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Biomedical subjects

K Biswas

Publications and source records attributed to K Biswas.

At least 19 recordsLinked to original sources

Recurrent lymphocytic hypophysitis in a woman 27 years after subtotal adrenalectomy for hypercortisolism possibly of autoimmune origin.

Lymphocytic hypophysitis commonly occurs in females in peripartum period but several unusual presentations have been reported. Here we report a rare case of recurrent lymphocytic hypophysitis in a woman who had subtotal adrenalectomy for hypercortisolism 27 years back. Polyglandular autoimmune endocrinopathy with an uncommon combination of Cushing's syndrome and recurrent hypophysitis is a strong possibility in this case. Treatment with steroids has been found to have beneficial effect.

Adrenalectomy↗

A proteomic approach to understanding the development of multidrug-resistant Candida albicans strains.

Resistance of the pathogenic yeast Candida albicans to the antifungal agent fluconazole is often caused by the overexpression of genes that encode multidrug efflux pumps ( CDR1, CDR2, or MDR1). We have undertaken a proteomic approach to gain further insight into the regulatory network controlling efflux pump expression and drug resistance in C. albicans. Three pairs of matched fluconazole-susceptible and resistant clinical C. albicans isolates, in which drug resistance correlated with stable activation of MDR1 or CDR1/2, were analyzed for differences in their protein expression profiles. In two independent, MDR1-overexpressing, strains, additional up-regulated proteins were identified, which are encoded by the YPR127 gene and several members of the IFD ( YPL088) gene family. All are putative aldo-keto reductases of unknown function. These proteins were not up-regulated in a fluconazole-resistant strain that overexpressed CDR1 and CDR2 but not MDR1, indicating that expression of the various efflux pumps of C. albicans is controlled by different regulatory networks. To investigate the possible role of YPR127 in the resistance phenotype of the clinical isolates, we constitutively overexpressed the gene in a C. albicans laboratory strain. In addition, the gene was deleted in a C. albicans laboratory strain and in one of the drug-resistant clinical isolates in which it was overexpressed. Neither forced overexpression nor deletion of YPR127 affected the susceptibility of the strains to drugs and other toxic substances, suggesting that the regulatory networks which control the expression of efflux pumps in C. albicans also control genes involved in cellular functions not related to drug resistance.

Antifungal Agents↗

The epothilones, eleutherobins, and related types of molecules.

Taxol is currently one of the most effective anticancer agents available. However, limitations due to multidrug-resistance (MDR) susceptibility and lack of aqueous solubility render it less than an ideal drug. These limitations, coupled with taxol's unique mechanism of tumor inhibition, involving the stabilization of microtubule assembly, have spurred the search for more effective chemotherapeutic agents. This review will discuss the chemistry and biology of some of the most promising new molecules with "taxol-like" activity. The extended family of microtubule-stabilizing agents now includes the epothilones, eleutherobins, discodermolide, laulimalide and WS9885B. The epothilones have emerged as one of the most exciting new candidates for detailed structure-activity-related studies. A review of our efforts in the synthetic and biological aspects of this research is presented, as are the latest developments reported from other laboratories in academia and the pharmaceutical industry. The synthesis and structure-activity studies of eleutherobins, as well as recent progress with discodermolide, laulimalide and WS9885B are also reviewed. An abundance of exciting advances in chemistry and biology have emerged from these studies, and it is hoped that it will ultimately result in the development of new and more effective chemotherapeutic agents in the fight against cancer.

Alkaloids↗

Gastric toxicity and mucosal ulceration induced by oxygen-derived reactive species: protection by melatonin.

