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Biomedical subjects

K C Das

Publications and source records attributed to K C Das.

At least 19 recordsLinked to original sources
PubMed1992

Lidocaine: a hydroxyl radical scavenger and singlet oxygen quencher.

Lidocaine, a local anaesthetic, has been shown to reduce ventricular arrhythmias associated with myocardial infarction and ischemic myocardial injury and its protective effects has been attributed to its membrane stabilizing properties. Since oxygen radicals are known to be produced during ischemia induced tissue damage, we have investigated the possible antioxidant properties of lidocaine and found that lidocaine does not scavenge O2-. radicals at 1 to 20 mM concentrations. However, lidocaine was found to be a potent scavenger of hydroxyl radicals and singlet oxygen. Hydroxyl radicals were produced in a Fenton type reaction and detected as DMPO-OH adducts by electron paramagnetic resonance spectroscopic techniques. Lidocaine inhibited DMPO-OH adduct formation in a dose dependent manner. The amount of lidocaine needed to cause 50% inhibition of that rate was found to be approximately 80 microM and at 300 microM concentration it virtually eliminated the DMPO-OH adduct formation. The production of OH.-dependent TBA reactive products of deoxyribose was also inhibited by lidocaine in a dose dependent manner. Lidocaine was also found to inhibit the 1O2-dependent 2,2,6,6-tetramethylpiperidine N-oxyl (TEMPO) formation in a dose dependent manner. 1O2 was produced in a photosensitizing system using Rose Bengal or Methylene Blue as photosensitizers and was detected as TEMP-1O2 adduct by EPR spectroscopy. The amount of lidocaine required to cause 50% inhibition of TEMP-1O2 adduct formation was found to be 500 microM. These results suggest that the protective effect of lidocaine on myocardial injury may, in part, be due to its reactive oxygen scavenging properties.(ABSTRACT TRUNCATED AT 250 WORDS)

Cyclic N-Oxides↗
PubMed1992

Antiarrhythmic agents. Scavengers of hydroxyl radicals and inhibitors of NADPH-dependent lipid peroxidation in bovine lung microsomes.

Antiarrhythmic drugs, e.g. lidocaine, quinidine, and procainamide have been suggested as a means of reducing myocardial damage. The mode of action of these drugs have been attributed to their "membrane-stabilizing" properties. However, as tissue ischemia reperfusion is reported to generate toxic species of oxygen, we investigated the oxygen radical scavenging properties of these drugs and their effect on NADPH-dependent lipid peroxidation. These antiarrhythmic drugs are found to be ineffective as superoxide radical scavengers but are potent scavengers of hydroxyl radical with rate constants of 1.8 x 10(10) M-1 s-1, 1.61 x 10(10) M-1 s-1, and 1.45 x 10(10) M-1 s-1 for quinidine, lidocaine and procainamide, respectively, as determined by deoxyribose assay. In EPR study, using 5,5-dimethyl-1-pyrroline N-oxide (DMPO) as a spin trap, lidocaine, quinidine, and procainamide caused a dose-dependent inhibition of DMPO-OH adduct formation. These drugs also caused a dose-dependent inhibition of NADPH-dependent lipid peroxidation when lung microsomes were incubated with NADPH in presence of Fe(3+)-ADP. We propose that the antiarrhythmic agents exert their beneficial effects, in part, by their ability to scavenge toxic species of oxygen and by reducing membrane lipid peroxidation.

Animals↗
PubMed1992

Local and systemic eosinophilia in patients with carcinoma of the uterine cervix undergoing radiation therapy: correlation with radiation response.

