Search PubMed⌕ Search

Biomedical subjects

C Prasad

Publications and source records attributed to C Prasad.

At least 109 records · Page 6Linked to original sources

Change in circulating cyclo(His-Pro) concentrations in rats after ingestion of oral glucose compared to intravenous glucose and controls.

Changes in circulating cyclo(His-Pro) (CHP) levels after ingestion of 0.5 g/kg of glucose (oral) were measured in 32 Sprague Dawley rats at varying time points between 0 (before glucose) and 60 minutes. Each rat provided one time point. CHP levels displayed a biphasic response rising from 933 +/- 56 pg/ml to 1083 +/- 287 pg/ml (p greater than 0.05), followed by a fall to 543 +/- 46 pg/ml (p = 0.002) and then a recovery to near baseline values. To further investigate this response, a separate group of rats were sampled sequentially after 3 g/kg oral glucose (n = 7), 0.6 g/kg I.V. glucose (n = 6) or controls given saline only (n = 14). CHP levels were significantly elevated in the oral glucose group at 5 (p = 0.048) and 12 (p = 0.02) minutes compared to controls, while the i.v. glucose group was not statistically different from controls. Comparison of the mean of the highest incremental response to baseline values in each group revealed a greater excursion in CHP levels after oral (p = 0.027) glucose than after I.V. (p = 0.08) glucose. These data suggest CHP is acutely and reversibly elevated after glucose ingestion in rats and that the response is greater after oral glucose than after i.v. glucose.

Administration, Oral↗

Isolation of cyclo(His-Pro)-like immunoreactivity from human urine and demonstration of its immunologic, pharmacologic, and physico-chemical identity with the synthetic peptide.

Measurements of cyclo(His-Pro) levels in human urine were carried out by specific radioimmunoassay. Cyclo(His-Pro)-like immunoreactivity in Human urine was found to be immunologically, pharmacologically, and physico-chemically identical to that of synthetic cyclo(His-Pro). The concentration of urinary cyclo(His-Pro) in 24-h collection was 1133.8 +/- 122.5 nmol/L, with a range of 606 to 1865 nmol/L. The daily excretion rate of cyclo(His-Pro) was 1812 +/- 248 nmol cyclo(His-Pro)/g creatinine, or 1814 +/- 199 nmol cyclo(His-Pro/day.

Adult↗

Chronic thyrotropin-releasing hormone decreases the affinity and increases the number of its own receptor in the spinal cord.

Effect of chronic thyrotropin-releasing hormone (TRH) treatment on the properties of spinal cord TRH-receptor was evaluated by Scatchard analysis of data on the saturation of specific binding of [methyl-His3-3H]TRH. Continuous subcutaneous administration of TRH (0.51 +/- 0.02 mg/kg/day) via an Alzetmini osmotic pump for ten days led to a substantial increase in both Bmax (control: 20.0 +/- 2.9, treated: 36.1 +/- 2.8 fmol/mg protein, P = 0.0018) and Kd (control: 7.6 +/- 0.8 treated: 11.7 +/- 1.8 nM, P = 0.0349) of the binding sites. These data suggest that chronic TRH treatment may not induce desensitization of physiologic/pharmacologic responses of TRH in the spinal cord.

Animals↗

Postnatal development of the spinal cord thyrotropin-releasing hormone receptor in male and female rats.

The density of the spinal cord thyrotropin-releasing hormone (TRH) receptor in male and female rats was measured during postnatal development. The younger rats of both sexes (11-16 days old) exhibited higher levels of TRH-binding than did adults. A comparison of the properties of receptor binding for young and adult spinal cords showed that the increased binding resulted solely from an increase in maximum binding capacity rather than a change in receptor affinity. Furthermore, no sex-dependent difference in the receptor property was found at any stage of development. In conclusion, these findings demonstrate that the differences in the maturation of TRH receptor itself may not be the cause of known gender-specific differences in the physiologic actions of TRH in the spinal cord of young rats.

