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Biomedical subjects

S R Maitra

Publications and source records attributed to S R Maitra.

At least 37 records · Page 2Linked to original sources
PubMed1992

Altered cellular calcium regulation and hepatic glucose production during hemorrhagic shock.

The relationship between intracellular Ca2+ and glucose production in the liver during early and late states of hemorrhagic shock was studied. Rats were anesthetized with intraperitoneal sodium pentobarbital and both femoral arteries and one femoral vein were cannulated. Rats were divided into two groups. One group was subjected to hemorrhagic shock by rapid withdrawal of blood to a mean arterial pressure of 40 mm Hg and maintained in shock for either 30 or 150 min. Rats in the control group were observed for the same time period. Hepatic glucose production was evaluated in both groups by a nonrecirculating liver perfusion model with and without lactate as a substrate. Intracellular free Ca2+ in hepatocytes was measured using the Ca2+ selective indicator Fura-2, under basal and epinephrine-stimulated conditions. Hyperglycemia and hyperlacticacidemia were observed in vivo at 30 min of hemorrhagic shock, whereas hypoglycemia and hyperlacticacidemia were observed at 150 min of shock. Hepatic glucose production in isolated perfused livers was significantly depressed at 30 min in animals subjected to shock (P less than 0.05). Lactate-induced glucose production was significantly attenuated at 30 and 150 min (P less than 0.05). Basal Ca2+, in isolated hepatocytes, at 30 and 150 min of hemorrhagic shock was significantly (P less than 0.05) higher than in controls. The hemorrhagic shock rat hepatocytes failed to evaluate intracellular free Ca2+ upon stimulation with 10(-5) M epinephrine. These results demonstrate that hemorrhagic shock is associated with an increase in hepatocyte intracellular Ca2+ concentration along with attenuation of hormone-mediated mobilization of calcium and substrate specific stimulation of hepatic glucose production.

Animals↗
PubMed1992

Effect of alpha-adrenergic blockage on cellular Ca2+ during endotoxic shock.

The effect of alpha-adrenergic receptor antagonists, phentolamine, and prazosin on cytosolic Ca2+ concentration, [Ca2+]i, was studied in hepatocytes during endotoxic shock. Rats were given intravenous injections of endotoxin (20 mg/kg), phentolamine (3 mg/kg) plus endotoxin (20 mg/kg), or prazosin (5 mg/kg) plus endotoxin (20 mg/kg). They were sacrificed 5 hr later, at which time the endotoxin-injected rats showed signs of shock. Isolated hepatocytes were prepared and employed for the measurement of [Ca2+]i under basal and hormone-stimulated (1 and 10 microM epinephrine) conditions by means of Quin 2 fluorescence technique. The apparent basal level of [Ca2+]i in endotoxic rat hepatocytes (mean +/- SE: 482 +/- 31 nM) was significantly higher (P less than 0.05) than in phentolamine plus endotoxin (242 +/- 73) and prazosin plus endotoxin (240 +/- 43) groups. A significant increase in hepatocyte [Ca2+]i occurred with epinephrine in the phentolamine plus endotoxin and prazosin plus endotoxin groups, but not in the group receiving endotoxin alone. Endotoxic rats showed a mortality rate of 75%, whereas phentolamine plus endotoxin and prazosin plus endotoxin groups showed a mortality rate of 38% and 20% respectively. These data suggest that the protective effect of alpha-adrenergic receptor antagonists during endotoxic shock may be mediated, in part, by attenuating the entrance of Ca2+ into endotoxic liver cells.

Animals↗
PubMed1991

T3 preserves respiratory function in sepsis.

Sepsis produces profound hypothyroidism. This hypothyroid state is associated with altered lung metabolism and structural integrity. We studied the respiratory function of rats during sepsis-induced hypothyroidism with or without T3 treatment. Forty-four male Holtzman rats underwent cecal ligation and puncture (CLP). Treatment was administered at six hours after surgery consisting of intraperitoneal injection of T3 (15 micrograms/kg, n = 19) or saline (n = 25). At 20 hours (Group A) or 30 hours (Group B) following CLP, respiratory drive was assessed by serial occlusion pressure technique (P0.1). The rats were killed and static elastance determined by serial air inflation to 10 cc. The lungs were excised for weight determination. The P0.1 values were significantly greater in T3-treated animals over controls in Group A (9.3 +/- 0.7 vs. 6.6 +/- 2.2, p less than 0.05 by t test); elastance was significantly improved by T3 treatment in Group B (p less than 0.05 by two-way ANOVA). Lung weight, pH, pO2, pCO2, respiratory rate (RR), and mortality were not significantly different between groups. Control animals were hypothyroid by 20 hours after CLP (T3 less than 12.5 ng/dL) whereas T3-treated animals were euthyroid (T3 = 145 +/- 43 ng/dL). Pulmonary dysfunction frequently accompanies sepsis; the euthyroid state appears protective. We found a significantly improved respiratory drive in septic animals with T3 treatment. Lung elastance was similarly improved in late sepsis with T3 treatment. The data suggest that T3 treatment preserves respiratory function in septic rats as evidenced by respiratory drive and compliance.

