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Biomedical subjects

T Sen

Publications and source records attributed to T Sen.

At least 19 recordsLinked to original sources
PubMed2006

Apoptosis is induced in leishmanial cells by a novel protein kinase inhibitor withaferin A and is facilitated by apoptotic topoisomerase I-DNA complex.

Protein kinase C (PKC) is an important constituent of the signaling pathways involved in apoptosis. We report here that like staurosporine, withaferin A is a potent inhibitor of PKC. In Leishmania donovani, the inhibition of PKC by withaferin A causes depolarization of DeltaPsim and generates ROS inside cells. Loss of DeltaPsim leads to the release of cytochrome c into the cytosol and subsequently activates caspase-like proteases and oligonucleosomal DNA cleavage. Moreover, in treated cells, oxidative DNA lesions facilitate the stabilization of topoisomerase I-mediated cleavable complexes, which also contribute to DNA fragmentation. However, withaferin A and staurosporine cannot induce cleavable complex formation in vitro with recombinant topoisomerase I nor with nuclear extracts from control cells. Taken together, our results indicate that inhibition of PKC by withaferin A is a central event for the induction of apoptosis and that the stabilization of topoisomerase I-DNA complex is necessary to amplify apoptotic process.

Animals↗
PubMed2004

Camptothecin induced mitochondrial dysfunction leading to programmed cell death in unicellular hemoflagellate Leishmania donovani.

The parasites of the order kinetoplastidae including Leishmania spp. emerge from most ancient phylogenic branches of unicellular eukaryotic lineages. In their life cycle, topoisomerase I plays a significant role in carrying out vital cellular processes. Camptothecin (CPT), an inhibitor of DNA topoisomerase I, induces programmed cell death (PCD) both in the amastigotes and promastigotes form of L. donovani parasites. CPT-induced cellular dysfunction in L. donovani promastigotes is characterized by several cytoplasmic and nuclear features of apoptosis. CPT inhibits cellular respiration that results in mitochondrial hyperpolarization taking place by oligomycin-sensitive F0-F1 ATPase-like protein in leishmanial cells. During the early phase of activation, there is an increase in reactive oxygen species (ROS) inside cells, which causes subsequent elevation in the level of lipid peroxidation and decrease in reducing equivalents like GSH. Endogenous ROS formation and lipid peroxidation cause eventual loss of mitochondrial membrane potential. Furthermore, cytochrome c is released into the cytosol in a manner independent of involvement of CED3/CPP32 group of proteases and unlike mammalian cells it is insensitive to cyclosporin A. These events are followed by activation of both CED3/CPP32 and ICE group of proteases in PCD of Leishmania. Taken together, our study indicates that different biochemical events leading to apoptosis in leishmanial cells provide information that could be exploited to develop newer potential therapeutic targets.

Animals↗
PubMed2004

Improved efficacy and tolerability of retinoic acid in acne vulgaris: a new topical formulation with cyclodextrin complex psi.

OBJECTIVES: Retinoic acid (RA) has long been used, both topically and systemically, for disorders of keratinization, acne and related disorders. In the present study, the efficacy and tolerability of topical RA prepared as a cyclodextrin beta complex (beta-CD) is investigated in 66 acne vulgaris patients. METHODS: This randomized, double-blind, placebo-controlled study compares nightly topical application of RA/beta-CD complex hydrogel formulation (0.025%), RA/beta-CD complex in moisturizing base (0.025%), hydrogel base, moisturizer base or a commercial RA gel (0.05%) in acne vulgaris patients. Improvement of acne was assessed using a 5-point improvement scale and by measuring sebum and moisture content of the skin using an SM 810 sebumeter/corneometer. RESULTS: After 3 months of treatment, mean scores of acne improvement on the 5-point scale were 4 with the RA/beta-CD complex hydrogel formulation, 4.1 with the RA/beta-CD complex in moisturizing base, 1.2 with hydrogel placebo base, 1.1 with moisturizer placebo base and 3 with the commercial RA product. All patients treated with the commercial product experienced local side-effects. One patient discontinued due to severe irritation. None of the patients treated with the RA/beta-CD complex in the moisturizing base and hydrogel formulation experienced significant local irritation, although the sebum content of the skin decreased after application of the RA/beta-CD preparations. This change was not significant compared to controls. The moisture content of the skin was better preserved in the group treated with the RA/beta-CD complex in the moisturizing base. CONCLUSION: The topical RA/beta-CD complex, in hydrogel and moisturizing base, was more effective than the twice concentrated commercial RA product. There were few topical side-effects with this new formulation, which increases patient compliance. Topical RA/beta-CD (0.025% RA) did not significantly reduce sebum secretion but may help to preserve optimum epidermal moisture content with the proper base formulation. This is the first study in the literature reporting efficacy and tolerability of the topical RA/beta-CD complex in acne vulgaris. We conclude that the topical RA/beta-CD complex displays an improved efficacy and tolerability profile and is an effective treatment alternative for acne vulgaris.

