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Biomedical subjects

S Kar

Publications and source records attributed to S Kar.

At least 127 records · Page 7Linked to original sources
PubMed1993

Experimental visceral leishmaniasis: role of trans-aconitic acid in combined chemotherapy.

We previously reported the effectiveness of trans-aconitic acid (TAA) as an antileishmanial compound. Inhibitory effects of TAA along with other antileishmanial compounds on transformation and in vitro multiplication in macrophage cultures of Leishmania donovani have been assessed. The efficacy of TAA in combined chemotherapy of experimental visceral leishmaniasis has also been evaluated along with those of commonly used antileishmanial compounds such as sodium stibogluconate, pentamidine, and allopurinol. TAA (2 mM) inhibited transformation of L. donovani amastigotes to promastigotes by 95.2%, whereas in combination with pentamidine (5 micrograms/ml), allopurinol (10 micrograms/ml), and sodium stibogluconate (50 micrograms of Sb per ml), it inhibited transformation by about 100, 99, and 98.5%, respectively. Sodium stibogluconate (20 micrograms of Sb per ml), pentamidine (2 micrograms/ml), and allopurinol (5 micrograms/ml) suppressed the amastigote burden in peritoneal macrophage cultures from BALB/c mice by 32.6, 56.1, and 46.3%, respectively. When these three drugs were used along with TAA (5 mM), the parasite loads were reduced by 100, 100, and 88.1%, respectively. TAA (5 mM) alone suppressed the amastigote burden by 59.5%. In experimental visceral leishmaniasis in hamsters (1-month model), TAA at a dose of 200 mg/kg of body weight per day suppressed the spleen parasite load by 73.5%, and TAA in combination with sodium stibogluconate (50 mg of Sb per kg per day), pentamidine (8 mg/kg/day), and allopurinol (15 mg/kg/day) inhibited the spleen parasite load by 98, 98.9, and 97%, respectively. Individually, these three drugs inhibited the parasite load by 35, 20, and 22%, respectively. TAA (400 mg/kg/day) inhibited the spleen parasite load by 99.8%, but an inhibitory effect of approximately 100% was noted when TAA was supplemented with an antileishmanial drug. TAA was administered in experimental animals through oral, intraperitoneal, and intramuscular routes; the intramuscular route was most effective.

Aconitic Acid↗
PubMed1993

Short-term synchronized retroperfusion before reperfusion reduces infarct size after prolonged ischemia in dogs.

BACKGROUND: Previous studies have demonstrated that synchronized coronary venous retroperfusion (SRP) can restore blood flow to the ischemic myocardium, resulting in infarct size reduction and improvement of the left ventricular function. Despite the nutritive blood flow achieved by SRP being relatively limited, SRP has been shown to improve washout of by-products from the ischemic myocardium. The aim of this study was to investigate whether short-term SRP immediately prior to reperfusion would attenuate the deteriorative phenomena following reperfusion. METHODS AND RESULTS: Closed-chest anesthetized dogs underwent 3 hours of left anterior descending coronary artery (LAD) occlusion. The dogs were then randomized into two groups: (1) control group (n = 9), in which the occlusion was immediately followed by 3-hour reperfusion; or (2) SRP group (n = 9), in which SRP was started 3 hours after occlusion and maintained for 30 minutes with sustained occlusion followed by 2.5-hour reperfusion with simultaneous discontinuation of SRP. There were no statistical differences between the groups in global hemodynamics and degree of ischemia measured by radiolabeled microspheres. Myocardial infarct size (triphenyltetrazolium method) expressed as percentage of risk area was significantly smaller in the SRP group (24 +/- 7%, mean +/- SEM) than in the control group (54 +/- 9%). The extent of myocardial hemorrhage expressed as percentage of infarct size was also significantly reduced in the SRP group (3 +/- 2%) compared with the control group (24 +/- 6%). The increase in end-diastolic wall thickness in the ischemic area after reperfusion assessed by two-dimensional echocardiography was significantly less in the SRP group. Blood flow measurements after reperfusion demonstrated the occurrence of no-reflow phenomenon only in the control group. Histological examination revealed extensive myocardial hemorrhages only in the control group, which extended into the nonnecrotic myocardium in four of nine hearts and extensive contraction band necrosis compared with the SRP group. CONCLUSIONS: Short-term SRP prior to reperfusion can reduce infarct size, myocardial hemorrhage, wall swelling, and no-reflow phenomenon. The mechanism of this beneficial effect is not clear but might be due to gradual reperfusion and washout of by-products from the ischemic myocardium before fully oxygenated arterial blood reperfusion.

