Biomedical subjects

S M Somani

Publications and source records attributed to S M Somani.

At least 37 records · Page 2Linked to original sources

PubMed1995

Effect of exercise training on antioxidant system in brain regions of rat.

The purpose of this investigation was to determine whether any alterations in antioxidant enzyme activities and levels of glutathione (GSH) in brain regions occurred following exercise training. Sprague-Dawley rats were given exercise training on a treadmill for 7.5 weeks and sacrificed 18 h after the last exercise along with the sedentary control rats. Different brain regions-cerebral cortex (CC), brainstem (BS), corpus striatum (CS), and hippocampus (H)-were isolated; GSH, oxidized glutathione (GSSG), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities were determined. The exercise training increased SOD activity significantly (130% of sedentary control) in BS and in CS. SOD activity in H was the lowest of all four brain regions. Different brain regions showed GSH-Px activity in decreasing order for CS < BS < CC < H. GSH levels were 43% less in BS than CC and CS. The ratio of GSH/GSSG significantly increased from 6.8 to 8.3 in CC, and from 9.4 to 13.5 in BS as a result of exercise training. Different brain regions contained different activities of antioxidant enzymes, as well as GSH and GSSG levels, which were preferentially altered as a result of exercise training to cope with oxidative stress.

Adaptation, Physiological↗

PubMed1995

Responses of antioxidant system to acute and trained exercise in rat heart subcellular fractions.

The effects of acute and trained exercise on antioxidant enzymes (AOE), glutathione (GSH), and malondialdehyde (MDA) were compared in rat heart subcellular fractions and red blood cells. Fischer-344 rats were exercised acutely to 100% VO2 max and another group of Fischer-344 rats were given trained exercise for 10 weeks. The AOE and MDA were measured by spectrophotometry and GSH and oxidized GSH (GSSG) by high pressure liquid chromatography. Trained exercise significantly increased cytosol GSH to 131% of sedentary control (SC). Acute exercise significantly increased mitochondrial superoxide dismutase, catalase, and glutathione peroxidase by 167%, 358%, and 129% of SC, respectively, whereas enzyme activities following trained exercise were increased by 133%, 166%, and 128% of SC. The mitochondria/cytosolic ratio for superoxide dismutase, catalase, and glutathione peroxidase after acute exercise increased to 1.9, 2.7, and 1.7, respectively, whereas the respective ratios of these enzymes after trained exercise were 1.3, 1.6, and 1.3. Acute exercise contributed to oxidative stress more than trained exercise. Acute exercise resulted in a larger increase in enzyme activities than trained exercise, possibly as a compensatory mechanism to cope with the enhanced production of superoxides and oxyradicals during exhaustive exercise.

Animals↗

PubMed1995

Mechanism of cisplatin ototoxicity: antioxidant system.

The dose and duration limiting toxic effects of cisplatin are ototoxicity and nephrotoxicity. While several studies have attempted to shed some light on the causes of nephrotoxicity, the reasons for ototoxicity induced by cisplatin are poorly understood. Therefore, this investigation was undertaken to delineate the potential mechanisms underlying cisplatin ototoxicity. The role of glutathione (GSH), oxidized glutathione (GSSG) and malondialdehyde levels, and antioxidant enzyme activities [superoxide dismutase, catalase, GSH peroxidase, and GSH reductase] were examined in cochlear toxicity following an acute dose of cisplatin. Male Wistar rats were treated with various doses of cisplatin. Pretreatment auditory brain stem evoked responses (ABR) were performed and then post-treatment ABRs and endocochlear potentials were also performed after three days. Acute cochlear toxicity (ototoxicity) was evidenced as elevated hearing thresholds and prolonged wave I latencies in response to various stimuli (clicks and tone bursts at 2, 8, 16 and 32 kHz) on ABRs. The endocochlear potentials were reduced (50% control) in cisplatin-treated rats as compared to control animals. The rats were sacrificed and cochleae isolated. The GSH, GSSG and malondialdehyde levels, and antioxidant enzyme activities were determined. Cisplatin ototoxicity correlated with a decrease in cochlear GSH [0.45 +/- 0.012 nmol/mg] after cisplatin administration compared to 0.95-012 nmol/mg in control cochleae (P < 0.05). Superoxide dismutase, catalase activities and malondialdehyde levels were significantly increased in the cochleae of cisplatin injected rats. Cochlear GSH-peroxidase and GSH reductase activity significantly decreased after cisplatin administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

Exercise training generates ascorbate free radical in rat heart.