Acne Vulgaris↗
PubMed2003

Macro-cellular silica foams: synthesis during the natural creaming process of an oil-in-water emulsion.

The room-temperature synthesis of a macro-mesoporous silica material during the natural creaming process of an oil-in-water emulsion is reported. The material has 3-dimensional interconnected macropores with a strut-like structure similar to meso-cellular silica foams with mesoporous walls of worm-hole structure. The material has very high surface area (approximately 800 m2 g(-1)) with narrow mesopore size distribution.

Journal Article↗
PubMed2002

Antioxidant activity of the methanol fraction of Pluchea indica root extract.

Studies were carried out to evaluate the influence of the methanol fraction of Pluchea indica Less root extract (PIRE), the dual inhibitors (BW 755C and phenidone) and vitamin on both in vivo and in vitro free radical-scavenging activities, CCl(4)-induced lipid peroxidation and the metabolism of arachidonic acid by lipoxygenase. PIRE produced significant antiinflammatory activity against glucose oxidase-induced paw oedema (in vivo), inhibited hydroxyl radical and superoxide generation, lysis of erythrocytes induced by hydrogen peroxide, CCl(4)-induced lipid peroxidation and also dioxygenase activity of lipoxygenase (both in the presence and absence of hydrogen peroxide). Significantly higher free radical-scavenging activity was observed with BW 755C and phenidone compared with PIRE. However, both BW 755C and phenidone stimulated hydroxyl radical generation compared with the observed inhibitory effects of PIRE and vitamin E.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗
PubMed2002

Effect of amitriptyline on gastric ulceration.

Amitriptyline significantly inhibited alcohol, aspirin, indomethacin and cold-restraint stress-induced ulceration. Secretory studies conducted in pyloric-ligated rats revealed that the drug, at the doses employed, significantly reduced total acidity and protein content. However, significant reductions of the gastric volume were only observed at the highest dose of the drug. In another set of experiments, when 50% alcohol (v/v) was administered to the pyloric-ligated rats pretreated with amitriptyline, it was observed that the drug significantly reduced the pH, total acidity and protein content.

Amitriptyline↗
PubMed2001

Bond-shift rearrangement in solid Li(3)P(7)(monoglyme)(3): a (31)P MAS NMR study.

The (31)P MAS NMR spectrum of solid Li(3)P(7)(monoglyme)(3) has been reinvestigated over a wide temperature range (-70 to +77 degrees C) and under conditions of better resolution (Larmor frequency of 162 MHz and spinning rate of approximately 30 kHz) than previously measured (121 MHz and 13 kHz). At low temperatures three spinning sideband (ssb) manifolds are observed: a singlet (centered at -45 ppm relative to 85% H(3)PO(4)) due to the apical atom (A) of the P(7)-cage trianion; a 1 : 1 : 1 triplet (at -110, -117, and -124.5 ppm) due to the negatively charged equatorial (E) atoms, and a one to two doublet (at -161 and -168.5 ppm) due to the basal (B) atoms. These results are consistent with the P(7) cage having nearly, but not perfect, C(3v) symmetry. The compound appears to be well ordered in the solid state with very little structural dispersity. On heating, the NMR lines broaden and eventually coalesce into a single ssb manifold. This behavior is ascribed to bond-shift rearrangement similar to the Cope rearrangement in bullvalene. A MAS 2D exchange experiment and a quantitative analysis of the 1D NMR lineshapes indicate that, unlike in solution where the rearrangement involves a single bond shift at a time, in the solid the process involves a succession of two bond shifts: The first leads to an intermediate species in which the rearranged P(7) cage is inverted, while in the subsequent step a second bond shift takes place that also restores the original orientation of the cage in the lattice. The overall effect of the double bond shift is equivalent to cyclic permutation of the phosphorus atoms within the five member rings of the P(7)-cage. The quantitative analysis of the dynamic lineshapes shows that this cyclic permutation proceeds at a different rate in one ring (k(d)(1)) than in the other two (k(d)(2,3)). The kinetic parameters for these processes are E(a)(1)=18.7 kJ/mol, E(a)(2,3)=58.0 kJ/mol, k(d)(1)(17 degrees C)=k(d)(2,3)(17 degrees C)=10(4) s(-1). No indications for independent threefold molecular jumps of the P(7) cage were found.

