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Biomedical subjects

R Kumar

Publications and source records attributed to R Kumar.

At least 685 records · Page 38Linked to original sources

Transdermal oestrogen for treatment of severe postnatal depression.

BACKGROUND: Postnatal depression can have long-term adverse consequences for the mother, for the marital relationship, and for the infant's psychological development. Such depressions can be severe and resistant to both support and counselling and to therapy with antidepressant drugs. We investigated the antidepressant efficacy of oestrogen given transdermally. METHODS: In a double-blind, placebo-controlled study, 61 women with major depression, which began within 3 months of childbirth and persisted for up to 18 months postnatally, were allocated randomly active treatment (n=34; 3 months of transdermal 17 beta-oestradiol 200 micrograms daily alone, then 3 months with added cyclical dydrogesterone 10mg daily for 12 days each month) or placebo (n=27; placebo patches and tablets according to the same regimen). The women were assessed monthly by self-ratings of depressive symptoms on the Edinburgh postnatal depression scale (EPDS) and by clinical psychiatric interview (schedule for affective disorders and schizophrenia [SADS]-change scale). FINDINGS: On pretreatment assessments the women in both groups were severely depressed (mean EPDS score 21.8 [SD 3.0] active group, 21.3 [2.9] placebo group; SADS scores, 66.3 [11.4] and 64.3 [10.7]). During the first month of therapy the women receiving oestrogen improved rapidly, and to a significantly greater extent than controls (mean EPDS scores 13.3 [SD 5.7] vs 16.5 [5.3]. Patients receiving placebo also improved over time but, on average, their scores did not fall below the screening threshold for major depression for at least 4 months. The estimated overall treatment effect of oestrogen on the EPDS was 4.38 points (95% Cl 1.89-6.87). None of a range of other factors (age, psychiatric, obstetric and gynaecological history, severity and duration of current episode of depression, and concurrent antidepressant medication), influenced the response to oestrogen. INTERPRETATION: This study has shown that transdermal oestrogen is an effective treatment for postnatal depression. Further studies are required to establish the minimum effective dose and shortest necessary duration of treatment as well as the mechanism of antidepressant action of oestrogen.

Administration, Cutaneous↗

Improving cancer radiotherapy with 2-deoxy-D-glucose: phase I/II clinical trials on human cerebral gliomas.

PURPOSE: Evaluation of tolerance, toxicity, and feasibility of combining large fraction (5 Gy) radiotherapy with 2-deoxy-D-glucose (2DG), an inhibitor of glucose transport and glycolysis, which has been shown to differentially inhibit repair of radiation damage in cancer cells. METHODS AND MATERIALS: Twenty patients with supratentorial glioma (Grade 3/4), following surgery were treated with four weekly fractions of oral 2DG (200 mg/kg body weight) followed by whole brain irradiation (5 Gy). Two weeks later, supplement focal radiation to the tumor (14 Gy/7 fractions) was given. Routine clinical evaluation, x-ray computerized tomography (CT), and magnetic resonance (MR) imaging were carried out to study the acute and late radiation effects. RESULTS: All the 20 patients completed the treatment without any interruption. The vital parameters were within normal limits during the treatment. None reported headache during the treatment. Mild to moderate nausea and vomiting were observed during the days of combined therapy (2DG + RT) in 10 patients. No significant deterioration of the neurological status was observed during the treatment period. Seven patients were alive at 63, 43, 36, 28, 27, 19, and 18 months of follow-up. In these patients, the clinical and MR imaging studies did not reveal any late radiation effects. CONCLUSIONS: Feasibility of administering the treatment (2DG + 5 Gy) is demonstrated by the excellent tolerance observed in all 20 patients. Further, the clinical and MR studies also show the absence of any brain parenchymal damage.

Adult↗

1,25-Dihydroxyvitamin D(3) receptors in developing dorsal root ganglia of fetal rats.

