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Biomedical subjects

K Prasad

Publications and source records attributed to K Prasad.

At least 91 records · Page 5Linked to original sources
PubMed1997

Regulation of AP-3 function by inositides. Identification of phosphatidylinositol 3,4,5-trisphosphate as a potent ligand.

As part of the growing effort to understand the role inositol phosphates and inositol lipids play in the regulation of vesicle traffic within nerve terminals, we determined whether or not the synapse-specific clathrin assembly protein AP-3 can interact with inositol lipids. We found that soluble dioctanoyl-phosphatidylinositol 3,4,5-trisphosphate (DiC8PtdIns(3,4, 5)P3) was only 7.5-fold weaker a ligand than D-myo-inositol hexakisphosphate in assays that measured the displacement of D-myo-[3H]inositol hexakisphosphate. In functional assays we found that both of these ligands inhibited clathrin assembly, but DiC8-PtdIns(3,4,5)P3 was more potent and exhibited a larger maximal effect. We also examined the structural features of DiC8-PtdIns(3,4, 5)P3 that establish specificity. Dioctanoyl-phosphatidylinositol 3, 4-bisphosphate, which does not have a 5-phosphate, and 4, 5-O-bisphosphoryl-D-myo-inosityl 1-O-(1, 2-O-diundecyl)-sn-3-glycerylphosphate, which does not have a 3-phosphate, were, respectively, 2-fold and 4-fold less potent than DiC8-PtdIns(3,4,5)P3 as inhibitors of clathrin assembly. Deacylation of DiC8-PtdIns(3,4,5)P3 reduced its affinity for AP-3 almost 20-fold, and also dramatically lowered its ability to inhibit clathrin assembly. The deacylated products of the soluble derivatives of phosphatidylinositol 3,4-bisphosphate and phosphatidylinositol 4, 5-bisphosphate were both not significant inhibitors of clathrin assembly. It therefore appears that the interactions of inositides with AP-3 should not be considered simply in terms of electrostatic effects of the highly charged phosphate groups. Ligand specificity appears also to be mediated by hydrophobic interactions with the fatty-acyl chains of the inositol lipids.

Acylation↗
PubMed1997

Antioxidant defense system in diabetic kidney: a time course study.

Oxygen free radicals (OFRs) have been suggested to be a contributory factor in complications of diabetes mellitus. In the present study, we investigated the lipid peroxide level measured as thiobarbituric acid reactive substances (TBARS) and activities of antioxidant enzymes viz., [superoxide dismutase (SOD), catalase (CAT) and glutathione-peroxidase (GSH-Px)] in the kidney of streptozotocin induced diabetic rats at various stages of development of diabetes. Sprague Dawley rats were divided into two groups: group I, control (n = 42) and group II, diabetic (n = 42). Each group was further subdivided into seven groups each consisting of six rats. Rats in subgroups were studied at weekly intervals (0 to 6 weeks). Blood glucose levels were estimated at the time of sacrifice. TBARS levels and activity of antioxidant enzymes were measured in kidney. The levels of TBARS in the diabetic group increased initially, dropped to baseline level after 2 weeks and then progressively increased at 5th and 6th week (p < 0.05). There was an increase in catalase activity at first week after that it decreased as compared to control group. However, GSH-Px activity in the diabetic group increased after 1 week and then remained at the same level except a small drop in the 2nd week. Total SOD and CuZn-SOD activity increased significantly in diabetic kidney as compared to controls at all time intervals, while Mn-SOD activity showed no change. The present findings suggest that oxidative stress accompanies at early onset of diabetes mellitus and the susceptibility of the kidney to oxidative stress during the early stages may be an important factor in the development of diabetic nephropathy.

Animals↗
PubMed1997

Unilateral meningeal thickening: a rare presentation of tuberculous meningitis.

