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Biomedical subjects

H Kumar

Publications and source records attributed to H Kumar.

At least 19 recordsLinked to original sources
PubMed1992

Oral, anti-inflammatory activity of a potent, selective, protein kinase C inhibitor.

The protein kinase C family of enzymes is thought to be important in mediating signal transduction. Ro 31-8830 is a novel, potent inhibitor of protein kinase C, derived from the non-selective protein kinase inhibitor staurosporine. In this paper we demonstrate the selectivity of Ro 31-8830 for protein kinase C over other protein kinases and its ability to inhibit protein kinase-C-mediated events in platelets and lymphocytes. In addition, we describe a novel system for the in vivo evaluation of inhibitors of protein kinase C, and we demonstrate the oral anti-inflammatory activity of Ro 31-8830. This finding has implications for the treatment of inflammatory disorders in the clinic.

Administration, Oral↗
PubMed1992

Repeated infection of cats with Brugia pahangi: parasitological observations.

Cats were repeatedly inoculated with infective larvae of Brugia pahangi. On parasitological grounds they could be divided into 5 groups. Group I--most cats (some 70%) became microfilaraemic (mf+) and retained high levels of microfilariae (mf) in their blood for over 2 years. In some Group I cats mf counts stabilized at high levels whilst in others mf counts continued to increase. Large numbers of fecund adult worms were recovered from their lymphatics. Adult counts were not made on the cats in the current experiments but over 100 adults have been recovered from 'super-susceptible' cats. Large amounts of B. pahangi adult antigen were consistently present in the serum of all Group I cats. About 30% of cats became amicrofilaraemic (mf-). In these cats the peak mf levels were seldom above 10,000 mf/ml. Group II--these cats had less than 10,000 mf/ml and low antigen levels. After more than 1 year of being repeatedly infected B. pahangi adult antigen slowly declined and eventually could no longer be detected in their serum and the number of mf declined very slowly after the fall in antigen levels. This shows that in Group II cats the adult worms die and as the cats are resistant to the development of the continuing weekly inoculation of L3 no new adults can develop. Group III--these cats became mf--during the first year of infection but remained B. pahangi antigen-positive for many weeks after this and, at autopsy, had living adults in their lymphatics.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Prognostic significance of reciprocal changes in acute myocardial infarction.

Study on 108 patients of acute myocardial infarction has shown the incidence of reciprocal ST depression in ECG in 58.3% patients. Those showing reciprocal changes had higher (65.0% Vs 15.5%) incidence of complication such as dysrhythmias, conduction disorders. hypotension, left ventricular failure or CCF which was more conspicuous in inferior myocardial infarction. There was higher incidence of complications (74.4% vs 18.7%) whenever ST depression was 2 mm or more (P < 0.001) and there was steep rise in complications whenever the ST depression persisted for 2 days and beyond.

Adult↗
PubMed1992

Experience of haemodialysis at the Kidney Centre.

Seventy-nine patients of end stage renal disease (ESRD) on maintenance haemodialysis were studied. Most of the cases were in their prime of life. The disease was equally common in both sexes and all ethnic groups. Chronic glomerulonephritis was the commonest cause followed by diabetes mellitus. Hypertension was the commonest associated illness. All patients were screened for hepatitis B surface antigen and antibody and those found negative were vaccinated. A-V fistula in the upper extremity was used as the vascular access in 93% cases. In 68% cases dialyzer was reused without any ill effect. Amongst the complications observed, hypotension was seen in 65%, psychological disorders in 52%, followed by nausea, vomiting, itching and cramps. Technical complications were related to A-V fistula in 45% cases. Forty three percent patients were maintained without blood transfusion and 88% showed improvement in their quality of life.

Adolescent↗
PubMed1992

Biochemical studies on mouse liver following Plasmodium berghei infection.

The lipid composition of mouse liver following infection with P. berghei was investigated. The liver lipid contents of infected animals were greatly increased mainly due to the accumulation of triacylglycerides. There was enhanced lipid concentration (85.29%). Significantly (23.7%) depleted liver cholesterol was also found in the mice. Similarly, phospholipid contents of liver were also decreased by 19.90 per cent. The liver from P. berghei infected mouse produced more lipid peroxide, as compared to control animals (314%). Significant depletion was also observed in carbohydrate, glycogen and glucose (79.1, 86.26 and 78.6% respectively) contents of liver at high parasitaemia. The lower contents of nucleic acid in the infected hosts observed in the study may be partly due to the absorption of nucleic acids by the parasites from the host cells.

Animals↗
PubMed1991

A novel conformationally restricted protein kinase C inhibitor, Ro 31-8425, inhibits human neutrophil superoxide generation by soluble, particulate and post-receptor stimuli.

