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Biomedical subjects

R P Sharma

Publications and source records attributed to R P Sharma.

At least 19 recordsLinked to original sources
PubMed2006

No scalpel vasectomy advocacy and community mobilisation--a personal experience.

The so called myths and taboos among the people of India are obstactes controlling population explosion and thereby the nation is being handicapped with economic development. To propagate awareness and information, the NSV Resource Center took up organising mega camps for the acceptance of NSV as the method of family planning and male participation. The awareness material has been developed to bring forth total sociocultural transformation through development of intense desire, strong determination, effective management and inclusion of a zeal of perpetual efforts both among the promoters and acceptors. The information modules have been developed to suit the requirements of various vehicles through which the message has to be spread. Awareness messages are generated through the inputs from sociocultural, economic, ethical, hygienic and administrative acumen. The materials prepared are disseminated through display hoardings, wall writings, distribution of pamphlets, audiovisual clips, face to face counselling, etc. Communication technology serves mobilising and educating people, especially rural populace. Some steps are suggested to reach remotest villages which are elaborated. Counselling is an essential part of motivation to the client. During the last 5 years a significant surge has been noticed in terms of access to new communication technologies. This may be employed to successfully implement the family planning programme.

Awareness↗
PubMed2004

Development and validation of CAPS and AFLP markers for white rust resistance gene in Brassica juncea.

White rust, caused by Albugo candida, is a very serious disease in crucifers. In Indian mustard (Brassica juncea), it can cause a yield loss to the extent of 89.9%. The locus Ac2(t) controlling resistance to white rust in BEC-144, an exotic accession of mustard, was mapped using RAPD markers. In the present study, we developed: (1) a more tightly linked marker for the white rust resistance gene, using AFLP in conjunction with bulk segregant analysis, and (2) a PCR-based cleaved amplified polymorphic sequence (CAPS) marker for the closely linked RAPD marker, OPB06(1000). The data obtained on 94 RILs revealed that the CAPS marker for OPB06(1000) and the AFLP marker E-ACC/M-CAA(350) flank the Ac2(t) gene at 3.8 cM and 6.7 cM, respectively. Validation of the CAPS marker in two different F(2) populations of crosses Varuna x BEC-144 and Varuna x BEC-286 was also undertaken, which established its utility in marker-assisted selection (MAS) for white rust resistance. The use of both flanking markers in MAS would allow only 0.25% misclassification and thus provide greater efficiency to selection.

Chromosome Mapping↗
PubMed2004

The mycotoxin fumonisin B1 transiently activates nuclear factor-kappaB, tumor necrosis factor alpha and caspase 3 via protein kinase Calpha-dependent pathway in porcine renal epithelial cells.

Fumonisin B1 (FB1) is a toxic mycotoxin produced by Fusarium verticillioides, predominantly present in corn. The principal biochemical responses of FB1 involve disruption of sphingolipid metabolism from the inhibition of ceramide synthesis leading to accumulation of free sphingoid bases, particularly sphinganine. The ability of FB1 to modulate signal transduction pathways plays a role in its toxicity. We recently reported that FB1 selectively and transiently activates protein kinase Calpha (PKCalpha) in porcine renal epithelial cells (LLC-PK1). The aim of current study was to investigate the effect of PKCalpha activation by FB1 on NF-kappaB activation and subsequently on TNFalpha gene expression and caspase 3 induction in LLC-PK1 cells. FB1 (1 micromol/L for 5 min) transiently activated PKCalpha and increased nuclear translocation of NF-kappaB, followed by their down-regulation at later time points. Preincubating the cells with the PKC inhibitor, calphostin C, prevented the activation of NF-kappaB by FB1. TNFalpha mRNA expression was increased after 15 min exposure to FB1 or the PKC activator, phorbol 12-myristate 13-acetate. In addition, an increase in caspase 3 activity was observed after addition of FB1 for 1 h. Calphostin C prevented both the FB1-induced increase in TNFalpha expression and caspase 3 activation. In summary, we hereby demonstrate that the FB1 activation of NF-kappaB and sequential induction of TNFalpha expression resulting in the subsequent increase in caspase 3 activity are all dependent on PKCalpha stimulation in LLC-PK1 cells.

