Biomedical subjects

R Kumar

Publications and source records attributed to R Kumar.

At least 613 records · Page 34Linked to original sources

PubMed1997

Dopamine efflux in the rat nucleus accumbens evoked by dopamine receptor stimulation in the entorhinal cortex is modulated by oestradiol and progesterone.

This study compared the effects of dopamine receptor stimulation in the entorhinal cortex on dopamine release in the nucleus accumbens, measured by in vivo microdialysis in conscious Sprague-Dawley rats, with and without oestradiol and progesterone priming. Nonselective dopamine receptor stimulation with apomorphine reduced dopamine release in the nucleus accumbens, an effect which was prevented by injection of cis-flupenthixol into the entorhinal cortex. Selective D1 receptor stimulation with SKF38393 increased dopamine release, whereas selective D2 receptor stimulation with quinpirole did not affect dopamine release. Combined administration of oestradiol and progesterone potentiated the response to apomorphine and prevented the response to SKF38393. The effects of single hormone administration on the response to apomorphine suggested that the modulation was primarily due to oestradiol enhancing effects of progesterone. Experiments with high [K+] suggested these hormonal effects were exerted predominantly in the entorhinal cortex. The present experiments have demonstrated that dopaminergic modulation of transmission in a cortico-striatal loop linking temporal and prefrontal cortex is regulated by oestradiol and progesterone. Dysfunction in this system in humans may give rise to affective and cognitive symptoms which may, if initiated by a postpartum fall in oestrogen and progesterone concentrations, constitute the core pathophysiology of puerperal psychosis.

Animals↗

PubMed1997

Synthesis and antiviral activity of 5-ethyl-5-halo-6-alkoxy-(or azido)-5,6-dihydro-2'-deoxyuridine diastereomers as potential prodrugs to 5-ethyl-2'-deoxyuridine.

A group of 5-ethyl-5-halo-6-alkoxy (or azido)-5,6-dihydro-2'-deoxyuridines, which differ in configuration at the C-5 and C-6 positions, were synthesized by the regiospecific addition of XR (X = I, Br, Cl; R = alkoxyl, azido) to the 5,6-olefinic bond of 5-ethyl-2'-deoxyuridine (EDU). In vitro antiviral (HSV-1, HSV-2, HCMV, VZV) activities were determined. Structure-activity studies showed that the C-5 halogeno (I, Br, Cl) and C-6 alkoxy (OMe, OEt) or azido, substituents were determinants of antiviral activity where the (5R,6R)-5 and (5S,6S)-6 diastereomers of 5-ethyl-5-iodo-6-methoxy-5,6-dihydro-2'-deoxyuridine exhibited greater potency against HSV-1, HSV-2, and HCMV than the related 5-chloro-6-ethoxy and 5-bromo (or chloro)-6-azido diastereomers. The most potent antiviral agents, (+)-trans-(5R,6R)-5 and (-)-trans-(5S,6S)-6 diastereomers of 5-ethyl-5-iodo-6-methoxy-5,6-dihydro-2'-deoxyuridine were approximately 2-to-8 fold more potent than the reference drug EDU against HSV-1 and HSV-2.

Antiviral Agents↗

PubMed1997

Globus pallidus internus pallidotomy for generalized dystonia.

The authors present a young boy with severe generalized dystonia treated with bilateral simultaneous pallidotomy. Microelectrode recordings with the patient under propofol anesthesia showed that the mean discharge rate of globus pallidus internus (GPi) neurons was between 21 and 31 Hz. This contrasts sharply with the mean GPi neuronal firing rates of approximately 80 Hz that are characteristic of Parkinson's disease. The patient had no immediate benefit from surgery, but a progressive improvement in both axial and limb dystonia began within 3 days. The Burke-Fahn-Marsden scores were 75 (maximum possible = 120) at baseline, 52 at 5 days, and 16 at 3 months after surgery. The mechanism of action of pallidotomy for dystonia and the reasons for the delayed and progressive improvement are unknown. Nevertheless, the magnitude of the improvement and the safety of the procedure in this one patient warrant a careful evaluation of pallidotomy for dystonia.

Anesthesia, General↗

PubMed1997

Frameless 3D volume registration of MR data sets for stereotactic pallidotomy.

Frameless 3D volume registration of Magnetic Resonance (MR) and computed (CT) data sets has been described by Kummar et al. [11]. Its use in 3D volume registration for stereotactic planning in patients undergoing pallidotomy is presented. Pre-operative examinations with the stereotactic frame and postoperative examinations without the stereotactic frame can be co-registered and reviewed for accuracy of planned and lesional coordinates.