We observed immunostaining for the 1,25-dihydroxyvitamin D(3) receptor (VDR) and calbindin-D(28k) in neurons, but not glial cells, of fetal rat dorsal root ganglia (DRG) from days 13 through 21 of gestation. Dispersed cultures of DRG collected from rat fetuses at gestational day 15 also contained epitopes for VDR and calbindin-D(28k) in neurons, but not in glial cells. 1,25-Dihydroxyvitamin D(3), through VDR, may perform significant functions in the development of neuronal cells.

Animals↗

Inhibition of vesicular stomatitis virus replication by epidermal growth factor in human epidermoid A-431 cells.

Here we report that epidermal growth factor (EGF) inhibits the replication of vesicular stomatitis virus (VSV) in human epidermoid carcinoma A-431 cells, as measured by reduction in infectious viral particle production, cell protection assay, and inhibition of viral protein synthesis. The observed antiviral effects of EGF were not apparently due to inhibitory effects on the initial events in VSV infection as postinfection treatment of cells with EGF also resulted in significant inhibition in the levels of viral proteins. The EGF-mediated inhibition of VSV protein synthesis was specific in nature as prior treatment of cells with an excess of anti-EGF receptor monoclonal antibody, which blocks EGF binding, reduced the inhibition of VSV proteins elicited by EGF. In summary, the observed antiviral action of EGF was an early effect of EGF and was mediated via an EGF-responsive cellular pathway(s) that could impair VSV replication.

Antiviral Agents↗

Whole blood harvested after granulocyte-colony stimulating factor (Neupogen) mobilization, and reinfused unprocessed after high-dose melphalan treatment, accelerates hematopoietic recovery in patients with multiple myeloma.

BACKGROUND: High-dose melphalan (HDM) is now a standard treatment for multiple myeloma (MM). Stem cell transplants are fast evolving as an alternative to bone marrow transplants because they are less traumatic and easier to perform. A study was undertaken to test if whole blood harvested after mobilizing peripheral blood stem cells with granulocyte-colony stimulating factor (G-CSF) reinfused as such (without stem cells being processed or concentrated through a cell separator) for rescue after HDM (dose 140-180 mg/m2) in MM accelerates hematopoietic recovery. METHODS: Eight consecutive patients with MM were given HDM after receiving 4-5 courses of infusional vincristine, doxorubicin, and dexamethasone (VAD) chemotherapy. Approximately 6 weeks after the last course of chemotherapy, at the start of the procedure, G-CSF (Neupogen) was given at a dose of 10 microgram/kg subcutaneously daily for 4 days to mobilize stem cells. All of the patients had brisk leukocytosis (18.4-64.6 x 10(9)/L). On day 0 (fifth day after G-CSF), 1 L of blood was removed by phlebotomy and kept at room temperature for 24 hours. This was followed by a rapid intravenous (i.v.) bolus of melphalan at a dose of 140 mg/m2 in the first three patients, 155 mg/m2 in the 4th, 170 mg/m2 in the 5th, and 180 mg/m2 in the 6th, 7th, and 8th patients, applies to all patients along with hydration and diuresis. Twenty-four hours later, I L of blood previously removed was transfused back to the patient without any processing through the cell separator. The numbers of mononuclear cells reinfused was between 0.76 and 3.2 x 10(8)/kg (mean: 1.82 x 10(8)/kg). The number of CD 34+ cells infused in 4 patients ranged from 1.9 to 2.8 x 10(6)/kg (mean: 2.35 x 10(6)/kg). G-CSF was restarted on day 2 at a dose of 5 microgram/kg and given daily until the granulocyte count was 0.5 x 10(9)/L or more for 3 consecutive days. Antibiotics were given whenever a patient developed pyrexia. Platelets were transfused if below 20 x 10(9)/L or for incidences of overt bleeding. RESULTS: Granulocyte counts touched 0 between Days 6 and 10, lasting for an average of 3.4 days. Duration of granulocyte count below 0.5 x 10(9)/L was 6.5 days (range: 5-9), and these rose to 1.0 or more x 10(9)/L by Day 13.7 (range: 13-16). The number of platelet transfusions given per patient was 2.5 (range: 0-4). Intravenous antibiotics were used for 9 days (range: 4-12), and patients were discharged on Day 19 (range: 16-22). Follow-up ranged from 45 to 380 days. CONCLUSIONS: Hematopoietic recovery was rapid in all patients, including those who received doses of melphalan higher than 140 mg/m2. This resulted in less need for platelet transfusions or antibiotics, and hospitalization was short. Our results are historically similar to conventional peripheral blood stem cell transplants but much better than autologous bone marrow transplants, indicating that whole blood after G-CSF provided sufficient progenitor cels for early engraftment. The procedure is less labor intensive insofar as it does not require separation and concentration of stem cells. It has the potential of becoming an alternative to autologous marrow and peripheral blood stem cell transplantation in patients with MM.