Airway Resistance↗
PubMed1991

Beneficial effects of diltiazem in hemorrhagic shock.

The role of calcium channel blockade on metabolic alterations in a hemorrhagic shock model was studied. Experiments were performed on anesthetized Sprague-Dawley rats to evaluate the effect of diltiazem on hyperglycemia and hyperlacticacidemia following hemorrhagic shock. Rats were bled rapidly to a blood pressure of 40 mm Hg and maintained at that level for 2 hr. At 30 min into hemorrhagic shock, rats received either saline or diltiazem (1.2 mg/kg, i.v.) as treatment. Blood samples were obtained preshock and at 30-min intervals. Plasma glucose and lactate increased significantly in both groups at 30 min. Diltiazem treatment significantly reduced the plasma glucose and heart rate during hemorrhagic shock (P less than 0.05). Plasma lactate increased similarly in both groups. Survival analysis indicates significant (P less than 0.05) improvement in the diltiazem-treated group. These data suggest that diltiazem has a beneficial effect in hemorrhagic shock in rats.

Animals↗
PubMed1991

Autologous fibrin gel: bactericidal properties in contaminated hepatic injury.

Fibrin glue is an effective hemostatic agent in a variety of clinical situations; its utility is limited by potential transmission of viral infection. We studied the bactericidal properties of fibrin gel (FG) in a murine contaminated hepatic injury model and in vitro by agar plate culture method. Intra-abdominal abscess formation and adhesion rate were assessed following controlled liver injury in association with abdominal contamination with 10(7) Bacteroides fragilis and hepatorrhaphy (H, n = 15) or FG (n = 12). Animals treated by hepatorrhaphy had a significantly greater intra-abdominal abscess rate (15/15 vs. 4/12, p less than 0.05) and adhesion rate (14/15 vs. 6/12, p less than 0.05) than animals treated with FG. Fibrin gel is bactericidal to Bacteroides fragilis, Enterobacter faecium, Escherichia coli, and Staphylococcus aureus but has no effect against Klebsiella pneumoniae or Pseudomonas aeruginosa; the plasma component appears active. Fibrin gel demonstrates significant improvement in adhesion formation and intra-abdominal abscess rate when compared with suture hepatorrhaphy. Fibrin gel appears protective in contaminated hepatic injury.

Abscess↗
PubMed1989

Alterations in cellular calcium and magnesium during circulatory/septic shock.

Hepatic cellular and mitochondrial Ca2+ and Mg2+ contents and the role of these ions in cellular dysfunction were studied in rat hemorrhagic and endotoxic models which simulate various facets of human circulatory/septic shock states. Hemorrhagic shock was induced by bleeding rats to a state of vascular decompensation at the mean arterial pressure of 40 mm Hg. Endodotoxic shock was ascertained after observing hypoglycemia, hyperlacticacidemia and hemorrhagic bowel lesions in rats injected with Salmonella enteritidis endotoxin (15-20 mg/kg). In a late stage of hemorrhagic shock, significant changes occurred in mitochondrial ion contents; Ca2+ increased and Mg2+ decreased as compared to controls. These ionic changes were correlated with depressed mitochondrial respiratory functions. Addition of 6 mM Mg2+ to shocked-rat isolated mitochondria significantly restored mitochondrial functions. In endotoxic shock, hepatic Mg2+ content was significantly lower compared to controls. Treatment of rats with the calcium antagonist, diltiazem, several minutes prior to endotoxin injections, resulted in restoration of hepatic cellular Mg2+ to control levels. Studies of hepatic intracellular Ca2+ regulation in endotoxic shock revealed (1) an elevation in free cytosolic Ca2+, (2) a blunting of catecholamine-mediated increase in cytosolic Ca2+ and (3) an inhibition of intracellular messenger-induced Ca2+ release by the endoplasmic reticulum.

Animals↗
PubMed1987

Effect of diltiazem on intracellular Ca2+ mobilization in hepatocytes during endotoxic shock.

