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Biomedical subjects

C Prasad

Publications and source records attributed to C Prasad.

At least 55 records · Page 3Linked to original sources

Limb anomalies in DiGeorge and CHARGE syndromes.

Limb anomalies are not common in the DiGeorge or CHARGE syndromes. We describe limb anomalies in two children, one with DiGeorge and the other with CHARGE syndrome. Our first patient had a bifid left thumb, Tetralogy of Fallot, absent thymus, right facial palsy, and a reduced number of T-cells. A deletion of 22q11 was detected by fluorescence in situ hybridization (FISH). The second patient, with CHARGE syndrome, had asymmetric findings that included right fifth finger clinodactyly, camptodactyly, tibial hemimelia and dimpling, and severe club-foot. The expanded spectrum of the DiGeorge and CHARGE syndromes includes limb anomalies.

Abnormalities, Multiple↗

Cyclo(His-Pro) augments the insulin response to oral glucose in rats.

Cyclo(His-Pro) (CHP) is a gut-brain peptide found in rat and man. Since plasma levels of CHP are altered by oral glucose ingestion, we wondered whether exogenous CHP might alter the insulin response to oral glucose ingestion. To this end, rats were given 3g/kg oral glucose load with either saline or increasing doses of CHP and plasma levels of insulin, C-peptide and glucose were measured. We found mean insulin but not C-peptide excursions and area under the insulin but not C-peptide response curves (AUC) were significantly higher in the CHP groups than controls despite similar glucose responses. In summary, these data show that in rats receiving oral glucose, CHP causes higher insulin excursions without any change in C-peptide suggesting that CHP may decrease hepatic insulin clearance.

Administration, Oral↗

Caloric intake and weight gain of rats depends on endogenous fat preference.

Within outbred colonies, subpopulations of rats exist that exhibit inherent preferences for one type of macronutrient over another (e.g., fat vs. carbohydrate). Prior investigations into the effect of dietary manipulations on consumption or weight gain have not taken into account endogenous macronutrient preferences. The purpose of this study was to examine whether inherent fat preferences translate into differences in caloric consumption and weight gain in rats when fed high-fat and high-carbohydrate diets. Rats that exhibited a preference for fat were identified using a previously described paradigm and were subsequently placed on either a high-fat or high-carbohydrate diet. Daily caloric intakes and weekly weights were monitored over a 28-day period and compared with data for animals with a low-fat preference on the same diets. By the conclusion of the study, the low-fat-preferring rats on the high-carbohydrate diet had consumed significantly more calories than the high-fat-preferrers maintained on the same diet. In contrast, the amounts of calories consumed on the high-fat diet were not significantly different between the low- and high-fat-preferring animals. Those animals with a preference for fat placed on a high-carbohydrate diet weighed significantly less by the end of study, even though they consumed the same number of calories as animals on the high-fat diet. We conclude that the outcome of nutritional studies designed to examine caloric intake and weight gain can be influenced by the innate macronutrient preference of the animal.

Animals↗

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↗

Cyclo (His-Pro) modulation of body temperature at hot ambient temperature in the desert rat (Mastomys natalensis).

Cyclo(His-Pro) (CHP) has been shown to facilitate cold-induced hypothermia in the desert rat Mastomys natalensis. In the present study, we examined the role of endogenous CHP in hyperthermia induced by hot ambient temperature (40 degrees C) in the above rodent species. The results of these studies show that housing rodents at 40 degrees C resulted in a altered distribution of CHP in the brain, with a rise in hypothalamic content accompanied by an increase in rectal temperature. While administration of exogenous CHP decreased hyperthermia, immunoneutralization of endogenous CHP increased hyperthermia. The results of these studies show that changes in endogenous CHP levels may affect body temperature regulation.

Animals↗

Elevated serum levels of cyclo (His-Pro), an endogenous inhibitor of pituitary prolactin secretion, in systemic lupus erythematosus patients.

Cyclo (His-Pro) or CHP is a cyclic dipeptide that is known to elicit many biologic activities including inhibition of pituitary prolactin (PRL) secretion. PRL stimulates humoral and cell mediated immune responses and hyperprolactinemia has been found in a subset of systemic lupus erythematosus (SLE) patients in association with active disease. To explore whether CHP may play a role in SLE patients, we measured, CHP and PRL levels in sera of 21 SLE patients and 11 normal controls. The results of this study show significantly (P < 0.001) high levels of CHP in SLE compared to controls. However, there was no significant correlation between serum PRL and CHP levels in SLE patients (r = 0.027, P = 0.29). The increase in serum levels of CHP may be in an attempt to increase hypothalamic content of dopamine which in turn would decrease pituitary PRL synthesis in hyperprolactinemic SLE patients.