Adult↗

In vivo biodistribution, pharmacokinetic parameters, and brain uptake of 5-halo-y-methoxy(or ethoxy)-5,6-dihydro-3'-azido-3'-deoxythymidine diastereomers as potential prodrugs of 3'-azido-3'-deoxythymidine.

A new class of 5-halo-6-alkoxy-5,6-dihydro-3'-azido-3'-deoxythymidine diastereomers (5-x-6-OR -5,6-dihydro-AZTs; X = I, Br, Cl; R = Me, Et) were evaluated as potential anti-AIDS prodrugs of 3'-azido-3'-deoxythimidine (AZT). In vivo regeneration of AZT from these 5-X-6-OR-5,6-dihydro-AZTs was examined in Balb/c mice after intravenous tail vein injection. The (5R,6R)- and (5S,6S)-5-bromo(or iodo)-6-methoxy-5,6-dihydro derivatives of AZT (BMAZT, IMAZT) were rapidly converted to AZT, resulting in AZT plasma concentrations after a 144 micromol/kg dose similar to those after an equivalent dose (144 microg/kg, 38.5 mg/kg) of AZT, whereas AZT was not detectable by HPLC after the same dose of the chloro diastereomer (5R,6R)-CMAZT. The interaction of AZT and the 5-X-6-methoxy-5,6dihydro-AZT diastereomers with the 6-[(4-nitrobenzyl)thio]-9-beta-D-ribofuranosylpurine equilibrative-sensitive nucleoside transporter in murine erythrocytes was also studied. The (5R,6R)- and (5S,6S)-5-X-6-OMe-5,6-dihydro-AZT diastereomers demonstrated a high affinity (K(i) = 0.2-0.5 mM) for the transporter relative to AZT (K(i) = 1.3 mM), with the exception of (5S,6R)-5-chloro-6-methoxy-5,6-dihydro-3'-azido-3'-deoxythymidine (CMAZT) which has a K(i) value larger than 1.5 mM. [2-(14)C]-Labeled (5R,6R)- and (5S,6S)-5-bromo-6-methoxy(or ethoxy)- 5,6-dihydro-3'-azido-3'-deoxythymidines were synthesized by the regiospecific addition of methyl hypobromite or ethyl hypobromite to the 5,6-olefinic bond of [2-(14)C]-AZT in high radiochemical yield [(5R,6R)-BMAZT, 48%, and (5S,6S)-BMAZT, 33%; (5R,6R)-BEAZT, 61%, and (5S,6S)-BEAZT, 15%), high radiochemical purity (>98%), and high specific activity (56mCi/mmol)]. The amounts of radioactivity in mouse brain after iv injection of [2-(14))C]-labeled (5R,6R)-BMAZT, (5S,6S)-BMAZT, or (5R,6R)-BEAZT were 2-4 fold higher that that for [2-(14)C]-AZT (P < 0.05). The radioactivity remaining in blood after dosing with these 5-bromo-6-alkoxy-5,6-dihydro-AZTs was up to 20-fold higher than after injection of [2-(14)C]-AZT at longer time intervals after injection. The amounts of radioactivity present in femoral bone following injection of [2(-14)C]-AZT, or these 5-bromo-6-alkoxy-5,6-dihydro-AZTs, were similar. Subcellular and regional distributions of [2-(14)C]-labeled AZT, (5R,6R)-BMAZT, or (5R,6R)-BEAZT in mouse brain after jugular vein injection did not show preferential concentration in any particular subcellular fraction nor a marked preferential regional localization for either AZT or these 5,6-dihydro prodrugs of AZT.

