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Biomedical subjects

P Kumar

Publications and source records attributed to P Kumar.

At least 415 records · Page 23Linked to original sources
PubMed1994

alpha-Trifluoromethyl-beta-alanyl glycine (F3MBAG): a novel mammalian metabolite of trifluridine (F3TdR).

19F NMR spectroscopy has been used to study further the metabolism of 5-trifluoromethyl-2'-deoxyuridine (trifluridine; F3TdR). The synthesis and characterization of alpha-trifluoromethyl-beta-alanyl glycine (F3MBAG), a putative new metabolite of F3TdR, are now reported. This study describes ex vivon and in vivo detection of F3MBAG and other previously reported metabolites of trifluridine, using 19F NMR spectroscopy, in male BALB/C mice bearing EMT-6 tumors. A parallel 19F NMR spectroscopic study was also performed on rats dosed with F3TdR, to observe the qualitative pattern of F3TdR metabolism in another species. Unexpectedly, 5-trifluoromethyl-5,6-dihydroxyuracil (DOHF3T), alpha-trifluoromethyl-beta-ureidopropionic acid (F3MUPA) and fluoride, which result from the metabolic degradation of F3TdR and which were detected in various biological samples from mice dosed with F3TdR, could not be identified in rat urine or in homogenized tissue extracts. The presence of these metabolites in intact tissues is uncertain since in this study 19F NMR spectroscopy of these samples always displayed a broad resonance "hump" across the range of chemical shifts that would encompass these metabolites. No clear explanation for the loss of spectroscopic resolution in this region has been rationalized. N-Carboxy-alpha-trifluoromethyl-beta-alanine (F3MBA-CO2), alpha-trifluoromethyl-beta-alanyl alanine (F3MBAA) and N-acetyl-alpha-trifluoromethyl-beta-alanine (Ac-F3MBA) were synthesized and characterized, but were not detected as metabolites in any of the biological specimens examined.

Animals↗
PubMed1994

Protective effects of lazaroids against oxygen-free radicals induced lysosomal damage.

Lipid peroxidation of membranes by oxygen free radicals has been implicated in various disease states. Different antioxidants and iron chelators have been used to reduce lipid peroxidation. Lazaroids have been used for the acute treatment of central nervous system disorders such as trauma and ischemia wherein lipid peroxidative processes take place. In this study we evaluated the effect of lazaroids (U-78518F and U-74389F) on the release of acid phosphatase activity and formation of malondialdehyde (MDA) in rat liver lyosomes subjected to exogenously generated oxygen free radicals. There was a significant increase in the acid phosphatase release and MDA formation in the presence of oxygen free radicals. This was prevented by both the lazaroids. In a separate study the effect of lazaroid U-74389F was seen on the zymosan-stimulated polymorphonuclear (PMN) leukocyte-derived chemiluminescence. The PMN leukocyte chemiluminescent activity was attenuated by the lazaroid in a dose-dependent manner. These studies suggest that lazaroids may inhibit lipid peroxidation and stabilize the membrane.

Acid Phosphatase↗
PubMed1994

Neutrophil adhesion and complement inhibition prolongs survival of cardiac xenografts in discordant species.

