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Biomedical subjects

A Prasad

Publications and source records attributed to A Prasad.

At least 19 recordsLinked to original sources

Comparison of coronary endothelial dynamics with electrocardiographic and left ventricular contractile responses to stress in the absence of coronary artery disease.

Coronary artery endothelial dysfunction has been proposed as a cause of myocardial ischemia and symptoms in patients with angina-like chest pain despite normal coronary angiograms, especially those with ischemic-appearing ST-segment depression during exercise (syndrome X). We measured coronary vasomotor responses to acetylcholine (3 to 300 microg/min) in 42 patients (27 women and 15 men) with effort chest pain and normal coronary angiograms who also had normal electrocardiograms and echocardiograms at rest. All patients underwent treadmill exercise testing and measurement of systolic wall thickening responses to dobutamine (40 microg/kg/min) during transesophageal echocardiography. There were no differences in the acetylcholine-stimulated epicardial coronary diameter (+5+/-13% vs +1+/-13%, p=0.386) and flow (+179+/-90% vs +169+/-96%, p=0.756), or in the systolic wall thickening responses (+134+/-65% vs +118+/-57%, p=0.445) from baseline values in the 12 syndrome X patients compared with the 30 patients with negative exercise test results. In patients in the lowest quartile of coronary flow responses to acetylcholine, dobutamine increased systolic wall thickening by 121+/-73%; 3 had ischemic-appearing ST-segment depression during this stress. This contractile response to dobutamine was no different than the increase in systolic wall thickening (129+/-48%, p=0.777) in patients in the highest quartile of coronary flow responses, 3 of whom also had ischemic-appearing ST-segment depression during this stress. Thus, coronary endothelial dysfunction in the absence of coronary artery disease does not account for ischemic-appearing ST-segment depression in patients with chest pain despite normal coronary angiograms. Further, coronary endothelial dysfunction is not associated with myocardial contractile responses to stress consistent with myocardial ischemia.

Acetylcholine

Induction of calcitonin gene-related peptide-like immunoreactivity in hippocampal neurons following ischemia: a putative regional modulator of the CNS injury/immune response.

Calcitonin gene-related peptide (CGRP) is a potent vasodilator and immune cell modulator. In two studies within the hippocampal formation (HF), CGRP-like immunoreactivity (CGRP-LI) was increased in the inner molecular layer of the dentate gyrus after adrenalectomy and in mossy cells after colchicine-induced destruction of granule neurons. Given the increase in CGRP-LI following damage to the granule cell region of the HF, we investigated another trauma model, ischemia, that targeted different areas of the HF, CA1 region, and subiculum to ascertain the regional expression of this peptide after insult. Following ischemia, light microscopic evaluation showed CGRP-LI in basket cell-like neuronal perikarya within the dorsal subiculum and CA1 region of the hippocampus and in varicose fibers within the CA2 region of the hippocampus. Control rats rarely expressed CGRP-LI within neurons in these regions. In ischemic brains, double-labeled immunocytochemistry with antibodies to various neural markers demonstrated co-localization of CGRP-LI primarily within surviving subicular and CA1 cells resembling interneurons containing parvalbumin-LI or calbindin-LI. Electron microscopic analysis of the CA1 region from ischemic brains showed that CGRP-LI was contained in terminals with numerous small synaptic vesicles that formed symmetric synapses with perikarya and large dendrites of pyramidal cells, some of which were degenerating. Collectively, the data from this study and our previous study indicate that damage induces CGRP-LI expression in interneurons and nonprincipal cells in the area of damage, and we hypothesize that CGRP expression in surviving neurons within damage-related regions of the hippocampus is likely to be an important, and possibly a protective, component of the response of the nervous system to injury.

Adrenalectomy

Effects of joint configuration for the arc welding of cast Ti-6Al-4V alloy rods in argon.