Aging↗

Chronic nicotine use blocks haloperidol-induced increase in striatal D2-dopamine receptor density.

Epidemiologic studies have suggested a positive association in man between nicotine use and the incidence of tardive dyskinesia, a disease characterized by dopaminergic supersensitivity after chronic neuroleptic therapy. In rats, repeated administration of neuroleptics results into dopaminergic supersensitivity and increased density of striatal D2-dopamine receptors. We investigated the effects of 6-week continuous nicotine intake on the neuroleptic (haloperidol)-induced increase in murine striatal D2-dopamine receptor density. Contrary to expectations, our data show that nicotine blocked the increase in D2-dopamine receptor density after neuroleptic administration.

Animals↗

Radioimmunoassay of cyclo(His-Pro) in unextracted human plasma: report of a normal range and definition of factors critical for successful assay.

A radioimmunoassay for cyclo(His-Pro) (CHP) in unextracted human plasma that can detect 40 pg has been developed. Elution profile of CHP-like immunoreactivity (CHP-LI) corresponded precisely to those of [3H] cyclo(His-Pro) by both high pressure liquid chromatography and Sephadex G-25 column chromatography. In addition plasma CHP-LI exhibited close immunoidentity with authentic CHP. Charcoal treatment of plasma containing [3H] cyclo(His-Pro) resulted in loss of both CHP-LI and [3H] cyclo(His-Pro) activity. Plasma frozen at draw and assayed at 0, 6 and 24 hours displayed no change in CHP-LI while an aliquot from the same sample maintained at 4 degrees C and assayed at the same time intervals showed a 50% rise (0 hrs-856 +/- 47 pg/ml; 24 hrs-1288 +/- 85 pg/ml) (+/- SE) over 24 hours. In addition, plasma drawn from 14 volunteers and immediately frozen until assay yielded a mean CHP value of 829 +/- 64 pg/ml (+/- SE) while that of 14 volunteers that was maintained at 25 degrees C for 90 minutes was significantly higher at 1085 +/- 34 pg/ml (+/- SE) (p less than 0.03). Taken together, these data suggest that CHP can be easily measured in a direct RIA of human plasma, however, failure to maintain the sample frozen from the time of draw until assay may yield spuriously elevated values.

Adult↗

Histidyl proline diketopiperazine (Cyclo [His-Pro]) in eating disorders.

The authors explored the role of Cyclo [His-Pro] (CHP) in 50 adolescents who fulfilled DSM III diagnostic criteria for anorexia nervosa and bulimia. CHP, a relatively new neuro modulator which has a role in inducing satiety, was assayed in serum during routine blood work. CHP levels correlated significantly with weight in restrictor (AN-R) (R = -0.449, P less than 0.05) and bulimic anorexics (AN-B) (R = +0.489, P less than 0.01). There was no significant correlation in normal-weight bulimics (NWB) (R = +0.556, P less than 0.01). It did not correlate with weight in a depressed control group. Longitudinal data on six patients showed a similar relationship between weight, purging and CHP binge/purge activity and/or weight changes of around 2 kilograms correlated with average CHP changes of 42%. Clinical material suggests changes in satiety during CHP changes consistent with a satiety disturbance model of these disorders.

Adolescent↗

TRH analog administration increases endogenous TRH levels in the central nervous system.

Experiments were carried out to increase the endogenous levels of TRH in brain and spinal cord. After 7 days of continuous oral ingestion of TRH analogs (D-pGlu-Leu-ProNH2, pGlu-Leu-Pro, pGlu-Pro-ProNH2, or pGlu-Leu-pyrrolidide), spinal cord and brain levels of TRH were elevated, whereas the content of TRH metabolite, cyclo(His-Pro), was decreased. In addition, the TRH analogs inhibited in vitro metabolism of [3H-Pro]-TRH by brain and spinal cord extracts. Our data show that certain TRH analogs can elevate tissue levels of TRH by inhibiting its metabolism. Furthermore, because these analogs do not affect interaction between TRH and its receptor, the elevated TRH can effectively enhance TRH-related bioactivity.