A rare case of tuberculous meningitis (TBM) causing unilateral thickening of meninges, is described here. The 50 year old male is presented with hemicranial headache and unilateral multiple cranial nerve involvement without any long tract signs. Magnetic resonance imaging (MRI) scan including enhanced studies showed a hemicranial thickening of the meninges. Biopsy of the meninges revealed tuberculosis. The patient improved gradually on antitubercular treatment (ATT). Follow-up at 6 months revealed significant improvement in neurological status. Though tuberculous involvement of the central nervous system (CNS) is very common in India, hemicranial meningeal involvement has never been reported.

Antitubercular Agents↗
PubMed1997

Mechanism of hydroxyl radical-induced modulation of vascular tone.

We investigated the effects of hydroxyl radicals (OH) generated by a .OH-generating system (dihydroxyfumarate [DHF], adenosine diphosphate [ADP], and FeCl3) on isolated rabbit aorta suspended in Krebs-Ringer solution. The .OH-generating system produced a concentration-dependent generation of .OH. .OH relaxed rabbit aorta and norepinephrine (NE)-precontracted aorta in a concentration-dependent manner. Mannitol completely prevented this relaxation. Relaxation was completely absent in preparations denuded of endothelium. The relaxant effect was reduced by 62% by an inhibitor of nitric oxide synthesis (NG-monomethyl-L-arginine), by 58% by an inhibitor of guanylate cyclase (methylene blue), by 48% by an inhibitor of cyclooxygenase (indomethacin), and by 83% by an adenosine triphosphate (ATP)-sensitive K+ channel blocker (glyburide). The inhibition of .OH-induced relaxation by a combination of indomethacin, methylene blue, and glyburide was not greater than by each of the individual agents. These results indicate that .OH produces a relaxation of the aorta that is completely endothelium-dependent and is partly mediated by an endothelium-derived relaxing factor (nitric oxide), vasodilatory arachidonic acid metabolites, and an ATP-sensitive K+ channel.

Animals↗
PubMed1997

Hydroxyl radical-scavenging property of secoisolariciresinol diglucoside (SDG) isolated from flax-seed.

Recently there has been a moderate resurgence in the use of flax-seed in a variety of ways including bread. The scientific basis of its use is very limited. There is some claim for beneficial effects in cancer and lupus nephritis. These claims could be due to its ability to scavenge oxygen radicals. However, its antioxidant activity is not known. Recently a method has been developed to isolate secoisolariciresinol diglucoside (SDG) from defatted flax-seed in large quantity (patent pending). We investigated the ability of SDG to scavenge .OH using high pressure liquid chromatography (HPLC) method. .OH was generated by photolysis of H2O2 (1.25-10.0 mumoles/ml) with ultraviolet light and was trapped with salicylic acid which is hydroxylated to produce .OH-adduct products 2,3-dihydroxybenzoic acid (DHBA) and 2,5-DHBA. H2O2 produced a concentration-dependent .OH as estimated by 2,3-DHBA and 2,5-DHBA. A standard curve was constructed for known concentrations of 2,3-DHBA and 2,5-DHBA against corresponding area under the peaks which then was used for measurement of 2,3-DHBA and 2,5-DHBA generated by UV irradiation of H2O2 in the presence of salicylic acid. SDG in the concentration range of 25, 50, 100, 250, 500, 750, 1000 and 2000 micrograms/ml (36.4, 72.8, 145.6, 364.0, 728.0, 1092.0, 1456.0 and 2912.0 microM respectively) produced a concentration-dependent decrease in the formation of 2,3-DHBA and 2,5-DHBA, the inhibition being 4 and 4.65% respectively with 25 micrograms/ml (36.4 microM) and 82 and 74% respectively with 2000 micrograms/ml (2912.0 microM). The decrease in .OH-adduct products was due to scavenging of .OH and not by scavenging of formed 2,3-DHBA and 2,5-DHBA. SDG prevented the lipid peroxidation of liver homogenate in a concentration-dependent manner in the concentration range from 319.3-2554.4 microM. These results suggest that SDG scavenges .OH and therefore has an antioxidant activity.