Animals↗
PubMed2003

Antifungal activity of the stem bark of Ailanthus excelsa.

The methanol extract of stem barks of Alianthus excelsa was partitioned with chloroform. The chloroform extract showed fungistatic and fungicidal activity against Aspergillus niger, A. fumigatus, Penicillium frequentence, P. notatum and Botrytis cinerea.

Ailanthus↗
PubMed2002

Fumonisin B1-induced localized activation of cytokine network in mouse liver.

Fumonisin B1 (FB1), a mycotoxin produced primarily by Fusarium veticillioides and related fungi, is a carcinogen and causative agent of various animal diseases. Our previous studies indicated the involvement of tumor necrosis factor-alpha (TNFalpha) in FB1-induced hepatotoxicity. Male B6,129 mice (five/group) were injected subcutaneously with vehicle or 2.25 mg/kg/day of FB1 for 5 days and sampled 1 day after the last treatment. FB1 treatment caused an increased expression of TNFalpha, interferon gamma (IFNgamma) and interleukin (IL)-12 p40 in liver without any changes in kidney or spleen, suggesting the localized site of their production. IL-1beta cytokine expression was increased in liver and kidney after FB1 exposure. Cells involved in TNFalpha production after FB1 treatment in liver were identified as Kupffer cells. FB1 increased alanine aminotransferase in plasma and increased apoptotic cells in liver. Selective increase in proinflammatory T helper (Th)1-cytokines (IL-12 and IFNgamma) and TNFalpha with no alteration in Th2-cytokines (IL-4, IL-6 and IL-10) suggest the involvement of IL-12, produced by Kupffer cells, in induction of IFNgamma production by natural killer (NK) cells and/or NK1+ T cells, which can undergo a positive amplification loop with TNFalpha produced by macrophages or other hepatic cells to elicit the toxic reaction.

Alanine Transaminase↗
PubMed2002

All-trans-retinoic acid-mediated modulation of p53 during neural differentiation in murine embryonic stem cells.

All-trans-retinoic acid (RA) plays an important physiological role in embryonic development and is teratogenic in large doses in almost all species. p53, a tumor suppressor gene encodes phosphoproteins, which regulate cellular proliferation, differentiation, and apoptosis. Temporal modulation of p53 by retinoic acid was investigated in murine embryonic stem cells during differentiation and apoptosis. Undifferentiated embryonic stem cells express a high level of p53 mRNA and protein followed by a decrease in p53 levels as differentiation proceeds. The addition of retinoic acid during 8-10 days of differentiation increased the levels of p53 mRNA and protein, accompanied by accelerated neural differentiation and apoptosis. Marked increase in apoptosis was observed at 10-20 h after retinoic acid treatment when compared with untreated controls. Retinoic acid-induced morphological differentiation resulted in predominantly neural-type cells. Maximum increase in p53 mRNA in retinoic acid-treated cells occurred on day 17, whereas maximum protein synthesis occurred on days 14-17, which coincided with increased neural differentiation and proliferation. Increased p53 levels did not induce p21 transactivation, interestingly a decrease in p21 was observed on day 17 on exposure to retinoic acid. The level of p53 declined by day 21 of differentiation. The results demonstrated that retinoic acid-mediated apoptosis preceded the changes in p53 expression, suggesting that p53 induction does not initiate retinoic acid-induced apoptosis during development. However, retinoic acid accelerated neural differentiation and increased the expression of p53 in proliferating neural cells, corroborated by decreased p21 levels, indicating the importance of cell type and stage specificity of p53 function.

Animals↗
PubMed2002

Persistence and reversibility of the elevation in free sphingoid bases induced by fumonisin inhibition of ceramide synthase.