Acquired Immunodeficiency Syndrome↗

RER, an evolutionarily conserved sequence upstream of the rhodopsin gene, has enhancer activity.

Previous transgenic mouse experiments localized the mammalian rhodopsin gene promoter to a region just upstream of the mRNA start site, and also suggested the existence of a second more distal regulatory region. A highly conserved 100-base pair (bp) sequence which is homologous to the red and green opsin locus control region is located 1.5-2 kilobases upstream of the rhodopsin gene (depending on the species). In order to test the activity of this 100-bp region, transgenic mice were generated with bovine rhodopsin promoter/lacZ constructs which differed only by the presence or absence of the sequence. Of 11 lines generated, all demonstrated photoreceptor-specific expression of the transgene, but the lines with the putative regulatory region showed significantly higher expression. Additional transgenic lines in which the region was fused to a minimal heterologous promoter did not show transgene expression in the retina. Gel mobility shift and DNase I footprint assays demonstrated that bovine retinal nuclear extracts contain retina-specific as well as ubiquitously expressed factors that interact with the putative regulatory region in a sequence-specific manner. These results indicate that the 100-bp sequence can indeed function in vivo as a rhodopsin enhancer region.

Animals↗

Synthesis and purification of soluble ligand binding domain of the human vitamin D3 receptor.

We expressed and purified milligram quantities of the ligand binding domain of the human 1,25-dihydroxyvitamin D3 receptor using a glutathione-S-transferase (GST) fusion protein expression system. Amino acids 105-427 were expressed in E. coli as a GST fusion protein at a reduced (20 degrees C) temperature and purified on glutathione sepharose. The fusion protein adsorbed to glutathione sepharose was cleaved with thrombin to yield soluble 105-427 human 1,25-dihydroxyvitamin D3 receptor. The 105-427 human 1,25-dihydroxyvitamin D3 receptor was further purified by Mono Q ion exchange chromatography and was characterized as a single band on SDS-polyacrylamide gel electrophoresis. The 105-427 human 1,25-dihydroxyvitamin D3 receptor bound 1,25-dihydroxyvitamin D3 with high affinity (Kd approximately 10(-9)M) and with a binding capacity of 47 pmoles/nmole protein. Large scale expression of 105-427 human 1,25-dihydroxyvitamin D3 receptor will provide human 1,25-dihydroxyvitamin D3 receptor ligand binding domain suitable for structural studies.

Base Sequence↗

The basic motif-leucine zipper transcription factor Nrl can positively regulate rhodopsin gene expression.

The retinal protein Nrl belongs to a distinct subfamily of basic motif-leucine zipper DNA-binding proteins and has been shown to bind extended AP-1-like sequence elements as a homo- or heterodimer. Here, we demonstrate that Nrl can positively regulate the expression of the photoreceptor cell-specific gene rhodopsin. Electrophoretic mobility-shift analysis reveals that a protein(s) in nuclear extracts from bovine retina and the Y79 human retinoblastoma cell line binds to a conserved Nrl response element (NRE) in the upstream promoter region of the rhodopsin gene. Nrl or an antigenically similar protein is shown to be part of the bound protein complex by supershift experiments using Nrl-specific antiserum. Cotransfection studies using an Nrl-expression plasmid and a luciferase reporter gene demonstrate that interaction of the Nrl protein with the -61 to -84 region of the rhodopsin promoter (which includes the NRE) stimulates expression of the reporter gene in CV-1 monkey kidney cells. This Nrl-mediated transactivation is specifically inhibited by coexpression of a naturally occurring truncated form of Nrl (dominant negative effect). Involvement of Nrl in photoreceptor gene regulation and its continued high levels of expression in the adult retina suggest that Nrl plays a significant role in controlling retinal function.