Hyperacute rejection results in rapid destruction of a discordant cardiac xenograft and is characterized by antibody deposition, complement activation, and platelet aggregation. The importance of neutrophils is unclear. Complement inhibition prolongs discordant cardiac xenograft survival. The purpose of this experiment was to determine the relative roles of complement and neutrophils. Selective inhibition of complement and neutrophil adhesion was used in a guinea pig-to-Lewis rat cardiac heterotopic xenotransplant model. NPC 15669 (N-[9H-(2,7-dimethylfluorenyl-9-methoxy)carbonyl]-L-leucine), a member of a new class of antiinflammatory agents termed leumedins, specifically prevents recruitment of neutrophils at inflammatory foci by inhibiting upregulation of the CD11b/CD18 adhesion molecule. Soluble complement receptor type 1 (sCR1, BRL 55730) is a potent inhibitor of the alternative and classical complement pathways. Group I (n = 13) received saline vehicle i.v. Group II (n = 15) was treated with NPC 15669 (10 mg/kg i.v. bolus) prior to reperfusion. Group III (n = 13) was treated with sCR1 (20 mg/kg i.v. bolus) prior to reperfusion. Group IV (n = 13) received both NPC 15669 and sCR1. Two xenografts were harvested at each interval time point (Groups I and II, 1, 2, 4, and 6 min; and Groups III and IV, 6, 15, 30, and 60 min). The remainder were followed to cessation of graft function. Graft survival was significantly increased in group IV and group III-375 +/- 13.4 min (mean +/- SD) and 112 +/- 29.4, respectively (P < .05), compared with 9.9 +/- 6.3 in group II and 8.7 +/- 4.9 in group I. Extreme interstitial hemorrhage and edema and contraction band injury were present in group I-III animals at end-stage, and neutrophil infiltration in group III. In group IV grafts, there was a decrease in these parameters despite the longer survival time, and at end-stage rejection the cellular infiltrate was primarily mononuclear. This study demonstrates that complement is an important mediator in early xenograft HYP injury. Combined treatment with NPC 15669 and sCR1 results in reduced histologic injury at all time points and longer graft survival than with sCR1 alone. These results suggest that neutrophil and complement activation play synergistic roles in the pathogenesis of xenograft hyperacute rejection. Neutrophil inhibition may prove to be an important component of multimodality therapy for hyperacute rejection, particularly in less-discordant transplants.

Animals↗
PubMed1994

Immunomodulation following zinc supplementation during chelation of lead in male rats.

Influence of zinc supplementation (30 and 45 mg kg-1, orally once for 5 days) during chelation of lead (0.3 mmol kg-1, chelating agent, i.p., once for 5 days) on some selected variables of the immune system was investigated in male rats. Treatment with CaNa2EDTA either alone or in combination with zinc (30 mg kg-1) produced a significant recovery in lead induced alteration in primary antibody forming cells to T-dependent antigen and the delayed-type hypersensitivity response to bovine albumin. However, biologically significant recovery was observed only with zinc at a dose of 45 mg kg-1. It is assumed that zinc depletion during lead exposure and chelation treatment lead to harmful effects on cellular proliferation by inhibiting DNA synthesis and various enzymes during mitosis. The zinc supplementation fulfills this requirement during proliferation and clonal expansion of immunocompetent cells augmenting the immune system.

Animals↗
PubMed1994

Altered sarcolemmal calcium channel density and Ca(2+)-pump ATPase activity in tachycardia heart failure.

Whether sarcolemmal (SL) calcium handling is altered in endstage heart failure produced by chronic rapid pacing is not known. To investigate this we paced 7 rabbits at a rate of 400 beats/min for 35 +/- 11 days. 6 animals served as non-paced controls. Purified left ventricular SL membranes were then prepared and tested for [3H]-nitrendipine binding and (Ca(2+) + Mg2+)-dependent ATPase (Ca(2+)-pump) activity. Results show a 50% reduction in calcium channel antagonist binding sites with Bmax values reduced from 450 +/- 40 to 230 +/- 8 fmoles/mg protein in response to chronic rapid pacing (P < 0.01). This change was accompanied by a modest decrease in Kd from 0.29 +/- 0.09 to 0.22 +/- 0.03 nM (not significant). Vmax values for the SL Ca(2+)-pump ATPase were decreased from 387 to 164 nmoles/mg protein/min (P < 0.01) with KCa2+ values reduced from 0.91 to 0.28 microM Ca2+ (P < 0.05) in response to tachycardia induced failure as compared to controls. ATPase activity in both groups was very sensitive to 25 microM calmidazolium and 5 microM vanadate. Results from this study indicate that both a reduction in SL calcium channel density and decrease in SL Ca(2+)-pump ATPase activity are evident in tachycardia heart failure. We conclude that sarcolemmal calcium handling is altered in heart failure induced by chronic rapid pacing and that such changes may contribute to systolic dysfunction associated with this model to heart failure.

