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Biomedical subjects

M Chandra

Publications and source records attributed to M Chandra.

At least 91 records · Page 5Linked to original sources
PubMed1994

Non-neoplastic renal lesions in Sprague-Dawley and Fischer-344 rats.

Incidences of non-neoplastic renal lesions in untreated Sprague-Dawley (1540) and Fischer-344 (491) rats were evaluated, tabulated, and compared. In Sprague-Dawley rats, the most frequently occurring lesion was chronic progressive nephropathy (68.5%) followed by tubular mineralization (30.9%), pelvic calculi (9.0%), brown pigmentation of the tubular epithelium (8.8%), hydronephrosis (5.1%), tubular dilatation (3.1%), and vascular mineralization (3.1%). In Fischer-344 rats, chronic progressive nephropathy (82.0%) was the most commonly occurring lesion followed by tubular mineralization (38.8%), vascular mineralization (2.2%), hydronephrosis (1.6%), and pelvic calculi (1.4%). In both strains, other lesions were less frequent.

Animals↗
PubMed1994

Upregulation of vascular endothelial growth factor expression induced by myocardial ischaemia: implications for coronary angiogenesis.

OBJECTIVE: The process of coronary collateral development is poorly understood. It is assumed that particular angiogenic factors are upregulated during episodes of myocardial ischaemia and act as a trigger for neovascularisation. However, the identity of these factors is unknown. The angiogenic factor vascular endothelial growth factor (VEGF) has been shown to be hypoxia inducible, so this factor may mediate ischaemia induced angiogenesis in the heart. The aim of this study was to examine hypoxia inducibility of VEGF in cultured myocardial cells as well as in normally perfused and ischaemic porcine myocardium. METHODS: (1) In vitro experiment: cultured rat myocardial cells were subjected to hypoxia, and steady state levels of VEGF mRNA were measured after 2 and 4 h of hypoxia. (2) In vivo experiment: myocardial ischaemia in pigs hearts was induced by repeated 2-10 min left anterior descending coronary artery occlusions, separated by 20 min of reperfusion. Hearts were retrieved after 6 h of intermittent ischaemia. Total RNA was extracted from normal and ischaemic zones of the heart and processed for RNA blot hybridisation analysis. RESULTS: In vitro experiment: as soon as 2-4 h after exposure of cultures to hypoxia, VEGF mRNA levels were significantly raised (6-10-fold). In vivo experiment: VEGF expression was significantly augmented in the ischaemic territory of the myocardium (three- to fivefold induction). Furthermore, polymerase chain reaction amplification of the reverse transcribed mRNA showed increased production of multiple forms of differentially spliced VEGF mRNA in the ischaemic myocardium. CONCLUSIONS: VEGF production in the myocardium is significantly upregulated by hypoxia in vitro and by ischaemia in vivo. These results suggest that VEGF is a likely mediator in the natural process of ischaemia induced myocardial neovascularisation.

Animals↗
PubMed1994

Halothane modifies ischemia-associated injury to the voltage-sensitive calcium channels in canine heart sarcolemma.

BACKGROUND: Recent experimental data suggest that functional and metabolic changes in the myocardium caused during ischemia and subsequent reperfusion may be attenuated by the volatile anesthetics through the prevention of intracellular calcium accumulation. The main purpose of the current research is to identify a mechanism responsible for the alterations of ischemia-associated injury to the voltage-sensitive Ca2+ channels (VSCC) in the sarcolemma during halothane anesthesia. METHODS: The effect of 10 min myocardial ischemia in canine heart and 20 min reperfusion on the function of the VSCC in the sarcolemma was examined in the presence or absence of 1.6 vol% halothane administered in vivo. The membranes were isolated through differential centrifugation/filtration from the ischemic (left anterior descending territory) and normally perfused myocardium. Comparison of binding characteristics in the ischemic and nonischemic zones was made using equilibrium-binding studies of a dihydropyridine calcium channel blocker, [3H]isradipine (0.05-1.0 nM), to the VSCC in the sarcolemma. Control studies were performed on membranes prepared from the same perfusion zones, but from hearts who were not exposed to ischemia. RESULTS: The control studies (n = 5) showed no difference in binding kinetics between the different zones in the heart. After 10 min of ischemia, a 50 to 95% increase in specific [3H]isradipine binding to the sarcolemmal membranes was observed as compared to control membranes (P < 0.001). The maximal binding capacity (Bmax) increased by 85%, whereas the dissociation constant (Kd) remained unchanged. In the reperfusion experiments, a moderately increased binding (of 32%) was observed with a 40% increase in Bmax (P = NS). In the presence of 1.6% inhaled halothane, the effect of ischemia was attenuated. A decrease of 32.1% to 41.8% in equilibrium binding was observed (31% decrease in Bmax; P < 0.03 and 0.02, respectively). CONCLUSIONS: Even a brief period of myocardial ischemia produces a marked increase in the available high-affinity binding sites in the VSCC, a finding that is well correlated with previous experimental observation of increased calcium ion influx to the myocardial cell. On reperfusion, some recovery of the ischemic changes in the VSCC was evident. The binding kinetics which characterize this early phase of cell injury were reversed by halothane anesthesia, indicating a possible reduction in calcium entry, which may represent one of the beneficial effects of the anesthetic in the ischemic heart.