Animals↗

Innervation of the spinal dura. Myth or reality?

STUDY DESIGN: Cranial and spinal dura from nine Sprague Dawley male rats were examined immunocytochemically for the presence of nerve fibers and mast cells and for innervation. The posterior longitudinal ligament and peridural membrane were also examined for these elements. OBJECTIVE: To examine the pattern of sensory innervation and the presence of mast cells in rat spinal dura. SUMMARY OF BACKGROUND DATA: The cranial dura is richly innervated and has a robust population of mast cells, which have been implicated in the pathogenesis of vascular headache. Moskowitz's explanation for vascular headache focused on the dura mater and neurogenic inflammation. Essential to his model are dural trigeminovascular fibers and mast cells. Previous studies provide contradictory and inconclusive results regarding spinal dural innervation. METHODS: Immunocytochemical techniques using antibodies to calcitonin gene-related peptide and substance P were used to identify sensory nerve fibers and antibodies to serotonin were used to identify mast cells. Specimens dissected included dura of the cranial vault in continuity with the dorsal cervical dura, dura of the skull base in continuity with the ventral cervical dura, lumbar dura, and posterior longitudinal ligament from the cervical and lumbar regions. RESULTS: A rich neural network and an abundant mast cell population were identified in the supratentorial and infratentorial cranial dura, both dorsally and ventrally. A paucity of nerve fibers and mast cells was observed in the cervical and lumbar dura; in contrast, these elements were prominent in the posterior longitudinal ligament and peridural membrane. CONCLUSIONS: Spinal dura does not have a rich innervation of calcitonin gene-related peptide- and substance P-positive nerve fibers or a robust population of mast cells. The spinal dura may serve as a protective covering. Unlike the cranial dura, it may not be implicated in the pathogenesis of pain. Additional studies on primate and human spinal dura are warranted to corroborate findings that the spinal dura may be relatively insensitive.

Animals↗

NDF induces expression of a novel 46 kD protein in estrogen receptor positive breast cancer cells.

Most human breast tumors start as estrogen-dependent, but during the course of the disease become refractory to hormone therapy. The transition of breast tumors from estrogen dependent to independent behavior may be regulated by autocrine and/or paracrine growth factor(s) that are independent of the estrogen receptor (ER). We have investigated the role(s) of NDF (neu-differentiation factor) in the biology of estrogen positive breast cancer cells by using MCF-7 cells as a model system. Treatment of MCF-7 cells with human recombinant NDF-beta 2 (NDF) inhibited the ER expression by 70% and this was associated with growth stimulation in an estrogen-independent manner. To explore the mechanism(s) of action of NDF in MCF-7 cells, we examined the expression of NDF-inducible gene products. We report here that NDF stimulated the levels of expression of a 46 kD protein (p46) (in addition to few minor proteins) in ER positive breast cancer cells including MCF-7, T-47-D, and ZR-75-R cells but not in ER negative breast cancer cells including MDA-231, SK-BR-3, and MDA-468 cells. This effect of NDF was due to induction in the rate of synthesis of new p46. The observed NDF-mediated induction of p46 expression was specific as there was no such effect by epidermal growth factor or 17-beta-estradiol, and inclusion of actinomycin D partially inhibited the p46 induction elicited by NDF. NDF-inducible stimulation of p46 expression was an early event (2-6 h) which preceded the period of down-regulation of ER expression by NDF. These results support the existence of NDF-responsive specific cellular pathway(s) that may regulate ER, and these interactions could play a role(s) in hormone-independence of ER positive breast cancer cells.