Butylene Glycols↗
PubMed1997

Inhibition of human lymphocyte function by organic solvents.

UNLABELLED: We studied the direct effect of reactive hydroxyl precursors and inhibitors on CD4+ T-cell function. We used hydrogen peroxide plus ferrous chloride as the hydroxyl radical-generating system and di-methyl sulphourea, di-methyl sulfoxide, pyrrolidine dithiocarbonate, methanol, and ethanol, at a noncytotoxic concentration, as inhibitors. The immune parameter studies were proliferation and interleukin-2 production by peripheral blood lymphocytes stimulated with anti-CD3 antibody, phytohemagglutinin and alloantigens; proliferation, interleukin-2 production and mRNA expression of interleukin-4 and interferon gamma by allogeneic CD4+ T-cell clones stimulated with alloantigens. The results show that lymphocytes produce significant amounts of reactive oxygen species as measured by malondialdehyde produced in cultures. The hydroxyl radical-generating system did not change any of the cellular responses studied although it doubled Malondialdehyde production. Hydroxyl radical scavengers significantly inhibited all responses at doses that didn't significantly decrease malondialdehyde production. DNA analysis failed to show evidence for apoptosis. CONCLUSION: Hydroxyl radical scavengers inhibit lymphocyte mitogenesis by a process that is independent of scavenging hydroxyl radicals.

Amitrole↗
PubMed1997

Catecholaminergic expression in 2N27 immortal neural cell line is enhanced by glial-derived factors.

The goal of this study was to examine the responsiveness of an immortalized catecholaminergic neuronal line, 2N27, to various growth factors and identify those which promote catecholaminergic expression. 2N27 is a newly established neural cell line derived from fetal rat mesencephalic tissue and, thus, contains tyrosine hydroxylase (TH), a reliable marker for catecholaminergic neurons. Using TH activity as a biochemical index, we examined the responsiveness to both recognized trophic factors (NGF, TGF-beta and basic- and acidic-FGF) as well as novel, glia-derived factors present in conditioned media from several glial sources. The glial cells included MACH, a normal cell line derived from aged mouse cerebral hemispheres NBCC, normal glia derived from newborn mouse cerebral hemispheres; and C-6 glioma cells, 2B clone, passage 72, predominately astrocytes. Cells were cultured in the presence of added factors from 0 to 3 days in vitro (DIV) and were harvested on day 4. We found that 2N27 neural cells responded differentially to growth factors. No change was observed in TH activity in response to NGF, TH activity even decreased in response to b-FGF ad TGF-beta addition to the culture medium. However, a dose dependent increase in TH activity was observed following treatment with a-FGF and the increase to a-FGF was associated to an increase in cell proliferation as compared to TH increase by cAMP associated to differentiation. However, the 2N27 cells responded with a marked increase in TH when cultured in the glial cell conditioned media. We conclude that immortal cells require a variety of microenvironmental signals to maintain their phenotype.

Animals↗
PubMed1997

Surgery in primary supratentorial intracerebral hematoma: a meta-analysis of randomized trials.

OBJECTIVES: To examine through a meta-analysis whether a treatment strategy of surgery plus the routine medical management saves lives and reduces disability in survivors of primary supratentorial intracerebral hematoma compared to routine medical management alone. MATERIAL AND METHODS: Computerized bibliographic search of published research, conference proceedings, monographs and experts yielded 373 articles, of which only four were randomized trials. The methodological quality of the trials was assessed by two observers (weighted kappa = 0.8). Two independent reviewers abstracted the data on patient sample, type of surgery and outcomes in terms of death and dependence versus independence. Based on the nature of the intervention and the results of test for homogeneity, we analyzed the results of craniotomy and endoscopic evacuation separately. RESULTS: Review of the three trials of craniotomy suggests that it increases the risk of death or dependence (pooled risk difference 13%, 95% CI 3% to 23%), though the study with the largest sample size was conducted in the pre-CT period. Reanalysis of the endoscopic evacuation trial data showed decrease in risk of death or dependence (risk difference -18%, 95% CI -36% to 0%), the effect being similar across the different subgroups of patients according to the site of hematoma, but probably larger in patients aged less than 60 years or hematoma size of more than 50 cc. CONCLUSIONS: The role of craniotomy and stereotactic surgery has not been adequately studied in randomized trials. The results of a single trial suggest that endoscopic evacuation is a promising form of treatment in patients with primary supratentorial intracerebral hematoma, but this finding needs confirmation in a larger trial.

