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Biomedical subjects

K S Kumar

Publications and source records attributed to K S Kumar.

At least 73 records · Page 4Linked to original sources
PubMed1994

Understanding the attitude of multidisciplinary teams working in leprosy.

This study investigated the attitude of health personnel who were working for the National Leprosy Eradication Programme (NLEP) in India to their leprosy patients. These personnel were studied individually and as homogeneous groups so that comparisons were possible within and among the groups, and between the groups in different regions who were conducting similar health programmes, with a difference in length of between 1 and 5 years. The sample population was the NLEP employees of 2 state governments, consisting of 8 health professional groups. A questionnaire was developed for each of these groups to elicit information on 5 aspects of the relationships with their patients. The main outcome of the study was that two-thirds of the personnel tested possessed the 'minimum desirable' interaction with their patients. The quality of their relationships differed only among work specialities, but was consistent within the same speciality in different regions; this pattern was unchanged after 5 years of a multidrug (MDT) programme. A further analysis showed that although they possessed a caring attitude towards patients from low socioeconomic classes, a domineering attitude towards these same patients was also prevalent. Analysis according to speciality revealed that laboratory technicians had the highest "desirable attitude" (74.67%) and health educators had the lowest (57.5%), while the rest of the team members fell in between. The stigma shown towards leprosy was higher among doctors when compared to the rest of the team members. Discussion is based on the performance, overall and in each of its 5 facets, of each the professional groups with reference to their job descriptions and with similar studies undertaken earlier.

Adult↗
PubMed1993

Involvement of superoxide dismutase and glutathione peroxidase in attenuation of radiation-induced hyperthermia by interleukin-1 alpha in rats.

Pretreatment with recombinant human interleukin-1 alpha (rhIL-1 alpha) 20 h before irradiation attenuates radiation-induced hyperthermia. Experiments were conducted to determine the role of antioxidant enzymes such as superoxide dismutase (SOD) and glutathione peroxidase (GSHPx) in rhIL-1 alpha-induced attenuation of radiation-induced hyperthermia. Radiation exposure increased SOD and decreased GSHPx levels in the hypothalamus, while treatment with rhIL-1 alpha increased GSHPx levels and had no effect on SOD levels. However, rhIL-1 alpha and irradiation together increased hypothalamic SOD level but prevented the fall in GSHPx level. Our results suggest that attenuation of radiation-induced hyperthermia by rhIL-1 alpha may involve stimulation of SOD and GSHPx because rhIL-1 alpha treatment and irradiation together increased hypothalamic GSHPx and SOD levels, and intracerebroventricular administration of SOD and GSHPx attenuated the radiation-induced hyperthermia.

Animals↗
PubMed1993

Effects of S-2-(3-methylaminopropylamino)ethyl phosphorothioic acid (WR-3689), alone or combined with caffeine, on catecholamine content of mouse hypothalamus.

S-2-(3-Methylaminopropylamino)ethylphosphorothioic acid (WR-3689) is a radioprotective agent that is behaviorally toxic at radioprotective doses. It was recently reported that the combination of WR-3689 and caffeine ameliorated behavioral toxicity (determined by locomotor activity in mice) compared with WR-3689 alone. Since catecholamines can modulate locomotor activity, we determined norepinephrine (NE) and dopamine (DA) content (using high-performance liquid chromatography) in the hypothalamus of mice after treatment with WR-3689, caffeine, and the combination of the two drugs. CD2F1 male mice were injected intraperitoneally with saline (control), WR-3689 (100 and 200 mg/kg), caffeine (20 and 40 mg/kg), or the combination of WR-3689 (200 mg/kg) and caffeine (40 mg/kg). Control values for NE and DA ranged between 200 and 220 pg/mg and 69 and 94 pg/mg of hypothalamic tissue, respectively. WR-3689 had no effect on the content of NE and DA. In contrast, NE increased to (mean +/- SE) 324 +/- 27 pg/mg and 377 +/- 61 pg/mg (P < 0.05) 4 hr after injections of 20 and 40 mg/kg of caffeine, respectively. Similarly, DA increased to 142 +/- 13 pg/mg (P < 0.05) 4 hr after injection of 40 mg/kg of caffeine. The combination of WR-3689 and caffeine had no effect on NE and DA contents when compared with control values. These results suggest that WR-3689 can affect catecholamine metabolism in the mouse hypothalamus, but the mode of action is not clear.

Amifostine↗
PubMed1992

Radioprotection by metals: selenium.

