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Biomedical subjects

S Kothari

Publications and source records attributed to S Kothari.

At least 19 recordsLinked to original sources

Effect of hydroxypropyl cellulose (HPC) on dissolution rate of hydrochlorothiazide tablets.

Hydrochlorothiazide (HCTZ) 60 mg strength tablets containing commonly used excipients and hydroxypropyl cellulose, marketed as either Klucel-EF (HPC, NF from Hercules, USA) or HPC-L (HPC, NF from Nippon Soda, Japan), as a binder were manufactured using identical aqueous wet granulation process. The tablets containing Klucel-EF as a binder exhibited higher dissolution rates than those manufactured using HPC-L. The granulations containing Klucel-EF or HPC-L showed no significant differences in compressibility and compactibility based on analysis performed using the Instron-Stress-Strain Analyzer. Both HPC grades met NF specifications and there were no differences for the NF test results in the certificates of analysis by their respective vendors. Further evaluation of both HPC grades indicated that the cloud point values for Klucel-EF and HPC-L in water were 39(+/- 1) and 48 degrees C, respectively. The differences in cloud points of Klucel-EF and HPC-L were correlated to the differences in the percent hydroxypropoxy content and the degree of molecular substitution, which were higher for Klucel-EF than for HPC-L. These structural features make Klucel-EF less hydrophilic. Since the cloud point of Klucel-EF was similar to the dissolution medium temperature of 37(+/- 2) degrees C, it may present a less viscous layer surrounding the HCTZ granules enabling faster dissolution of the drug.

Cellulose↗

In vivo and in vitro evidence for autocrine DCoH/HNF-1alpha transcription of albumin in the human epidermis.

The presence of albumin in the human epidermis has been reported more than a decade ago, but until now, it was assumed that this protein is synthesized in the liver and transported to the avascular skin. To our knowledge, transcription of albumin in the human epidermis was never considered. In this report, we present for the first time evidence for autocrine synthesis of albumin in the human epidermis in keratinocytes in situ and in vitro. Using double immunofluorescence labelling, we identified that albumin colocalized together with its transcription factor PCD/DCoH/HNF-1alpha in suprabasal keratinocytes in human full-thickness skin sections and in keratinocytes cultured in serum-free medium. Moreover, albumin and HNF-1alpha protein expression was confirmed by Western blotting in undifferentiated and differentiated keratinocytes as well as in human epidermal suction blister roof extracts. Reverse-transcriptase polymerase chain reaction analysis from human epidermal keratinocytes and epidermal suction blister roofs revealed the transcription of albumin. Using in vivo fluorescence excitation spectroscopy at the surface of human skin, we confirmed albumin as a major constituent yielding a lambda(max) at 295 nm, which was assigned to the single tryptophan 214 fluorophore in this protein. This in vivo result is in agreement with albumin concentrations of 10(-3) M, underlining the importance of this protein in epidermal homeostasis.

Albumins↗

Molecular evidence that halo in Sutton's naevus is not vitiligo.

Both halo naevus and vitiligo are acquired leucodermas of unknown aetiology. To date a significant contribution of oxidative stress through accumulation of hydrogen peroxide (H2O2) has been documented in the pathomechanism of vitiligo but not in halo naevus. Both epidermal pterin-4a-carbinolamine dehydratase (PCD) and catalase are sensitive markers to follow H2O2 concentration-dependent deactivation of these proteins. In situ protein expression of PCD and catalase was examined in full-skin biopsies from skin phototype-matched controls (n=5), untreated and treated vitiligo patients (n=5) and patients with untreated halo naevus in association with vitiligo (n=3). Vitiligo was treated with pseudocatalase (PC-KUS) only. Catalase levels were determined in epidermal suction blister extracts using fast protein liquid chromatography (FPLC). In addition, epidermal H2O2 levels were followed in vivo by Fourier-transform Raman spectroscopy. The results of this study ruled out a contribution of H2O2 in the millimolar range in the depigmentation process of halo naevus as previously documented in vitiligo. Therefore, it can be concluded that both leucodermas exercise distinct concentration-dependent H2O2 signalling in their pathomechanisms.

Catalase↗

Predicting the reduction of parasitaemia following exchange transfusion in severe Plasmodium falciparum malaria: comparison of two mathematical formulae.