Adult↗

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↗

The bioactive peptide cyclo(His-Pro) may be absorbed following ingestion of nutritional supplements that contain it.

OBJECTIVE: Food contains a number of peptides with potential bioactivity. We previously found ng/mliter to mcg/mliter quantities of cyclo(His-Pro)-like immunoreactivity in a number of foods and nutritional supplements. A number of activities have been attributed to cyclo(His-Pro) (CHP), including appetite inhibition and inhibition of insulin secretion in vitro. We wondered whether the cyclo(His-Pro)-like immunoreactivity present in nutritional supplements might be absorbed and, if so, whether parameters of insulin secretion would be altered. METHODS: After performing a pilot study which suggested some common nutritional supplements contain CHP, a follow-up study was done to confirm and expand the findings of the pilot study. Eight fasting volunteers ingested approximately 250 mL of a CHP-containing supplement one day, and then an equienergetic CHP-free supplement the next. RESULTS: Blood drawn for CHP, insulin, glucose, and C-peptide a number of times on both days revealed that when volunteers ingested CHP-containing supplements, CHP levels at 120 minutes were significantly higher than baseline (7.69 +/- 0.50 pmol/mL vs. 9.18 +/- 0.48 pmol/mL; p = 0.011 in the CHP group and 7.90 +/- 0.85 pmol/mL vs. 7.22 +/- 0.73 pmol/mL, p > 0.3 in the CHP-free group) and significantly higher than levels achieved when they drank CHP-free supplements. Levels of glucose, insulin, and C-peptide were not different in the two groups. CONCLUSION: CHP in nutritional supplements may be absorbed when ingested orally and does not grossly affect glucose or parameters of insulin secretion.

Absorption↗

A paradoxical elevation of brain cyclo(His-Pro) levels in hyperphagic obese Zucker rats.

Several studies suggest a role for endogenous cyclo(His-Pro) or CHP in appetite regulation. In the present study, we have examined the regional brain distribution of CHP in hyperphagic obese Zucker rats and their lean littermates. The data show a significant elevation in the levels of CHP in many brain regions, including hypothalamus of the obese rat. Within the hypothalamus, the lateral hypothalamic (LH) nucleus of obese rats had significantly higher levels of CHP when compared to that of the lean littermates. Administration of dehydroepiandrosterone, a steroid hormone known to decrease food intake and body weight gain, to obese rats led to decrease in the levels of CHP in the LH. These data further suggest a role for the endogenous CHP in attenuating food intake.

Animals↗

Biology of enterostatin. II. Development of enzyme-linked immunosorbentassay (ELISA) for enterostatin (Val-Pro-Asp-Pro-Arg), the procolipase activation peptide.

Enterostatins belong to a family of pentapeptides (e.g., Val-Pro-Asp-Pro-Arg in pig, horse, dog, and rat; Ala-Pro-Gly-Pro-Arg in human and chicken; and Val-Pro-Gly-Pro-Arg in rat) derived from the amino-terminus of procolipase after the action of trypsin. Pharmacologic studies with Val-Pro-Asp-Pro-Arg have suggested a role for this peptide in appetite regulation and pancreatic insulin secretion. Studies into the distribution of enterostatins or the role of endogenous peptides have not been possible due to the lack of a suitable method for enterostatin assay. To this end, we raised a highly specific antibody and developed an enzyme-linked immunosorbent assay for Val-Pro-Asp-Pro-Arg. Using the newly developed assay we have shown the presence of Val-Pro-Asp-Pro-Arg-like immunoreactivity (2455 +/- 440 pmol/g) in the rat brain.

Amino Acid Sequence↗

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↗

Occurrence of haemagglutination-inhibition antibodies against egg drop syndrome 1976 virus in broilers.

From a total of 22 broiler flocks 347 serum samples were screened by the haemagglutination inhibition (HI) test and 114 (32.9%) were positive for antibodies to egg drop syndrome 1976 (EDS'76). The HI titres of the serum samples ranged from 2 to 9 log2 and the overall geometric mean titre was 3.9 log2. Of the serum samples 82.5% showed HI titres between 2(2) to 2(5) and the most frequent titre was 2(3). All the flocks were positive and the flock prevalence of HI antibodies ranged from 13.3 to 46.6 per cent. The age distribution of HI antibodies and their titres have also been recorded. The widespread prevalence of EDS'76 virus infection in broilers and its likely significance are discussed.

Adenoviridae↗

Epididymal fat depot lipoprotein lipase activity is lower in animals with high endogenous fat preferences.

