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Biomedical subjects

S Iyengar

Publications and source records attributed to S Iyengar.

At least 109 records · Page 6Linked to original sources
PubMed1989

Genetic studies of type 2 (non-insulin-dependent) diabetes mellitus: lack of association with seven genetic markers.

Type 2 (non-insulin-dependent) diabetes mellitus, a disease of complex aetiology, has been reported to be nonrandomly associated with several polymorphic markers in human populations. These data, plus evidence of a high prevalence of Type 2 diabetes mellitus in American Indians and mixed populations, such as Mexican-Americans, which is only partially attributable to the prevalence of obesity in these populations, makes it imperative that the nature of such associations be clarified in relation to genetic susceptibility to Type 2 diabetes mellitus. The present paper reports the results of tests of association between Type 2 diabetes mellitus and seven polymorphic markers: the blood groups - ABO, Rhesus, Duffy and Kell (K and KP) - haptoglobin and group specific component; among Anglo and Hispanic populations in the San Luis Valley of Colorado, USA. The sample population consisted of 788 individuals of which 398 were Anglo subjects (97 Types 2 diabetes mellitus patients and 301 normal individuals) and 390 Hispanic subjects (191 Type 2 diabetes mellitus patients and 199 normal individuals). Association between Type 2 diabetes mellitus and genetic markers in patients was tested using the G2 statistic within each ethnic class using normal frequencies as a comparison. Results of the tests indicated that only the Kell blood group was significantly associated with Type 2 diabetes mellitus at a 5% level among the Anglo subjects (G2 = 5.16, 1df). This significant value can be explained by chance alone, if multiple comparisons are taken into account. Our tests have not shown the previously reported haptoglobin or Rhesus blood group associations seen in Mexican-Americans in San Antonio, Texas.

Blood Group Antigens↗
PubMed1989

Modulation of mesolimbic dopaminergic projections by beta-endorphin in the rat.

Intracerebroventricular injection of beta-endorphin stimulated the metabolism of dopamine in a dose-dependent, opiate antagonist-reversible manner. Local injections into the nucleus accumbens also caused similar increases, indicating that the actions of this peptide on mesolimbic dopaminergic projections were occurring at opioid receptor sites within the nucleus accumbens. Tolerance experiments suggested that epsilon opioid receptors may be involved in mediating these effects in the n. accumbens, unlike in the striatum.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1989

The dopamine autoreceptor agonist, (+/-)-trans-1,3,4,4a5,10b-hexahydro-4-propyl-2H [1]benzopyrano [3,4-b] pyridin-9-ol hydrochloride (CGS 15855A), modulates striatal dopamine metabolism and prolactin release.

The effects of apomorphine and the putative dopamine autoreceptor agonist, CGS 15855A, were evaluated in several functional assays that are modulated by pre- or post-synaptic D2 receptors. These included release of prolactin in vivo and in vitro from cultured lactotrophs; levels of dihydroxyphenylacetic acid (DOPAC) in the striatum; levels of acetylcholine (ACh); in the striatum and concentrations of cyclic guanosine monophosphate (cyclic GMP) in the cerebellum. The secretion of prolactin was inhibited by CGS 15855A in vitro and in vivo and which also decreased the levels of DOPAC in the striatum at doses 5-25 times less than those required to increase ACh in the striatum and levels of cGMP in the cerebellum. In contrast, apomorphine possessed a dose-ratio between 1.5 and 8.6 for these assay systems. These data suggest that CGS 15855A is a selective dopamine autoreceptor agonist which preferentially stimulates D2 receptors on lactotrophs and dopaminergic neurons as compared to D2 receptors on cholinergic interneurons in the striatum.

Animals↗
PubMed1989

In vivo modulation of the N-methyl-D-aspartate receptor complex by D-serine: potentiation of ongoing neuronal activity as evidenced by increased cerebellar cyclic GMP.