Animals↗
PubMed1993

Suspected nafcillin-induced interstitial nephritis.

OBJECTIVE: To present a case of nafcillin-induced interstitial nephritis. METHODOLOGY: Case report and literature review. SETTING: Hospital. RESULTS: Three days following initiation of nafcillin therapy for staphylococcal pneumonia, an 80-year-old woman developed allergic manifestations and progressive renal impairment suggestive of acute allergic interstitial nephritis. These manifestations were completely reversed within 96 hours of cessation of nafcillin therapy. CONCLUSIONS: In the clinical setting of acute renal failure in a patient on nafcillin therapy, acute interstitial nephritis should be considered. Prompt cessation of nafcillin therapy has generally been associated with reversal of symptoms and an improvement in renal function.

Acute Disease↗
PubMed1993

Mutation at codon 249 of p53 gene in a human hepatoblastoma.

G-to-T transversion at codon 249 of the p53 gene has been shown to be specifically associated with human hepatocellular carcinomas, particularly that subset associated with exposure to the chemical hepatocarcinogen aflatoxin B1. We surveyed 47 North American adult hepatocellular carcinomas and three childhood liver tumors for codon 249 mutation. We report here a case of childhood hepatoblastoma in a patient, without known exposure to aflatoxin B1 or hepatitis B or C virus, whose tumor had a mutation at codon 249 involving G-to-T transversion.

Adolescent↗
PubMed1992

Fiber-optic ammonia sensor for measuring synaptic glutamate and extracellular ammonia.

A fiber-optic ammonia gas sensor designed for neurochemical applications is presented. Parameters evaluated in terms of effect on the steady-state and dynamic response of this sensor include the indicator dye, concentrations of indicator and total ammonia nitrogen in the internal solution, volume of the internal solution, structure of the gas-permeable membrane, and temperature. The final ammonia sensor responds over the concentration range from 7 to 3000 nM with a limit of detection of 7 nM and response times ranging from 2 to 5 min. Glutamate oxidase is immobilized at the tip of this ammonia sensor to provide a glutamate biosensor with a detection limit of 0.1 microM when operated at pH 7.8. In addition, this ammonia sensor is used to measure extracellular ammonia levels in perfused retinal and eye-cup tissue preparations. These measurements indicate a calcium-dependent, potassium-evoked release of ammonia during these depolarization conditions.

Ammonia↗
PubMed1992

Quantitative autoradiographic distribution of calcitonin gene-related peptide (hCGRP alpha) binding sites in the rat and monkey spinal cord.