These studies determined (1) the time course for sphingoid base elevation in the small intestines, liver, and kidney of mice following a single 25 mg/kg body weight (bw) oral dose (high dose) of fumonisin B(1) (FB(1)), (2) the minimum threshold dose of FB(1) that would prolong the elevated sphingoid base concentration in kidney following the single high dose, and (3) the importance of the balance between the rate of sphingoid base biosynthesis and degradation in the persistence of sphingoid base accumulation. Following the high dose of FB(1), there was an increase in sphinganine in intestinal cells and liver that peaked at 4 to 12 h and declined to near the control level by 48 h. In kidney, sphinganine peaked at 6-12 h but remained elevated until 72 h, approaching control levels at 96-120 h. Oral administration of 0.03 mg FB(1)/kg bw (low dose) for 5 days had no effect on the sphingoid bases in kidney. However, following an initial high dose, daily administration of the low dose prolonged the elevation in kidney sphinganine compared to mice receiving a single high dose. Thus, a single exposure to a high dose of FB(1) followed by daily exposure at low levels will prolong the elevation of sphinganine in kidney. In cultured renal cells FB(1) was rapidly eliminated, but elevated sphinganine was persistent. This persistence in renal cells was rapidly reversed in the presence of the serine palmitoyltransferase inhibitor (ISP-1), indicating that the persistence was due to differences in the rates of sphinganine biosynthesis and degradation. The in vivo persistence in kidney may be due to similar differences.

Acyltransferases↗
PubMed2002

Construction of an RAPD linkage map and localization of QTLs for oleic acid level using recombinant inbreds in mustard (Brassica juncea).

RAPD markers were employed for construction of a linkage map and localization of QTLs for oleic acid level using a set of 94 recombinant inbred lines (RILs) of mustard (Brassica juncea L.) as a mapping population. Only 30% of the 235 random primers used were useful in terms of polymorphism detected and the reproducibility of those patterns. Normal Mendelian segregation was observed for the majority of the 130 markers obtained with 71 informative primers; only 13.1% deviated (P < 0.01) from the expected 1:1 ratio. One-hundred and fourteen markers were assigned to 21 linkage groups (LGs) covering a total length of 790.4 cM with an average distance of 6.93 cM between markers. Two quantitative trait loci (QTL) for oleic acid level were mapped to 14- and 10.6-cM marker intervals on two different LGs. Both loci together explained 32.2% of phenotypic variance. One major QTL explained 28.5% of the trait variance observed in this species.

Breeding↗
PubMed2001

Self-association of model transmembrane alpha-helices is modulated by lipid structure.

We have developed a fluorescence quenching method using peptides containing 3,5-dibromotryrosine to measure oligomerization of model transmembrane alpha-helices in lipid bilayers. Peptides of the type Ac-LysLysGlyLeu(m)XLeu(n)LysLysAla-amide where X is tryptophan or 3,5-dibromotyrosine were found to form heterodimers in bilayers of phosphatidylcholine in the liquid-crystalline phase. The free energy of dimer formation changed little with increasing number of Leu residues from 16 to 22 but increased with increasing phospholipid fatty acyl chain length, with a slope of about 0.5 kJ mol(-1) per fatty acyl chain carbon. Peptides were excluded from lipid in the gel phase, resulting in increased levels of oligomerization. Addition of cholesterol to form the liquid-ordered state led to increased dimerization but without phase separation. The presence of phosphatidylethanolamine had little effect on dimerization.

Amino Acid Sequence↗
PubMed2001

Gender-related differences in subacute fumonisin B1 hepatotoxicity in BALB/c mice.