Brain Mapping↗

PubMed1997

Hydropericardium syndrome (HPS) in India: a preliminary study on the causative agent and control of the disease by inactivated autogenous vaccine.

Hydropericardium syndrome (HPS) in broiler birds of 3 to 6 weeks of age was recorded for the first time in the Haldwani area of Nainital district (UP) in India in November, 1994. The overall mortality in 6 poultry farms was 61.62 per cent. The disease was experimentally transmitted by bacteria free infected liver homogenate extract passed through membrane filters of 0.22 and 0.1 mu APD. The aetiological agent was inactivated by heat treatment at 56 degrees C for one hour and 80 degrees C for 10 min. A precipitin band was demonstrated in agar gel immunodiffusion and counter immunoelectrophoresis using infected liver homogenate extract as antigen and homologous antisera raised in the laboratory. The disease was effectively controlled by formalinised and heat inactivated autogenous vaccine prepared from the infected livers of birds which died of natural infection.

Animals↗

PubMed1997

Effects of scopolamine on delayed-matching-to-sample and paired associates tests of visual memory and learning in human subjects: comparison with diazepam and implications for dementia.

Two experiments examined dose-related effects of 200, 400 and 600 micrograms scopolamine (n = 24, s.c.) and 5 and 10 mg diazepam (n = 6, PO) on parallel tests of visual memory and learning taken from the CANTAB battery. Scopolamine significantly impaired accuracy of performance on a delayed matching to sample test of visual recognition memory in a dose- and delay-dependent manner, but had only marginal decremental effects on a test of visuospatial paired associates learning. Scopolamine significantly lengthened decision times in a visual search matching to sample task at the 400 and 600 micrograms doses, without significantly affecting accuracy. The drug also impaired performance on tests of spatial (on accuracy and response time measures) and pattern (on response time only) memory. Most of the deleterious effects on scopolamine were removed by covariance analyses with indices of subjective sedation, but the effects of delayed matching accuracy and latency remained. By contrast, diazepam significantly impaired paired associates learning but affected delayed matching to sample in a delay-independent manner. These results suggest that scopolamine can produce selective deficits in tests of short-term visual recognition memory which do not depend on overall impairments in arousal and which contrast with deficits in visual associative learning produced by diazepam. They have implications for the pharmacological modelling of dementia and memory disorders in man and for the neurochemical substrates of the short-term recognition memory and associative learning for visual stimuli.

Adult↗

PubMed1997

Effects of cGMP on L-type calcium current of adult and newborn rabbit ventricular cells.

OBJECTIVE: Cyclic GMP has been shown to be in some respects an inhibitory modulator of heart function. Various studies on the modulation of cardiac L-type calcium current (ICa) by cGMP in different species show inconsistency and the role of cGMP remains unclear and controversial. The present study was focused on the differences in the modulation of basal ICa by cGMP in adult and newborn rabbit ventricular cells. METHODS: Enzymatically isolated adult and newborn (1-4-day-old) rabbit ventricular myocytes were used to measure ICa under whole-cell voltage clamp conditions with internal perfusion of isolated cells. RESULTS: We have shown that in adult ventricular cells, the intracellular perfusion of 8BrcGMP did not produce any effect on basal ICa, while intracellular perfusion of 8BrcGMP or 8CPT-cGMP in newborn ventricular cells significantly and reversibly increased basal ICa without changing the voltage dependence for activation of ICa. Both methylene blue and LY-83583 (which inhibit guanylyl cyclase and thus lower cGMP levels), in adult ventricular cells, failed to produce any significant effect on basal ICa, while in newborn ventricular cells the application of methylene blue or LY-83583 produced irreversible inhibition of basal ICa. Similarly, KT-5823, an inhibitor of cGMP-dependent protein kinase, also inhibited basal ICa in newborn ventricular cells but not in adult ventricular cells. However, extracellular application of methylene blue during the intracellular perfusion of 8BrcGMP was unable to inhibit ICa. Extracellular application of nitrosoglutathione which releases nitric oxide produced a significant increase in ICa in newborn but not in adult ventricular cells. Intracellular application of a cAMP-dependent protein kinase inhibitor peptide blocked the stimulatory effect of cAMP but not of 8CPT-cGMP, while the stimulatory effect of nitrosoglutathione on ICa was not blocked by the presence of a phosphodiesterase inhibitor (isobutylmethyl-xanthine). CONCLUSIONS: We propose that, for newborn rabbit ventricular cells, cGMP plays a crucial role in maintaining basal ICa by a mechanism mediated via protein-kinase-G-dependent phosphorylation of calcium channels or some associated protein.

