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Biomedical subjects

R D Mehta

Publications and source records attributed to R D Mehta.

16 recordsLinked to original sources

Divalproex sodium in the management of post-herpetic neuralgia: a randomized double-blind placebo-controlled study.

BACKGROUND: Post-herpetic neuralgia is difficult to treat. Divalproex sodium (valproic acid and sodium valproate in molar ratio 1:1) has been used successfully in the management of various painful neuropathies. AIM: To study the effectiveness and safety of divalproex sodium in the management of post-herpetic neuralgia. DESIGN: Randomized double-blind placebo-controlled trial. METHODS: We enrolled 48 consecutively attending out-patients with post-herpetic neuralgia, out of whom three were excluded (two had insufficient pain, one withdrew consent). Quantification of pain was by Short Form-McGill pain questionnaire (SF-MPQ), visual analogue scale (VAS), present pain intensity score (PPI) and 11 point Likert scale (11 PLS) at the beginning of the study, after 2 weeks, 4 weeks and at the end of the study (8 weeks). We also assessed patients' global impression of change by questionnaire at the end of the study. RESULTS: After 8 weeks treatment with 1000 mg/day divalproex sodium, there was significant reduction in pain: SF-MPQ, 20.47 +/- 2.29 to 11.90 +/- 6.52 (p < 0.0001); PPI 4.0 +/- 0.52 to 1.95 +/- 1.29 (p < 0.0001); VAS 70.17 +/- 9.21 to 31.27 +/- 29.74 (p < 0.0001) and 11 PLS 6.97 +/- 0.73 to 3.63 +/- 2.34 (p < 0.0001) in comparison to placebo (means +/- SEM). The 'global impression of change' questionnaire showed much or moderate improvement in pain in 58.2% of patients receiving divalproex vs. 14.8% of those receiving placebo. The drug was well tolerated by all patients, except one who developed severe vertigo after 10 days of treatment. DISCUSSION: Divalproex sodium provides significant pain relief in patients of post-herpetic neuralgia, with very little incidence of adverse reactions. These data provide a basis for longer trials in a larger group of patients.

Adult↗

Sweat dermatitis.

Explore the source record for details and available documents.

Adolescent↗

The role of rifampicin in the management of cutaneous leishmaniasis.

We assessed the efficacy of rifampicin in the treatment of cutaneous leishmaniasis (oriental sore) using a double-blind placebo-controlled study. We studied 46 patients with cutaneous leishmaniasis, of whom 23 received rifampicin (group A) and another 23 received placebo (group B) for a period of 4 weeks. Each patient was assessed clinically for size of lesion, type of lesion, duration of lesion, number of lesions, and distribution of lesions, initially, and at the end of 1 week, 2 weeks and 4 weeks. Biochemical tests including enzyme studies were done to detect any toxic effects of the drug. Group A patients received rifampicin 1200 mg/day in two divided doses and group B patients received two doses of an identical placebo capsule. Seventeen (73.9%) of the 23 patients receiving rifampicin had complete healing. Two (8.6%) had partial healing and four (17.3%) showed no response, whereas out of 23 patients receiving placebo one patient (4.3%) showed complete healing, eight (34.7%) patients showed partial healing and 14 (60. 98%) patients showed no healing or exacerbation of lesion. The difference was statistically significant in favour of response to rifampicin. This dose of rifampicin was well-tolerated and no side-effects were seen in any patient. In cases of cutaneous leishmaniasis where injectable treatment is not feasible or not acceptable, as in cases of multiple lesions, rifampicin is a better alternative oral treatment. It is simple to administer, cheap, more effective and less toxic than other available oral drugs, and well-tolerated by patients.

Adolescent↗

Preclinical assessment of hypocrellin B and hypocrellin B derivatives as sensitizers for photodynamic therapy of cancer: progress update.

Hypocrellins are perylenequinone pigments with substantial absorption in the red spectral region and high singlet oxygen yield. They are available in pure monomeric form and may be derivatized to optimize properties of red light absorption, tissue biodistribution and toxicity. In vitro screening of synthetic derivatives of the naturally occurring compound, hypocrellin B (HB), for optimal properties of cyto-(dark) toxicity and phototoxicity resulted in selection of three compounds for preclinical evaluation: HBEA-R1 (ethanolaminated HB), HBBA-R2 (butylaminated HB) and HBDP-R1 [2-(N,N-dimethylamino)-propylamine-HB]. Extinction coefficients at 630 nm (epsilon 630) are 6230, 6190 and 4800, respectively; and 1O2 quantum yields, phi, 0.60, 0.32 and 0.42. Intracellular uptake is essentially complete within 2 h (HBEA-R1, HBBA-R2) and 20 h (HBDP-R1). Greatest uptake is associated with lysosomes and Golgi. The HBEA-R1 and HBBA-R2 elicit phototoxicity in vitro primarily via the type II mechanism, with some type I activity under stringently hypoxic conditions. Transcutaneous phototherapy with HBEA-R1 permanently ablates EMT6/Ed tumors growing in the flanks of Balb/c mice, with minimal cutaneous effects. The HBBA-R2 does not elicit mutagenic activity in strains TA98 and TA100 of Salmonella typhimurium. Further development of selected hypocrellin derivatives as photosensitizers for photodynamic therapy is warranted.