Fumonisin B1 (FB1), a potent mycotoxin prevalent in corn, is a carcinogen and causative agent of various animal diseases. Species and sex variations to chronic FB1 toxicity have been reported. Free sphingoid bases and cytokine levels are the two major biochemical alterations of FB1 in vivo and may explain any sex differences in FB1 toxicity. Male and female BALB/c mice (5/group) were injected subcutaneously with either saline vehicle or 2.25 mg/kg/day of FB1 for 5 days. One day after the last injection females showed a greater increase in circulating alanine aminotransferase and greater number of apoptotic cells in liver after FB1 treatment than males, indicating greater hepatotoxicity. Peripheral leukocytic counts, including neutrophils, were increased in females only after FB1 treatment. The increased toxicity in females correlated with a greater increase of sphinganine and sphingosine levels in liver after FB1 treatment compared to males. No sex differences in kidney sphinganine or sphingosine levels were observed after FB1 treatment. Previously we have shown the induction of tumor necrosis factor alpha (TNFalpha) in FB1-induced hepatotoxicity. While in males FB1 treatment caused increased expression of TNFalpha, interleukin (IL)-12 p40, interferon gamma (IFNgamma), IL-1beta, IL-6 and IL-10, females showed an increased expression of IL-6 only, and a downward modulation of IFNgamma, indicating gender differences in cytokine pathways in liver activated by FB1. The basal expression of TNFalpha, IL-12 p40, IL-1beta and IFNgamma in liver of females was higher compared to males. Gender differences in alterations of free sphingoid bases and cytokine modulation after FB1 treatment suggest their possible involvement in sex-dependent differential hepatotoxicity in mice.

Alanine Transaminase↗
PubMed2001

Fumonisin-induced tumor necrosis factor-alpha expression in a porcine kidney cell line is independent of sphingoid base accumulation induced by ceramide synthase inhibition.

Previous studies have shown that fumonisin B1 (FB1) inhibits ceramide synthase, resulting in accumulation of free sphinganine and sphingosine. Tumor necrosis factor-alpha (TNFalpha) plays an important role in FB1 toxicity and the expression of TNFalpha mRNA in liver and kidney is increased following FB1 exposure in mice. The objective of the current study was to investigate whether these two events (sphingoid bases accumulation and TNFalpha induction) are dependent on each other. An increase in expression of TNFalpha mRNA was detected in LLC-PK1 cells as early as 4 h after FB1 treatment but decreased to the control levels after 8 h. A positive linear correlation was observed between the expression of TNFalpha mRNA and FB1 concentration. Increases of intracellular sphingoid bases were also detected after 4 h of FB1 treatment and progressively increased until 24 h. Exposure of the cells to sphinganine or sphingosine did not significantly alter the expression of TNFalpha. Inhibition of sphingoid base biosynthesis by ISP-1, a specific inhibitor of serine palmitoyltransferase, the first enzyme in de novo sphingolipid biosynthesis, efficiently blocked the accumulation of free sphingoid bases in response to FB1, but it did not prevent the induction of TNFalpha expression. Results indicate that FB1-induced increase in TNFalpha expression is independent of sphingoid base accumulation-induced by ceramide synthase inhibition in LLC-PK1 cells.

Acyltransferases↗
PubMed2001

Decreased fumonisin hepatotoxicity in mice with a targeted deletion of tumor necrosis factor receptor 1.

Fumonisin B1 (FB1), a mycotoxin produced by Fusarium verticillioides and related fungi infests corn and other cereals, and causes a variety of toxic effects in different mammalian species. Hepatotoxicity is a common toxic response in most species. The cellular responses of FB1 involve inhibition of ceramide synthase leading to accumulation of free sphingoid bases and a corresponding induction of tumor necrosis factor alpha (TNFalpha). We recently reported that FB1 hepatotoxicity was considerably reduced in a mouse strain lacking tumor necrosis factor receptor 2 (TNFR2 or TNFR1b). To further investigate the relative contribution of the two TNFalpha receptors (TNFR1 and TNFR2 or P55 and P75 receptors) we evaluated the hepatotoxicity of FB1 in male C57BL/6J mice (WT) and a corresponding TNFR1 knockout (TNFRKO) strain, genetically modified by a targeted deletion of this receptor. The hepatotoxic effects of five daily injections of 2.25 mg/kg per day of FB1 were observed in WT but were reduced in TNFRKO, evidenced by the microscopic evaluation of the liver and increased concentrations of circulating alanine aminotransferase and aspartate aminotransferase. FB1 induced the expression of TNFalpha, and similar increases in free sphinganine and sphingosine in livers of both WT and TNFRKO mice. Results indicated that both P55 and P75 receptors are required for FB1-induced hepatotoxicity and TNFalpha plays an important role in such response in mouse liver.