Direct intracerebellar injections of N-methyl-D-aspartate (NMDA) or D-serine elicited dose-dependent increases in cerebellar cyclic GMP levels, in vivo in the mouse. The actions of D-serine were antagonized by the competitive NMDA receptor antagonist 3-(2-carboxypiperazin-4-yl) propyl-1-phosphonic acid and by the phencyclidine receptor agonist MK-801, observations supporting actions at the NMDA-coupled glycine receptor. In addition, the actions of D-serine were antagonized by a partial agonist (D-cycloserine) and an antagonist (HA-966) of the NMDA-coupled glycine receptor. These data are all consistent with D-serine acting at the NMDA-coupled glycine receptor and represent the first demonstration of glycine receptor potentiation of ongoing NMDA-mediated neuronal activity in the CNS, rather than potentiation of exogenous NMDA.

Animals↗
PubMed1988

Estimating the age-at-onset function using life-table methods.

In the analysis of dominantly inherited diseases, the age-at-onset function is often estimated from the observed age-at-onset distribution of cases. This estimate is confounded with the age distribution of the population from which the cases were sampled and is accurate only if there are no competing causes of death. In this paper, we present a straightforward method for calculating a more accurate age-at-onset function under etiologic heterogeneity. We use the life-table approach and survival analysis methods. This method is illustrated using data on first-degree relatives of probands from two sets of families with high cancer incidence: one with breast/ovarian cancer and the other with colon cancer. A comparison of the estimated age-at-onset function obtained by the two methods is presented. In both cases, colon cancer as well as breast/ovarian cancer, the estimates of onset probabilities based on proportion of cases, are consistently higher than those obtained by the life-table method. For breast/ovarian cancer, this difference is not as striking as it is in the case of colon cancer; nevertheless, the method using proportion of cases tends to give a lower estimate of the age-at-onset function (higher probability of being affected at lower age) than the life-table approach.

Actuarial Analysis↗
PubMed1987

Mu-, delta-, kappa- and epsilon-opioid receptor modulation of the hypothalamic-pituitary-adrenocortical (HPA) axis: subchronic tolerance studies of endogenous opioid peptides.

In opiate-naive rats, the endogenous opioid peptides, beta-endorphin, dynorphin(1-13) and Met-Enk-Arg-Phe (MEAP) and the synthetic enkephalin analogue D-Ala2-D-Leu5-Enk (DADLE) potently stimulated plasma corticosterone in a dose-dependent, naloxone reversible manner. To characterize their in vivo affinities, the effects of these peptides on plasma corticosterone release were tested in rats made tolerant to morphine, U50488H, DADLE/morphine or beta-endorphin. These cross-tolerance studies showed that dynorphin and MEAP exerted their action on plasma corticosterone release at kappa-opioid receptors. The action of DADLE occurred at delta-opioid receptors, while the action of beta-endorphin occurred principally at another receptor site. These results indicate that there is independent modulation of the hypothalamic-pituitary-adrenal axis by endogenous opioid peptides at mu-, delta- and kappa-opioid receptors. In addition there may be modulation by beta-endorphin at a separate site that we suggest could be a central epsilon-receptor site. This cross-tolerance paradigm, using a neuroendocrine model, provides in vivo evidence for the action of centrally active endogenous opioid peptides at multiple and independent opioid receptors.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1987

Reversal of the actions of morphine on mesocortical dopamine metabolism in the rat by the kappa agonist MR-2034: tentative mu-2 opioid control of mesocortical dopaminergic projections.

Morphine was shown to enhance dopamine metabolism, as assessed by increased dihydroxyphenylacetic acid measurements, in the mesocortical dopaminergic projections of the rat (cingulate, pyriform and prefrontal cortices). In contrast, the kappa agonist MR-2034 did not alter dopamine metabolism but did antagonize the actions of morphine. Similar antagonism of the actions of morphine were noted in the striatum and olfactory tubercle. These data suggest that the mesolimbic and mesocortical dopaminergic projections may possess a mu-2 opioid receptor regulation as previously defined for the nigrostriatal pathway.