STATEMENT OF PROBLEM: Titanium and its alloys are more commonly used in prosthodontics and welding has become the most common modality for their joining. Studies on the welding of titanium and its alloys have not quantified this value, though its importance has been suggested. PURPOSE: This study compared the strength and properties of the joint achieved at various butt joint gaps by the arc-welding of cast Ti-6Al-4V alloy tensile bars in an argon atmosphere. MATERIAL AND METHODS: Forty of 50 specimens were sectioned and welded at four gaps. All specimens underwent tensile testing to determine ultimate tensile strength and percentage elongation, then oxygen analysis and scanning electron microscopy. RESULTS: As no more than 3 samples in any group of 10 actually fractured in the weld itself, a secondary analysis that involved fracture location was initiated. There were no differences in ultimate tensile strength or percentage elongation between specimens with weld gaps of 0.25, 0.50, 0.75, and 1.00 mm and the as-cast specimens. There were no differences in ultimate tensile strength between specimens fracturing in the weld and those fracturing in the gauge in welded specimens; however, as-cast specimens demonstrated a higher ultimate tensile strength than welded specimens that fractured in the weld. Specimens that fractured in the weld site demonstrated less ductility than those that fractured in the gauge in both welded and as-cast specimens, as confirmed by scanning electron microscopy examination. The weld wire showed an oxygen scavenging effect from the as-cast parent alloy. CONCLUSIONS: The effects of the joint gap were not significant, whereas the characteristics of the joint itself were, which displayed slightly lower strength and significantly lower ductility (and thus decreased toughness). The arc-welding of cast titanium alloy in argon atmosphere appears to be a reliable and efficient prosthodontic laboratory modality producing predictable results, although titanium casting and joining procedures must be closely controlled to minimize heat effects and oxygen contamination.

Alloys

Morphine modulates proliferation of kidney fibroblasts.

Renal interstitial scarring is an important component of heroin-associated nephropathy. Kidney fibroblasts have been demonstrated to play a role in the development of renal scarring in a variety of renal diseases. We studied the effect of morphine, an active metabolite of heroin, on the proliferation of kidney fibroblasts. Morphine at a concentration of 10(-12) M enhanced (P < 0.001) the proliferation of kidney fibroblasts (control, 67.5 +/- 2.0 vs. morphine, 112.2 +/- 10.1 x 10(4) cells/well). [3H]thymidine incorporation studies further confirmed these results. Morphine at concentrations of 10(-12) M to 10(-10) M also modulated mRNA expression of early growth related genes (c-fos, c-jun and c-myc). Morphine at concentrations of 10(-8) to 10(-4) M promoted apoptosis of kidney fibroblasts and also enhanced the synthesis of p53 by kidney fibroblasts. We speculate that morphine-induced kidney fibroblast proliferation may be mediated through the activation of early growth related genes, whereas morphine induced kidney fibroblast apoptosis may be mediated through the generation of p53. The present in vitro study provides a hypothetical basis for the role of morphine in the development of renal interstitial scarring in patients with heroin-associated nephropathy.

Animals

Laparoscopy in the diagnosis and management of Crohn's disease.

We have tried to evaluate the role of laparoscopy and laparoscopic-assisted surgery in the management of Crohn's disease. Over a 4-year period, we had 38 patients, of which 23 patients were suspected to have Crohn's disease and were admitted for diagnostic laparoscopy while 15 patients had already had a biopsy confirmation of Crohn's disease in the past and were admitted for specifically planned procedures. In the first group of 23 patients, 11 were found not to have Crohn's disease. In the remaining 12 patients, three were proven to have Crohn's disease, but no surgical procedure was undertaken. The remaining nine patients underwent laparoscopic-assisted procedures, of which two required conversion to a laparotomy because of intra-abdominal abscesses. All 15 patients in the second group underwent laparoscopic or laparoscopic-assisted procedures. In total, 14 patients were spared a potential diagnostic laparotomy and could go home the next day. The remaining 24 patients underwent procedures requiring longer hospital stays; five had a purely laparoscopic procedure, 17 had a laparoscopic-assisted procedure, and two required a laparotomy. Although there was little difference in the median stay for patients treated laparoscopically or by laparotomy, it is thought that the extent or severity of the disease process influenced the length of the stay rather than the approach used. The complication rate was similar to that found in Crohn's patients undergoing open surgery. It remains to be seen whether those in the laparoscopically treated group have less adhesive complications than those treated by laparotomy. It is our belief that laparoscopy is a valuable aid in the diagnosis of Crohn's disease. It remains to be proven whether or not laparoscopic-assisted surgery will be of significant value in the treatment of this condition.