Animals↗
PubMed2001

Antibacterial activity of Ailanthus excelsa (Roxb).

The antibacterial activity of different fractions of a methanol extract obtained from the dried stem bark of Ailanthus excelsa (Roxb) was studied using different bacterial strains. The ethyl acetate fraction inhibited the growth of all test bacteria. The MIC of the EA fraction was found to be 6 mg/disc.

Anti-Bacterial Agents↗
PubMed2001

Superselective arterial embolization for the treatment of lower gastrointestinal hemorrhage.

PURPOSE: To evaluate the technical feasibility, efficacy of hemostasis, recurrent bleeding, and ischemia resulting from superselective embolization of acute lower gastrointestinal (GI) hemorrhage. MATERIALS AND METHODS: Fifty-two superselective mesenteric artery catheterization procedures were undertaken in 48 patients with angiographic evidence of lower GI bleeding. Embolization was performed only if the arterial recta leading to the bleed could be successfully catheterized (n = 39). The lesions treated were located in the colon (n = 33) and jejunum (n = 6). In 28 of 39 procedures, embolization was achieved by delivering polyvinyl alcohol (PVA) particles (150-500 microm) through a microcatheter. Microcoils were used as the sole embolic agent in four procedures and a combination of microcoils and PVA particles were used in another four. Gelfoam particles were used in three of our earliest procedures. Of the 35 patients who underwent embolization, 25 were evaluated for objective evidence of ischemia by endoscopy (n = 16) and/or histologic evaluation of the surgical specimen (n = 9); the remaining 10 patients were followed clinically. RESULTS: Embolization was successful in 39 procedures involving 35 patients. Immediate hemostasis was achieved after embolization in all but two patients. Recurrent bleeding occurred in 12 other patients, eight patients underwent surgery, three were managed medically, and one underwent successful repeat embolization. Of the 25 patients evaluated for ischemia, mucosal ischemia was demonstrated in six (24%), but they remained asymptomatic and developed no sequelae as a result of ischemic changes on long-term follow-up. There was no incidence of clinically significant intestinal ischemia. Embolization alone was the definitive treatment in 44% patients (21 of 48). Reasons for unsuccessful superselective catheterization (27%) were small vessel spasm, cessation of bleeding, and vessel tortuosity. CONCLUSION: Superselective embolization is a feasible, safe, and effective technique for treating acute lower GI hemorrhage.

Adult↗
PubMed2001

Gender-dependent immunosuppression following subacute exposure to fumonisin B1.

The effects of fumonisin B1 (FB1), a mycotoxin produced by Fusarium lertcillioides, on the immune system are controversial; FB1 exposure causing immunosuppression in poultry, swine, bovine and rodents species and immunostimulation in rodent species. The current study was conducted to examine the effects of FB1 on the immune system of BALB/c mice and to determine if there is sex specificity. Female and male mice (five per group) received five daily subcutaneous (s.c.) injections of 2.25 mg/kg/day of FB1, on the following day tissues were collected for immunological examinations. FB1 treatment dramatically reduced relative spleen and thymus weights in females, whereas there was no effect on organ weights in males. Exposure to FB1 reduced splenic cellularity and the basal rate of lymphocyte proliferation in females only. In addition, phytohemagglutinin (PHA-P)-induced T-lymphocyte and LPS-induced B-lymphocyte proliferation were reduced in female mice. Splenocytes from female mice exposed to FB1 showed a reduced expression of interleukin-2 mRNA. These changes occurred in the absence of alterations in tumor necrosis factor alpha or interleukin-1beta mRNA expression. Phenotypic analysis indicated that FB treatment caused a relative increase in the T-lymphocyte population in the spleen of female mice only. In contrast, FB1 dramatically reduced the immature CD4+/CD8+ double positive cell population in the thymus of females. No changes were evident in the thymocyte populations of male mice treated with FB1. The results of this study indicate that FB1 is immunosuppressive in mice; the magnitude of FB1-induced immunosuppression is highly dependent on sex, females being more susceptible than males.