Activities of Daily Living↗
PubMed1997

Prevention of Hypercholesterolemic Atherosclerosis by Garlic, an Antixoidant.

BACKGROUND: Investigations of the effects of high cholesterol diet in the presence and absence of garlic on the genesis of atherosclerosis, the blood lipid profile, aortic tissue lipid peroxidation product malondialdehyde, chemiluminescence, a marker for antioxidant reserve and activity of antioxidant enzymes (superoxide dismutase, catalase, and glutathione peroxidase were made in rabbits. METHODS AND RESULTS: Four groups of 10 rabbits each were studied: group 1 was given regular rabbit chow, group 2 was given rabbit chow diet supplemented with garlic powder (300 mg twice daily orally), group 3 was given 1% cholesterol diet, group 4 was given 1% cholesterol diet supplemented with garlic powder (300 mg twice daily orally). Blood concentration of triglyceride, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and very low-density lipoprotein cholesterol were measured before and after 4 and 10 weeks of experimental diets. The aorta was removed at the end of protocol (10 weeks) for assessment of atherosclerotic changes (gross and microscopic), malondialdehyde concentration, chemiluminescence, and activity of antioxidant enzymes. Total cholesterol, low density-lipoprotein cholesterol and ratio of low-density lipoprotein cholesterol/high-density lipoprotein cholesterol and ratio of low-density lipoprotein cholesterol/high-density lipoprotein cholesterol increaserd in group 3 and 4; the increase was smaller in group 4 than in in group 3 although not significant. Serum high-density lipoprotein cholesterol decreased to a similar extent in groups 3 and 4. Serum triglyceride and very low-density lipoprotein cholesterol remained unchanged in group 3 but increased in group 4. These values were significantly higher than those in group 1. Garlic in rabbits with control diet decreased the levels of triglyceride and very low density lipoprotein but did not affect the levels of total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol and the ratio of low-density lipoprotein cholesterol/high-density lipoprotein cholesterol. There was an increase in aortic tissue malondialdehyde, chemiluminescence, and activities of catalase and glutathione peroxidase in group 3 compared with those in group 1. Levels of aortic malondialdehyde, chemiluminescence, catalase, and glutathione peroxidase were lower in group 4 compared with group 3; however, values for malondialdehyde and chemiluminescence were lower and that of catalase and glutathione peroxidase were higher in group 4 compared with group 1. Superoxide dismutase activity was similar in all the four groups. Malondialdehyde, chemiluminescence, and activity of catalase of aortic tissue decreased while activity of glutathione peroxidase increased in group 2. Atherosclerotic changes were lower in group 4 compared with group 3. Histologic changes were practically similar in groups 3 and 4. CONCLUSIONS: Increased levels of malondialdehyde, chemiluminescence, and antioxidant enzymes associated with development of atherosclerosis suggests a role for oxygen free radicals in the pathogenesis of hypercholesterolemic atherosclerosis. The protection afforded by garlic was associated with decrease in aortic malondialdehyde and chemiluminescence inspite of no change in serum cholesterol. These findings suggest that oxygen free radicals are involved in the genesis and maintenance of hypercholesterolemic atherosclerosis and that use of garlic can be useful in preventing the development of hypercholesterolemic atherosclerosis.

Journal Article↗
PubMed1997

Menstrual bleeding in a female infant with congenital adrenal hyperplasia: altered maturation of the hypothalamic-pituitary-ovarian axis.