1-Methyl-3-isobutylxanthine↗

PubMed1997

Activation of P388D1 macrophage cell line by chemotherapeutic drugs.

It has been found that certain antineoplastic drugs impart their function with a distinct duality. Besides being tumoricidal, they are capable of acting as immunopotentiator. This led us to investigate the effect of cytosine arabinoside (CA), vincristine sulphate (VS), cyclophosphamide (CS), mitomycin C (MMC), hydroxy urea (HU) and lipopolysaccharide (LPS) on a macrophage cell line P388D1. Supernatants collected from P388D1 cells treated with CA, VS, CS, MMC, HU or LPS demonstrated enhanced production of tumor necrosis factor (TNF) confirmed by bioassay on L929 tumor target cells and increased interleukin-1 (IL-1) production by standard thymocyte proliferation bioassay. Also, supernatants showed increased amounts of nitric oxide and lysozyme using Griess reaction and reduction in turbidity of Micrococcus lysodeikticus, respectively. The above findings demonstrate that these drugs may be used not only as chemotherapeutic agents but also as macrophage-activating agents.

Animals↗

PubMed1997

Postnatal depression in Japanese women who have given birth in England.

A total of 98 Japanese mothers who became pregnant in England were monitored from 36 weeks gestation to 3 months postpartum. Psychiatric status was assessed by self-report, using a Japanese translation of the Edinburgh Postnatal Depression Scale (EPDS) and by an interview with Japanese psychiatrists, using Japanese translations of the Schedule for Affective Disorders and Schizophrenia (SADS) and Research Diagnostic Criteria (RDC). Rates of depression were similar to those observed in Japanese women having babies in Japan. Twelve mothers (12%) were categorised as having new onsets of depression (six major and six minor depressive disorder) during the 3 months following delivery. Depression was associated with having had a stressful life event or obstetric but without grandmothers' support-depressed and non-depressed women were equally likely to have had their mothers visit England to attend the delivery. Women who became depressed had significantly higher EPDS scores at 1 month postpartum than those who remained well. However, depressions were not detected when the EPDS was used as a screening instrument. With an EPDS cut-off of greater than 12, the criterion used in western samples, sensitivity was zero. Lowering the criterion to improve the instrument's sensitivity merely reduced its specificity. These results suggest that Japanese women may be less likely to express depressive symptoms by self-report, at least when instruments designed for western samples are used.

Adult↗

PubMed1997

Density and distribution of cattle lice (Phthiraptera:Haematopinidae, Linognathidae, Trichodectidae) on six steers.

The density and distribution of four species of cattle louse, Bovicola bovis (L.). Haematopinus eurysternus (Nitzsch), Linognathus vituli (L.), and Solenopotes capillatus (Enderlein), were elucidated from the hides of six slaughtered steers. Adult and nymphal lice were first removed from one hide by hand and the location of each specimen mapped. The remaining lice were removed by a detergent wash, and KOH dissolution of hide and hair. Lice from the remaining five hides were removed using KOH dissolution of cattle hair and subsequent filtration of the effluent. Bovicola bovis was most abundant, followed by H. eurysternus, L. vituli and S. capillatus. Significant variation was observed in B. bovis, H. eurysternus and L. vituli population densities. Solenopotes capillatus population densities did not differ significantly. All species were contagiously distributed, i.e. 'clumped', suggesting species dependent predilection sites. Predilection sites were ranked according to louse density to facilitate the development of field sampling strategies. Additional biological data were gathered on sex and life stage ratios for each species.

Animals↗

PubMed1997

Tourette syndrome. Secondary tic disorders.

The putative relationship between a variety of neurologic and neuropsychiatric disorders, which have been reported in association with tics, is reviewed. Tics also may be increased or exacerbated by drugs affecting a variety of neurotransmitter systems. Recognition and study of these secondary tic disorders may further our understanding of basal ganglia physiology and the pathogenesis of Tourette syndrome.

Adult↗

PubMed1997

Arsenate resistance as a possible marker in the differentiation of environmental and clinical isolates of Vibrio parahaemolyticus.