Effects of Salmonella enteritidis endotoxin on intracellular Ca2+ mobilization were studied in hepatocytes. Rats were given intravenous injections of saline (control), endotoxin (20 mg/kg), or endotoxin (20 mg/kg) plus diltiazem (1.2 mg/kg). They were killed 5 h later, at which time endotoxin-injected rats showed signs of shock. The involvement of myoinositol 1,4,5-trisphosphate (IP3) and arachidonic acid (AA) in intracellular Ca2+ mobilization was tested using saponin-permeabilized hepatocytes. Added Ca2+ was sequestered by intracellular organelles in the presence of ATP until the medium free Ca2+ concentration was lowered to a near steady-state level. In control cells subsequent addition of 10(-6) M IP3 and AA, respectively, caused a rapid increase in free Ca2+ concentration from 130 +/- 31 to 257 +/- 54 nM (P less than 0.01) and from 111 +/- 21 to 196 +/- 37 (P less than 0.01). By use of experimental conditions designed to permit selective Ca2+ accumulation, it was determined that all of the Ca2+ released by IP3 and AA originated from the endoplasmic reticulum. The intracellular release of Ca2+ by IP3 and AA was significantly attenuated in endotoxic shock. Treatment of endotoxic rats with a calcium channel blocker, diltiazem, effected an increase in free Ca2+ concentration by IP3 from 124 +/- 18 to 240 +/- 41 nM (P less than 0.01) and by AA from 109 +/- 15 to 192 +/- 32 (P less than 0.01). These data suggest that during endotoxic shock there is an attenuation of IP3- and AA-induced intracellular Ca2+ release, which could be prevented by treatment of animals with diltiazem.

Animals↗
PubMed1987

Effect of diltiazem on altered cellular calcium regulation during endotoxic shock.

Cellular free and exchangeable Ca2+ were quantitated in livers of rats injected with saline (control), Salmonella enteritidis endotoxin (20 mg/kg), or diltiazem (0.8-1.2 mg/kg) plus the endotoxin (20 mg/kg). Injection of endotoxin alone resulted in signs of endotoxic shock in animals 5 h later. All rats were killed 5 h postinjection, and their livers were excised. Hepatocytes were prepared for the measurement of cytosolic [Ca2+] under basal and hormone-stimulated (1 and 10 microM epinephrine) conditions by means of quin 2 fluorescence technique. Liver slices were labeled with 45Ca, and the radioactivity was washed out to determine cellular exchangeable Ca2+. The apparent basal level of cytosolic Ca2+ in endotoxic rat hepatocytes [525 +/- 92 (SE) nM] was significantly (P less than 0.05) higher than in controls (146 +/- 23). A significant increase in the basal [Ca2+] occurred after stimulation with epinephrine in controls but not in endotoxic rat hepatocytes. In the endotoxic rats receiving diltiazem, basal [Ca2+] was significantly lower than in rats given endotoxin alone, and a significant elevation of cytosolic [Ca2+] with epinephrine also occurred. The cellular exchangeable Ca2+ in endotoxic rats (564 +/- 27 nmol/g) was significantly higher than in controls (427 +/- 23). Diltiazem treatment of endotoxic rats restored the exchangeable Ca2+ level to that found in controls. The endotoxic accumulation of cellular Ca2+ and its restoration toward control levels by diltiazem could be due to catecholamine-mediated Ca2+ influx and its blockade by diltiazem.

Animals↗
PubMed1986

Release of kallikrein and tonin from the rat submandibular gland.

The interaction of neurotransmitters and hormones with specific receptors on the plasma membranes of cells results in enzyme secretion from exocrine glands. However, the effects of agonists on the release of kallikrein and tonin from the rat submandibular gland have not yet been evaluated systematically. The purpose of the present study was to investigate the effects of norepinephrine, isoproterenol, methacholine, and cholecystokinin on the simultaneous release of kallikrein and tonin from the rat submandibular gland. Submandibular gland slices were incubated in vitro at 37 degrees C in a modified Krebs-Ringer medium containing 0.2% each of glucose and bovine serum albumin and bubbled with a gas mixture of 95% O2 and 5% CO2. Glandular kallikrein and tonin secreted into the incubation medium were determined by specific radioimmunoassays. Norepinephrine at 10(-5) M concentration increased kallikrein secretion from a control value of 7.7 +/- 1.5 to 114.7 +/- 26.9 ng/min/mg tissues (p less than .01), and at 10(-4) M concentration kallikrein secretion increased to 265.9 +/- 58.3 ng/min/mg tissue (p less than .01). Similarly, norepinephrine at 10(-5) M enhanced the release of tonin from a basal rate of 4.4 +/- 0.6 to 57 +/- 14.4 ng/min/mg tissue (p less than .05), and at 10(-4) M the rate increased to 91.3 +/- 20.0 ng/min/mg tissue (p less than .01). In contrast, isoproterenol, methacholine, and cholecystokinin did not increase the secretion of kallikrein or tonin. We conclude that the secretion of kallikrein and tonin from rat submandibular glands upon sympathetic stimulation is mediated through stimulation of alpha-adrenoceptors only.

