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Biomedical subjects

R P Sharma

Publications and source records attributed to R P Sharma.

At least 163 records · Page 9Linked to original sources
PubMed1988

Self-limiting acrodermatitis enteropathica. A follow-up study of three interrelated families.

A variant of acrodermatitis enteropathica is described that has its onset before weaning and clears when the child starts its normal solid diet. A pedigree with three interrelated families is reported where 10 children were afflicted with this variant. They had symptoms of hypozincemia for a brief period during infancy. At the time of this study, they were symptom-free and their serum zinc levels were found to be within normal limits. The term "self-limiting acrodermatitis enteropathica" is proposed for the variant. In one lactating mother, the mammary zinc secretion was determined and was found to be deficient and unresponsive to oral zinc supplements. The possible mode of inheritance is also discussed.

Acrodermatitis↗
PubMed1988

Evaluation of pesticide immunotoxicity.

Immunotoxicologic effects have been reported for a number of pesticides. Since pesticides represent a large range of chemical classes, different types of chemicals may affect the complex immune system by a variety of mechanisms. A preliminary evaluation of pesticides for immunotoxicologic potential can best be incorporated in general subacute and chronic toxicity testing, with additional groups assigned for initial host-sensitivity assays. For chemicals that are possible candidates for immunotoxicity in preliminary assays, a comprehensive immunotoxicity screening has been suggested. Finally, emphasis should be given to mechanistic investigations to objectively assess the immunotoxicity of a new chemical and possible extrapolation to man. Animal models need to be developed for detecting the autoimmunologic potential of pesticides. This paper provides a brief listing of various approaches currently employed in the evaluation of immunotoxicity.

Animals↗
PubMed1988

Study of serum zinc level in leprosy.

Serum Zinc level was estimated in different types of leprosy by 'Dithiazone extraction' method in 75 leprosy patients comprising 15 each of Tuberculoid-Tuberculoid (TT); Borderline Tuberculoid (BT); Borderline Borderline (BB); Borderline Lepromatous (BL) and Lepromatous Lepromatous (LL). These findings were evaluated in comparison to 15 normal subjects serving as controls. Serum zinc level was observed to be significantly low in all types of leprosy except tuberculoid leprosy (TT). No significant difference was observed in serum zinc levels before and after 90 days of dapsone Therapy. The findings of our study are of considerable importance as zinc deficiency can be one of the factors involved in non-specific suppression of cell mediated Immunity (CMI) in lepromatous leprosy.

Adult↗
PubMed1987

Structure-toxicity relationships of the tetramethylated tetralin and indane analogs of retinoic acid.

The teratogenicity of retinoids containing either tetramethylated tetralin (Ro 13-6307 or Ro 13-2389) or tetramethylated indane (Ro 13-4306) ring system substitutions was compared to the teratogenic potency of all-trans-retinoic acid. Single oral doses, administered to Syrian Golden hamsters at 10:00 A.M. on day 8 of gestation, induced a syndrome of malformations identical to that induced by treatment with all-trans-retinoic acid. These retinoids failed to induce signs of maternal hypervitaminosis A at doses associated with a significant teratogenic response. The tetramethylated tetralin retinoids and indane retinoid were 18 and 2.4 times as embryotoxic on a molar basis, respectively, as all-trans-retinoic acid. Introduction of a supplementary ring in the side-chain restricted polyene chain flexibility and maintained the hydrophobic plane of the chain. The present results are consistent with previous studies showing that the presence of or biotransformation to a free acid congener was necessary for retinoid teratogenic activity in hamsters and that increasing conformational restriction of acidic retinoids increased teratogenic potency.

Abnormalities, Drug-Induced↗
PubMed1987

Vanadate-dependent oxidation of pyridine nucleotides in rat liver microsomal membranes.

An enzymatic Na3VO4-dependent system for the oxidation of reduced pyridine nucleotides in purified rat liver microsomes was characterized. The system has a pH optimum of 6.5, and appears to be specific for vanadate, since activity in the presence of a related transition metal, molybdate, was not detected. Vanadate-dependent oxidation occurred with a concomitant consumption of O2 and, contrary to previous reports, preferred NADPH over NADH. At pH 6.5, the NADPH/NADH oxidase activity ratio was greater than 2:1. Sodium vanadate-dependent oxidation of NADH was inhibited by rotenone, antimycin A, NaN3, and NaCN. Conversely, Na3VO4-dependent NADPH oxidation was slightly affected by rotenone, but was insensitive to antimycin A, NaN3, NaCN, or quinacrine. Vanadate-dependent oxidation of either pyridine nucleotide was inhibited by the addition of either superoxide dismutase or catalase, indicating that both superoxide and hydrogen peroxide may be intermediates in the process. Linear sucrose gradient purification of the microsomes showed that the vanadate-dependent system for NADPH oxidation resides primarily in the endoplasmic reticulum. These studies indicate the existence of separate and distinct enzymatic systems for vanadate-stimulated oxidation of NADPH and NADH in mammalian microsomal membranes, and argue against an exclusive role of endogenous superoxide in the process.