Animals↗

One-year continuous low-dose nicotine intake does not alter body weight of rats.

An accelerated loss of dopaminergic neurons with advancing age leads to Parkinson's disease. The incidence of this disease is suggested to be lower in nicotine users. As the body ages, the number of dopamine receptors in the striatum decrease, an effect that has been shown to be slowed by reduction in body weight via dietary manipulations. To investigate the potential role of nicotine in aging of dopaminergic neurons, therefore, using a dose of nicotine that has no effect on body weight becomes essential. The results presented here show that administration at up to 1.0 mg% nicotinewater to rats for one year does not alter their body weight.

Administration, Oral↗

Distribution pattern of cell bodies and fibers with neurotensin-like immunoreactivity in the cat hypothalamus.

Neurotensin is widely distributed in the central and peripheral nervous systems. Extensive radioimmunoassay and immunohistochemical studies in rats show that the neurotensin immunoreactive perikarya and fibers are most prominent in the hypothalamus. Radioimmunoassay studies have suggested that the levels of neurotensin in the hypothalamus of cats may be six times higher than that of rats. We studied the distribution pattern of neurotensin immunoreactivity within the hypothalamus of the cat by avidin-biotin modification immunohistochemical methods: (1) to define its distribution pattern within the hypothalamus, and (2) to compare our findings with the patterns that have been described in rats. Results show that neurotensin immunoreactive cell bodies and fibers are most prominent in the rostral and intermediate regions of the cat hypothalamus. Cell bodies with neurotensin-like immunoreactivity are seen maximally in the medial preoptic region, the infundibular nucleus, and the lateral hypothalamus. The neurotensin positive fibers are dense in the periventricular regions of the entire rostro-caudal extent of the hypothalamus. This pattern of distribution of neurotensin immunoreactivity is similar to that described in rats. The suprachiasmatic nuclei of the cat hypothalamus, however, contained a significant number of neurotensin immunoreactive cell bodies, an observation not noted in the rat hypothalamus. The neurotensin immunoreactive neurons were more numerous in the lateral hypothalamus than has been reported in rats, but the paraventricular nucleus of the hypothalamus in cats contained fewer neurotensin immunoreactive perikarya. The presence of neurotensin immunoreactive perikarya in the suprachiasmatic nucleus and the apparent increase in the number of neurotensin immunoreactive neurons in the lateral hypothalamus may account for the increased levels of neurotensin reported in cats. Neurotensin has been speculated to play a role in nociception, thermoregulation, and control of arterial pressure by acting as a hormone or a neurotransmitter. Details of the pattern of colocalization of neurotensin with that of other neuropeptides and neurotransmitters will aid in our understanding of its role in these functions.

Animals↗

Neuropeptide-dopamine interactions. II. Cyclo (His-Pro) augmentation of amphetamine- but not apomorphine-induced stereotypic behavior.

Histidyl-proline diketopiperazine (cyclo [His-Pro]) not only exists in the basal ganglia of rodents, monkeys, and humans, but also exhibits a variety of biologic activities, some of which appear to be mediated via dopaminergic mechanisms. We investigated the potential modulation by cyclo (His-Pro) of amphetamine- and apomorphine-induced stereotypic behavior, a behavior that is associated with the activation of postsynaptic dopamine receptor. Administration of amphetamine to rats resulted in a dose-dependent increase in stereotypic behavior that was further augmented if animals were pretreated with cyclo (His-Pro). Although apomorphine also led to a dose-related progression in the stereotypic behavior, the apomorphine effects were not modified by cyclo (His-Pro) pretreatment. We conclude that cyclo (His-Pro) either acts indirectly at the presynaptic dopamine site or modulates other neurotransmitters to potentiate actions of amphetamine.