Animals↗
PubMed1986

Effect of sodium restriction and corticosteroids on glandular kallikrein in plasma and in the submandibular gland.

We investigated whether sodium restriction or mineralocorticoid influence the release of submandibular kallikrein into the blood and/or the concentration of kallikrein in glandular tissue. For this we measured submandibular gland blood flow, arterial and submandibular gland venous kallikrein, and kallikrein in glandular homogenates of male Sprague-Dawley rats after one week of either low sodium or deoxycorticosterone acetate (DOCA) treatment. We also studied the effect of dexamethasone on the concentration of kallikrein in gland tissue and peripheral plasma. Kallikrein in plasma and in homogenates was measured by radioimmunoassay. Blood flow was determined by timed collections of venous outflow. Kallikrein release was calculated as the arteriovenous difference in kallikrein times the rate of submandibular gland plasma flow. The concentration of kallikrein in arterial plasma, the basal submandibular kallikrein release into blood, and the concentration of kallikrein in submandibular gland tissue were all higher during low sodium than during normal sodium intake (20.1 +/- 3.6 ng/ml vs 10.7 +/- 0.5, p less than 0.05; 0.40 +/- 0.09 ng/min/100 g bw vs 0.18 +/- 0.02, p less than 0.05, and 81.6 +/- 5.5 micrograms/mg protein vs 65.1 +/- 4.0, p less than 0.05, respectively). In contrast, DOCA treatment did not affect the concentration of kallikrein in arterial plasma, the basal release of kallikrein from the submandibular gland into blood, or the concentration of kallikrein in the gland. Dexamethasone in doses that did not affect the normal growth of the animals had no significant effect on the concentration of kallikrein either in submandibular gland tissue or in peripheral plasma.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenalectomy↗
PubMed1986

Role of calcium and calmodulin in release of kallikrein and tonin from rat submandibular gland.

We investigated the role of calcium and calmodulin as intracellular mediators of kallikrein and tonin release induced by norepinephrine (NE). We studied the secretion rate of kallikrein and tonin from submandibular gland of rat in response to NE in the presence or absence of calcium, two calcium blockers, and four different calmodulin antagonists. Submandibular gland slices were incubated in vitro, and glandular kallikrein and tonin secreted into the incubation medium were determined by direct radioimmunoassays and expressed as nanograms per minute per milligram tissue. NE (10(-5) and 10(-4) M) increased the kallikrein secretion from the control value of 8.2 +/- 2.6 to 134.9 +/- 41.4 (P less than 0.05) and to 191.2 +/- 62.7 (P less than 0.05), and the release of tonin from a basal rate of 3.5 +/- 0.6 to 51.5 +/- 9.1 (P less than 0.05) and to 64.4 +/- 13.7 (P less than 0.05). The deletion of calcium and addition of EGTA into the incubation medium significantly attenuated the secretion of kallikrein and tonin induced by NE. Nifedipine, at concentrations which inhibit voltage-dependent calcium channels, did not affect the release of kallikrein and tonin, and only a high concentration (10(-4) M) reduced the release. TMB-8, a blocker of intracellular calcium, had no effect either. Phenothiazines, triflupromazine (10(-6) M) and trifluoperazine (10(-4) M), decreased significantly the kallikrein release elicited by 10(-5) M NE.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Clearance and metabolism of glandular kallikrein in the rat.

This study was undertaken to characterize the clearance of circulating rat glandular kallikrein and to determine the contribution of various organs and the urinary excretion to the removal of glandular kallikrein from the bloodstream. We injected either active 125I-kallikrein or kallikrein inactivated with phenylmethylsulfonyl fluoride (125I-PMSF-kallikrein) intravenously into intact or nephrectomized rats and then studied the disappearance rate of trichloroacetic acid (TCA)-precipitable radioactivity from the circulation. Inactivation by PMSF markedly reduced the binding of kallikrein to plasma protease inhibitors. The removal rate of the acid-precipitable radioactivity fit a biexponential curve for both active and inactive kallikrein. In the intact rats approximately 50% of the radioactivity was removed from the circulation 30 min after the injection of active 125I-kallikrein. Removal of the kidneys did not significantly affect the clearance of active kallikrein. On the other hand, inactive 125I-PMSF-kallikrein was removed from blood faster than active 125I-kallikrein in normal animals. Approximately 50% of the radioactivity was removed from the circulation 8 min after the injection, and the half-life of inactive 125I-PMSF-kallikrein was markedly prolonged by bilateral nephrectomy. Active 125I-kallikrein was taken up by tissues, particularly the liver and the kidney. In urine, less than 2% of the radioactivity was excreted in 60 min as TCA-precipitable material. We concluded that glandular kallikrein is cleared rapidly from the circulation of the rat, probably in the form of a complex with a plasma protease inhibitor.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