Strains of Vibrio parahaemolyticus were isolated from clinical, marine and freshwater fish of Calcutta, West Bengal, India. Drug and metal resistance characteristics were compared for differentiation of clinical and environmental strains. Eighteen out of the twenty environmental isolates were resistant to arsenate, unlike the clinical isolates which were all susceptible. All the thirty-five isolates of V. parahaemolyticus were resistant to ampicillin and streptomycin.

Animals↗

PubMed1997

Anti-invasive activity of alkaloids and polyphenolics in vitro.

Invasiveness, the ability of certain tumour cells to migrate beyond their natural tissue boundaries, often leads to metastasis, and usually determines the fatal outcome of cancer. The need for anti-invasive agents has led us to search for possibly active compounds among alkaloids and polyphenolics. One hundred compounds were screened in an assay based on the confrontation of invasive human MCF-7/6 mammary carcinoma cells with fragments of normal embryonic chick heart in vitro. Anti-invasive activity was frequently found among chalcones having a prenyl group. Six compounds were found to inhibit invasion when added to the culture medium at concentrations as low as 1 microM. For at least three of them the anti-invasive effect could be associated with a cytotoxic effect on the MCF-7/6 cells, but not on the heart tissue. This selective cytotoxicity was substantiated by different methods, such as histology and growth assays (volume measurements, cell counts, MTT and sulforhodamine B assays). The anti-invasive effects of the compounds could neither be ascribed to induction of apoptosis nor to the promotion of cell-cell adhesion. Our data indicate that among the alkaloids and polyphenolics a number of molecules can inhibit growth and invasion of human mammary cancer cells via selective cytotoxicity.

Alkaloids↗

PubMed1997

Enhanced anti-proliferative activity of the combination of tamoxifen plus HER-2-neu antibody.

HER-2/neu overexpression has been associated with poor prognosis in human breast cancer. Many of these cancers are also ER-positive. A logical therapeutic approach for patients who are ER-positive and overexpress HER-2/neu may be to block both the ER and the HER-2/neu pathways. In our study, we used both the MTT tetrazolium dye assay and 3H-thymidine incorporation to measure the effects of the anti-estrogen Tamoxifen or the 4D5 anti-HER-2/neu antibody alone or in combination on the growth of BT474 human breast cancer cells which express ER and overexpress HER-2/neu. We found an enhanced inhibitory effect on cell proliferation with the combination of Tamoxifen and the antibody compared to that seen by either agent alone. This simultaneous interruption of both the ER and the HER-2/neu pathways may be relevant in the clinical treatment of patients who are both ER-positive and overexpress HER-2/neu.

Antibodies, Monoclonal↗

PubMed1997

Randomized, double-blind, placebo-controlled trial of fish oil and mustard oil in patients with suspected acute myocardial infarction: the Indian experiment of infarct survival--4.

In a randomized, placebo-controlled trial, the effects of treatment with fish oil (eicosapentaenoic acid, 1.08 g/day) and mustard oil (alpha-linolenic acid, 2.9 g/day) were compared for 1 year in the management of 122 patients (fish oil, group A), 120 patients (mustard oil, group B), and 118 patients (placebo, group C) with suspected acute myocardial infarction (AMI). Treatments were administered about (mean) 18 hours after the symptoms of AMI in all three groups. The extent of cardiac disease, rise in cardiac enzymes, and lipid peroxides were comparable among the groups at entry into the study. After 1 year total cardiac events were significantly less in the fish oil and mustard oil groups compared with the placebo group (24.5% and 28% vs. 34.7%, p < 0.01). Nonfatal infarctions were also significantly less in the fish oil and mustard oil groups compared with the placebo group (13.0% and 15.0% vs. 25.4%, p < 0.05). Total cardiac deaths showed no significant reduction in the mustard oil group; however, the fish oil group had significantly less cardiac deaths compared with the placebo group (11.4% vs. 22.0%, p < 0.05). Apart from the decrease in the cardiac event rate, the fish oil and mustard oil groups also showed a significant reduction in total cardiac arrhythmias, left ventricular enlargement, and angina pectoris compared with the placebo group. Reductions in blood lipoproteins in the two intervention groups were modest and do not appear to be the cause of the benefit in the two groups. Diene conjugates showed a significant reduction in the fish oil and mustard oil groups, indicating that a part of the benefit may be caused by the reduction in oxidative stress. The findings of this study suggest that fish oil and mustard oil, possibly due to the presence of n-3 fatty acids, may provide rapid protective effects in patients with AMI. However, a large study is necessary to confirm this suggestion.