Calcitonin gene-related peptide (CGRP) has been implicated in various spinal functions on the basis of its presence in the substantia gelatinosa and motoneurons and the biological effects induced by intrathecal CGRP injections. We investigated here the comparative distribution of [125I]hCGRP alpha binding sites in various segments of the rat and monkey spinal cord. The immunocytochemical localization of CGRP-like material in rat spinal cord was also evaluated for comparison. In the rat spinal cord, high densities of [125I]hCGRP alpha binding sites were observed in lamina I, in a U-shaped band that included lamina X and the medial parts of laminae III-IV and in the intermediolateral and intermediomedial nuclei. The substantia gelatinosa (lamina II) contained relatively lower, but still significant, densities of [125I]hCGRP alpha binding sites, while the ventral horn showed low amounts of specific labeling. CGRP-like immunoreactive fibers, on the other hand, were heavily concentrated in laminae I-II and in the reticulated portion of lamina V of the dorsal horn. Immunoreactivity to CGRP antiserum was also noted in fibers around the central canal and in a number of motoneurons of the ventral horn. In the monkey spinal cord, [125I]hCGRP alpha binding sites were present in lamina I in a U-shaped band that included lamina X and the medial portions of laminae V-VI. Relatively low levels of [125I]hCGRP alpha binding were detected in laminae II to IV of the dorsal horn, while the ventral horn was more enriched with specific [125I]hCGRP alpha binding sites. Thus, it appears that the autoradiographic distribution of [125I]hCGRP alpha sites is species dependent in the spinal cord. Additionally, some differences are observed between the localization of [125I]hCGRP alpha binding sites and immunoreactive material in the rat spinal cord. These differences may be relevant to the purported roles of CGRP-like peptides in spinal functions such as nociception, control of sympathetic output, and motor control.

Animals↗
PubMed1992

Quantitative autoradiographic localization of [125I]neuropeptide Y receptor binding sites in rat spinal cord and the effects of neonatal capsaicin, dorsal rhizotomy and peripheral axotomy.

Using in vitro quantitative receptor autoradiography the present study reports on the distribution and possible changes of [125I]neuropeptide Y (NPY) binding sites in the rat spinal cord following neonatal capsaicin treatment, dorsal rhizotomy and sciatic nerve section. In control spinal cord the highest density of [125I]NPY binding sites was noticed in the superficial layers of the dorsal horn whereas low-to-moderate densities of [125I]NPY binding sites were detected in the deeper dorsal horn and in the ventral horn. In comparison with control rats, neonatally treated capsaicin rats showed a significant (P less than 0.001) bilateral decrease in [125I]NPY binding sites in the superficial layers of the dorsal horn. Unilateral dorsal rhizotomy and unilateral sciatic nerve section also exhibited a significant (P less than 0.05) depletion in [125I]NPY labeling in the superficial layers of the dorsal horn ipsilateral to the surgery. These results suggest that a certain proportion of [125I]NPY receptor sites is located on the primary afferent fibers of the superficial layers of the dorsal horn. This peptide thus could play an important role in the modulation of nociceptive transmission by acting directly on primary afferent terminals.

Animals↗
PubMed1992

The high-risk unstable angina patient. An approach to treatment.

Unstable angina, an intermediate stage in acute coronary ischaemic syndromes, accounts for about 50% of all admissions to the coronary care units in the United States today. It may progress to myocardial infarction in 15% of cases in the first 2 days, and the in-hospital mortality rate is 5%. The pathological hallmark of this syndrome, confirmed by angioscopy, is fissure of the atherosclerotic plaque within the coronary artery, leading to platelet adhesion and aggregation and fibrin-platelet thrombus formation, which may accelerate progression of the stenotic lesion. Management of unstable angina is aimed at ameliorating symptoms and reducing ischaemia, improving ventricular function, preventing recurrent ischaemia, myocardial infarction and death, and lastly, containing progression of the underlying coronary artery disease. Acute management includes bedrest, aspirin, heparin, nitroglycerin (glyceryl trinitrate) infusion and beta-blockers and calcium channel blockers in selected cases. After the patient is clinically stabilised, provocative tests and angiography may be performed, to be followed by angioplasty or bypass surgery, if necessary. In cases that are refractory to optimal medical therapy, interventions should be performed on a more emergent basis. Long term management includes aspirin and beta-blockers, if there is prior infarction, and control of the conventional risk factors.

Angina, Unstable↗
PubMed1992

Coronary veins: an alternate route to ischemic myocardium.