Animals↗
PubMed1987

Agonist action of the agonist/antagonist analgesic butorphanol on dopamine metabolism in the nucleus accumbens of the rat.

The action of butorphanol, an opiate agonist/antagonist, was studied on dopamine (DA) metabolism in several mesocortical and mesolimbic areas and compared with its effects on the nigrostriatal DA pathway. While butorphanol had a bell-shaped dose-response relationship for elevation of DA metabolites in the striatum, it had no action on DA metabolites in the entorhinal, prefrontal, pyriform and cingulate cortices and in the olfactory tubercle. In all of these areas morphine stimulated dopamine metabolism (except for the entorhinal cortex). In contrast, in the nucleus accumbens, butorphanol increased the levels of dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 3-methoxytyramine (3-MT) with no increase in DA steady state levels. This effect was reversible by both opiate antagonists, naloxone and WIN 44441-3 and appears to be mu-opioid receptor-mediated.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1987

The clinical picture of major depression in children and adolescents.

Symptom frequency and severity were compared in two sequential clinically referred samples of 95 children and 92 adolescents, aged 6 to 18 years, all medically healthy, assessed with the Schedule for Affective Disorders and Schizophrenia for School Age Children, Present Episode, who met unmodified Research Diagnostic Criteria for major depressive disorder (MDD). There were no significant differences between the two groups in the majority of depressive symptoms. However, prepubertal children had greater depressed appearance, somatic complaints, psychomotor agitation, separation anxiety, phobias, and hallucinations, whereas adolescents had greater anhedonia, hopelessness, hypersomnia, weight change, use of alcohol and illicit drugs, and lethality of suicide attempt, but not severity of suicidal ideation or intent. Adolescents with a duration of the depressive episode of two years or greater had significantly higher rates of suicidal ideation and intent, lethality, and number of suicide attempts than youngsters with depressive episodes of shorter duration. A principal components factor analysis of psychiatric symptoms was carried out in all 296 youngsters evaluated during the same period who met DSM-III criteria for any Axis I diagnosis. The majority had an affective disorder. Factors were quite similar for both adolescents and children and included an "endogenous" and an "anxious" factor, as in many studies of adult depression. In addition, three other factors were found: negative cognitions, appetite and weight changes, and a conduct factor. Suicidal ideation was a component of both the negative cognitions factor and the conduct factor.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1987

The endogenous kappa agonist, dynorphin(1-13), does not alter basal or morphine-stimulated dopamine metabolism in the nigrostriatal pathway of the rat.

Dopaminergic pathways in the brain of the rat have been shown to possess both mu and delta opioid regulatory inputs. In contrast, studies with synthetic kappa opiate agonists have demonstrated a lack of regulation of these dopaminergic systems by kappa opioids. The present authors have extended these observations, to study the effects of the putative endogenous kappa agonists, dynorphin (1-13), on the metabolism of nigrostriatal dopamine in the rat after intraventricular administration. The stability of the intraventricularly administered dynorphin was confirmed in vivo by measuring corticosterone in plasma in the same animals utilized for neurochemical analyses. This is a neuroendocrine parameter which has been demonstrated to possess central regulation by independent mu and kappa receptors. While morphine given parenterally elevated both the level of corticosterone in plasma and the central metabolism of dopamine, neither the parenteral administration of the kappa agonist, U50488H, or the intraventricular administration of dynorphin altered central metabolism of dopamine. However, in both cases, levels of corticosterone in plasma were dramatically elevated, clearly demonstrating the bioavailability of the kappa agonists. The actions of morphine on the metabolism of dopamine, which can be antagonized by pretreatment with synthetic kappa agonists, were not antagonized by dynorphin(1-13). To summarize, the present data indicated that the nigrostriatal dopaminergic pathway in the rat lacks kappa opioid regulation. In addition, while synthetic kappa agonists also possessed mu antagonist actions, the endogenous ligand, dynorphin, did not.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1986

Opiate actions on mesocortical dopamine metabolism in the rat.