Animals↗

Safrole, eugenol and methyleugenol induce intrachromosomal recombination in yeast.

Deletion of an integrated plasmid, a specific type of intrachromosomal recombination, was evaluated for inducibility with the phenylpropenes safrole, eugenol and methyleugenol in the yeast Saccharomyces cerevisiae. These phenylpropenes are found in food products, spices, pharmaceuticals and clove cigarettes. Safrole and eugenol are known carcinogens in animals and methyleugenol is a suspected carcinogen. These phenylpropenes are not detectable by the Ames assay and most other short-term tests used currently in predictive carcinogenesis. Like safrole, which has been shown to be nonmutagenic with the Ames assay, eugenol and methyleugenol were found to be nonmutagenic with the Ames assay. In contrast, with the yeast assays which screen for intra- and inter-chromosomal recombination in logarithmic phase cultures, all 3 compounds gave a positive dose-related response. These results demonstrate further that the yeast system can be modified easily to detect various genetic endpoints and that it deserves serious consideration as a test system for predictive carcinogenesis.

Adenine↗

Carcinogens induce intrachromosomal recombination in yeast.

To identify environmental carcinogens there is a need for inexpensive and reliable short-term tests that can be used to predict the carcinogenic potential of any given substance with high accuracy. The Ames assay, which is based on the induction of mutations in Salmonella typhimurium, is the most extensively used short-term test but certain human or animal carcinogens exist that are persistently undetectable as mutagens with the Ames assay or with other short-term tests. There is a need for a short-term test to detect those carcinogens that are missed by the Ames assay. Carcinogenesis is in many cases associated with genome rearrangement. Because of this association a system screening for intrachromosomal recombination that results in genome rearrangement has been constructed for potential use as a short-term test in the yeast Saccharomyces cerevisiae. Evaluation of this recombination system shows that it is readily inducible by a variety of mutagenic as well as non-readily inducible by a variety of mutagenic as well as non-mutagenic carcinogens, including carcinogens that are not detectable by the Ames assay or by various other short-term tests, such as safrole, urethane, ethionine, auramine, methylene chloride, carbon tetrachloride, cadmium sulfate, aniline, dimethylhydrazine, aminotriazole, acetamide, thiourea and DDE. The present report shows the data for these as well as for additional agents, their response profiles with different concentrations of the agents and the protocol for the DEL system.

Carcinogenicity Tests↗

Genetic activity in yeast assays of reputed nonmutagenic, carcinogenic N-nitroso compounds and methapyrilene hydrochloride.

Methapyrilene hydrochloride (MPHC), N-nitrosomethylaniline (NMA), N-nitrosomethyl-3-carboxypropylamine (NMCP) and N-nitrosodiethanolamine (NDELA) are reputed to be nonmutagenic carcinogens because they are genetically inactive in Salmonella mutagenesis tests but produce cancer in rats. We have assayed these compounds for their genetic activity with diploid strains D7, D7-144, and RMO52 of Saccharomyces cerevisiae. The compounds MPHC and NMA were highly toxic to the cells and induced gene conversion and reverse mutations in strains D7, D7-144 and RMO52. Metabolic activation was not required for this activity. However, in acidic (pH 5) medium, the genetic activity and cell toxicity of MPHC and NMA were markedly reduced. Ascorbic acid suppressed the mutagenicity and toxic effects of MPHC. Mutagenicity of NDELA was enhanced in strain D7-144 when cells were treated in acidic medium. At pH 7, NDELA was not mutagenic. NMCP induced reversed mutations in strains D7-144 and RMO52 in the absence of metabolic activation. Our results indicate that the four carcinogens, MPHC, NMA, NMCP and NDELA, require different physiological conditions for the expression of their genetic activity.

Aminopyridines↗

Genetic activity of diethylstilbestrol in Saccharomyces cerevisiae: enhancement of mutagenicity by oxidizing agents.

Diethylstilbestrol (DES), a synthetic estrogen, is known to cause cancer in humans and experimental animals. Although it has been established that DES can induce unscheduled DNA synthesis, sister-chromatid exchange, and cell transformation in various short-term tests, the efforts to demonstrate its mutagenic activity in bacterial and mammalian systems have largely failed. It has been shown that DES can covalently bind to DNA after being oxidized either chemically, in the presence of iodine and hydrogen peroxide, or metabolically, by mammalian cells in tissue culture and also in the presence of rat-liver microsomes. We studied genetic activity of DES in growing cultures of the strains XV185-14C and D5 of S. cerevisiae in the presence and absence of oxidizing agents, namely, iodine and hydrogen peroxide. We demonstrated that DES alone exhibits a weak mutagenic response in the strain XV185-14C. On the other hand, the treatment of cells with DES in the presence of iodine or hydrogen peroxide plus ferrous sulfate induced a large increase in the frequency of induced mutations in strain XV185-14C and mitotic recombination and gene conversion in strain D5. This enhancement in the genetic activity of DES in our test assays in the presence of chemical oxidative systems indicates that DES undergoes oxidation to produce a genetically active metabolite.