Animals↗
PubMed1994

Spontaneous metastasizing mucinous adenocarcinoma in the ileum of a Sprague-Dawley rat.

Spontaneous tumours of the rat small intestine are extremely rare. A control Sprague-Dawley male rat from a carcinogenicity bioassay had a mucinous adenocarcinoma in the ileum. Tumour metastasis was observed in the mesenteric lymph node, lung, and seminal vesicles. Gross and histopathological features of this neoplasm are described and discussed.

Adenocarcinoma, Mucinous↗
PubMed1994

Assessment of the possible role of iron and copper in cisplatin-induced nephrotoxicity in the rat.

Nephrotoxic lesions induced by cisplatin in rats are characterized by acute tubular necrosis in the outer stripe of the medulla. The purpose of this study was to examine the potential role of changes in metal binding proteins, and iron and copper content in urine and renal tissue in cisplatin-induced nephrotoxicity. Cisplatin was administered intravenously to groups of 20 rats at single doses of 0, 1, 2.5, and 5 mg/kg and rats were sacrificed at 1, 2, 3 and 6 days after treatment. Increased serum BUN and creatinine were observed at a dose of 5 mg/kg cisplatin on day 2 through day 6. Increased urinary copper excretion coincided with necrosis and increased BUN and creatinine on day 3 in the high-dose group. Evidence of renal injury was apparent histologically as karyomegaly at all dose levels as early as 48 hours after injection of cisplatin, prior to increases in urinary copper levels. No change in the distribution of metal binding proteins (transferrin, ferritin, ceruloplasmin, and metallothionein) evaluated by immunohistochemical staining, was seen. Based upon these results, it is unlikely that changes in metal excretion play a primary role in cisplatin-induced nephrotoxicity however, changes in nuclear function indicated by karyomegaly may be involved in early renal injury.

Animals↗
PubMed1994

Laparoscopic cholecystectomy in the first trimester of pregnancy.

Symptomatic biliary tract disease in the pregnant patient has always been problematical. The advent and widespread application of laparoscopic cholecystectomy has led to a re-evaluation of the role of surgery in this clinical situation. We report on the use of laparoscopic cholecystectomy on a patient in the first trimester of pregnancy.

Acute Disease↗
PubMed1994

Platelet serotonin uptake in duodenal ulcer patients.

Platelet serotonin uptake was measured in 10 duodenal ulcer patients and 10 controls by determining the concentration of radioactivity in platelets after incubation with tritium-labelled serotonin binoxalate. Platelet 5-HT uptake in ulcer patients (312.0 +/- 125.0 CPM/10(7) platelets) was significantly higher than that in the control group (186.0 +/- 53.0 CPM/10(7) platelets; p < 0.01). Since the kinetics of 5-HT uptake by platelets may be a reflector of enhanced serotonergic activity, this finding may have implications in future therapeutic strategies for this disease.

Adult↗
PubMed1993

Serotonergic mechanisms in hypertension.

Serotonin and abnormal serotonergic activity (both central and peripheral) may play a role in pathogenesis of essential hypertension. Serotonin acts chiefly via three types of receptors namely S1, S2 and S3 serotonergic receptors. Besides being vasoactive, it has some inotropic and chronotropic properties and also affects blood rheology. It has stimulating effect on renin and aldosterone secretion. The action of other vasoactive substances like norepinephrine and angiotensin II are amplified. All these physiological effects of serotonin strongly support the hypothesis that it may be involved in hypertension. The advent of serotonin antagonists in lowering blood pressure has further substantiated this hypothesis.

Animals↗
PubMed1993

Platelets in essential hypertension.