Journal Article↗
PubMed2001

An unusual paratyphoid fever.

Salmonella typhi is known to produce acalculous cholecystitis and related gall bladder perforation. Following is a documentation of a patient of sub-phrenic abscess and gall bladder perforation which was possibly a result of Salmonella paratyphi A.

Biopsy, Needle↗
PubMed2000

Effect of dothiepin on gastric ulceration mediated by lipid derived eicosanoids.

Dothiepin, a tricyclic antidepressant, significantly inhibited the development of gastric ulcers induced by alcohol, aspirin, indomethacin and Shay's pyloric ligation. Antisecretory studies in pyloric ligated rats revealed that the drug at a dose of 100 mg/kg significantly reduced total acidity, gastric output and protein content. In another set of experiments, dothiepin significantly reduced gastric output, total acidity and protein content in pyloric ligated rats which received 50% alcohol (v/v) 30 minutes after the administration of dothiepin.

Animals↗
PubMed2000

Preliminary studies on the anti-inflammatory and analgesic activity of the methanolic fraction of the root extract of Tragia involucrata Linn.

Tragia involucrata has been widely used in the traditional medicinal system for the treatment of a variety of diseases. The effect of methanolic extract of T. involucrata was studied in different experimental animal models and it was revealed that the extract possesses significant analgesic and anti-inflammatory activity.

Analgesics, Non-Narcotic↗
PubMed1999

Neuropsychopharmacological profile of the methanolic fraction of Bryophyllum pinnatum leaf extract.

Neuropharmacological studies were conducted in experimental animals (rats and mice) with the methanolic fraction of Bryophyllum pinnatum leaf extract. The fraction produced alteration of behaviour pattern, caused dose-dependent potentiation of pentobarbitone sleeping time and had significant analgesic activity. Significant reduction of exploratory behaviour and loss of residual curiosity were among the effects observed with the fraction. The observations suggest that the methanolic fraction of Bryophyllum pinnatum possesses a potent CNS depressant action.

Analgesia↗
PubMed1998

Studies on the possible mechanism of the gastric mucosal protection by Calotropis procera--involvement of 5-lipoxygenase pathway.

The role of chloroform fraction of Calotropis procera root extract on different experimental ulcer models in rats was investigated. The extract demonstrated significant anti-ulcer activity against aspirin, indomethacin, ethanol, indomethacin + ethanol, or stress-induced ulcerations. Significant inhibition of gastric secretory volume and total acidity in pylorus ligated rats were observed to occur with the extract. It was also observed that the root extract significantly inhibited arachidonic acid metabolism induced by soyabean lipoxygenase. The results suggest that the anti-ulcer activity of the extract might be attributable to the inhibition of 5-lipoxygenase (5-LO).

Animals↗
PubMed1993

Studies on the mechanism of anti-inflammatory and anti-ulcer activity of Pluchea indica--probable involvement of 5-lipooxygenase pathway.

The effect of the methanolic fraction of Pluchea indica Less. root extract was evaluated on various models of inflammation and ulcer in vivo to assess the role of P. indica on the 5-lipoxygenase pathway of prostaglandin synthesis. Studies presented here reveal significant antiinflammatory activity of the fraction on Arachidonic acid, Platelet activation factor and Compound 48/80-induced paw oedema. There was significant inhibition of spontaneous as well as compound 48/80-induced histamine release from mast cells. Ulcer studies revealed significant protective action of the fraction on indomethacin, alcohol and indomethacin-alcohol induced ulceration. There was significant decrease of gastric volume and acidity in pylorus ligated rats. Studies also showed, significant protective action of the same on gastric mucosa.

Animals↗