Forty-nine patients with squamous carcinoma of the uterine cervix undergoing supervoltage 60Co radiotherapy were investigated to determine the significance of quantitation of eosinophils in the tumour tissue as well as in blood. The blood absolute eosinophil count (AEC) at presentation was higher in patients with Stages III and IV disease (0.52 +/- 0.09 x 10(9)/l, mean +/- SEM) when compared with early stages (Stages I and II, 0.35 +/- 0.07 x 10(9)/l). Forty-four patients (90%) showed a steady rise in AEC during the course of therapy. The patients showing good radiation response (n = 13, greater than or equal to 50% regression), displayed a more pronounced rise in AEC during the course of radiotherapy (0.66 +/- 0.24 x 10(9)/l) and had more eosinophils in the tumour tissue (7.4 +/- 0.66/oil immersion field) than the poor responders (n = 36, less than 50% regression, rise in eosinophil count 0.22 +/- 0.04 x 10(9)/l, eosinophils in tumour tissue 2.9 +/- 0.55/oil emersion field, P less than 0.0001 for both parameters). We conclude that quantitation of eosinophils in blood and tumour tissue before and during radiotherapy in patients with squamous carcinoma of the uterine cervix is useful in predicting radiation response.

Blood Cell Count↗
PubMed1991

Studies on the mechanism of synthesis and release of the procoagulant activity from leukaemic cells.

The synthesis and release of procoagulant activity (PCA) from leukaemic leucocytes was studied in an in vitro culture system stimulated by endotoxin. Puromycin, actinomycin-D, vinblastine, colchicine, dibutyryl cyclic AMP and ouabain were added to the culture system to study some of the metabolic processes of these cells in relation to synthesis and release of PCA. It was found that production of PCA is an active process and depends on new protein synthesis. The release of PCA from cells can be inhibited by vinblastine, an inhibitor of microfilament and microtubules in the cell. The optimal release of PCA occurs at pH 7.2-7.4 at 37 degrees C and is not inhibited by the ATPase inhibitor ouabain. Dibutyryl cyclic AMP inhibits the release/synthesis of PCA. Gram negative septicaemia and endotoxinaemia are capable of increased production and release of PCA from leukaemic cells and could contribute to the coagulation failure seen in this disease.

Blood Coagulation Factors↗
PubMed1991

Plasma vitamin B12 binding proteins correlate with disease activity in patients with rheumatoid arthritis.

The unsaturated vitamin B12 (cobalamin) binding capacity (UB12BC), transcobalamin (TC) I, II and III were measured in plasma and synovial fluid of 55 patients (10 men and 45 women, 25-60 years of age) with rheumatoid arthritis. The vitamin B12 binding proteins in 55 clinically and haematologically normal subjects of similar age group and sex were also studied as controls. The mean plasma concentrations of UB12BC, TCI, II and III were all significantly raised in patients with rheumatoid arthritis (RA) as compared to the normal controls. The increase of all vitamin B12 binding proteins in these patients showed a positive correlation with the increase of total proteins and globulin concentrations, and a negative (inverse) correlation with the albumin concentrations in the plasma, suggesting that these biochemical changes may be systemic consequences of the inflammatory and immunological processes characteristic of rheumatoid arthritis. The UB12BC, TC I and TC III concentrations in the synovial fluid were significantly higher than the corresponding plasma concentrations of these vitamin B12 binding proteins in patients with RA. Vitamin B12 binding proteins in the synovial fluid in these patients were probably at least partly produced locally by inflammatory cells. The mean levels of plasma transcobalamins in patients with severe disease activity were significantly higher than in patients with median or least disease activity. Therefore these proteins may be further studied as possible additional markers of disease activity in patients with RA.

Adult↗
PubMed1989

In vitro DNA synthesis by megaloblastic bone marrow: effect of folates and cobalamins on thymidine incorporation and de novo thymidylate synthesis.