A novel, bis-indolylmaleimide, Ro 31-8425, bearing a conformationally restricted side chain, inhibits protein kinase C isolated from rat brain and human neutrophils with a high degree of selectivity over cAMP-dependent kinase and Ca2+/calmodulin-dependent kinase. It also inhibits phorbol ester-induced intracellular events known to be mediated by protein kinase C (p47 phosphorylation in intact platelets, CD3 and CD4 down-regulation in T-cells). Ro 31-8425 inhibited superoxide generation in human neutrophils activated by both receptor stimuli (formyl-methionyl-leucylphenylalanine, opsonized zymosan, IgG and heat aggregated IgG) and post-receptor stimuli (1,2-dioctanoylglycerol and fluoride). The compound also blocked antigen driven, but not IL-2 induced, T-cell proliferation. These results support a central role for protein kinase C in the activation of the respiratory burst and antigen-driven T-cell proliferation.

Animals↗
PubMed1991

Circulating filarial antigen in cats infected with Brugia pahangi is indicative of the presence of adult worms.

Using counterimmunoelectrophoresis with rabbit antisera raised against soluble extracts of adult females of Brugia pahangi parasite antigen was detected in the serum of all cats repeatedly infected with B. pahangi. Antigen was never detected in uninfected cats. The antigen was associated with the presence of adult worms. Antigen was detected consistently in a cat that was amicrofilaraemic but at autopsy harboured only two or three adult worms. Conversely, some cats showed slowly declining numbers of microfilariae and, in these, circulating antigen declined before the number of microfilariae. Eventually no antigen was detectable in circulation whereas microfilariae, although in diminishing numbers, were still present. At autopsy no adult worms were found in these cats. Antigen also appeared in several cats before they became microfilaraemic.

Animals↗
PubMed1991

Knowledge and perceptions of residents regarding case management of acute diarrhea.

The knowledge and perceptions about case management of acute diarrhea were studied amongst 330 resident doctors working in Pediatric Departments of various Medical Colleges in the country. Our observations highlight the inadequacies in the medical curriculum and deficient clinical training in the management of acute diarrhea in the teaching institutions. Knowledge of signs of dehydration was correctly perceived by only 79.8% interns, 80.9% house physicians and 81.1% postgraduate students. It was appalling to observe that despite spending 1-3 years in pediatric wards, the knowledge and perceptions of postgraduate students had not significantly improved. On the contrary, the responses of postgraduate students were poorer as compared to interns in their perceptions of use of ORT in moderate dehydration (p less than 0.005) and in presence of vomiting (p less than 0.05). Adequate thrust on diarrhea and its management during undergraduate as well as during postgraduate teaching and proper training in diarrhea case management with "hands on training" needs to be viewed as a priority in the teaching institutions.

Acute Disease↗
PubMed1991

Vaccination of rhesus monkeys against Plasmodium knowlesi with aqueous suspension of MDP as an adjuvant.

In these investigations two types of antigen preparations were used: (i) Whole Antigen (WAg), and (ii) Soluble Antigen (SAg). For immunization, Muramyl Dipeptide (MDP) was employed as an adjuvant. Highest reciprocal antibody titre values were recorded in ELISA and IHA tests from animals immunized by WAg-MDP. Skin reactions in animals sensitized with WAg-MDP combination showed a well developed zone of erythema with induration after 24 hours of intradermal injection. Animals immunized with WAg-MDP showed a maximum leukocyte migration inhibition. All the animals in experimental and control groups showed patent infection following challenge with live parasites. Animals belonging to the control groups showed 100% mortality. On the basis of these experiments it could be concluded that MDP preparation afforded some protection to the test animals.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1991

Novel, potent and selective inhibitors of protein kinase C show oral anti-inflammatory activity.

Clarification of the precise role of protein kinase C (PKC) in cellular functional responses has been hampered by a lack of potent, selective inhibitors. The structural lead provided by staurosporine, a potent but non-selective protein kinase (PK) inhibitor, was used to derive a series of bis(indolyl)maleimides of which the most potent, Ro 31-8425 (I50: PKC = 8 nM) showed 350-fold selectivity for PKC over cAMP-dependent protein kinase. Ro 31-8425 antagonised cellular processes triggered by phorbol esters (potent, specific PKC activators) and inhibited the allogeneic mixed lymphocyte reaction, suggesting a role for PKC in T-cell activation. Methylation of the primary amine in Ro 31-8425 produced an analogue. Ro 31-8830 which, when administered orally, produced a dose-dependent inhibition of a phorbol ester-induced paw oedema in mice (minimum effective dose = 15 mg/kg). Ro 31-8830 also selectively inhibited the secondary inflammation in a developing adjuvant arthritis model in the rat. The results presented here suggest that these selective inhibitors of PKC may have therapeutic value in the treatment of T-cell-mediated autoimmune diseases.

Administration, Oral↗