The ultrastructure and adenosine diphosphate induced aggregatory response of platelets of 39 patients with essential hypertension have been studied. Both, transmission and scanning electron microscopy showed the co-existence of various morphological forms of platelets suggestive of activation. The hypertensive platelets also exhibited increased sensitivity to ADP induced aggregation confirming the activated state of platelets; the degree of activation correlated well with the levels of diastolic blood pressure.

Adenosine Diphosphate↗
PubMed1993

Intraperitoneal production of erythropoietin with continuous ambulatory peritoneal dialysis.

Higher hematocrit and serum erythropoietin (EPO) levels have previously been shown in end-stage renal disease patients treated with continuous ambulatory peritoneal dialysis (CAPD) compared with hemodialysis. We investigated whether EPO was produced intraperitoneally in CAPD patients. EPO concentration was 3.5 +/- 0.3 mU/ml by radioimmunoassay in 26 samples of peritoneal dialysis effluent obtained from 15 CAPD patients. EPO was not detectable in the fresh unused dialysate. No correlation was observed between EPO levels in the serum and dialysis effluent. Peritoneal macrophages were isolated from the dialysis effluent of 9 CAPD patients after an overnight dwell. The culture supernatant obtained after 24 h of in vitro culture of a million cells yielded EPO of 3.5 +/- 0.3 mU/ml. Our study demonstrated that peritoneal macrophages from CAPD patients produce EPO on in vitro stimulation, and EPO is present in the dialysis effluent of CAPD patients.

Adolescent↗
PubMed1993

Hypertension secondary to renin-secreting juxtaglomerular cell tumor: case report and review of 38 cases.

A 15-year-old girl with severe high renin hypertension caused by a juxtaglomerular cell tumor (JCT) was successfully treated with the calcium channel blocker nifedipine until surgical removal effected a permanent cure. This case was incorporated into a review of the 37 cases previously published. Comparison of the children and adolescents with the adult population showed that the features of JCT were similar in the two groups except for the average duration of symptoms prior to diagnosis (pediatric group 2.6 years vs. 6.0 years for the adult group). Analysis of all 38 cases demonstrated the following: 1. Teenagers constituted the largest single population with JCT (39%) and approximately two-thirds of the entire population were female. 2. Many patients failed to show persistent hypokalemia despite high plasma renin activity and secondary hyperaldosteronism. 3. Renal angiography was initially negative in more than half the cases. 4. Renal vein renin failed to show lateralization to the affected kidney in 52% of the cases. 5. Computerized tomography demonstrated a renal mass in all of the cases in which it was performed, even when other imaging studies were negative. 6. Calcium channel blockers may evolve as the preferred treatment for the high renin hypertension of JCT.

Adenocarcinoma↗
PubMed1993

New experimental technique to study blood cardioplegia in the isolated, perfused rat heart.

Blood cardioplegia has been extensively studied clinically and in the large animal experimental model. We describe here a modification of the original Langendorff technique to study continuous warm blood cardioplegia in the isolated, perfused rat heart. The excised heart is mounted on the perfusion apparatus and perfused with Krebs-Henseleit buffer. Prearrest hemodynamics are recorded. The shed blood in the mediastinal cavity (8 to 12 mL) is collected, filtered, and reconstituted into cardioplegic solution (hematocrit, 0.20; K+, 15 mmol/L). Hearts are arrested and maintained at 37 degrees C by continuous recirculation of blood cardioplegia for 1 hour. The blood cardioplegia system consists of a Silastic tubing oxygenator, peristaltic pump, and two filters (40 microns pore size). The heart is reperfused with Krebs-Henseleit solution, and postarrest hemodynamics are recorded. Percentage recovery of peak left ventricular pressure, heart rate, and coronary flow were 98.5 +/- 3.1, 102 +/- 4.2, and 98.5 +/- 4.5 (mean +/- standard error of the mean; n = 6), respectively. Myocardial oxygen consumption during arrest was 57 microL.min-1.g-1 dry wt, which is 10% of the myocardial oxygen consumption of a beating heart in in-vivo and ex-vivo models. These results suggest the feasibility of studying blood cardioplegia in the isolated, perfused rat heart model under controlled conditions. Continuous warm blood cardioplegic arrest provided excellent myocardial protection for 1 hour in this model.

Animals↗
PubMed1993

Platelet ultrastructural morphology and its relevance in essential hypertension.