The de novo pathway of thymidylate synthesis (i.e., methylation of dUMP to dTMP) is directly folate dependent and indirectly vitamin B12 (cobalamins) dependent. In deficiency of these vitamins, this pathway is impaired, and exogenous deoxyuridine (dU) fails to suppress adequately in vitro incorporation of [3H]thymidine (3H-TdR) into DNA via the salvage pathway (i.e., abnormal dU suppression). This abnormality is corrected by the addition of folate compounds (analogues) and/or vitamin B12 depending on the nature of the underlying deficiency. We studied the effects of addition of PteGlu, 5-methyl THF (5-CH3-FH4), 5-formyl-THF (5-CHO-FH4), and hydroxy-cobalamin (OH-cbl) on 3H-TdR incorporation into DNA and thymidine kinase activity (salvage pathway), and on [3H]deoxyuridine (3H-dU) incorporation and dU suppression values (de novo pathway) in cultures of normal and megaloblastic bone marrows. The results showed that 3H-TdR incorporation into DNA and the salvage enzyme, thymidine kinase, activity were greater and 3H-dU incorporation into DNA less in megaloblastic cells as compared with normal cells. The addition of folates significantly reduced 3H-TdR incorporation and thymidine kinase activity and enhanced 3H-dU incorporation in folate and vitamin B12-deficient cells except that 5-CH3-FH4 had no effect on vitamin B12-deficient cells. None of these additives had any significant effect on normal cells. This study also showed that the addition of the deficient vitamin(s) to the "control tubes" in the dU suppression test is inappropriate, as these vitamins may at least partially correct the defect in cellular DNA synthesis caused by the deficiencies of these vitamins and may mask these deficiencies in the results of the in vitro correction of the dU suppression abnormalities in mild cases of megaloblastic anemia.

Adolescent↗
PubMed1989

Serum and red cell ferritin content in the evaluation of iron status in rheumatoid arthritis.

We measured the basic (spleen type) ferritin content in the serum and red cells of 72 patients with rheumatoid arthritis in order to evaluate their significance in detecting true iron deficiency that may coexist with an altered metabolism of iron. Sixteen patients had no anaemia, and their serum and red cell ferritin contents were within the normal range (serum ferritin 16 to 286 micrograms/l; red cell ferritin, 5 to 44 ag/cell). Twenty patients had normocytic normochromic anaemia, and 36 patients had microcytic hypochromic anaemia. In these anaemic patients, the serum ferritin level ranged from 0 to 12 micrograms/l in 4, 13 to 55 micrograms/l in 19, 56 to 110 micrograms/l in 16, and exceeded 110 micrograms/l in 17 patients. The red cell ferritin content was subnormal (less than 5 ag/cell) in 4/20 patients in the normocytic normochromic group, and in 15/36 patients in the microcytic hypochromic group. Oral iron therapy given for 4-6 weeks to 9 patients with subnormal red cell ferritin resulted in an increase in the haemoglobin concentration; no such response was observed in patients with normal red cell ferritin content, irrespective of the serum ferritin concentrations. These observations indicate that red cell ferritin content is a more reliable index of true iron deficiency than serum ferritin concentrations in rheumatoid arthritis, and is capable of predicting the response to iron therapy.

Adult↗
PubMed1989

Pancytopenia in nutritional megaloblastic anaemia. A study from north-west India.

We have analysed 139 consecutive cases (71 males and 68 females) of nutritional megaloblastic anaemia over a period of four and a half years. The majority of these patients belonged to the low socio-economic class and many of them were strict vegetarians. Sixty one percent were in the second and third decades of life. At the time of presentation, 46% had mild hepatomegaly, 42% fever, 34% mild splenomegaly and 20% bleeding manifestations. Of 102 cases in whom the biochemical parameters were available, vitamin B12 deficiency was detected in 76%, folate deficiency in 6.8%, combined B12 and folate deficiency in 8.8%; the remaining 7.8% had normal vitamin levels at presentation. All 139 patients had severe anaemia, 80.5% had thrombocytopenia and 43.8% had neutropenia as well as thrombocytopenia. It appears that during progression (in terms of duration) of megaloblastosis, anaemia is followed by thrombocytopenia and then neutropenia. Infection and bleeding in these patients may be aggravated by impaired functions of neutrophils and platelets, respectively.