Acute myocardial ischemia is the primary cause of concern during myocardial infarction and unstable angina, and the cornerstone of modern therapy is rapid establishment of antegrade blood flow. The ultimate success of reperfusion depends on the duration and severity of ischemia before revascularization. Even brief ischemia occurring during angioplasty may cause reversible myocardial dysfunction. Several interventions are available to minimize the negative effects of acute myocardial ischemia. Synchronized coronary venous retroperfusion is a myocardial support technique in which autologous arterial blood is shunted from the femoral artery into the ischemic myocardium via the coronary sinus. Retroperfusion has been studied clinically during angioplasty and has been shown to ameliorate and delay the onset of ischemia. It has also been beneficial during abrupt closure of the coronary artery after angioplasty as a bridge to definitive therapy. Preliminary reports have indicated the efficacy of retroperfusion in medically refractory unstable angina. Because of its retrograde approach, this technique may serve as an alternate route to an otherwise inaccessible, ischemic myocardium for delivery of blood and other cardioprotective agents.

Angioplasty, Balloon, Coronary↗
PubMed1992

Prevalence of malaria in Ao Nagas and its association with G6PD and HbE.

Glucose-6-phosphate dehydrogenase (G6PD) and hemoglobin E (HbE) were studied among 708 malarial patients and control groups of Ao Nagas from the Mokokchung District of Nagaland in the extreme northeast of India. The data suggest that malaria is an important ecologic factor in maintaining the high frequency of G6PD deficiency and HbE among the Ao Nagas. Although migrations from adjoining populations that have a high frequency of both these traits could have contributed to the presence of these genes in the Ao Nagas, malaria also could be an essential determinant in maintaining the current high frequency in present-day Ao Nagas.

Ethnicity↗
PubMed1991

Biochemical and immunological characterization of exometabolites from an Indian strain of Leishmania donovani promastigotes grown in a chemically defined medium.

Exometabolites (EXOM) of an Indian strain of Leishmania donovani promastigotes isolated from a chemically defined medium by ultrafiltration consisted of proteins, glycoproteins, lipid and lipophosphopolysaccharide (LPPS). LPPS of Mr 40-28 kDa in SDS-PAGE could be labelled metabolically with [32P]-phosphate and recovered in the aqueous phase of hot-phenol-water extraction of EXOM (PE-Aq) along with a glycoprotein of Mr 150-130 kDa (GP150-130). These two molecules could be eluted from DE-52 column with 200 mM NaCl (D2). The 300 mM NaCl (D3) and 400 mM NaCl (D4) eluates from DE-52 column contained one unsaturated polar lipid component. The LPPS had Rf value of 0.65-0.75 in Thin Layer Chromatography (TLC) using saturated phenol water solvent system. EXOM revealed 15 bands in SDS-PAGE of which proteins of Mr 84, 66, 56, 50 and 29 kDa were prominent. When EXOM were fractionated through Con A-Sepharose column, the fraction eluted with alpha-methyl-D-mannoside (Con A-E) had seven bands as revealed by SDS-PAGE of which 25, 16, 13 and 12 kDa glycoproteins were prominent. The antigens present in EXOM can be classified as slower anodic migrating and faster anodic migrating antigens as revealed by immunoelectrophoresis (IEP). The slower anodic migrating antigens, LPPS and GP150-130 recovered in PE-Aq and D2 did not cross-react with kala-azar patients' sera but cross-reacted with homologous anti-promastigote sera. Two faster anodic migrating antigens which could be recovered in organic phase of hot phenol extraction of EXOM (PE-O) and eluted in D3 and D4 and Con A-E, cross-reacted with kala-azar patients' sera. The antigens of both the classes were sensitive to periodic acid oxidation.

Animals↗
PubMed1991

Quantitative autoradiographic localisation of [125I]endothelin-1 binding sites in spinal cord and dorsal root ganglia of the rat.

The autoradiographic distribution of [125I] endothelin (ET)-1 binding sites was studied in the spinal cord and dorsal root ganglia of developing and adult rat. In the spinal cord, high density of [125I]ET-1 binding sites were diffusely distributed throughout the grey matter whereas in the ganglia discrete silver grains were localised primarily on the satellite cells. A variation in the density of binding sites was evident, particularly in the spinal cord, during development. These data, in conjunction with other reports, suggest a possible neuromodulatory role for ET-1 in spinal cord and dorsal root ganglia of the rat.