The actions of parenteral morphine were examined with regard to dopamine metabolism in the mesocortical dopaminergic pathways of the rat. The effects of morphine on dopamine metabolism in the prefrontal, cingulate, pyriform and entorhinal cortices were compared with the actions of morphine on the metabolism of dopamine in the striatum and olfactory tubercle. In all tissues, except the entorhinal cortex, morphine significantly elevated the dopamine metabolites dihydroxphenylacetic acid and homovanillic acid. These data, along with previous studies of various pharmacological agents, clearly indicate that the mesocortical dopaminergic projections possess unique opioid and non-opioid regulatory inputs.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1986

Effects of kappa opiate agonists on neurochemical and neuroendocrine indices: evidence for kappa receptor subtypes.

Four kappa opiate agonists, U-50488H, MR-2034, EKC and tifluadom, elevated plasma corticosterone and decreased plasma TSH in a dose-dependent manner. These effects were naloxone-reversible. However, WIN 44441-3, a long acting narcotic antagonist, was unable to reverse the effects of U-50488H and MR-2034 upto doses of 5 mg/kg. U-50488H and MR-2034 but not tifluadom or EKC, also increased levels of DOPAC and HVA in the olfactory tubercle. This effect was also naloxone-reversible but not WIN 44441-3 reversible. Tifluadom and EKC did not increase DOPAC and HVA. The differential responses of the tested kappa agonists to WIN 44441-3 antagonism and dopamine metabolism in A10 neurons suggest that the kappa agonists can be separated into two groups. This is the first physiological evidence suggestive of kappa opioid receptor subtypes.

Animals↗
PubMed1986

Benzodiazepine interactions with central thyroid-releasing hormone binding sites: characterization and physiological significance.

Thyrotropin-releasing hormone (TRH) and several TRH analogs were examined in the [3H]-3-Me-His2-TRH ([3H]MeTRH) receptor-binding assay in rat amygdala, striatal and cortical membranes. The benzodiazepine, chlordiazepoxide, as reported in the literature was found to displace [3H]MeTRH with an IC50 value of 3.6 X 10(-7) M in amygdala membranes. Midazolam was, however, identified as being 6-fold more active than chlordiazepoxide with an IC50 value of 6.3 X 10(-8) M. The effect of these benzodiazepines on [3H]MeTRH binding did not appear to be related to their anxiolytic activity because the novel pyrazoloquinoline nonsedating anxiolytic, CGS 9896 was without effect on [3H]MeTRH binding at concentrations up to 1 X 10(-5) M. Chlordiazepoxide had similar activity in cortical membranes whereas midazolam was some 5 times less active in this preparation than in amygdala. Both compounds were weak displacers of [3H]MeTRH binding in striatal membranes, being at least two orders of magnitude less potent than in amygdala. In contrast TRH and its analogs, RX 77368 and DN-1417, were approximately 2 to 8 times more active in striatum than amygdala membranes. TRH and DN-1417 were less active in cortical membranes whereas RX 77368 was some three times more active than in striatum and amygdala. In three test procedures indicative of TRH agonist activity; thyroid-stimulating hormone release, reversal of pentobarbital sleeping time in mice and elevation of cerebellar cyclic GMP levels, the benzodiazepines were found to be devoid of activity, whereas TRH and related compounds produced their expected responses.(ABSTRACT TRUNCATED AT 250 WORDS)

Amygdala↗
PubMed1986

Kappa opiate agonists modulate the hypothalamic-pituitary-adrenocortical axis in the rat.