Vaginal bleeding during the neonatal period is commonly related to the withdrawal of maternal estrogens. Vaginal bleeding has also been reported in female infants with congenital adrenal hyperplasia and has been proposed to be due to a treatment-induced activation of the hypothalamic-pituitary-ovarian axis. We report a female infant with the salt-losing form of congenital adrenal hyperplasia due to 21-hydroxylase deficiency, who had the onset of vaginal bleeding at 3 months of life. Adrenal steroid suppression had been achieved by 2.5 weeks of age. At the time of bleeding, imaging studies revealed an enlarged right ovary with a dominant 3-cm cyst and additional small cysts that had not been seen on the newborn sonogram. The uterus was enlarged and stimulated. Three weeks later (1 week after the cessation of bleeding), repeat ultrasound demonstrated a marked decrease in the size of the right ovary, and the dominant cyst was no longer seen. The patient had a heightened FSH response to GnRH and elevated levels of estradiol for age. At 5 months of age, no further episodes of sustained vaginal bleeding were observed. Repeat hormonal levels were prepubertal, and pelvic sonogram demonstrated no evidence of stimulation. The findings in our patient suggest that a decline in adrenal androgens after glucocorticoid treatment resulted in an increase in gonadotropin levels, which then triggered a transient and augmented end-organ response (menses). Further, we suggest that our infant's hormonal findings may reflect a delay in the timely development of the negative restraint by sex steroids on gonadotropins that is normally observed in infancy.

Adrenal Hyperplasia, Congenital↗
PubMed1997

Cardiac depression and cellular injury in hemorrhagic shock and reinfusion: role of free radicals.

We investigated the effect of hemorrhagic shock and reinfusion on the cardiac function and contractility, plasma CK and CK-MB activity and lactate concentration, oxyradical-producing activity of polymorphonuclear leukocytes (PMNL-CL), cardiac chemiluminescence (LV-CL), antioxidant enzyme activity [superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-PX)] and malondialdehyde (MDA) concentration in anesthetized dogs to determine the role of oxyradicals in cardiac depression and cellular injury in hemorrhagic shock and reinfusion. The dogs were assigned into three groups: I (sham), 4 h duration; II (S + R), 2 h of shock followed by reinfusion for 2 h; III (SOD + S + R), as II but pretreated with PEG-SOD. Hemorrhagic shock was produced by withdrawal of blood to maintain the mean arterial pressure at 50 +/- 5 mm Hg. Cardiac function and contractility were depressed during hemorrhagic shock. Plasma CK, CK-MB and lactate increased during shock. Following reinfusion after 2 h of shock hemodynamic parameters and plasma lactate tended to return towards control values. Plasma CK and CK-MB, PMNL-CL and cardiac MDA, total-, Mn- and CuZn-SOD activity increased while LV-CL decreased. In spite of the increase in the antioxidant reserve, there was oxidative damage. Pretreatment with SOD attenuated the deleterious effects of shock and reinfusion on the cardiovascular function, plasma CK, and CK-MB, PMNL-CL, cardiac MDA, SOD, and LV-CL. Protection was incomplete for cardiovascular function and plasma CK and CK-MB. These results suggest that oxyradicals may partly be involved in the deterioration of cardiovascular function and cellular injury during hemorrhagic shock and reinfusion.

Animals↗
PubMed1996

Antitumor activity of the R- and S-enantiomers of RS-2-[[hydroxy[[2-[ (octadecyloxy)methyl]tetrahydrofuran-2-yl]methoxy]-phosphinyl]oxy]-N, N,N,-trimethylethylaminium hydroxide inner salt.

