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Biomedical subjects

A Prasad

Publications and source records attributed to A Prasad.

At least 109 records · Page 6Linked to original sources

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↗

Developmental expression of functional GABAA receptors containing the gamma 2 subunit in neurons derived from embryonal carcinoma (P19) cells.

The expression of the gamma 2 subunit into functional GABAA receptors has been examined in the embryonal carcinoma (EC) cell line P19, a pluripotent cell line which differentiates into a neuronal phenotype after exposure to retinoic acid. Whole-cell voltage-clamp recordings were used to examine the characteristics of the GABA receptors expressed in P19 cells at different times after exposure to retinoic acid. Messenger RNA for both the gamma 2L and gamma 2S splice variants of the GABAA receptor increased dramatically following differentiation of P19 EC cells with retinoic acid. By 12 days after retinoic acid treatment, while both mRNAs were present, there was an approximately 10-fold greater abundance of gamma 2S mRNA compared to gamma 2L. However, at this same time point neurons derived from P19 cells stained intensely with a polyclonal antibody raised against a peptide fragment specific for the gamma 2L subunit. A significant increase in both the affinity for GABA and the maximum current amplitude elicited by GABA occurred between 7 and 12 days after retinoic acid treatment. In contrast, the ability of the benzodiazepine agonist flurazepam to potentiate GABA-induced membrane current was the same at 7 and 12 days after retinoic acid treatment. These data suggest that the gamma 2 subunit of the GABAA receptor is expressed early following differentation of P19 cells into a neuronal phenotype, and that this subunit is incorporated into functional GABAA receptors. Moreover, the gamma 2S and gamma 2L splice variants of this subunit may be co-expressed in neurons derived from P19 cells. The observed affinity change for GABA may reflect a time-dependent change in the expression of alpha and/or beta subunits of the GABAA receptor, as occurs in developing neuronal tissue both in vitro and in vivo.

Amino Acid Sequence↗

Anterior sagittal anorectoplasty for anorectal malformations and perineal trauma in the female child.

Vestibular fistula and perineal ectopic anus are the most common anorectal malformations in female children. Anterior saggital anorectoplasty (ASARP) was used to treat 416 patients with these anomalies, as well as cases of perineal canal and third-degree perineal tear, during a 20 year period. Preliminary colostomy was performed in only four patients, who had a perineal tear. For ASARP, a midline incision was made and the rectum was separated from the vagina and placed in the center of the sphincteric muscle complex. The perineal body was reconstructed, and normal appearance of the perineum was achieved. Six patients had complications postoperatively (4 had secondary hemorrhage, 2 had wound infection). One patient with hemorrhage and one with infection required laying open of the wound and revision surgery after 12 weeks. Both recovered well. Of the 416 patients, 397 returned for follow-up 12 weeks after the surgery. Of these, 390 had a normal-looking perineum and normal defecation. Of the remaining seven patients, three had retraction of the rectum, one had recurrence of the fistula, and another had acquired perineal canal. These five children required revision ASARP and recovered successfully. The other two patients had mucosal prolapse, which reduced spontaneously. Three hundred twenty-six children of the 416 patients have had follow-up beyond the age of 3 years. Of these, 291 had normal bowel habits without the use of laxatives. Of the other 35, four had fecal impaction of unknown etiology, which was managed conservatively, 6 had anal stenosis (four underwent posterior Barrow's flap interposition and two responded to dilatation), and 25 had a posterior ledge that caused constipation and required cutback. Overall, eight patients (1.9%) required revision ASARP and 40 others (9.8%) had minor complications. This operation provides consistently good results, and the authors recommend it for the management of anorectal malformations and perineal trauma in female children.

Adolescent↗

Electron microscopic examination of skin biopsy as a cost-effective tool in the diagnosis of lysosomal storage diseases.

In this report, we have summarized our 9-year experience of over 100 proven cases of lysosomal storage disease using electron microscopic evaluation of skin biopsies as a screening tool. The skin biopsy was very specific in establishing the diagnosis in only two disorders, namely neuronal ceroid lipofuscinosis and mucolipidosis IV. Although the biopsy was not diagnostic in other categories of storage diseases, it proved to be highly sensitive and provided valuable clues to direct further investigations on the basis of morphologic appearance of stored material and the cell type affected. Only in two cases of biochemically proven lysosomal storage disease was the morphologic diagnosis unable to be confirmed. We have compared the cost of screening for storage disorders using skin biopsy with the cost of performing multiple lysosomal enzyme assays. Our findings indicate that the skin biopsy, although more expensive than a single enzyme assay, provides an efficient, rapid, cost-effective tool to screen for more than 35 lysosomal storage disorders.