A preliminary study of platelet ultrastructural morphology by transmission electron microscopy in patients with established essential hypertension was carried out. Platelets of hypertensive patients were found to be in various stages of 'platelet activation'. According to the degree of transformation observed, platelets were classified into six forms: discoid, pseudotubular, membranous, saccular, pseudopodical and hyaline and correlated to the severity of hypertension. The pseudopodical and hyaline types platelets were particularly observed in severely hypertensive patients, and/or those with clinical evidence of target organ damage. Platelet ultrastructural changes may form the basis of a better understanding of the aetiology and pathogenesis of essential hypertension, and may serve as a marker in assessing the extent of underlying in vivo endothelial injury and tendency to thrombotic complications.

Aged↗
PubMed1993

Naturally occurring atriocaval mesotheliomas in rats.

Atriocaval mesotheliomas were observed in two control Sprague-Dawley rats out of a total of 2889 rats examined. Both neoplasms were located at the base of the interventricular septum. Microscopically, the neoplasms consisted of varying proportions of glandular structures and a fibrous tissue stroma. Glandular structures were lined by a single layer of cuboidal to low columnar epithelium with cells containing a moderate amount of eosinophilic fibrillar to granular cytoplasm and a pleomorphic vesicular round nucleus with coarsely clumped chromatin and often a single eccentric prominent nucleolus. Epithelial cells were stained with antibodies raised against both vimentin and cytokeratin. Electron microscopical features included the presence of microvilli, terminal bars composed of modified tight junctions and desmosomes at the lateral and apical borders, and numerous tonofilaments associated with desmosomes.

Animals↗
PubMed1993

The morphology, immunohistochemistry, and incidence of hematopoietic neoplasms in mice and rats.

Hematopoietic neoplasms in the rodent may be classified into lymphoid or nonlymphoid neoplasms. Lymphoid neoplasms include the following morphologic types: follicular center cell, lymphoblast (lymphocytic), immunoblast, plasma cell, and large granular lymphocyte (LGL). Nonlymphoid hematopoietic neoplasms include histiocytic sarcoma, granulocytic leukemia, erythroid leukemia, and mast cell tumors. Most types of hematopoietic neoplasms, exclusive of LGL lymphoma (leukemia), are more common in mice than in rats. Specific strains of mice have a hematopoietic tumor incidence of more than 50% in aged animals. Some strains of rats (i.e., Fischer-344) may have an incidence of over 50% of LGL lymphoma in aged animals. The tumor type and incidence are characteristic for each rat or mouse strain. Hematopoietic neoplasms have been better characterized immunomorphologically in mice than in rats. The specific cell type and tissue of origin for hematopoietic neoplasms may be important for safety evaluation of chemicals. Specific chemicals may induce specific types of these tumors, which may be the same or different from the spontaneous types. Lymphoid cell neoplasms should not be grouped with nonlymphoid neoplasms in determining the toxicity and carcinogenicity of test substances.

Animals↗
PubMed1993

Platelet serotonin kinetics in acute myocardial infarction before and after thrombolysis.

Platelet count, platelet serotonin uptake and platelet serotonin content were analysed in 21 subjects consisting of 11 patients of evolving acute myocardial infarction (AMI) and 10 matched healthy controls before and after administration of streptokinase. Platelet counts were significantly reduced in AMI with a subsequent rise following thrombolysis. Platelet 5-HT uptake was also significantly increased in AMI and following thrombolysis, it showed a trend towards normalization. Platelet 5-HT content was significantly increased in AMI with no further significant change following thrombolysis. The results suggest that platelet activation as revealed by reduced platelet count and altered platelet serotonin kinetics, occurs in AMI and this activation is inhibited following thrombolysis. Further, it is also apparent that it is not the reperfusion but the thrombolytic agent that is responsible for inhibition of platelet activation.

Blood Platelets↗
PubMed1993

Laparoscopic cholecystectomy in critically ill cardiac patients.

From August 1989 to January 1993, the authors performed laparoscopic biliary operations in 900 patients, 13 of whom had severe cardiac dysfunction. Nine patients were Goldman Class IV, and four patients were Goldman Class III. Three patients had recent myocardial infarction, five patients were known to have low left ventricular ejection fractions (10%, 21%, 25%, 26%, and 30%), one had severe myocardial ischemia, one had severe congestive heart failure, and one was in profound shock. Nine patients underwent successful laparoscopic cholecystectomy. Laparoscopic cholecystostomies were performed in three patients. One operation was converted to an open cholecystectomy. There was one death within 30 days of surgery. With appropriate hemodynamic monitoring and adequate perioperative support of cardiac function, laparoscopic cholecystectomy can be performed safely for acute cholecystitis in patients with severe cardiac disease. When compared with historical controls, laparoscopic cholecystectomy appears to be safer than open cholecystectomy.

Acute Disease↗