Exercise generates free radicals and can cause damage to the tissues. This investigation shows the formation of ascorbate radicals during exercise training (ET) which reduce the toxicity of free radicals. Male Fischer-344 rats (n = 8) (77 weeks old) were given exercise training (ET) on a treadmill with a low intensity of exercise that gradually increased from the first to the ninth week resulting in an average increase in respiratory exchange ratio, oxygen consumption rate and heat production. The sedentary control (SC) rats (n = 8) were not exercised and maintained under the same conditions. The heart tissues from different SC and ET rats were analyzed for ascorbate free radical (Asc.-) using electron paramagnetic resonance (EPR). The heart tissue from the ET and not from the SC rat showed the presence of Asc.-. This Asc.- was characterized by an EPR spectrum which showed doublet with a hyperfine coupling constant of 1.89 Gauss (0.189 mT). The benefit of exercise could be attributed to the formation of ascorbate radical in the heart muscle of the old rat. Exercise training can provide protection to the heart tissue against oxidative damage via ascorbate ion and vitamin E.

Animals↗

PubMed1994

Adenosine acts as an endogenous activator of the cellular antioxidant defense system.

Oxygen free radicals have been implicated in the pathogenesis of ischemic cell injuries. These free radicals are normally scavenged by antioxidant enzymes. Adenosine is normally released during ischemia and protects against ischemic injuries by interacting with adenosine receptors (ARs). The mechanism underlying its cytoprotective action is unclear. In this report, we provide evidence that activation of a unique A3AR in rat basophilic leukemia cells (RBL-2H3) leads to a 2 to 3 fold increase in activity of superoxide dismutase, catalase and glutathione peroxidase and also increases in the activity of glutathione reductase. Similar increases in enzyme activity were elicited in bovine and human endothelial cells, rat cardiac myocytes and smooth muscle cells. Increases in enzyme activity were attenuated by theophylline (an antagonist of the A3AR) and by pertussis toxin, implicating a role of A3AR/Gi protein in the activation. Importantly, activation of the A3AR decreased the degree of lipid peroxidation in these cells. These data provide strong evidence that the cytoprotective action of adenosine during ischemic cell injuries is mediated, at least in part, via a novel mechanism-activation of the cellular antioxidant enzymes.

Adenosine↗

PubMed1994

Effect of concurrent exercise and physostigmine on lactate and pyruvate in plasma, muscle, and brain tissue of rats.

The purpose of this investigation was to determine the effect of physostigmine (Phy) and/or concurrent exercise on lactate, pyruvate, and L/P ratio in plasma, skeletal muscle, and brain tissue in male Sprague-Dawley rats. The Phy-dosed (Phy-D) and Phy-dosed + concurrent acute exercise (Phy-D + CAE) groups elicited significantly higher L/P ratios in plasma compared to the acutely exercised (AE) group at 30 min postexercise. Physostigmine dosing, with or without exercise, resulted in significantly lower muscle pyruvate levels, from 30 to 50 min postdrug administration, in Phy-D and Phy-D + CAE groups compared to the AE group. In the brain, lactate values were significantly elevated in the acutely exercised groups at 5 min postexercise with or without Phy dosing. However, at 15 to 30 min postexercise, lactate values were significantly elevated in the Phy-D + CAE compared to the AE group. These data suggest that when Phy is administered prior to a 20-min moderately intensive exercise bout, there is an accumulation of lactate for a prolonged period of time in recovery.

Animals↗

PubMed1993

Concurrent acute exercise alters central and peripheral responses to physostigmine.

This study reports the modulatory effects of physostigmine (Phy) and concurrent acute exercise on the time course of cholinesterase (ChE) activity, the rate of decarbamylation (Kd), and half-time of recovery of ChE in red blood cells (RBC) and various tissues of rats. Acute exercise equivalent to 80% VO2-max (maximal oxygen consumption) transiently increased the RBC ChE activity, whereas Phy decreased ChE activity in RBC and various tissues. Physostigmine along with concurrent acute exercise increased the Kd in RBC, brain, and heart by 56.4%, 66.7%, and 139%, respectively, compared to Phy alone. The Kd in diaphragm and muscle decreased to 14.1% and 56.2%, respectively, compared to Phy alone. The variation in Kd might be due to the effect of concurrent acute exercise on the redistribution of Phy in various tissues of rat as a result of changes in blood flow.