Biopsy↗

Day case laparoscopic cholecystectomy: a safe and cost effective procedure.

OBJECTIVE: To evaluate the safety and cost effectiveness of laparoscopic cholecystectomy as a day case procedure. SETTING: District hospital, England. SUBJECTS: 103 patients undergoing laparoscopic cholecystectomy. INTERVENTIONS: Laparoscopic cholecystectomy by a standard four cannula technique. Propofol anaesthesia, prophylactic antiemetics and pre-emptive analgesia were given in all cases. MAIN OUTCOME MEASURES: Morbidity and cost. RESULTS: 103 patients have undergone laparoscopic cholecystectomy, 51 of them as day cases. Patients were selected for day treatment if they were under 60 years old, they wanted to go home the same day, they had no history of jaundice or any anaesthetic contraindication, and if there was an adult at home to look after them. Three of those selected as day cases required overnight admission, one because of severe pain and two who required a drain overnight. The median hospital stay was 12 hours (range 10-28 hours) and the cost of the operation was about pounds 419. CONCLUSION: This is a safe and cost-effective procedure and should be considered in selected patients.

Adult↗

Augmentation of dietary fat preference by chronic, but not acute, hypercorticosteronemia.

Numerous studies have documented a role for corticosterone in appetitive behavior, including caloric intake and dietary fat preference. In the present study, we have examined the mechanism(s) underlying modulation of dietary fat preference by corticosterone. The results of these studies show a) an increased fat preference with increased basal urinary output, or decreased stimulation of corticosterone output on fasting, b) elevation of fat preference following chronic, but not acute, hypercorticosteronemia produced by exogenous corticosterone administration, and c) emergence of hypercorticosteronemia prior to the development of increased fat preference in developing rats. These observations have led us to suggest that increased fat preference after chronic hypercorticosteronemia may be secondary to changes in the levels or actions of agents known to affect fat intake.

Animals↗

Agmatine: a novel endogenous vasodilator substance.

The purpose of the study was to investigate the effects of agmatine, an endogenous clonidine-displacing substance (CDS), on systemic hemodynamics in the anesthetized rat. Bolus intravenous (i.v.) injections of agmatine decreased systemic arterial pressure (SAP) and systemic vascular resistance in a dose-dependent manner. The development of acute tachyphylaxis to the systemic vasodepressor response to agmatine did not induce cross-tachyphylaxis to the systemic vasodepressor responses to bradykinin, isoproterenol and nitroglycerin. The present data demonstrate agmatine, as a CDS and agonist for imidazoline (I) receptors, possesses marked systemic vasodilator activity in the rat. The present data suggest that activation of I receptors may represent a novel mechanism of vasodilation in vivo.

Agmatine↗

Capillary rarefaction in the forearm skin in essential hypertension.

OBJECTIVE: To determine whether there is a reduction in human forearm skin capillary density in essential hypertension. SUBJECTS AND METHODS: We compared the number of capillary loops in the forearm skin of 12 patients with established, uncomplicated essential hypertension (mean blood pressure 180/109 mmHg) with that in carefully matched control subjects, using intravital capillaroscopy and fluorescein angiography. RESULTS: There was a significant reduction in forearm skin capillary density in the hypertensive patients compared with the normotensive subjects. This represents a reduction by approximately 20% in capillary density. Capillary density was inversely correlated with blood pressure in the hypertensive patients alone (r = -0.4, P < 0.05) and in the whole group. CONCLUSION: The present study demonstrates a reduction in capillary density in the forearm of patients with essential hypertension. If this rarefaction in the forearm is also present in other vascular beds, it could result in an approximately 20% increase in peripheral resistance, which might play an important additional role in determining blood pressure.

Adult↗

Exacerbation of groin hernias after laparoscopy.

The incidence of pneumoperitoneum-related complications of laparoscopy is quite low. The more common complications are due to improper placement of the needle during insufflation and those related to the cardiorespiratory system. We describe two cases who underwent prolonged laparoscopic surgery and presented postoperatively with hernia.

Aged↗