The R- and S-enantiomers of 2-[[hydroxyl[[2-[(octadecyloxy) methyl]tetrahydrofuran-2-yl]methoxy]-phosphinyl]oxy]-N,N,N,- trimethylethylaminium hydroxide salt (SRI 62-834) have been evaluated in several assays to determine potential antitumor activity. The S-enantiomer showed slightly greater cytotoxic activity than the R- or RS-forms against several murine tumor cell lines. In the mouse Meth A fibrosarcoma model, the S-enantiomer was ca. 4 times more effective than the R-isomer in controlling size of tumor growth and increasing the number of survivors.

Animals↗
PubMed1996

Evaluation of hydroxyl radical-scavenging property of garlic.

Garlic has been reported to provide protection against hypercholesterolemic atherosclerosis and ischemia-reperfusion-induced arrhythmias and infarction. Oxygen free radicals (OFRs) have been implicated as causative factors in these diseases and antioxidants have been shown to be effective against these conditions. The effectiveness of garlic in these disease states could be due to its ability to scavenge OFRs. However, the OFR-scavenging activity of garlic is not known. Also it is not known if its activity is affected by cooking. We therefore investigated, using high pressure liquid chromatography, the ability of garlic extract (heated or unheated) to scavenge exogenously generated hydroxyl radical (.OH). .OH was generated by photolysis of H2O2 (1.2-10 mumoles/ml) with ultraviolet (UV) light and was trapped with salicylic acid (500 nmoles/ml). H2O2 produced .OH in a concentration-dependent manner as estimated by .OH adduct products 2,3-dihydroxybenzoic acid (DHBA) and 2,5-DHBA. Garlic extract (5-100 microliters/ml) produced an inhibition (30-100%) of 2,3-DHBA and 2,5-DHBA generated by photolysis of H2O2 (5.00 pmoles/ml) in a concentration-dependent manner. Its activity is reduced by 10% approximately when heated to 100 degrees C for 20, 40 or 60 min. The extent of reduction in activity was similar for the three heating periods. Garlic extract prevented the .OH-induced formation of malondialdehyde in the rabbit liver homogenate in a concentration-dependent manner. It alone did not affect the MDA levels in the absence of .OH. These results indicate that garlic extract is a powerful scavenger of .OH and that heating reduces its activity slightly.

Animals↗
PubMed1996

Prospective angiographic study of the abnormalities of systemic venous connections in congenital and acquired heart disease.

UNLABELLED: Angiographic definition of systemic venous connections was obtained prospectively in 780 consecutive patients with congenital heart disease and 102 patients with acquired valvular heart disease undergoing cardiac catheterization. Attempts were made to enter the innominate vein and perform a balloon occlusion angiogram in each patient. In patients with congenital heart disease, bilateral superior vena cava were present in 32/771 patients (approximately 4%) with levocardia and 3/9 patients with dextrocardia. Among patients with bilateral superior vena cava (n = 35), an innominate vein of variable size that could be entered was present in six patients. Small tributaries connecting the right and left superior vena cava were found and entered in six patients. The superior vena cava was entered via its connection to morphologic left atrium in five patients and via the coronary sinus in 17 patients. Abnormalities of the inferior vena cava were seen in 7/780 patients. The following abnormalities of the inferior vena cava were noted: azygous continuation of rightsided inferior vena cava in levocardia -- 3 patients, hemiazygos continuation of the leftsided inferior vena cava in levocardia -- 1 patient, azygos continuation of the leftsided inferior vena cava in dextrocardia -- 1 patient, interruption of inferior vena cava below the liver with a plexus of veins joining the azygos vein -- 1 patient, and an inferior vena cava draining into the leftward aspect of the common atrium -- 1 patient. Abnormalities of the systemic venous connections were seen in 2/102 patients with acquired heart disease: bilateral superior vena cava in 1 patient and bilateral inferior vena cava in 1 patient. CONCLUSIONS: Abnormalities of systemic venous connections were seen in approximately 5% patients with congenital heart disease and approximately 2% patients with acquired heart disease. Small tributaries or an innominate vein of variable size often connect left and right superior vena. Contrast material can be injected into these connections to document the presence of bilateral superior vena cava.

Adolescent↗