Adolescent

Leptin expression in adipose tissue from obese humans: depot-specific regulation by insulin and dexamethasone.

We investigated the in vitro regulation of leptin expression in adipose tissue from severely obese women and men before and after culture with insulin (7 nM) and/or dexamethasone (25 nM). Leptin mRNA and leptin secretion were two- to threefold higher in subcutaneous vs. omental adipose tissue before culture. Dexamethasone transiently increased leptin mRNA approximately twofold in both depots after 1 day of culture [P < 0.01 vs. basal (no hormone control)], but leptin secretion was only increased in omental adipose tissue (P < 0.005 vs. basal). Insulin did not increase leptin mRNA in either depot but increased leptin secretion approximately 1.5- to 3-fold in subcutaneous tissue throughout 7 days of culture (P < 0.05 vs. basal). The combination of insulin and dexamethasone increased leptin mRNA and leptin secretion approximately two- to threefold in both depots at day 1 (P < 0.005 vs. basal or insulin) and maintained leptin expression throughout 7 days of culture. We conclude that insulin and glucocorticoid have depot-specific effects and function synergistically as long-term regulators of leptin expression in omental and subcutaneous adipose tissue from obese subjects.

Abdomen

A new condensable composite for the restoration of posterior teeth.

Undoubtedly the greatest resistance of clinicians to use composite resins in posterior teeth relates to technique sensitivity, time consumption, and complexity. Placing conventional posterior composite resins does not take into account that composites differ considerably from amalgam. This is particularly true with respect to its physical characteristics, especially insertion and packing properties. The development of a posterior composite resin that can be placed by an amalgam carrier and subsequently packed or condensed as an amalgam, should assist clinicians greatly in their ability to successfully restore class II cavity preparations. Acknowledgment is expressed to Bruce Small, DMD, for the clinical dentistry and slides.

Composite Resins

10 questions about Lyme neuroborreliosis.

The diagnosis of Lyme neuroborreliosis requires a high index of suspicion and chronological correlation of the clinical findings and laboratory data. The limitations of serologic tests must be understood. Cerebrospinal fluid anti-Borrelia burgdorferi antibody index is currently the best indicator of Lyme neuroborreliosis.

Antibodies, Bacterial

The role of nitric oxide in coronary vascular effects of estrogen in postmenopausal women.

BACKGROUND: At physiological concentrations, 17beta-estradiol selectively enhances endothelium-dependent coronary vasodilation by an unknown mechanism in postmenopausal women. METHODS AND RESULTS: To assess the contribution of nitric oxide (NO) to the vascular effects of estradiol, we measured coronary epicardial and microvascular responses to intracoronary acetylcholine (range, 3 to 300 microg/min for 2 minutes) before and after intracoronary estradiol 75 ng/min for 15 minutes in 20 estrogen-deficient women, 16 of whom had angiographic evidence of atherosclerosis or risk factors for atherosclerosis. This testing was repeated after inhibition of NO synthesis with intracoronary N(G)-monomethyl-L-arginine (L-NMMA) 64 micromol/min for 5 minutes. Estradiol increased acetylcholine-stimulated coronary flow from 54+/-48% (mean+/-SD) above baseline values before estradiol infusion to 100+/-63% above baseline values (P=.007) and decreased coronary resistance from 32+/-21% to 46+/-15% below baseline values (P=.007) at a coronary sinus estradiol concentration of 1725+/-705 pmol/L (470+/-192 pg/mL). Estradiol also tended to lessen the severity of acetylcholine-induced epicardial coronary artery vasoconstriction from 8+/-11% to 3+/-11% below baseline values (P=.123). However, during L-NMMA infusion, estradiol no longer potentiated the effects of acetylcholine on coronary flow dynamics; coronary flow increased 39+/-46% above baseline values and coronary resistance decreased 19+/-30% below baseline values (both P<.001 versus pre-L-NMMA responses). The epicardial diameter decreased 8+/-11% below baseline values (P=.06 versus pre-L-NMMA response). CONCLUSIONS: The effects of estradiol at physiological concentrations on endothelium-dependent coronary vasodilator responsiveness in postmenopausal women are mediated by enhanced bioavailability of NO, which may be responsible in part for the cardioprotective effects of estrogen.