Adult↗

PubMed1997

Inhibition of rat brain protein kinase C by lipid soluble psychotropics.

Lipid soluble psychotropics inhibit brain PKC-catalyzed phosphorylation of exogenous and endogenous proteins to varying degrees. These drugs were better inhibitors of Ca2+/PL-dependent phosphorylation of histones (H) than that of Ca2+/PL-independent protamine sulfate (PrSO4): antidepressants/antipsychotics displayed IC50 of 0.1 to 0.16 mM towards H and 0.3 to 4.0 mM towards PrSO4 phosphorylation. Sedatives/anesthetics were less efficient inhibitors with much higher IC50 of 1.3 to 40 mM. Phosphorylation of a Ca(2+)-dependent but PL-independent p80 protein and of a cluster of Ca2+/PL-dependent proteins, p16-20, in brain was also inhibited by the antidepressants/antipsychotics but not by the sedatives/anesthetics. Phorbol ester binding studies revealed that these inhibitors do not compete for DAG binding site(s) on PKC. However, both drug-PL and drug-PKC interactions seem to be relevant in their mechanism of action. Furthermore, our data suggest that the hydrophobic nature of the propanamine side chain or its N-methylated version as well as the tricyclic nucleus influence drug-PKC interaction. Although many of these drugs have other accepted modes of action, modulation of PKC activity in brain, may be yet another aspect to be considered in their mechanism of action.

Anesthetics↗

PubMed1997

Expression of polycystin in mouse metanephros and extra-metanephric tissues.

The presence of messenger RNA for the mouse homologue of the polycystic kidney disease 1 gene (PKD1) was demonstrated by reverse transcription-polymerase chain reaction (RT-PCR) methods in mouse embryo messenger RNA. A single locus for the PKD1 gene was detected on mouse chromosome 17 by fluorescent in situ hybridization. Immunoprecipitation of proteins from [35S] methionine-labeled mouse metanephric explants with an anti-polycystin antibody (Pc1) revealed high molecular weight bands, the highest being > 400 kDa. Immunoperoxidase staining of mouse embryos with Pc1 revealed expression of polycystin as early as day 8 gestation. The expression was seen in epithelial cells of the ureteric bud, in condensing blastemal cells of the developing metanephros and, subsequently, in cells of the nascent tubules. In addition, Pc1 immunoreactivity was seen in hepatocytes and biliary epithelium, cardiac and skeletal muscle, neural tissue, gut, and bronchial epithelium. In post-natal and adult mouse kidney and liver persistent slight to moderate immunoreactivity was observed. Immunofluorescent studies of cultured 13-day mouse metanephroi revealed polycystin expression in ureteric bud epithelium, early glomerular structures (that is, condensates, S-shaped and comma-shaped bodies) and in proximal and distal tubular epithelia. These data indicate that the mouse has a single gene homologous to human PKD1 on chromosome 17, and polycystin is expressed in a variety of tissues during embryonic development.

Age Factors↗

PubMed1997

Coal tar therapy in palmoplantar psoriasis: old wine in an old bottle?

BACKGROUND: Palmoplantar psoriasis (PPP) is a disabling condition which is usually resistant to most of the available therapeutic modalities. Coal tar is an accepted therapy for psoriasis which has not been well studied for PPP. METHODS: Thirty patients with a plaque type of PPP were allocated into two groups: Group A (19 patients) were treated with 6% crude coal tar (CCT) ointment and Group B (11 patients) were treated with white petrolatum and salicylic acid. In both groups, ointment was applied and left on overnight. Wearing of gloves and socks during the night and application of emollients in the day was routinely advised. The lesions were assessed for erythema, scaling, and induration (ESI) every 2 weeks for a total of 8 weeks. Patients with greater than 50% improvement were considered to have good improvement. Side-effects, if any, were also monitored. RESULTS: In Group A, 76.5% of patients (13/17) showed good improvement, whereas only 45.5% of patients (5/11) in Group B showed the same magnitude of improvement (P < 0.05). No side-effects were reported by any patient in either of the groups. CONCLUSIONS: Crude coal tar is a safe, effective, and inexpensive modality for the treatment of PPP. We recommend coal tar under occlusion, along with the liberal use of emollients, as the first line of therapy for all cases of PPP.

Administration, Topical↗