Animals↗

PubMed1993

Effect of physostigmine and exercise on choline acetyltransferase and acetylcholinesterase activities in fast and slow muscles of rat.

The interaction of physostigmine (Phy) and exercise on choline-acetyltransferase (ChAT) and acetylcholinesterase (AChE) have been studied in the fast extensor digitorum longus (EDL) and slow soleus muscles of rat. ChAT decreased significantly by trained exercise in EDL muscle and Phy prolonged this effect even up to 24 h. Soleus muscles showed a small increase of ChAT due to exercise but Phy + exercise did not change significantly. Both EDL and soleus showed a marked decrease in AChE activity due to subacute administration of Phy + trained exercise, exhibiting an additive effect. No recovery was observed in ChAT and AChE activities of EDL even after 24 h in Phy + trained exercise group. Our results suggest that Phy and exercise has significant effect on the synthetic (ChAT) and degradative (AChE) enzymes of acetylcholine in active EDL muscle. Exercise has prolonged the inhibitory effect of Phy on ChAT and AChE activities both in active EDL and passive soleus muscles. This study showed that Phy + exercise modified the functional activity of cholinergic system in EDL and soleus muscles.

Acetylcholinesterase↗

PubMed1993

Automated compounder for adding ingredients to parenteral nutrient base solutions.

The effects of using an automated compounder for adding ingredients to parenteral nutrient (PN) base solutions was evaluated. Work-sampling methods were used to determine the amount of time spent by pharmacists and technicians in the production of PN solutions before and after the implementation of an automated device for adding ingredients to PN base solutions. Costs of materials and supplies were evaluated before and after the PN compounder was implemented. Qualitative (sterility) and quantitative (accuracy) analyses were performed by the hospital laboratory. A personnel time savings of 5.4 minutes per PN solution (1.0 full-time equivalent [FTE]) was shown. There was also an additional 0.5 FTE saved in activities not directly related to PN production. There was a 1.5% increase in pharmacist time (mean +/- S.D. preimplementation, 12.66 +/- 2.33 minutes; postimplementation, 12.85 +/- 1.96 minutes) and a significant 27.9% decrease in technician time (mean +/- S.D. preimplementation, 20.29 +/- 2.47 minutes; postimplementation, 14.62 +/- 2.24 minutes) per PN solution. The break-even point for personnel and supply costs was 33 PN solutions. Qualitative analysis resulted in one positive culture preimplementation and no positive cultures postimplementation. Quantitative analysis showed an improvement in compounding accuracy. The use of an automated compounder for adding ingredients to PN base solutions resulted in personnel time savings and improved accuracy.

Automation↗

PubMed1992

Endurance training changes central and peripheral responses to physostigmine.

Whether the pharmacodynamics of physostigmine (Phy) [rate of decarbamylation of cholinesterase (ChE) enzyme] (Kd) is altered due to acute and/or trained exercise in brain and various tissues of rat has been addressed. Acute exercise (AE) + Phy increased, whereas endurance training (ET) + Phy decreased ChE activity in brain, red blood cells (RBC), and various tissues as compared to Phy alone. The Kd of brain ChE was significantly increased (181% of control) by AE + Phy and decreased (66% of control) by ET + Phy as compared to Phy alone. There was a slight increase (114% of control) in Kd of RBC-ChE in AE + Phy as compared to Phy alone. The Kd of heart ChE was significantly decreased (44% of control) by ET + Phy as compared to Phy alone. The Kd of diaphragm ChE was significantly increased (384% of control) in AE + Phy and decreased (80% of control) in ET + Phy as compared to Phy alone. The Kd of muscle ChE significantly decreased (67% of control) by AE + Phy as compared to Phy alone, but ET + Phy did not affect the Kd in muscle. These results suggested that AE and ET have opposite effects on Kd after Phy administration.

Animals↗

PubMed1992

Effect of physostigmine on plasma lactate and pyruvate in untrained/trained rats.

