volunteers responded only to the first two immunizations. The boosters given on days 40 and 70 were ineffective, probably because of the presence of substantial amounts of circulating antibody to oFSH. Of the antibodies generated to oFSH, 25-45% bound hFSH with a mean binding affinity of 0.65 x 10(9) +/- 0.53 M(-1). The binding capacities at the time of high (30-80 days of immunization) and low (>110 days) titres were 346 +/- 185 and 10.5 +/- 5.8 ng hFSH/ml respectively. During the period of high titre, free serum FSH (value in normal males 1-5 ng/ml) was not monitorable. A 50 microl aliquot of the antiserum obtained from different volunteers between days 30 and 80 and on day 140 blocked binding of (125)I-labelled hFSH to its receptor by 82 +/- 9.7 and 53 +/- 12.2% respectively. The antibody produced was specific for FSH, and no significant change in the values of related glycoprotein hormones (luteinizing hormone/testosterone and thyroid stimulating hormone/thyroxine) were recorded. Seminal plasma transferrin, a marker of Sertoli cell as well as of seminiferous tubular function, showed marked reduction (30-90%) following immunization with oFSH. Considering that endogenous FSH remained neutralized for approximately one sperm cycle only (65 days), the reduction in sperm counts (30-74%) exhibited by some volunteers is encouraging. Immunization with oFSH did not result in any significant changes in haematology, serum biochemistry or hormonal profiles. There was no production of antibodies capable of interacting with non-specific tissues. It is concluded that it should be possible to obtain a sustained long-term blockade of endogenous FSH action in men by using oFSH as an immunogen. This is a prerequisite for obtaining significant reduction in the quality and quantity of spermatozoa produced, thus leading to infertility.

Adult↗
PubMed1997

Protein, not adenosine or adenine nucleotides, mediates platelet decrease in endothelial permeability.

Platelets and platelet-conditioned medium (PCM) decrease endothelial protein permeability in vitro. Adenosine and a > 100-kDa protein have previously been implicated as the soluble factors released from platelets that decrease endothelial permeability. The objective of this study was to further investigate the role of adenosine in this platelet response. Measurements of adenosine and its precursor adenine nucleotides by high-performance liquid chromatography were correlated with the assessment of permeability by 125I-labeled albumin clearance and electrical resistance across endothelial cell monolayers derived from the bovine pulmonary artery. PCM contained micromolar concentrations of AMP, ADP, and ATP, but adenosine was below detectable levels (< or = 0.1 microM). Adenosine deaminase, an enzyme that converts adenosine to inactive inosine, or an adenosine-receptor antagonist did not block the platelet- or PCM-mediated decrease in endothelial permeability. A < 3-kDa fraction of PCM that contained micromolar concentrations of AMP and ADP did not affect endothelial permeability, whereas a > 3-kDa fraction that contained much reduced levels of AMP and ADP significantly decreased permeability. This activity of PCM was sensitive to insoluble trypsin. This study rules out adenosine and adenine nucleotides as primary factors in the platelet-induced decrease in endothelial permeability and suggests that the active factor is a protein.

Adenine Nucleotides↗
PubMed1997

A rare case of a liveborn with free, de novo and partial trisomy 12 and an unusual phenotype.

Individuals with free and total trisomy 12 are rare and always mosaic. Incidences of partial trisomy 12 are more frequent and are classified into trisomy 12p and trisomy 12q. The phenotype of both trisomy 12p and trisomy 12q is well described in the literature. We report here, the rare occurrence of a liveborn with free and de novo trisomy 12, albeit not the whole chromosome. The clinical description of this infant includes characteristics of trisomy 12p and trisomy 12q syndromes. Few additional anomalies present in the infant are unaccounted for by both syndromes. We anticipate that these characteristics are caused by trisomy 12q13, which to our knowledge has not been reported in a trisomy before.

Chromosomes, Human, Pair 12↗
PubMed1997

Curative effects of mandur bhasma on liver and kidney of albino rats after induction of acute hepatitis by CCl(4).

Hepatocurative effects of mandur bhasma were studied in albino rats after induction of acute hepatitis by CCl4 liquid paraffin and CCl4 + liquid param. Recovery of the liver was studied with reference to histological architecture and differential counts of degenerated, recovering and recovered hepatocytes. Alterations in the kidney were also studied histologically. Hepatotoxins were given (s.c.) daily for 11 days. Mandur bhasma was given (po) for 7 days to normal, CCl4, liquid paraffin and CCl4 + liquid paraffin treated rats from day 12 to day 18. There were no spontaneous liver and kidney recoveries within a week after the cessation of the treatments of hepatotoxins. Mandur bhasma treatment showed conspicuous recoveries of liver and kidney within a week and total recoveries were noticed after two weeks. Biochemical alterations in lipid peroxidation, glucose-phosphatase and total proteins were studied during present work. The alterations in the histology and biochemical parameters of liver and kidney show hepatocurative potency of mandur bhasma.

Animals↗
PubMed1996

Two patients with duplication of 17p11.2: the reciprocal of the Smith-Magenis syndrome deletion?