Adult

Perineal canal.

Perineal canal (PC) is a rare anomaly constituting 4% of all anorectal malformations. Sixty patients (56 females and 4 males) with PC managed over the past 27 years are reported. The ages ranged from 2 days to 13 years. The chief symptom was passage of fecal matter through both the anus and the fistula. One girl had undergone previous, unsuccessful surgery. All our patients were treated by anterior sagittal anorectoplasty (ASARP), which allowed anatomic exposure and accurate repair of the anomaly. In 49 patients without any perineal inflammation primary ASARP was undertaken. Surgery was delayed in 11 patients with perineal excoriations and/or active inflammation. One patient died post-operatively due to unrelated causes and 1 developed a recurrence. Anal dilation was required in 7 cases. Fifty patients were seen at first follow-up 12 weeks after surgery. All were continent and had normal defecation without the use of laxatives. Thirty-four could be followed up to the age of 3 years; they were continent with normal bowel habits. There was no shift in the position of the anus and no instance of rectal dilation. Individualization of the management and operation by the anterior sagittal approach thus offers good results in this uncommon anorectal anomaly.

Adolescent

Dehydroepiandrosterone decreases behavioral despair in high- but not low-anxiety rats.

Outbred Sprague-Dawley rats exhibit considerable heterogeneity within a population when evaluated for a variety of biologic functions, such as dietary fat intake, alcohol preference, and expression of anxiety. To understand the neuroendocrine basis for depression and anxiety, we routinely assess outbred rats for behavioral despair (Porsolt's test), anxiety (elevated plus-maze), and urinary excretion of a variety of hormones. In one such study, we observed a significant correlation (r2 = 0.337; n = 30; p < 0.01) between the level of anxiety and the degree of behavioral despair. Within the above population, two distinct subgroups emerged: one with high anxiety and the other with low anxiety. We next evaluated the effect of dehydroepiandrosterone (DHEA), an anxiolytic neurosteroid, on the despair response in the two groups of rats. Treatment of high-anxiety rats with DHEA significantly diminished behavioral despair. In contrast, DHEA did not affect behavioral despair in low-anxiety rats. In conclusion, the results presented here show DHEA to be effective as an antidespair agent in rats with both high anxiety and despair.

Animals

Pressure modulates monocyte migration.

Migration of monocytes into the subendothelial space of the aorta has been considered to be an important event in the development of atherosclerosis. Because hypertension is commonly associated with atherosclerosis, we studied the effect of applied pressure on the migration of monocytes. Direct applied pressure increased the migration (P < .001) of monocytes across a filter when compared with normal atmospheric pressure. The migration of monocytes was found to be directly related to the amount of the applied pressure. Amlodipine, a calcium channel blocker, attenuated the migration of monocytes under normal as well as increased pressure conditions in a dose-dependent manner. These studies provide a basis to speculate on the role of direct pressure in the migration of monocytes into the subendothelial space and the possibility that vasoactive agents may modulate the migration of monocytes independent of their pressure-lowering effect.

Amlodipine

Calcitonin gene-related peptide level in the rat dentate gyrus increases after damage.