Uncontrolled hydrochloric acid secretion and ulceration of the stomach mucosa due to various factors are serious global problems. Although the mechanism of acid secretion from the parietal cell is now well understood, the processes involved in gastric ulceration are still not clear. Among various causes of gastric ulceration, lesions caused by stress, alcohol consumption, Helicobacter pylori infection and due to use of nonsteroidal antiinflammatory drugs have been shown to be mediated largely through the generation of reactive oxygen species, especially the hydroxyl radical. A number of excellent drugs have proven useful in controlling hyperacidity and ulceration but their long-term use is associated with disturbing side-effects. Hence, the search is still on to find a compound possessing antisecretory, antiulcer and antioxidant properties which will serve as a therapeutic agent to reduce gastric hyperacidity and ulcers. This article describes the role of reactive oxygen species in gastric ulceration, drugs controlling them with their merits and demerits and, the role of melatonin, a pineal secretory product, in protecting against gastric lesions. In experimental studies, melatonin has been shown to be effective in reducing mucosal breakdown and ulcer formation in a wide variety of situations. Additionally, the low toxicity of melatonin supports further investigation of this molecule as a gastroprotective agent. Finally, we include a commentary on how melatonin research with respect to gastric pathophysiology can move forward with a view of eventually using this indole as a therapeutic agent to control gastric ulceration in humans.

Animals↗

Melatonin protects against stress-induced gastric lesions by scavenging the hydroxyl radical.

The antiulcer effect of melatonin on gastric lesions caused by restraint-cold stress or by indomethacin (IMN) was studied with the intent of determining the mechanism of action of the indole. Melatonin dose-dependently prevents both stress and IMN-induced gastric damage with around 90% inhibition at a dose of 60 mg per kg BW. When compared with already-marketed antiulcer drugs, such as ranitidine and omeprazole, melatonin was found to be more effective than ranitidine but less effective than omeprazole in preventing stress ulcer. When compared with other antioxidants, melatonin was more potent than glutathione and essentially equipotent to alpha-tocopherol in blocking stress-induced ulcer. As stress-induced gastric lesions are mainly caused by oxidative damage due to hydroxyl radicals (*OH), the effect of melatonin in scavenging the *OH generated during stress conditions, as well as in an in vitro model system, was studied. The results indicate that melatonin at the dose of 60 mg per kg BW caused an 88% reduction of endogenous *OH during stress. Melatonin was also highly effective in scavenging *OH generated in vitro by a Cu2+-ascorbate system. In this case, melatonin at 100 microM reduced *OH by 80%. Melatonin was also found to be a more potent radical scavenger than benzoate, a known *OH scavenger. The results indicate that melatonin prevents stress-induced gastric lesions by scavenging the endogenous *OH. As it also protects against IMN-induced gastric damage, it probably also offers gastroprotection by maintaining endogenous prostaglandin levels.

Animals↗

Hypothalamic hamartoma as a cause of precocious puberty in neurofibromatosis type 1: patient report.

Precocious puberty resulting from hypothalamic hamartoma is well known. Neurofibromatosis type 1 can also present with precocious puberty. However, hypothalamic hamartoma as the cause of precocious puberty in patients with neurofibromatosis type 1 has never been described in the literature. This rare occurrence of these two together in a patient with precocious puberty is reported.

Adult↗

Dexamethasone makes the gastric mucosa susceptible to ulceration by inhibiting prostaglandin synthetase and peroxidase--two important gastroprotective enzymes.

The plausible mechanism by which dexamethasone makes the gastric mucosa susceptible to ulceration has been studied. As acid aggravates ulcer, the role of dexamethasone on acid secretion was first investigated. Dexamethasone stimulates both basal and drug (mercaptomethylimidazole)-induced gastric acid secretion by 100 and 50% respectively in male Wister rats 24 h after intramuscular administration at the dose of 1 mg/kg body wt. This stimulated acid secretion is 93% blocked by cimetidine indicating increased liberation of histamine in the process. Pretreatment of dexamethasone before 24 h produces ulcer in 30% of the pylorus- ligated rats and aggravates the ulcer index by 82% in both pylorus and esophagus ligated rats. The incidence of ulceration in the latter cases is also increased by 25%. As mucosal prostaglandin synthetase and peroxidase play an important role in gastroprotection through biosynthesis of prostaglandin and by scavenging endogenous H2O2 respectively, the effect of dexamethasone on the activities of these gastroprotective enzymes were studied. Prostaglandin synthetase and peroxidase activities of the mucosa are significantly inhibited by 87 and 83% respectively by 24-h pretreatment with dexamethasone. The results indicate that dexamethasone makes the mucosa prone to ulceration by inhibiting the activity of prostaglandin synthetase to block the gastroprotective action of prostaglandin and also by inhibiting the peroxidase, thereby elevating the endogenous H2O2 level to generate more reactive hydroxyl radical responsible for the mucosal damage.