Two mathematical models to predict the level of parasitaemia after exchange transfusion in severe malaria have been described. One formula, described by Wilkinson and colleagues, calculates the level from the total volume of blood exchanged whereas the other, derived by Van den Ende and colleagues, is recursive and gives estimates of the reduction in parasitaemia after each aliquot of exchange. The accuracies of predictions based on these two formulae were compared using data collected from 20 patients undergoing partial exchange transfusion (40 ml blood/kg body weight). The transfusions led to significant changes in the mean (S.D.) haemoglobin concentrations, which rose from 8.9 (2.4) to 10.1 (1.5) g/dl, and in the median levels of parasitaemia, which fell from 16.5% (interquartile range = 12.8%-28.8%) to 4.5% (interquartile range = 1.2%-9.3%). The median level of post-transfusion parasitaemia predicted by the Van den Ende formula (6.6%, with an interquartile range of 4.5%-10.2%) was similar to that observed, whereas that predicted by the Wilkinson formula (7.2%, with an interquartile range of 5.6%-12.4%) was significantly higher (P = 0.018). However, the median difference between the predictions based on the two formulae was represented by a parasitaemia of only 1.0% (interquartile range = 0.6%-1.85%). Thus, although the Van den Ende formula is more accurate than the Wilkinson, the difference is unlikely to be clinically significant.

Adolescent↗

The proteome of maize leaves: use of gene sequences and expressed sequence tag data for identification of proteins with peptide mass fingerprints.

As a first step in establishing a proteome database for maize, we have embarked on the identification of the leaf proteins resolved on two-dimensional (2-D) gels. We detected nearly 900 spots on the gels with a pH 4-7 gradient and over 200 spots on the gels with a pH 6-11 gradient when the proteins were visualized with colloidal Coomassie blue. Peptide mass fingerprints for 300 protein spots were obtained with matrix assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometer and 149 protein spots were identified using the protein databases. We also searched the pdbEST databases to identify the leaf proteins and verified 66% of the protein spots that had been identified using the protein databases. Sixty-seven additional protein spots were identified from expressed sequence tags (ESTs). Many abundant leaf proteins are present in multiple spots. Functions of over 50% of the abundant leaf proteins are either unknown or hypothetical. Our results show that EST databases in conjunction with peptide mass fingerprints can be used for identifying proteins from organisms with incomplete genome sequence information.

Electrophoresis, Gel, Two-Dimensional↗

Evidence suggesting that high intake of fluoride provokes nephrolithiasis in tribal populations.

The present study was designed to evaluate the role of fluoride in urolithiasis in humans. Two areas were selected for this purpose, a fluoride endemic area (EA) and a fluoride non-endemic area (NEA). The prevalence of uroliathiasis was 4.6 times higher in EA than in NEA. Furthermore, the prevalence was almost double in subjects with fluorosis than without fluorosis in the endemic area. No relationship was observed between urolithiasis and the duration of fluorosis. The fluoride levels in drinking water ranged from 3.5 to 4.9 ppm in EA and subjects from this area excreted more fluoride. A comparison of normal subjects (NS) from EA and NEA revealed that endemic subjects tend to have slightly higher mean serum thiobarbituric acid reactive substance (TBAR) levels and excrete more oxalate and fluoride than their non-endemic counterparts. The urinary stone formers (SF) from the two areas showed a similar tendency, though again the difference was not significant. Citrate excretion in SF was almost normal in the EA, but NEA SF had significantly lower excretion levels. Urinary stones from endemic patients had higher fluoride, oxalate and calcium levels than those from non-endemic patients. In vitro studies suggested that fluoride did not influence the heterogonous mineralization of calcium oxalate. In conclusion, the data suggest that fluoride in vivo may behave as a mild promoter of urinary stone formation by (a) excretion of insoluble calcium fluoride, (b) increasing oxalate excretion and (c) mildly increasing the oxidative burden.

Adult↗

Neurological manifestations of HIV disease.

We report the results of neurological evaluation of 1,527 HIV positive subjects. Neurological complications were seen in 457 patients (481 neurological events). The prevalence was 20.24% of patients attending the out-patient clinic and in 44.57% of in-patients. Involvement of all levels of neuraxes was documented. The commonest manifestations were neuropathies, including herpes zoster (28.27%), meningitis (17.88%) and mass lesions (16%). Cryptococcal meningitis was clearly commoner than tubercular meningitis (67.44% vs 18.60% of all cases of meningitis, respectivelv). Amongst mass lesions, 14/24 single lesions and 27/38 multiple lesions responded to anti-toxoplasma treatment and were diagnosed as CNS toxoplasmosis. In abscence of biopsy, it would be prudent to initiate empirical anti-toxoplasma treatment for all HIV patients with mass lesions and assess clinical and radiological response. To our knowledge this is the largest series of neurological manifestations of HIV disease documented in Indian literature.

Adult↗

GABA agonists and gabapentin for spastic hypertonia.

Spasticity is a result of an imbalance between the afferent excitatory and descending inhibitory pathways after central nervous system damage. Its pharmacologic control is believed to result from the antagonism of inhibitory mechanisms (gamma-aminobutyric acid [GABA] or glycine-mediated antagonism of excitatory mechanisms), or both. Because GABA receptor sites are widely present in the central nervous system, it is amenable to pharmacologic manipulation.

Acetates↗

Risk assessment of the menopausal patient.