Animals↗
PubMed2001

A double-blind, randomized, prospective evaluation of the efficacy and safety of risperidone versus haloperidol in the treatment of schizoaffective disorder.

The relative efficacy and safety of risperidone versus haloperidol in the treatment of schizoaffective disorder was studied. Sixty-two patients (29 depressed type; 33 bipolar type) entered a three-site, randomized, double-blind, 6-week trial of risperidone (up to 10 mg/day) or haloperidol (up to 20 mg/day). Trained raters assessed baseline, weekly, and end-of-study levels of psychopathology with the Positive and Negative Syndrome Scale (PANSS), the 24-item Hamilton Rating Scale for Depression (HAM-D-24) and the Clinician-Administered Rating Scale for Mania (CARS-M). The authors were unable to statistically distinguish between risperidone and haloperidol in the amelioration of psychotic and manic symptoms. In addition, there was no difference in worsening of mania between the two agents in either subgroup (i.e., depressed or bipolar subgroups). For the total PANSS, risperidone produced a mean decrease of 16 points from baseline compared with a 14-point decrease with haloperidol. For the total CARS-M scale, risperidone and haloperidol produced mean change scores of 5 and 8 points, respectively, and for the CARS-M Mania subscale, 3 and 7 points, respectively. Additionally, risperidone produced a mean decrease of 13 points from the baseline 24-item HAM-D, compared with an 8-point decrease with haloperidol. In those patients who had more severe depressive symptoms (i.e., HAM-D baseline score >20), risperidone produced at least a 50% mean improvement in 12 (75%) of 16 patients in comparison to 8 (38%) of 21 patients receiving haloperidol. Haloperidol produced significantly more extrapyramidal side effects and resulted in more dropouts caused by any side effect. There was no difference between risperidone and haloperidol in reducing both psychotic and manic symptoms in this group of patients with schizoaffective disorder. Risperidone did not demonstrate a propensity to precipitate mania and was better tolerated than haloperidol. In those subjects with higher baseline HAM-D scores (i.e., >20), risperidone produced a greater improvement in depressive symptoms than haloperidol.

Adult↗
PubMed2001

Sphingolipid perturbations as mechanisms for fumonisin carcinogenesis.

There is a great deal of evidence that altered sphingolipid metabolism is associated with fumonisin-induced animal diseases including increased apoptotic and oncotic necrosis, and carcinogenesis in rodent liver and kidney. The biochemical consequences of fumonisin disruption of sphingolipid metabolism most likely to alter cell regulation are increased free sphingoid bases and their 1-phosphates, alterations in complex sphingolipids, and decreased ceramide (CER) biosynthesis. Because free sphingoid bases and CER can induce cell death, the fumonisin inhibition of CER synthase can inhibit cell death induced by CER but promote free sphingoid base-induced cell death. Theoretically, at any time the balance between the intracellular concentration of effectors that protect cells from apoptosis (decreased CER, increased sphingosine 1-phosphate) and those that induce apoptosis (increased CER, free sphingoid bases, altered fatty acids) will determine the cellular response. Because the balance between the rates of apoptosis and proliferation is important in tumorigenesis, cells sensitive to the proliferative effect of decreased CER and increased sphingosine 1-phosphate may be selected to survive and proliferate when free sphingoid base concentration is not growth inhibitory. Conversely, when the increase in free sphingoid bases exceeds a cell's ability to convert sphinganine/sphingosine to dihydroceramide/CER or their sphingoid base 1-phosphate, then free sphingoid bases will accumulate. In this case cells that are sensitive to sphingoid base-induced growth arrest will die and insensitive cells will survive. If the cells selected to die are normal phenotypes and the cells selected to survive are abnormal, then cancer risk will increase.

Animals↗