Animals↗
PubMed1991

Increased calcitonin gene-related peptide (CGRP), substance P, and enkephalin immunoreactivities in dorsal spinal cord and loss of CGRP-immunoreactive motoneurons in arthritic rats depend on intact peripheral nerve supply.

The distribution of peptides thought to be involved in pain modulation--substance P, calcitonin gene-related peptide (CGRP), and enkephalin--were studied in the spinal cord and dorsal root ganglia of polyarthritic rats and in rats with one sciatic nerve sectioned prior to induction of arthritis. In arthritic rats there was a bilateral increase of CGRP- and substance P-immunoreactive fibers and appearance of enkephalin-immunoreactive cell bodies in the dorsal horn of the lumbar (L4) spinal cord when compared to controls. In the corresponding dorsal root ganglia there were significant increases of CGRP- (P less than 0.02) and substance P- (P less than 0.001) immunoreactive cell bodies compared to controls. In the ventral horn of the control rats CGRP-immunoreactive motoneurons were abundant but were significantly (P less than 0.001) reduced in the arthritic spinal cord. Less pronounced changes were seen in the contralateral L4 spinal cord of arthritic rats with unilateral sciatic nerve section. In the ipsilateral dorsal horn, however, CGRP- and substance P-immunoreactive fibers were markedly depleted, and no enkephalin cell bodies were present. Furthermore, a number of CGRP-immunoreactive motoneurons were observed. In the ipsilateral L4 ganglia CGRP- (P less than 0.02) and substance P- (P less than 0.02) immunoreactive cells were significantly decreased compared to the contralateral side. The data suggest that pain perception is linked to complex interactions between CGRP, substance P, and enkephalin in sensory pathways and an intact peripheral input. The loss of CGRP-immunoreactive motoneurons may reflect muscular dysfunction associated with the arthritic condition.

Animals↗
PubMed1991

Preservation of regional myocardial ultrasonic backscatter and systolic function during brief periods of ischemia by synchronized coronary venous retroperfusion.

This study examines the effects of brief periods of ischemia on average and cardiac cycle-dependent variation of regional ultrasonic backscatter paralleled with changes in regional myocardial contraction, and to what extent these changes could be reversed by synchronized coronary venous retroperfusion. In five closed-chest dogs, the left anterior descending coronary artery was occluded on four occasions for a 2-minute period and retroperfusion was applied randomly to two of the coronary occlusions. Complete functional recovery was allowed between the occlusions. Two-dimensional echocardiographic images were obtained before and at the peak of the 2-minute occlusion period. Regional myocardial contraction as measured by fractional area change and systolic wall thickening during untreated occlusions decreased from 33.9 +/- 14.0% to -0.15 +/- 6.2%, and from 22.0 +/- 1.8% to -17.9 +/- 2.2%, whereas during retroperfusion-treated occlusions it changed from 37.4 +/- 8.5% to only 23.4 +/- 11.2% (p less than 0.005 versus baseline), and from 24.1 +/- 2.8% to only 12.7 +/- 2.0% (p less than 0.005 versus baseline), corresponding to a preservation of 62% and 52% of baseline regional contraction, respectively. Average regional gray level (arbitrary units) during untreated coronary occlusions exhibited a significant increase in the ischemic regions, from 5.6 +/- 2.7 at baseline to 11.5 +/- 4.4 during occlusion (p less than 0.005); during retroperfusion-treated occlusions, average gray level increased from 4.7 +/- 3.6 to only 6.3 +/- 3.6 (NS). Untreated coronary artery occlusions resulted in a systolic increase in gray level in the ischemic region, followed by a diastolic decrease.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Coronary venous retroinfusion of deferoxamine reduces infarct size in pigs.