The need exists for compounds that will protect individuals from high-dose acute radiation exposure in space and the agents that might be less protective but less toxic and longer acting. Metals and metal derivatives provide a small degree of radioprotection (dose reduction factor < or = 1.2 for animal survival after whole-body irradiation). Emphasis is placed here on the radioprotective potential of selenium (Se). Both the inorganic salt, sodium selenite, and the organic Se compound, selenomethionine, enhance the survival of irradiated mice (60Co, 0.2 Gy/min) when injected IP either before (-24 hr and -1 hr) or shortly after (+15 min) radiation exposure. When administered at equitoxic doses (one-fourth LD10; selenomethionine = 4.0 mg/kg Se, sodium selenite = 0.8 mg/kg Se), both drugs enhanced the 30-day survival of mice irradiated at 9 Gy. Survival after 10-Gy exposure was significantly increased only after selenomethionine treatment. An advantage of selenomethionine is lower lethal and behavioral toxicity (locomotor activity depression) compared to sodium selenite, when they are administered at equivalent doses of Se. Sodium selenite administered in combination with WR-2721, S-2-(3-aminopropylamino)ethylphosphorothioic acid, enhances the radioprotective effect and reduces the lethal toxicity, but not the behavioral toxicity, of WR-2721. Other studies on radioprotection and protection against chemical carcinogens by different forms of Se are reviewed. As additional animal data and results from human chemoprevention trials become available, consideration also can be given to prolonged administration of Se compounds for protection against long-term radiation effects in space.

Aerospace Medicine↗
PubMed1992

Behavioral toxicity of selected radioprotectors.

Effective radioprotection with minimal behavioral disruption is essential for the selection of protective agents to be used in manned spaceflight. This overview summarizes the studies on the behavioral toxicity of selected radioprotectors classified as phosphorothioates (WR-2721, WR-3689), bioactive lipids (16, 16 dimethylprostaglandin E2(DiPGE2), platelet activating factor (PAF), leukotriene C4), and immunomodulators (glucan, synthetic trehalose dicorynomycolate, and interleukin-1). Behavioral toxicity was examined in laboratory mice using a locomotor activity test. For all compounds tested, there was a dose-dependent decrease in locomotor behavior that paralleled the dose-dependent increase in radioprotection. While combinations of radioprotective compounds (DiPGE2 plus WR-2721) increased radioprotection, they also decreased locomotor activity. The central nervous system stimulant, caffeine, was able to mitigate the locomotor decrement produced by WR-3689 or PAF.

16,16-Dimethylprostaglandin E2↗
PubMed1991

Surface hydrophobicity of "rheumatogenic" and "nephritogenic" strains of group A streptococci and the ultrastructural surface feature of pharyngeal cells exposed to group A streptococci.

The present study was carried out to determine the surface hydrophobicity of group A streptococcal strains responsible for rheumatic fever (RF), "rheumatogenic" strains (RG strains) and strains causing glomerulonephritis, "nephritogenic" strains (NG strains) in relation to their adhesion to human pharyngeal cells. Scanning electronmicroscopic (SEM) studies were carried out to the difference, if any, in the adherence of group A streptococci (M type 5) to pharyngeal and buccal cells (PEC and BEC). By employing two techniques for hydrophobicity determination, salt aggregation titre (SAT) and n-hexadecane binding technique, it was observed that RG strains (M5, M1 and M6) were more hydrophobic than NG strain, M49. However, NG strain M12 was almost equally as hydrophobic as RG strains. The adherence of RG strains, except M1 and M24, to PEC was greater in number than that of NG strains. Although M1 strain was hydrophobic, its adherence to PEC was less. Pepsin and trypsin treatment with streptococci reduced the hydrophobicity and adherence of RG and NG strains to PEC. SEM studies revealed firmly adhered indigenous bacteria on PEC and BEC. Streptococci (M5) adhered more to PEC than to BEC. SEM studies also showed that PEC had a peculiar ultrastructural surface feature to which streptococci adhered. These findings suggest that streptococcal hydrophobicity alone does not determine their adhesion to PEC. The surface nature of PEC might be a characteristic feature of the epithelial cells that allows streptococci to adhere and colonize or it might be a consequence of streptococcal adhesion.

Alkanes↗
PubMed1990

Advances in radioprotection through the use of combined agent regimens.

The most effective radioprotective agents exhibit toxicities that can limit their usefulness. It may be possible to use combinations of agents with different radioprotective mechanisms of action at less toxic doses, or to reduce the toxicity of the major protective compound by adding another agent. With regard to the latter possibility, improved radioprotection and reduced lethal toxicity of the phosphorothioate WR-2721 was observed when it was administered in combination with metals (selenium, zinc or copper). The known mechanisms of action of potential radioprotective agents and varying effects of different doses and times of administration in relation to radiation exposure must be considered when using combined-agent regimens. A number of receptor-mediated protectors and other biological compounds, including endotoxin, eicosanoids and cytokines, have at least an additive effect when administered with thiol protectors. Eicosanoids and other bioactive lipids must be administered before radiation exposure, whereas some immunomodulators have activity when administered either before or after radiation exposure. For example, the cytokine interleukin-1 administered simultaneously with WR-2721 before irradiation or after irradiation enhances the radioprotective efficacy of WR-2721. The most effective single agents or combinations of protectors result in a decrement in locomotor activity, an index of behavioral toxicity. Recent evidence indicates that administration of the CNS stimulant caffeine mitigates the behavioral toxicity of an effective radioprotective dose of the phosphorothioate WR-3689 without altering its radioprotective efficacy. These examples indicate that the use of combinations of agents is a promising approach for maximizing radioprotection with minimal adverse effects.