J.M. and H.G. are two unrelated male patients with developmental delay. Cytogenetic analysis detected a duplication of 17p11.2 in both patients. The extent of the duplicated region was determined using single copy DNA probes: cen-D17S58-D17S29-D17S258-D17S71-D17S445-+ ++D17S122-tel. Four of the six markers, D17S29, D17S258, D17S71, and D17S445, were duplicated by dosage analysis. Fluorescent in situ hybridization (FISH) analysis of H.G., using cosmids for locus D17S29, confirmed the duplication in 17p11.2. Because the deletion that causes the Smith-Magnesis syndrome involves the same region of 17p11.2 as the duplication in these patients, the mechanism may be similar to that proposed for the reciprocal deletion/duplication event observed in Hereditary Neuropathy with Liability to Pressure Palsies (HNPP) and Charcot-Marie-Tooth Type 1A disease (CMT1A).

Abnormalities, Multiple↗
PubMed1996

Epidermal enzymes as penetration enhancers in transdermal drug delivery?

Epidermal enzymes play an important role in the process of differentiation of keratinocytes. The present preliminary in vitro study was undertaken to observe if topical enzyme treatment influenced permeation of compounds across the skin. Due to the noted function and importance of phosphatidylcholine metabolism during maturation of the barrier lipids, the effects of topical application of the phosphatidylcholine dependent phospholipase C enzyme (not present in epidermis) on skin penetration of three model drugs, viz. benzoic acid, mannitol and testosterone, were studied. Similar studies were also carried out using epidermal enzymes like triacylglycerol hydrolase, acid phosphatase, and phospholipase A2 (present in epidermis). Pretreatment of skin with phospholipase C significantly enhanced permeation of benzoic acid, mannitol, and testosterone relative to untreated skin. Triacylglycerol hydrolase (neutral) increased the penetration of mannitol 3-fold and had no effect on benzoic acid penetration. Topical application of acid phosphatase did not alter the permeation of any of these compounds. Phospholipase A2 significantly enhanced permeation of benzoic acid and mannitol while it did not have any effect on the penetration of testosterone. These results for the first time demonstrate that enzymes may remarkably affect and/or regulate the permeation of topically applied compounds.

Drug Delivery Systems↗
PubMed1996

Effect of topical laurocapram (Azone) on the in vitro percutaneous permeation of sodium lauryl sulfate using human skin.

The probability of simultaneous cutaneous exposure to surfactants and penetration enhancers could occur frequently during routine skin treatment. This study ascertains whether pre-exposure of skin to laurocapram would affect the penetration of a model surfactant, sodium lauryl sulfate (SLS). In vitro experiments with human skin were performed to compare the penetration of SLS after pretreatment with (1) different concentrations of laurocapram, (2) after repeated SLS treatments, (3) untreated controls, and (4) water-control. Pre-exposure to laurocapram enhanced penetration of SLS compared to all other treatments (p < 0.05). Since subsequent pre-exposure of skin to laurocapram increased SLS penetration, the chances of an elevated skin irritation reaction at the exposed site may therefore be possible. Pre-exposure of the skin with SLS did not increase the SLS flux values significantly, compared to the laurocapram pretreated skin. From these results it can be proposed that proper care and precautions may be necessary after exposure of skin to laurocapram and also to various other percutaneous enhancers. Further in vivo correlations are essential to define the clinical implications of this study, especially as related to irritant dermatitis.

Administration, Topical↗
PubMed1996

Differential irritant skin responses to topical retinoic acid and sodium lauryl sulphate: alone and in crossover design.

Topically applied all-trans retinoic acid (RA) is often associated with skin irritation. A detailed quantification of RA-induced functional changes in stratum corneum is, however, still limited. Using non-invasive bioengineering techniques of measurements of transepidermal water loss (TEWL), stratum corneum hydration and cutaneous blood flow (CBF), we quantified the irritant effects of 0.05% and 0.1% RA in ethanol on normal skin compared with 1% sodium lauryl sulphate (SLS) in water as a model irritant in a 24-h occlusive patch-test assay. Additionally, in order to document data possibly related to the mechanism of action, skin responses to both compounds applied in tandem was also investigated over 18 days. The extent of the irritant response to 0.05 and 0.1% RA, respectively, were similar, implying analogous irritation potency. While RA caused more intense scaling than SLS, other skin responses to RA were significantly weaker than those due to SLS. An increase in TEWL, on day 7, in RA-exposed sites indicates a secondary delayed impairment of the stratum corneum (SC) barrier. In a tandem-design assay, pretreatment with RA appeared to reduce the irritant effects of SLS on SC hydration and CBF. In contrast, pre-exposure to SLS showed a synergestic response in erythema, scaling and TEWL. Our results demonstrate that RA, like SLS, is capable of impairing SC water barrier function, which may be responsible, in part, for the irritation associated with its topical use. However, the distinctive biological responses to these compounds suggest a different mode of action of RA and SLS. In addition, the precise reason for the unique results observed in the tandem-design assays is not clear.

Administration, Topical↗