Gene Expression Regulation, Neoplastic↗

Ontogeny of the 1,25-dihydroxyvitamin D3 receptor in fetal rat bone.

To gain insights into 1,25-dihydroxyvitamin D3 receptor (VDR) function during fetal bone development, we examined fetal rat tissues from gestational days 13-21 for the presence and distribution of VDR using immunohistochemistry. Prior to ossification, VDR epitopes were observed in the mesenchyme condensing to form skeletal tissues, on day 13 in the developing vertebral column and limbs, and on day 17 of gestation in developing calvaria. Immunostaining for VDR was seen in proliferating and hypertrophic chondrocytes and in osteoblasts of limb buds and the vertebral column by day 17 of gestation. In calvaria, VDR epitopes were observed in osteoblasts by gestational day 19. VDR immunostaining was also evident in the skin of fetal limbs at all gestational ages examined. We show for the first time that the VDR appears very early in the developing fetal rat skeleton, suggesting that the VDR, in concert with its ligand, 1,25-dihydroxyvitamin D3, may play a role in the differentiation of mesenchymal precursors into bone tissue.

Animals↗

Chimeric hemoglobins--hybrids of human and swine hemoglobin: assembly and stability of interspecies hybrids.

Transgenic swine expressing human HbA contained only one of two types of the anticipated interspecies hybrids, namely H alpha 2 P beta 2 (H = human, P = swine). In an attempt to establish whether the absence of the swine alpha and human beta (P alpha 2 H beta 2) hybrid in vivo is a reflection of the lack of complementarity between the interspecies chains to generate appropriate interfaces, we have undertaken the in vitro assembly of swine alpha and human beta chimeric tetramer. In contrast to the in vivo transgenic swine system, in vitro the hybrid of swine alpha human beta chain is assembled readily and the hybrid exhibits normal cooperative oxygen binding. Both the swine alpha human beta and the human alpha swine beta interspecies hybrids are stable around neutral pH and do not segregate into parent tetramers even when mixed together. On the other hand, nearly complete exchange of P alpha chain of P alpha 2 H beta 2 hybrid occurs in the presence of H alpha chain at pH 6.0 and room temperature, resulting in the formation of HbA. However, very little of such an exchange reaction takes place at pH 7.0. These results suggest that the thermodynamic stability of P alpha 2 H beta 2 hybrid is lower compared to that of HbA. In contrast, P beta chain of H alpha 2 P beta 2 hybrid is refractory to exchange with H beta chain at pH 7.0 as well as at pH 6.0, suggesting that the stability of H alpha 2 P beta 2 is higher compared to that of HbA (H alpha 2 H beta 2). The swine alpha human beta chimeric Hb undergoes subunit exchange reaction with human alpha-chain in the presence of 0.9 M MgCl2, at pH 7.0. This demonstrates the lower thermodynamic stability of the intradimeric interactions of the heterodimer even at neutral pH. A synergistic coupling of the intra- and interdimeric interactions of the swine alpha and human beta chain heterodimer is essential for the thermodynamic stability of the chimeric Hb under the physiological conditions. Accordingly, we speculate that the lower thermodynamic stability of P alpha H beta heterodimer (compared to the homodimers H alpha H beta and P alpha P beta) facilitates its segregation into the homodimers by subunit exchange reaction involving either H alpha or P beta. This molecular aspect by itself or possibly along with other cellular aspects of the swine system results in the absence of P alpha 2 H beta 2 hybrid in transgenic swine expressing HbA.

2,3-Diphosphoglycerate↗

Adenosine and carbachol are not equivalent in their effects on L-type calcium current in rabbit ventricular cells.