Animals↗
PubMed1987

Effects of mycotoxins in cultured kidney cells: cytotoxicity of aflatoxin B1 in Madin-Darby and primary fetal bovine kidney cells.

The cytotoxicity of aflatoxin B1, a fungal metabolite and an important food contaminant, was evaluated in an established cell line, Madin-Darby bovine kidney (MDBK) cells, and in primary fetal bovine kidney (PFBK) cells. Cells were grown in monolayers and treated with media containing AFB1 for 24 hr. Both culture systems were sensitive to the chemical; the PFBK cultures were approximately four times more susceptible to the cytotoxic effect. Cell multiplication decreased in both systems in long-term cultures. Adherence of MDBK cells was only slightly reduced at the toxic concentrations of the chemical. Electron microscopy revealed condensation of chromatin, separation of nuclei from the cytoplasm, cytoplasmic vacuolization, and loss of surface microvilli. Results indicated differential sensitivity of the two culture systems.

Aflatoxin B1↗
PubMed1987

Dose and time related effects of T-2 toxin on mitogenic response of murine splenic cells in vitro.

The effects of T-2 toxin in vitro on murine splenic cells were investigated. Cells from syngeneic male NFS/N mice were cultured with three concentrations of either lipopolysaccharide (LPS), pokeweed mitogen (PWM), phytohaemagglutinin (PHA), or concanavalin A (Con A), for 48 h. T-2 toxin (10(-12)-10(-8)M) was added at the beginning or 24 h after initiation of the cultures. Exposure to T-2 toxin (10(-11)-10(-10)M) after 24 h increased 3H-thymidine uptake by splenic cells. Stimulation by PWM increased dramatically while the response to LPS was increased to a lesser extent in this system. Conversely, exposure to T-2 toxin decreased T-cell responses to both PHA and Con A. Exposing cells to T-2 toxin at the initiation of culture increased Con A stimulation; LPS and PWM responses decreased following 48 h exposure. When splenic cells were pre-treated for 60 or 90 min at 0 degrees C with 10(-9)M T-2 toxin the responses to both PWM and LPS increased. Increased 3H-thymidine uptake was also observed following 90 min exposure to T-2 toxin alone at either 0 or 37 degrees C. The increased PWM response and the mitogenic phenomenon observed when cells were exposed only to T-2 toxin were consistent with previously observed effects of in vivo T-2 toxin exposure.

Animals↗
PubMed1987

Effects of repeated doses of aspartame on serotonin and its metabolite in various regions of the mouse brain.

Following a finding that single doses (approximating to average intakes and to potential 'over-use') of aspartame administered orally to mice caused significant increases in norepinephrine and dopamine concentrations in various brain regions, the effect of repeated exposure to aspartame was studied. Male CD-1 mice were given a daily oral dose of 0, 13, 133 or 650 mg/kg for 30 days and 1 day after the last dose the animals were decapitated and their brain regions were quickly isolated. Analyses of the different regions for catecholamine and indoleamine neurotransmitters and their major metabolites indicated that the increases in adrenergic chemicals observed shortly after a single exposure were not apparent after repeated dosing. In contrast, concentrations of serotonin and its metabolite, 5-hydroxyindoleacetic acid, were decreased in several regions. An increased supply of phenylalanine may be responsible for a decrease in tryptophan uptake by the brain tissue or for a depression in tryptophan conversion to serotonin.

Animals↗
PubMed1987

Studies of immune function of CD-1 mice exposed to aflatoxin B1.

The immunotoxic potential of aflatoxin B1 (AFB1), a secondary metabolite of Aspergillus flavus and a known animal hepatocarcinogen, was evaluated in CD-1 mice. Male mice received 0, 0.03, 0.145 or 0.70 mg/kg of AFB1 orally every other day for 2 weeks in a corn oil:ethanol vehicle. Splenic lymphocytes were cultured in the presence of lipopolysaccharide (LPS), phytohemagglutinin (PHA), or pokeweed mitogen (PWM). A dose-related inhibition of [3H]thymidine uptake in lymphocyte cultures, with or without the above mitogens, was observed after 2 weeks of AFB1 exposure. Synthesis of DNA was decreased in mixed lymphocyte cultures. Primary antibody production by splenic cells, from animals challenged with a T-dependent antigen (sheep red blood cells), was affected by AFB1. No effects were observed, however, when animals were challenged with a T-independent antigen (LPS). A dose-related suppression of a delayed-type hypersensitivity reaction to keyhole limpet hemocyanin was observed. The results suggested that AFB1 was immunotoxic in CD-1 mice.

Aflatoxin B1↗
PubMed1987

Alteration of humoral and cellular immunity in manganese chloride-treated mice.