Animals↗
PubMed1989

Radiation-induced volatile hydrocarbon production in platelets.

Generation of volatile hydrocarbons (ethane, pentane) as a measure of lipid peroxidation was followed in preparations from platelet-rich plasma irradiated in vitro. The hydrocarbons in the headspace of sealed vials containing irradiated and nonirradiated washed platelets, platelet-rich plasma, or platelet-poor plasma increased with time. The major hydrocarbon, pentane, increased linearly and significantly with increasing log radiation dose, suggesting that reactive oxygen species induced by ionizing radiation result in lipid peroxidation. Measurements of lipid peroxidation products may give an indication of suboptimal quality of stored and/or irradiated platelets.

Blood Platelets↗
PubMed1988

Opposite effects of WR-2721 and WR-1065 on radiation-induced hypothermia: possible correlation with oxygen uptake.

Ionizing radiation induces hypothermia in guinea pigs. While systemic injection of the radioprotectant S-2-(3-aminopropylamino)ethylphosphorothioic acid (WR-2721) did not block hyperthermia induced by exposure to 10 Gy of gamma radiation, central administration did attenuate it. The dephosphorylated metabolite of WR-2721, N-(2-mercaptoethyl)-1,3-diaminopropane (WR-1065), accentuated radiation-induced hypothermia by both routes of administration. In brain homogenates, oxygen uptake was inhibited by WR-2721 but elevated by WR-1065. These results suggest that the antagonism of radiation-induced hypothermia found only after central administration of WR-2721 is due to its direct actions and not to its dephosphorylated metabolite and that this effect may be correlated with the inhibition by WR-2721 of oxygen uptake.

Amifostine↗
PubMed1987

Selenium pretreatment enhances the radioprotective effect and reduces the lethal toxicity of WR-2721.

Although WR-2721, S-2-(3-aminopropylamino)ethylphosphorothioic acid, is an effective radioprotector, its use is limited by its toxicity. Combining WR-2721 with other agents might decrease its toxicity and/or increase its effectiveness. The effect of selenium (Se) pretreatment on the acute toxicity and radioprotective effect of WR-2721 was studied in male CD2F1 mice. Injection of 1.6 mg/kg Se 24 hr before WR-2721 (800-1200 mg/kg, IP) decreased the lethality of WR-2721 significantly. Lower doses of Se were also effective, but simultaneous administration was not effective. Se injection alone (1.6 mg/kg) 24 hr before cobalt-60 irradiation increased the survival (dose reduction factor, DRF = 1.1) significantly. A synergistic effect on post-irradiation survival was observed when Se was injected 24 hr before WR-2721 (200-600 mg/kg IP 1/2 before irradiation). For example, after exposure to 22 Gy (1 Gy/min), 30-day survival was 100% when mice were treated with both Se and 600 mg/kg WR-2721, and was 13% with WR-2721 alone. The DRF after 400 mg/kg WR-2721 was 2.6 with Se compared to 2.2 without Se pretreatment. Alkaline phosphatase activity in bone marrow cells and serum was significantly depressed after treatment with 1.6 mg/kg Se, suggesting that a retardation of conversion of WR-2721 to its active free sulfhydryl form through the action of alkaline phosphatase might be partly responsible for the effects of Se. Other possible mechanisms related to the antioxidant properties of Se are under investigation.

Alkaline Phosphatase↗
PubMed1986

Inhibition of glutathione peroxidase and glutathione transferase in mouse liver by misonidazole.

The mechanisms of toxicity and sensitization by the radiosensitizer misonidazole [1-(2-nitro-1-imidazolyl)-3-methoxy-2-propanol] are not well understood. We report here on the inhibition of total glutathione peroxidase (GSHPx), selenium-dependent glutathione peroxidase (selenium-GSHPx) and glutathione transferase (GSHTx) activities by misonidazole. Mouse liver cytosol GSHPx and selenium-GSHPx were inhibited in vitro with 0.5 mM misonidazole. On administration of the drug intraperitoneally (800 mg/kg) to mice, it was found that GSHPx, selenium-GSHPx, and GSHTx were inhibited in homogenate, cytosol, and microsomal fractions of mouse liver. GSHPx was depressed in all fractions up to 60-70% of control values, with maximum depression occurring in the cytosol and homogenate fractions in less than 2 hr. Recovery of activity was slower in the microsomes. In general, the pattern of depression of selenium-GSHPx was parallel to that of GSHPx except in microsomes, where GSHPx is minimal. Quantitatively, selenium-GSHPx was least affected. GSHTx was inhibited 70-80% of control values in cytosol and homogenate with recovery by 24 hr, whereas a second period of depression occurred at 24 hr in the microsomes. The inhibition of peroxide-metabolizing enzymes may lead to elevation of intracellular peroxide levels, contributing to the radiosensitizing effect and/or toxicity of misonidazole.

Animals↗