Adolescent↗
PubMed1989

Serum vitamin B12 levels in an Indian population: an evaluation of three assay methods.

Serum vitamin B12 levels were measured in 300 Indian subjects, comprising 165 haematologically normal volunteers, 78 cases of nutritional megaloblastic anaemia and 57 patients with myeloproliferative disorders. Each sample was assayed by three different techniques: i) a microbiological assay using Euglena gracilis as the test organism; ii) radioisotope dilution assay, using pure intrinsic factor as the B12 binder and haemoglobin-coated charcoal for separation of bound from free vitamin B12; iii) radioisotope dilution assay using intrinsic factor as the vitamin B12 binder and DEAE cellulose for separation of bound from free vitamin B12. Results by the three methods correlated closely at normal and high levels of serum B12: at low levels microbiological assay and radio-assay using haemoglobin-coated charcoal correlated well but DEAE cellulose failed to detect 16 of 68 patients with vitamin B12 deficiency. The radioisotope dilution assay tended to yield higher values of serum vitamin B12 than did the microbiological assay. In none of the healthy volunteers was a clearly low value found by any of the techniques, but 20 of them had low serum B12 levels. Radioisotope dilution assay using haemoglobin-coated charcoal is recommended as an accurate assay procedure for developing countries like India, where ready-made kits are not easily available and vitamin B12 deficiency states are common.

Anemia, Megaloblastic↗
PubMed1988

Functional and ultrastructural changes of platelets in malarial infection.

This paper describes changes in the circulating platelets of 25 patients with acute malaria within 2 to 6 days of onset of illness. Thrombocytopenia was observed in 10 out of 15 patients with Plasmodium falciparum infection, and in 4 out of 9 patients with P. vivax infection. One patient with a mixed infection of both species had a disseminated intravascular coagulation. Platelet antibody was detected in the sera of 8 out of 11 cases by the complement lysis inhibition technique and indirect immunofluorescence. The mean platelet antibody concentrations in the sera of 11 patients and 53 control subjects were 122.70 +/- 80.25 ng/10(7) platelets and 36.69 +/- 18.72 ng/10(7) platelets, respectively. An inverse relationship between the platelet count and platelet antibody levels in serum supported the view that thrombocytopenia in malaria may be partly immune-mediated. Platelet aggregation responses to agonists such as ADP, adrenaline, collagen and ristocetin revealed hyperactivity. Ultrastructural study of unstimulated platelets from patients revealed several changes such as centralization of dense granules, glycogen depletion, and formation of pseudopods and microaggregates, indicating in vivo activation of the platelets, which may also lead to thrombocytopenia.

Adolescent↗
PubMed1988

Serum and leukocyte lactate dehydrogenase activity in leukaemias.

Lactate dehydrogenase (LHD) content of serum and leukocytes was examined in 42 haematologically normal healthy volunteers and in 34 patients suffering from various types of leukaemia. All patients were studied at the time of presentation and before any therapeutic intervention. Serum LDH was elevated in all types of leukaemia. In acute myeloid leukaemia (AML) a significant elevation of leukocyte LDH activity (p less than 0.005) was noted. In acute lymphoblastic leukaemia leukocyte (ALL), LDH was significantly elevated when compared to normal lymphocyte LDH (p less than 0.01) levels, but not when compared to total normal leukocyte LDH levels. In chronic leukaemias, leukocyte LDH levels were not significantly different from the normal. Comparison of LDH isoenzyme pattern in peripheral blood cells with that of serum, both in normal and in leukaemia cases showed more "M" type enzyme in the cells than in the serum. However, the "M" type enzyme was significantly elevated only in AML cases (p less than 0.005). Serum LDH and peripheral blood leukocyte count compared in normal subjects and in leukaemia cases showed no correlation.

Adult↗