Systemic injections of opiate agonists were made in male rats to elucidate the involvement of multiple opioid receptors in the stress response. As an index of activity in the hypothalamic-pituitary-adrenocortical axis, plasma corticosterone was measured by radioimmunoassay. Rats were injected with ethylketocyclazocine (EKC), U50488H, MR2034, bremazocine or tifluadom and sacrificed 1 hr later. These kappa agonists produced potent, dose-dependent, stereospecific increases in plasma corticosterone levels at doses far below those needed to elicit analgesia. These effects were reversed by opiate antagonists, naloxone or Win 44441-3, which by themselves caused dose-dependent decreases in plasma corticosterone. Animals made tolerant to the prototype kappa agonist, U50488H, showed an attenuated response to an acute injection of the drug. However, when animals made tolerant to morphine were injected acutely with U50488H, the drug caused a dramatic increase in corticosterone levels. In hypophysectomized rats, U50488H and L-EKC did not increase plasma corticosterone. The agonist/antagonists, butorphanol and cyclazocine, when injected, behaved like kappa agonists and increased plasma corticosterone levels potently. The mu opiates, morphine and etorphine, also had similar effects but were less potent and efficacious than the kappa agonists. The delta agonist D-Ala-D-Leu enkephalin showed similar results, confirming a mu and delta opioid input into the hypothalamic-pituitary-adrenocortical axis. There were concomitant increases in plasma adrenocorticotropin in morphine-, D-Ala-D-Leu enkephalin-, L-EKC- and U50488H-treated rats which were also seen in adrenalectomized rats. D-EKC and D-cyclazocine, which bind to sigma sites, had no effect on corticosterone.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1986

Kappa isoreceptors: neuroendocrine and neurochemical evidence.

It has become clear, in the area of opiate research, that there are multiple opioid receptors and endogenous ligands. The functional roles of these opioid systems are being established as these concepts evolve and as our analytical capabilities become more sophisticated and thorough. When complete dose-response studies are performed and a number of antagonists are examined, a clearer definition of isoreceptor populations may also occur. Such appears to be the case with kappa agonists, which may in fact comprise two groups of compounds (table 1). This separation into two groups has also been observed in the dog cerebral artery (table 1) (Altura et al. 1984). Taken together, these data are sufficient to propose the testable hypothesis that there are kappa isoreceptor populations in the brain that probably subserve a vast array of discrete and different regulatory functions.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1984

Comparison of computerized tomography and excretory urography in detection and evaluation of renal masses.

The ability of excretory urography and computerized tomography to detect renal masses was compared in 120 consecutive cases. Computerized tomography consistently provided more information than excretory urography, usually was able to distinguish renal tumors from cysts and provided additional useful information regarding staging of renal neoplasms and the presence of unsuspected associated pathological conditions.

Contrast Media↗
PubMed1983

Role of serotonin in estrogen-progesterone induced luteinizing hormone release in ovariectomized rats.

Pharmacological agents were used to manipulate the surge of luteinizing hormone (LH) induced by progesterone in ovariectomized rats primed with estradiol benzoate. The LH surge was abolished with p-chlorophenylalanine (PCPA), an inhibitor of tryptophan hydroxylase, and restored by 5-hydroxytryptophan, a serotonin precursor. Serotonin receptor agonists, quipazine and N-N-dimethyl-5-methoxytryptamine, were also capable of inducing an LH surge in rats pretreated with PCPA. The serotonin reuptake blocker chlorimipramine was ineffective in stimulating LH release in PCPA blocked animals. Another reuptake blocker, zimelidine was only partially effective in this regard. These two reuptake blockers, as well as amitriptyline, when injected to non-PCPA treated rats led to the reduction or inhibition of the expected LH surge. Four serotonin receptor antagonists, cyproheptadine, methysergide, cinanserin and SQ-10,631, were each able to reduce or abolish the progesterone induced surge of LH. These results suggest that some of the reuptake blockers of serotonin are also capable of inhibiting receptor binding for this neurotransmitter and strongly indicate that serotonin has a stimulatory role in the steroid induced release of LH in castrated rats.

5-Hydroxytryptophan↗