Cytochrome P-450 Enzyme System↗

Mutants of Saccharomyces cerevisiae and Candida utilis with increased susceptibility to digestive enzymes.

Mutants of Candida utilis and a haploid strain of Saccharomyces cerevisiae were isolated, after ultraviolet light mutagenesis, which had increased sensitivities to snail gut enzymes (ses). Three of the five S. cerevisiae mutants tested had increased sensitivities to porcine pepsin, all were more susceptible to a sequential treatment with pepsin, lipase, peptidase, and trypsin, four were sensitive to osmotic shock, and two had increased glucan/mannan ratios in their cell walls. All combinations of mutants showed positive complementation in heterozygous diploids, although complementation between one pair, which had the same phenotype, was incomplete, indicating that four to five different cistrons were involved. All mutations were found to be recessive. Haploid strains bearing pairs of ses mutations were not markedly more sensitive to mammalian digestive enzymes than strains with single mutations. Rat-feeding experiments with three mutants and the parental strains indicated that the protein was efficiently utilized in all cases. Net protein ratios for the two mutants of S. cerevisiae tested were slightly higher than that for their parent, but the differences were of marginal significance.

Candida↗

Modulation in cytochrome P-420 and P-450 content in Saccharomyces cerevisiae according to physiological conditions and genetic background.

The diploid strain D5 of Saccharomyces cerevisiae, relative to other strains of yeast, has a large amount of cytochrome P-450 present during the logarithmic phase of growth and a low amount of cytochrome P-420. As the stationary phase of growth is approached, an increasing intensity of absorbance is observed at 420 nm. If the cells are suspended in buffer during mid-logarithmic growth, the absorbance at 450 nm disappears and absorbance at 420 nm is increased after the cells have been held in buffer for 24 h. At late logarithmic growth, the absorbance at 450 nm is still retained after the cells have been held in buffer for 24 h. Within 44 h of the time of harvest, the absorbance at 450 nm disappears completely and the absorbance at 420 nm is intense. Cytoplasmic petite variants of strain D5 have less of both cytochromes P-450 and P-420 than does the grande D5 strain; the absorbances at 450 and 420 nm are retained up to 96 h when the cells are held in buffer. Haploid spores of strain D5 exhibit absorbances at 450 and 420 nm during the logarithmic phase of growth, and these absorbances are retained after the cells are held in buffer for 24 h. An hypothesis is proposed which states that cytochrome P-450 is the membrane-bound form and cytochrome P-420 is free in the cytosol; the cytochromes interconvert and are active in either state until the associated enzymes disassociate.

Animals↗

Genetic activity in Saccharomyces cerevisiae and thin-layer chromatographic comparisons of medical grades of pyrvinium pamoate and monopyrvinium salts.

The pamoate, chloride, and iodide salts of pyrvinium, a cyanine dye with anthelmintic properties, were studied in a diploid mitotic recombination and gene conversion assay system (strain D5 of Saccharomyces cerevisiae) and a haploid yeast reversion assay (strain XV185-14C). With the use of a thin-layer chromatographic (TLC) detection technique, samples of pyrvinium pamoate from several sources were found to contain different numbers and quantities of impurities. All samples of pyrvinium pamoate and the monopyrvinium salts were recombinogenic in strain D5 and mutagenic in strain XV185-14C; the degree of genetic activity varied among the tested medical grades of pyrvinium pamoate. Monopotassium pamoate was found to be genetically inactive in both strains. Light-catalyzed degradation did not enhance the genetic activity of pyrvinium in either of the yeast strains; the degraded samples were not mutagenic.

Chromatography, Thin Layer↗

Hypopigmented lesions in early leprosy--a clinical and histological study.

26 Patients of leprosy presenting with hypopigmented lesions were divided on morphological grounds into 3 Sub groups, Group I (9 patients) with well-defined single patch with moderate to complete sensory loss; Group II (8 patients) with single ill-defined lesion having partial sensory loss; and Group III (9 patients) having multiple hypo-pigmented patches with mild to moderate sensory loss. Epidermal atrophy was a conspicuous histological finding in all groups. Only patients in Group I showed epitheloid cells in dermal infiltrate with erosion of epidermis in one case. This group may be labelled as maculoanesthetic leprosy. Patients in Group II and III showed mononuclear cell infiltrate in dermis, around neurovascular bundles and appendages. They were histologically consistent with indeterminate leprosy. Follow-up biopsy after six to eight months of treatment showed healing of the lesion of reduction in the infiltrate in most cases.

Adolescent↗