Calcitonin gene related peptide-like immunoreactivity (CGRP-LI) was examined in rat dentate gyrus (DG) following damage to granule cells by adrenalectomy or intrahippocampal colchicine injections. In normal DG, CGRP-LI was present in a diffuse hand within the inner third of the molecular layer (ITML) and in hilar cells. Following the experimental procedures, levels of CGRP-LI increased bilaterally in the ITML and in hilar interneurons resembling mossy cells. Ultrastructural analysis of the ITML revealed that CGRP-LI is associated with large, dense-core vesicles within axon terminals which form asymmetrical synapses with dendritic spines, and within dendritic spines. The increase in CGRP-LI level following granule cell damage suggests a protective role for CGRP in the response to hippocampal injury.

Adrenalectomy

Heterogeneity in the performance of outbred Sprague-Dawley rats in an elevated-plus maze test: a possible animal model for anxiety disorder.

A wide variation in the performance of inbred rats measured in the evaluated plus maze test suggests a possible genetic basis for anxiety response (AR). To gain further insight into the role of genetics in AR, we have characterized AR in male outbred S-D rats. Rats were placed in the black compartment (BC) facing the wall opposite the aperture and time needed for the animal to exit BC was noted. All rats underwent 3 successive trials 1-1.5 hrs apart. Naive rats showed a wide variation in their AR in trial 1(mean = 89 +/- 19 sec, range = 5-360 sec). Sixty-eight% of the rats exhibiting low AR exited BC in < 30 sec, whereas 16% stayed in for the entire 360 sec (high AR). On successive testing, there was a progressive increase in AR which reached to max on second trial (Trial 1: 89 +/- 19, Trial 2: 171 +/- 23, Trial 3: 210 +/- 22 sec, p < 0.0001). The time spent in BC on successive trials increased for most rats (33/44), decreased for some (2/44), showed min to no change (5/44) or erratic response (4/44) for others. In conclusion wide variation in the AR in outbred rats could be exploited to study genetic and neurochemical mechanisms of anxiety.

Animals

Short-term consumption of a diet rich in fat decreases anxiety response in adult male rats.

Short- and long-term changes in the composition of dietary macronutrients [protein (P), carbohydrate (C), and fat (F)] alter neurochemistry and behavior in animals. We examined whether short-term intake of a diet rich in P, C, or F affected their anxiety response (AR). AR of Sprague-Dawley rats was measured in an elevated plus maze. Rats were placed in the black compartment facing the wall opposite the aperture, and the time (max. 360 s) it took to enter the white compartment with all four paws was noted. Rats were fed Purina chow and tap water unless otherwise indicated. On repeated testing (three times on the same day) AR increased and, consequently, most rats spent the entire 360 s in the dark. Whereas most rats exhibited low anxiety response in trial 1, which increased during successive trials (low-high group), some exhibited high initial anxiety that remained unchanged (high-high group). To determine whether macronutrients may alter AR, groups of low-high and high-high rats were tested three times on the same day and then put on a P, C, or F diet for 7 days. On day 8, they were again tested for AR in a single trial and the results compared with those of the third trial of the previous test (preC: 302 +/- 39, post-C: 294 +/- 42, p > 0.05; pre-P: 305 +/- 35, post-P: 297 +/- 43, p > 0.05; pre-F: 321 +/- 17, post-F: 241 +/- 24sec, p = 0.009; n = 30; mean +/- SEM). The results show that a diet rich in F, but not P or C, decreases AR in rats.

Animals

Agmatine enhances caloric intake and dietary carbohydrate preference in satiated rats.

Agmatine is a decarboxylated metabolite of arginine endogenous to the brain. In vitro, agmatine inhibits binding of clonidine to alpha 2-adrenergic and imidazoline receptors. We have shown that acute administration of agmatine increases caloric intake and dietary carbohydrate preference in satiated rats. In contrast, agmatine does not modulate caloric intake in hungry rats. Furthermore, repeated administration of high doses of agmatine does not decrease its ability to stimulate appetite.

Agmatine