Animals↗
PubMed1994

A review of triage and management of burns victims following a nuclear disaster.

The field of combined injury is relatively unfamiliar to burn surgeons. The mortality and morbidity of combined injury victims is higher than that of the injuries separately. The secondary consequences of radiation exposure, e.g. immunosuppression, infection, bleeding and fluid and electrolyte loss, significantly affects the management plan for burn victims. Increased work loads on medical personnel and the hospital further affects the management plan and outcome adversely. Based on previous experiences and experimental studies by various authors, a plan for management of burn victims in nuclear casualties is presented for effective utilization of available resources for overloaded burn centres in emergency situations. The proper recording of the experience of such situations is stressed.

Burns↗
PubMed1994

Early tangential excision and skin grafting as a routine method of burn wound management: an experience from a developing country.

This study assessed the feasibility of performing early tangential excision and skin grafting for burn wounds 'routinely' in a developing country. An analysis of mortality, morbidity and hospital stay was carried out for 90 burns patients with deep partial skin loss burns out of 202 admissions, who underwent 'early' tangential excision and skin grafting. Overall survival rate was 86.5 per cent. Children below 14 years of age with burns < or = 40 per cent TBSA (total body surface area) had no mortality, 93.5 per cent of adult patients with burns < or = 60 per cent TBSA survived in contrast to those with burns of > 60 TBSA per cent who all died. Morbidity for contractures and hypertrophic scars was nil to minimal. The mean hospital stay for adult patients with major burns was 30 days, with minor burns it was 18.7 days. We conclude that in developing countries, early tangential excision and skin grafting can and should be done routinely for all minor burns and for the major burns who are admitted to a well-equipped burns centre, but not for very 'extensive burns', until biological skin substitutes are more readily available.

Adult↗
PubMed1994

Epidemiological determinants of burns in paediatric and adolescent patients from a centre in western India.

A 1-year prospective study of 112 burn patients up to 19 years of age aimed to identify and study the determinants and mortality experiences in these burn patients and found flame burns to be the commonest, followed by scalds and electric burns. All burns other than those caused by electricity were commoner in females, more so between 15 and 19 years of age. Burns were more frequent in winter and 85 per cent of them were domestic. Nearly all burns took place during day time with a higher incidence between 06.00-09.00 h and 14.00-21.00 h. The patient fatality rate (41.1 per cent) was associated with total burn surface area. Referral time-lag was an important determinant of mortality especially in less severe burns. As would be expected, hospital stay was significantly longer in survivors.

Accidents↗
PubMed1994

Detection of botulinum toxin using an evanescent wave immunosensor.

Using fluorescein isothiocyanate (FITC)-streptavidin, quartz fibre-immobilized antibody (FiAb) and the evanescent wave component of a light beam, detection of Botulinum Toxin-B (BoTX) is described. Exposure of 3-aminopropyltriethoxysilane/glutaraldehyde (APTS/GA) treated quartz fibres to increasing amounts of anti-BoTX Ab indicated toxin binding to increase in a linear fashion up to approximately 125 ng added Ab. Quantitation of bound BoTX and FiAb by Dot-Blot analysis using avidin-Horseradish peroxidase (HRP) conjugation indicated the presence of 0.27 and 0.67 pmoles, respectively. Inclusion of nonbiotinylated BoTX in sampling mixtures reduced fluorescence in a dose-dependent manner over a narrow concentration range (0-300 ng). Exposure of FiAb to a variety of venoms resulted in no reduction of BoTX binding suggesting detection of BoTX via immobilized anti-BoTX Ab to be very specific.

Biosensing Techniques↗