Menopause is a physiologic event that gives a woman the opportunity to become involved in a preventive health program. Menopause is not a disease; however, it does cause symptoms in a significant percentage of women. Medical evaluation with an emphasis on health maintenance and lifestyle measures is important for menopausal women. Tailoring an individual program for women, which may include HRT and other therapeutic options, is guided by the menopausal risk assessment.

Alzheimer Disease↗

Evidence for circulating bone marrow-derived endothelial cells.

It has been proposed that hematopoietic and endothelial cells are derived from a common cell, the hemangioblast. In this study, we demonstrate that a subset of CD34(+) cells have the capacity to differentiate into endothelial cells in vitro in the presence of basic fibroblast growth factor, insulin-like growth factor-1, and vascular endothelial growth factor. These differentiated endothelial cells are CD34(+), stain for von Willebrand factor (vWF), and incorporate acetylated low-density lipoprotein (LDL). This suggests the possible existence of a bone marrow-derived precursor endothelial cell. To demonstrate this phenomenon in vivo, we used a canine bone marrow transplantation model, in which the marrow cells from the donor and recipient are genetically distinct. Between 6 to 8 months after transplantation, a Dacron graft, made impervious to prevent capillary ingrowth from the surrounding perigraft tissue, was implanted in the descending thoracic aorta. After 12 weeks, the graft was retrieved, and cells with endothelial morphology were identified by silver nitrate staining. Using the di(CA)n and tetranucleotide (GAAA)n repeat polymorphisms to distinguish between the donor and recipient DNA, we observed that only donor alleles were detected in DNA from positively stained cells on the impervious Dacron graft. These results strongly suggest that a subset of CD34+ cells localized in the bone marrow can be mobilized to the peripheral circulation and can colonize endothelial flow surfaces of vascular prostheses.

Animals↗

Surface chemistry of a high-copper dental amalgam.

In amalgam, mercury is intended to take the form of stable intermetallic compounds. Any mercury leakage must therefore come from free mercury not involved in such compounds. Thus, a knowledge of the exact surface chemistry of dental amalgam is necessary if this phenomenon is to be understood. From XPS and EDS analyses, a model of the surface chemistry of amalgam is proposed which fully characterizes all the phases that are present. The data show the surface to have a composition different from that of the bulk, being comprised of a hydrocarbon deposit and adsorbed water covering the intermetallic phase gamma2 (Sn(6-8)Hg), tin (iv) oxide, and mercury in a free state. After amalgamation, the amount of mercury at the surface decreases with time and eventually attains a constant concentration, where it is all involved in the gamma2 phase, leaving no free mercury. A model is proposed for the surface of amalgam and the changes in this model with time.

Copper↗

Oncostatin M induces basic fibroblast growth factor expression in endothelial cells and promotes endothelial cell proliferation, migration and spindle morphology.

Oncostatin M (OSM), a pleiotropic cytokine originally isolated from supernatants of the U937 histiocytic lymphoma cell line, has been shown to have regulatory effects on a wide variety of cultured and tumor cells. We investigated the effects of OSM on basic fibroblast growth factor (bFGF) gene expression in bovine arterial endothelial (BAE) cells. Levels of bFGF mRNA transcripts were low in uninduced BAE cells, were maximal at 8 hours of exposure to OSM, and returned to control levels by 24 hours. Induction of bFGF mRNA transcripts by OSM was dose-dependent. Nuclear transcriptional run-on analysis demonstrated that exposure of BAE cells to OSM stimulated bFGF gene transcription. OSM treatment of BAE cells enhanced the synthesis of bFGF protein as determined by ELISA assays. Immunocytochemistry studies demonstrated the presence of low levels of bFGF protein within the cytoplasm in uninduced cells. After stimulation for 8 hours with OSM there was significant staining for bFGF in the cytoplasm. However, 24 hours after exposure to OSM, bFGF antigen was located only within the nuclei. Western blot analysis demonstrated that OSM stimulated predominantly the synthesis of a 22 kDa form of bFGF. In addition, OSM stimulated endothelial cell proliferation and migration as well as acquisition of a spindle shape. Phosphorothioate antisense oligonucleotide directed against bFGF inhibited OSM induced BAE cell proliferation and spindle shape formation but had only a minimal effect on migration. The levels of the 22 kDa form of bFGF were reduced by antisense treatment indicating that OSM induced proliferation and morphology change is likely to be regulated by intracellular bFGF. Our studies suggest that OSM released at sites of vascular injury could stimulate angiogenesis by inducing bFGF synthesis, endothelial cell proliferation and migration.

Animals↗

Synthetic implant surfaces. 1. The formation and characterization of sol-gel titania films.

Sol-gel has been used to prepare thin titania films. We have investigated the effects of dip rate, sintering temperature and time on the chemical composition of the films, their physical structure and thickness, and adherence to a silica substrate. Our aim has been to produce films that mimic as closely as possible the natural oxide layer that is found on titanium. These films are to be used as substrates in an in vitro model of osseointegration.

1-Propanol↗