Physostigmine (Phy) is metabolized to eseroline, a phenolic compound that appears to alter mitochondrial functions. The effect of Phy on recovery from exercise and on time course of plasma lactate and pyruvate levels following an acute bout of exercise (AE) was examined in untrained and trained (ET) rats. Phy alone elicited significantly higher plasma lactate and pyruvate levels than sedentary control. AE + Phy had a significantly higher plasma lactate and pyruvate levels compared to AE 2 min postadministration. From 5-30 min postexercise, lactate and pyruvate levels did not differ between these two acutely exercised groups. ET + Phy exhibited significantly lower levels of plasma lactate and pyruvate from 5-60 min postexercise compared to ET. The data show that the "additive" effect of Phy on postexercise plasma lactate and pyruvate levels can be attenuated by an enhanced fitness level in these rats.

Animals↗

PubMed1992

Evolving to provide pharmaceutical care without additional resources in a university hospital.

Our department is committed to a process of continuous quality improvement focusing on delivering the best possible pharmaceutical care services. Three committees, each with representation from pharmacists and pharmacy technicians from all areas of the department, were convened in 1991 to 1992 to further identify areas for service enhancement and to plan for the future. Based on the recommendations of these committees, further expansion in ambulatory services is a priority. Other changes will include further automation of the drug-distribution system, examination of the role of the pharmacy technician, development of an automated patient-care system with direct physician order entry, computerized documentation of clinical interventions, and reaffirmation of the role of the pharmacist as the professional responsible for proper use of medications at UMHC.

Centralized Hospital Services↗

PubMed1992

Influence of age on caloric expenditure during exercise.

Young (147 +/- 2 g) and adult (322 +/- 7 g) male Sprague Dawley rats were subjected to an incremental treadmill protocol and assessed via the Oxyscan Metabolic System in order to determine if differences exist relative to oxygen consumption (VO2, expressed in ml/kg/min), respiratory exchange ratio (RER) and caloric expenditure of two different age groups. The young rats attained a higher VO2 (81.55 +/- 1.22) compared to adult rats (68.97 +/- 2.05) at a maximal level of exercise. The adult rats became dependent upon carbohydrates as the primary source of energy until reaching 52% VO2 max, whereas the young rats did not resort to carbohydrate utilization as a primary fuel source until reaching 87% VO2max. At peak exercise, the adult animals burned only 15% less kcal/kg/h than the young rats, but the adult rats burned 37% more carbohydrate than the young animals. These data suggest that as exercise intensity increases, younger rats can more readily maintain a higher level of oxygen consumption accompanied by a more efficient use of fat as an energy source compared to adult rats. The clinical implication of this finding suggests that during the growth and development years of life, fat plays a significant role in energy expenditure needs and may therefore be more important than currently believed in young children's nutritional intake.

Aging↗

PubMed1991

Effect of cholinesterase inhibitor and exercise on choline acetyltransferase and acetylcholinesterase activities in rat brain regions.

This study sought to determine whether the choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) enzymes in the brain were affected in a regionally selective manner by chemical and physical stressors: 1) subacute administration of physostigmine (Phy); 2) exercise; and 3) the combination of these two stressors. ChAT and AChE activities in corpus striatum were significantly decreased due to Phy as well as Phy + exercise. This suggests that corpus striatum is affected by chemical stressors but more so by the combination of chemical and physical stressors. The brainstem is the only region which showed inhibition of ChAT activity due to exercise. Subacute Phy also inhibited brainstem ChAT activity. The hippocampus showed significant decrease in ChAT activity due to Phy + exercise but not due to Phy alone. These results suggest that the brain regions involved with control of motor, autonomic and cognitive functions were affected by subacute Phy and exercise. These data are consistent with the hypothesis that the responsiveness of these brain regions to different stressors is a function of the level of ongoing cholinergic activity and that elevations in ACh levels due to AChE inhibition may have long-term effects on the regulation of ChAT and AChE activities through a negative feedback mechanism.

Acetylcholinesterase↗

PubMed1990

Brain regional distribution of physostigmine and its relation to cerebral blood flow following intravenous administration in rats.