The efficacy of coronary venous retroinfusion of the iron chelator deferoxamine was studied in 24 pentobarbital-anesthetized open chest pigs with a 60 min occlusion of the left anterior descending coronary artery followed by 3 h of reperfusion. Eight retrogradely treated pigs were given 10 mg/kg body weight of deferoxamine by way of the anterior interventricular vein and eight systemically treated pigs received the same doses of deferoxamine intravenously. Drug infusions lasted for 5 min, beginning 15 min before reperfusion. Eight control pigs received systemic intravenous saline solution. Myocardial area at risk and necrotic area were assessed by the monastral blue dye and the triphenyltetrazolium chloride staining method, respectively. There were no significant differences in hemodynamics or regional myocardial function (sonomicrometry) among the groups. Infarct size expressed as percent of risk area was 73.9 +/- 13.5% in the control group, 70.6 +/- 16.4% in the systemically treated group and 48.5 +/- 21.4% (p less than 0.05) in the retrogradely treated group. In conclusion, deferoxamine significantly reduced infarct size after coronary occlusion only when given regionally by way of the coronary vein. Because there was no significant hemodynamic effect caused by deferoxamine infusion, it is suggested that this drug prevents postischemic reperfusion injury by a direct cardioprotective effect.

Animals↗
PubMed1991

Synchronized coronary venous retroperfusion for support and salvage of ischemic myocardium during elective and failed angioplasty.

To determine the safety and efficacy of synchronized coronary venous retroperfusion during brief periods of ischemia, 30 patients undergoing angioplasty of the left anterior descending coronary artery were studied. Each patient underwent a minimum of two angioplasty balloon inflations. Alternate dilations were supported with retroperfusion; the unsupported inflations served as the control inflations. Synchronized retroperfusion was performed by pumping autologous femoral artery blood by means of an electrocardiogram-triggered retroperfusion pump into the great cardiac vein through a triple lumen 8.5F balloon-tipped retroperfusion catheter inserted percutaneously from the right internal jugular vein. Clinical symptoms, hemodynamics and two-dimensional echocardiographic wall motion abnormalities were analyzed. Retroperfusion was associated with a lower angina severity score (0.8 +/- 1 vs. 1.2 +/- 1) and delay in onset of angina (53 +/- 31 vs. 37 +/- 14 s; p less than 0.05) compared with the control inflations. The magnitude of ST segment change was 0.11 +/- 0.14 mV with retroperfusion and 0.16 +/- 0.17 mV without treatment (p less than 0.05). The severity of left ventricular wall motion abnormality was also significantly (p less than 0.01) reduced with retroperfusion compared with control (0.7 +/- 1.4 [hypokinesia] vs. -0.3 +/- 1.6 [dyskinesia]). There were no significant changes in hemodynamics, except in mean coronary venous pressure, which increased from 8 +/- 3 mm Hg at baseline to 13 +/- 6 mm Hg with retroperfusion. Four patients required prolonged retroperfusion for treatment of angioplasty-induced complications. The mean retroperfusion duration in these patients was 4 +/- 2 h (range 2 to 7). In the three patients who underwent emergency bypass surgery, the coronary sinus was directly visualized during surgery and found to be without significant injury. There were no major complications. Minor adverse effects were transient atrial fibrillation (n = 2), jugular venous catheter insertion site hematomas (n = 4) and atrial wall staining (n = 1), all of which subsided spontaneously. Thus, retroperfusion significantly reduced and delayed the onset of coronary angioplasty-induced myocardial ischemia and provided effective supportive therapy for failed and complicated angioplasty.

Aged↗
PubMed1991

Duffy blood groups and malaria in the Ao Nagas in Nagaland, India.

Blood samples from 324 malarial patients and 384 healthy individuals belonging to the Ao tribal community have been examined for Duffy blood group systems. The complete absence of Duffy-negative individuals among the Ao Nagas suggests that selection for resistance to vivax malaria by means of the Duffy-negative phenotype has not been available in the southeast Asian regions including the Ao Nagas.

Duffy Blood-Group System↗