Amphetamine↗

Cyclo(His-Pro): its distribution, origin and function in the human.

Cyclo(His-Pro), or histidyl-proline diketopiperazine, is a cyclic dipeptide endogenous to blood, cerebrospinal fluid (CSF), semen, brain, spinal cord, and gastrointestinal tract of humans. Although a part of cyclo(His-Pro) clearly appears to be derived from the limited proteolysis of thyrotropin-releasing hormone by Pyroglutamate aminopeptidase, the biosynthetic origin of the remainder of the peptide can only be speculated. The levels of this peptide in blood and CSF fluctuate in health and disease in a manner appropriate for a physiologically active endogenous molecule.

Central Nervous System↗

Adrenal insufficiency in the acquired immunodeficiency syndrome.

Patients with the acquired immunodeficiency syndrome (AIDS) often have signs and symptoms suggestive of adrenal insufficiency. Reports in the literature suggest that adrenal insufficiency may be relatively common in patients with AIDS based on the finding of destructive adrenal lesions in a large number of the patients studied. In no series, however, has standard testing for adrenal reserve been done in an unselected population of patients with AIDS. We found a normal response to a standard, short adrenocorticotropic hormone test in 11 consecutive patients with AIDS (P less than .0005). Thus, although adrenal involvement by various destructive lesions may be common in patients with AIDS, clinically significant adrenal insufficiency does not appear to be common.

Acquired Immunodeficiency Syndrome↗

Thyrotropin-releasing hormone and cyclo (His-Pro)-like immunoreactivities in the cerebrospinal fluids of 'normal' infants and adults, and patients with various neuropsychiatric and neurologic disorders.

Levels of thyrotropin-releasing hormone (TRH) - and cyclo(His-Pro) (CHP)-like immunoreactivities and the activity of enzyme Pyroglutamate aminopeptidase (PAPase) were measured in cerebrospinal fluid (CSF) of over 100 normal adults (NA) and infants, and adult patients with various neurologic and neuropsychiatric disorders (NNDA). Levels of TRH and CHP in CSF of over 70% of the NA group were below 50 and 500 pg/ml respectively. The TRH- and CHP-like immunoreactivities in the remainder of the 30% of NA specimens exhibiting higher peptide concentrations were enzymatically and chromatographically characterized and were found to behave like authentic peptides. The levels of both of these peptides were significantly elevated in the CSF of most of the NNDA patients. An elevation in the CSF level of CHP was significantly correlated with the level of TRH, but not PAPase. Results from this study suggest that CSF elevation of TRH level may be due to a nonspecific response to stress that may be associated with hospitalization, myelogram procedure, and/or the neurologic and neuropsychiatric diseases for which the patients were admitted.

Adult↗

Is all cyclo(His-Pro) derived from thyrotropin-releasing hormone?

Cyclo(His-Pro), or histidyl-proline diketopiperazine, is an endogenous cyclic dipeptide that is ubiquitously distributed in tissues and body fluids of both man and animals. This cyclic dipeptide is not only structurally related to thyrotropin-releasing hormone (TRH, pGlu-His-ProNH2), but it can also arise from TRH by the action of the enzyme pyroglutamate amino-peptidase (pGlu-peptidase). The data on the distribution of TRH, cyclo(His-Pro), and pGlu-peptidase under normal and abnormal conditions are summarized and potential relationships analyzed. We conclude that all of the cyclo(His-Pro) cannot be derived from TRH. Two additional sources of cyclo(His-Pro) are suggested. It is proposed that 29,247 molecular weight TRH prohormone, prepro TRH, which contains 5 copies of TRH sequence, can be processed to yield cyclo(His-Pro). Thus, both TRH and cyclo(His-Pro) share a common precursor, prepro[TRH/Cyclo(His-Pro)].

Animals↗