Animals↗

Parallel synthesis and screening of a solid phase carbohydrate library.

A solid phase carbohydrate library was synthesized and screened against Bauhinia purpurea lectin. The library, which contains approximately 1300 di- and trisaccharides, was synthesized with chemical encoding on TentaGel resin so that each bead contained a single carbohydrate. Two ligands that bind more tightly to the lectin than Gal-beta-1,3-GalNAc (the known ligand) have been identified. The strategy outlined can be used to identify carbohydrate-based ligands for any receptor; however, because the derivatized beads mimic the polyvalent presentation of cell surface carbohydrates, the screen may prove especially valuable for discovering new compounds that bind to proteins participating in cell adhesion.

Acylation↗

Evaluation of antimuscarinic activity in human volunteers: a teaching aid in clinical pharmacology.

The antimuscarinic activity of oxyphenonium bromide, diphenhydramine hydrochloride and astemizole were evaluated in six volunteers. The parameters used were salivary secretion, heart rate and pupillary size. The results indicated that the changes in heart rate and pupillary size and measurements were not convenient parameters for class room demonstration. However, salivary secretion and dryness of mouth were found to be reliable parameters for measurement. It was concluded that simple procedures like evaluation of antimuscarinic activity could be introduced as teaching aids in clinical pharmacology for undergraduate students.

Adult↗

Incidence of helminthic infections and comparative study of pyrantel pamoate with levamisole and mebendazole in hospital patients at Barisal, Bangladesh.

A study was carried out to find out the incidence of helminthic infections in hospitalized patients at Sher-e-Bangla Medical College, Barisal and to determine the comparative efficacy of pyrantel pamoate, levamisole, and mebendazole. It was observed that 76.2 per cent of total hospitalized patients were infected with intestinal helminths. Polyparasitism (52.6 per cent) was more frequent than single infection (21.8 per cent). Amongst these, 47.5 per cent was suffering from Asearis lumbricoides (AL), 42.5 per cent from Hookworm (H.W) and 65.8 per cent from trichuris trichura (TT). Out of 255 cases examined separately, 40 per cent was suffering from Enterobious vermicularis (EV) infection. The comparative study showed that mebendazole produced egg negative stool in 90.9 per cent of AL, 95.6 per cent of HW and 86.8 per cent of TT after eight days of treatment. On the other hand, pyrantel pamoate cured AL in 93.3 per cent, HW in 78.5 per cent and TT in 34.2 per cent eases. Levamisole cured 75 per cent AL, 4.1 per cent H.W. and 22.2 per cent TT within the same period.

Adolescent↗

Chemical constituents of Gentianaceae XXIV: Anti-Mycobacterium tuberculosis activity of naturally occurring xanthones and synthetic analogs.

Anti-Mycobacterium tuberculosis H37 RV data are presented for the individual xanthones of Canscora decussata Schult and Swertia purpurascens Wall (Gentianaceae); a few, from the former species, showed significant activity. Additionally, sturcture--activity relationships of these compounds are evaluated on the basis of the minimum inhibitory concentration data of 18 naturally occurring xanthones bearing 1,3,5- 1,3,5,6-, 1,3,6,7-, 1,3,5,8-, 1,3,5,6,7-, and 1,3.6,7,8-oxygenated patterns and six synthetic analogs.

Antitubercular Agents↗