3H-labeled physostigmine (50 micrograms.kg-1) was administered intravenously to rats, and its concentration in brain tissue and spinal cord was assessed by quantitative autoradiography. Regional cerebral blood flow (rCBF) was measured with iodo-14C-antipyrine autoradiography in control rats and in animals injected i.v. with a dose of physostigmine similar to that used for the distribution studies. Tissue concentration of 3H-physostigmine was correlated with rCBF for 37 brain regions. A high degree of correlation was found at 0.5 min after drug injection, r (correlation coefficient) = 0.87. This association decreased at later times (5 min r = 0.73, 12 min r = 0.24). Structures with high cholinesterase activity (caudate-putamen, amygdala, hippocampus) showed greater retention of physostigmine over time. The highest initial physostigmine concentrations were found in regions lacking a blood-brain barrier (pineal bland, median eminence, choroid plexus) (range = 10.4-23.8 nCi/mg) and the lowest in white matter (corpus callosum, internal capsule, hippocampus commisure, spinal cord dorsal column) (range = 1.2-2.6 nCi/mg). Initial concentrations of the drug in the areas in which physostigmine induced vasodilatation (motor, sensory, temporal and occipital cortex, claustrum, and superior collicullus) were not different from concentrations in areas of comparable basal rCBF in which no such effect was observed. Variations in drug access to brain regions, then, do not explain the topographical variations of the cerebrovascular action of physostigmine.

Animals↗

PubMed1990

Effect of exercise on propranolol pharmacokinetics.

The effect of submaximal exercise on the pharmacokinetics of low dose intravenous propranolol was studied in 15 healthy human subjects. There was a wide individual variation in the results for each subject and a large difference in the degree of changes with exercise. The effect of exercise on the pharmacokinetics of propranolol, a flow limited drug, is marked but variable. This phenomenon may have profound effects on patients taking the drug regularly who exercise intermittently and drug doses may have to be adjusted.

Adult↗

PubMed1990

Eseroline, a metabolite of physostigmine, induces neuronal cell death.

The toxic effects of physostigmine, an anticholinesterase drug, and its metabolite eseroline were investigated in three neuronal cell culture systems, mouse neuroblastoma N1E-115, rat glioma C6, and neuroblastoma-glioma hybrid NG 108-15. Physostigmine and eseroline (0.5 nM) elicited a time-dependent leakage of lactic acid dehydrogenase (LDH) from all three cell types. An increased release of [14C]adenine nucleotides was also detected from cells when they were prelabeled with [14C]adenine. Eseroline was comparatively more toxic than the parent compound, physostigmine. Eseroline elicited a dose- and time-dependent leakage of LDH and release of adenine nucleotides from the neuronal cells. A nonneuronal cell line, rat liver ARL-15, was comparatively the most resistant cell type to eseroline toxicity. The concentrations of eseroline needed for 50% release of adenine nucleotides or 50% leakage of LDH from NG-108-15 and N1E-115 cells in 24 hr ranged from 40 to 75 microM. The concentrations of eseroline needed to obtain similar responses in C6 and ARL-15 cells were much higher and ranged from 80 to 120 microM. Phase contrast microscopy showed extensive damage to three neuronal cell lines at concentrations of eseroline as low as 75 microM. The loss of ATP from N1E-115 cells exceeded 50% when they were treated with 0.3 mM eseroline for 1 hr--at which time the leakage of LDH was not detectable. It seems that eseroline causes neuronal cell death by a mechanism involving loss of cell ATP. Thus, the formation of eseroline may contribute to the toxic effect of physostigmine.

Adenine Nucleotides↗

PubMed1990

Effect of paraxanthine on FFA mobilization after intravenous caffeine administration in humans.

Because it has previously been shown that it takes much more caffeine to cause fat mobilization in vitro than in vivo, it has been suggested that there may be an active metabolite working with caffeine causing an increase in lipolysis in vivo. To determine the relationship between the appearance of paraxanthine (caffeine's major dimethylxanthine metabolite) and free fatty acid (FFA) mobilization after intravenous caffeine administration, 10 men were studied at rest after receiving a dose of 4 mg/kg lean body mass. Venous blood samples were obtained before dosing and at minutes 5, 10, 15, 30, 45, 60, 90, 120, 150, and 180. Serum levels of FFA, glycerol, caffeine, and paraxanthine were determined in duplicate. Concentrations of FFA and glycerol were corrected for plasma volume changes. A high negative correlation was seen between decreases in caffeine and increases in FFA (r = -0.90) and a high positive correlation was seen between the appearance of paraxanthine and FFA (r = 0.93). It was concluded that paraxanthine may play a role in increased lipolysis after caffeine administration in humans.

Adult↗