Immunological effects of manganese chloride (MnCl2) were determined in male CD-1 mice injected (ip) daily with MnCl2 (0, 1, 3, or 10 mg/kg) for 4 wk. Liver and spleen weights increased in the 10-mg/kg MnCl2 treatment group. The weights of thymus, kidney, and adrenal glands were not affected by MnCl2 treatment. No significant differences in peripheral erythrocyte or leukocyte counts were observed; however, packed cell volumes decreased in the medium- and high-dose groups. Manganese treatment significantly increased the uptake of [3H]thymidine (3H-TdR) by cultured splenic cells. The lymphoproliferative responses to phytohemagglutinin (PHA) and concanavalin A (Con A) increased at all levels of MnCl2 exposure. No differences in the responses to lipopolysaccharide (LPS) were observed. Mixed lymphocyte responses increased significantly with exposure to 10 mg MnCl2/kg. Another immunological alteration induced by MnCl2 was a dose-dependent immunosuppressive effect on the development of antibody-forming cells. The production of anti-sheep red blood cell antibody (alpha-SRBC) nearly ceased following exposure to 10 mg MnCl2/kg. This effect was apparently reversible, as the number of plaque-forming cells in the 10-mg/kg treatment group increased after MnCl2 treatment had been halted for 2 wk. The alpha-SRBC titer also decreased significantly in the 10-mg/kg treatment group, corresponding to the reduction of antibody producing cells. MnCl2 treatment was immunomodulatory to the reduction of antibody producing cells. MnCl2 treatment was immunomodulatory in male CD-1 mice, as indicated by the increase in mitogen and mixed lymphocyte responses and decrease in antibody production.

Animals↗
PubMed1987

Portal hypertension workup by DSA.

To provide information for preoperative planning, combined, selective intravenous (IV) and intraarterial (IA) digital subtraction angiography (DSA) studies were performed on 42 portal hypertension patients scheduled for portal systemic shunt procedures. Selective IV-DSA was performed to demonstrate the hepatic venous system, left renal vein, and inferior vena cava. Portal venous anatomy, direction of flow, and portal systemic collaterals were evaluated by selective IA-DSA. In addition, selective IA-DSA was performed postoperatively on 8 patients to assess shunt patency. Technically adequate DSA studies, suitable for surgical planning or postoperative assessment, were obtained in all of the 50 patients examined. Patient or internal organ motion was not a limiting factor in any study. Such use of DSA represents an efficacious, safe, and cost-effective alternative to conventional film-screen angiography for the evaluation of patients with portal hypertension.

Angiography↗
PubMed1987

Persistence of vanadium compounds in lungs after intratracheal instillation in rats.

Translocation and tissue distribution of two different forms of vanadium compounds, orthovanadate (soluble) and vanadium pentoxide (less soluble), were investigated. Groups of randomly selected rats were injected intratracheally with radiolabeled vanadium (48V) compounds and the animals were sacrificed at 1, 7 and 28 days after treatment. Blood, lungs and other major organs and tissues, namely liver, kidney, spleen, heart, testes, brain, muscle, and bone were sampled and the vanadium contents determined by gamma spectrometry. The less soluble form of vanadium (vanadium pentoxide) was eliminated from the lungs at a slow but exponentially linear rate, whereas the soluble form was translocated rapidly from this organ and exhibited a non-linear decline. Compared to the less soluble form, significantly less vanadium was retained in lungs 7 and 28 days after intratracheal instillation of vanadate. One day after treatment significantly higher concentrations (approximately 4 times) of vanadium after orthovanadate were observed in liver, kidney, spleen and bone compared to the pentoxide. However, tissue residues at 7 and 28 days indicated that both forms of vanadium were rapidly eliminated, except from bone and lungs. Results suggest a prolonged retention of less soluble forms of vanadium and possible health effects following repeated occupational exposure.

Animals↗
PubMed1986

Neurobiochemical alterations induced by the artificial sweetener aspartame (NutraSweet).

The dipeptide aspartame (NutraSweet) is a newly approved and widely used artificial sweetener in foods and beverages. Consumption of aspartame (ASM) has been reported to be responsible for neurologic and behavioral disturbances in sensitive individuals. Unfasted male CD-1 mice were dosed orally with 13, 130, or 650 mg/kg ASM in corn oil, while control animals received corn oil alone. Three hours after dosing, the animals were killed, and the concentrations of the catecholamines norepinephrine (NE) and dopamine (DA), catecholamine metabolites 3-methoxy-4-hydroxymandelic acid (VMA), homovanillic acid (HVA), and dihydroxyphenylacetic acid (DOPAC), the indoleamine serotonin (5-HT), and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) were determined by electrochemical high-performance liquid chromatography in six brain regions. ASM exerted its primary effect on adrenergic neurotransmitters in various brain regions. In the hypothalamus, the region richest in NE, increases in NE concentrations of 12, 49, and 47% were found in the low, medium, and high dose groups, respectively, relative to control. Significant increases of NE in the medulla oblongata and corpus striatum were also observed. Increases of the catecholamine DA and catecholamine metabolites VMA, HVA, and DOPAC were seen in various regions. The indoleamine serotonin and its metabolite 5-HIAA were unaffected by ASM treatment. These findings are consistent with ASM-induced increases in the brain catecholamine precursor amino acids phenylalanine and tyrosine, as reported earlier. Such observed alterations in brain neurotransmitter concentrations may be responsible for the reported clinical and behavioral effects associated with ASM ingestion.

Animals↗