Adenosine is one of the most important inhibitory modulators of heart function, producing negative inotropic, chronotropic and dromotropic effects and is also a major regulator of coronary circulation. The decrease in contractility by adenosine is mediated through inhibition of adenylyl cyclase by Gi-proteins coupled to adenosine receptors. However, little is known about the developmental differences in the effect of adenosine on cardiac cells. We have now shown that there is a striking developmental difference in the inhibitory effect of adenosine on isoproterenol-stimulated ICa between adult and newborn rabbit ventricular cells. Adenosine had no significant inhibitory effect on 0.1 muM isoproterenol-stimulated ICa in adult cells, while it completely blocked the 10 muM isoproterenol-stimulated ICa in newborn cells with an inhibitory potency similar to carbachol in newborn cells. Similarly, adenosine did not decrease the isoproterenol-stimulated cAMP levels in adult cells while it inhibited isoproterenol-stimulated cAMP levels significantly and equipotently to carbachol in newborn. However, for forskolin-stimulated ICa and cAMP levels in newborn cells, adenosine had a much lower inhibitory potency than carbachol. In adult cells, forskolin-stimulated ICa and cAMP levels were not affected by adenosine. We showed previously that the Gia3 isoform of inhibitory G protein was present in newborn cell membranes, but not detectable in adult cell membranes. We have now used a synthetic decapeptide corresponding to the C-terminal sequence of Gia3 in the patch pipette and have shown a selective partial block of the inhibitory action of adenosine for isoproterenol-stimulated ICa, suggesting that the inhibitory action of adenosine on ICa is mediated primarily through the Gia3 pathway.

Adenosine↗

Enhanced thermogenesis in rats by Panax ginseng, multivitamins and minerals.

Substances which enhance endurance for physical and mental work and increase non-specific resistance to stress during a prolonged stay in physiologically adverse habitats are called 'adaptogens'. Panax ginseng is well known for its anti-stress and adaptogenic properties. In the present study, adaptogenic activity by the intake of a herbo-vitamin-mineral preparation (HVMP) containing P. ginseng and multivitamin-mineral preparation (MVMP) was evaluated using the cold-hypoxia-restrained (C-H-R) animal model. The aim was to determine whether the cold tolerance and recovery from acute hypothermia mediated by P. ginseng was modified by simultaneous intake of additional vitamins and minerals. Results suggest that the adaptogenic effect of HVMP was more or less the sum total of its two components P. ginseng and MVMP. In HVMP, P. ginseng was found to be effective for developing resistance to cooling and MVMP helped in stimulating faster recovery from acute hypothermia.

Acclimatization↗

Immunohistochemical detection and distribution of the 1,25-dihydroxyvitamin D3 receptor in rat reproductive tissues.

Vitamin D3, via its active metabolite 1,25-dihydroxyvitamin D3, plays a critical part in male and female reproduction in the rat. 1,25-Dihydroxyvitamin D3 activity is mediated by an intracellular receptor (VDR). VDR distribution in reproductive tissue has not been studied using antibodies against the receptor. We developed a polyclonal antibody against the VDR and used it to examine VDR distribution in male and female rat reproductive tissues. In rat testes, VDR epitopes were observed in seminiferous tubules, specifically in spermatogonia, Sertoli cells and spermatocytes. Spermatozoa stained faintly. Epithelial cells of the epididymis, seminal vesicles and prostate also expressed VDR epitopes. In the female rat reproductive tract, immunostaining for VDR was seen in ovarian follicles, specifically in granulosa cells. Weaker VDR immunostaining was observed in follicular thecal cells and in the ovarian stroma and germinal epithelium. Corpus luteal cells stained intensely for VDR. Epithelium of fallopian tubes and the uterus also contained VDR epitopes. Both nuclear and cytoplasmic VDR immunostaining was observed in male and female rat reproductive tissues. We conclude that the VDR is widely distributed in male and female reproductive tissues and that it is likely to mediate actions of 1,25-dihydroxyvitamin D3 in the tissues.

Animals↗