Adipose tissue lipoprotein lipase (LPL) is a key enzyme responsible for the clearance of circulating triglycerides and has been linked to certain pathologic states such as obesity. In order to investigate whether an animal's endogenous fat-preference is associated with differences in adipose tissue LPL, we measured enzyme activity in epididymal fat from high- and low-fat preferring rats. Utilizing a 24h ad libitum feeding paradigm, four groups of outbred adult male Sprague-Dawley rats were screened separately for their macronutrient preferences. Animals exhibiting high- or low-fat preferences were identified and placed back on standard chow. LPL activity was measured in epididymal fat under chow fed or fasted conditions. Epididymal fat LPL activity was significantly less in the high-fat-preferring animals relative to the low-fat-preferring, in both the standard chow-fed state (p = 0.014) and fasted (p = 0.0007) state. LPL activity in heart ventricle and brown adipose tissue was also measured from the same animals. Activity in heart ventricle and brown adipose tissue was significantly lower in the high-fat-preferring group as compared with the low-fat-preferring only following a 24h fast (p = 0.0012 for heart and p = 0.0085 for brown adipose, high- versus low-fat preferring). The data indicate that differences in tissue LPL activity exist between animals with inherent differences in fat preference. Future comparative studies between the two groups of fat-preferring animals could lead to important clues to the regulation of the LPL.

Animals↗

REM sleep deprivation alters dopamine D2 receptor binding in the rat frontal cortex.

REM sleep deprivation (RSD) of rats results in facilitation of dopaminergic behavior and an increase in striatal D2 receptor density. To determine whether RSD results in changes in D2 receptor in other brain regions, receptor affinity (Kd) and density (Bmax) were measured in the anteromediofrontal (AM), cingulate (CN), and sulcal cortex (SL) in four groups of rats: 1), RSD96 group (RSD for 96 h; small pedestal/water tank method), 2) RSD24 group (large pedestals for 72 h then small pedestals for 24 h), 3) tank control group (TC; large pedestals for 96 h), and 4) cage control group. In separate groups, ambulation was recorded for 30 min following treatments. Group RSD96 showed an increase in activity compared to TC, and TC was increased compared to CC (p < 0.05 for all). In group RSD24, the AM showed an increase in Bmax and Kd (p < 0.05), but there were no effects by RSD96. In the CN, Bmax and Kd were decreased by RSD96 (p < 0.05) but not RSD24. In the SL, Bmax was increased by RSD96, but not RSD24, whereas Kd was increased in both RSD groups (p < 0.05).

Animals↗

Attenuation of alcohol-induced hypothermia by cyclo (His-Pro) and its analogs.

Acute administration of cyclo (His-Pro) to rats cause a dose-dependent decrease in ethanol-induced hypothermia. Bromination of the imidazole moiety of histidine in cyclo (His-Pro) resulted in a significant increase in its potency to attenuate ethanol hypothermia. In contrast, benzylation of the imidazole moiety of histidine or the substitution of one or both of the amino acids in cyclo(His-Pro) led to a total loss of its thermomodulatory activity. In conclusion, it appears from these preliminary data that it may be possible to design analogs of CHP that may be effective antagonists for ethanol hypothermia.

Animals↗

Bioactive cyclic dipeptides.

Cyclic dipeptides are among the simplest peptide derivatives commonly found in nature. Most cyclic dipeptides found to date appear to have emerged as by-products of fermentation and food processing. However, many are endogenous to members of animal and plant kingdoms; these include cyclo(Pro-Leu), cyclo(Pro-Val), cyclo(Pro-Phe), cyclo(Ala-Leu), cyclo(Pro-Tyr), cyclo(Pro-Trp), and cyclo(His-Pro). Although the five cyclic dipeptides--cyclo(His-Pro), cyclo(Leu-Gly), cyclo(Tyr-Arg), cyclo(Asp-Pro), and cyclo(Pro-Phe)--exhibit interesting physiological and/or pharmacological activities in mammals, only one of these, cyclo(His-Pro), has been conclusively shown to be endogenous to mammals. On the other hand, cyclo(Leu-Gly), cyclo(Tyr-Arg), and cyclo(Asp-Pro) are structurally related to endogenous peptides Pro-Leu-Gly-NH2 (melanocyte-stimulating hormone release inhibiting factor), Tyr-Arg (kyotorphin), and Val-Pro-Asp-Pro-Arg (enterostatin), respectively, which may serve as precursor peptides. It needs to be determined, however, whether these peptides can indeed result from the processing of their respective precursors. In conclusion, it appears that cyclic dipeptides are a relatively unexplored class of bioactive peptides that may hold great promise for the future.

Animals↗