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Biomedical subjects

N K Mello

Publications and source records attributed to N K Mello.

At least 19 recordsLinked to original sources
PubMed1992

Hyperprolactinemia and macrocytosis in women with alcohol and polysubstance dependence.

Chronic alcoholism and drug abuse are often associated in women with derangements of reproductive function such as amenorrhea, anovulation, luteal phase dysfunction and early menopause. Endocrine profiles were studied of the first 18 women (aged 17-58) admitted consecutively to a Massachusetts hospital for treatment of alcohol/polysubstance dependence under civil commitment. Twelve women were diagnosed as alcohol dependent according to criteria established in DSM-III-R. Their daily alcohol consumption ranged from 42-324 grams. Six women were diagnosed as polysubstance dependent. In addition to alcohol (84-831 g/day), cocaine was the most frequently abused drug followed by tranquilizers, marijuana and opiates. Over 60% of alcohol-dependent women of reproductive age had either hyperprolactinemia or macrocytosis (increased mean corpuscular volume, MCV), or both. Over 60% of the polysubstance-dependent women of reproductive age had either hyperprolactinemia or increased MCV. Over 80% of alcohol-dependent women of postmenopausal age had either hyperprolactinemia or increased MCV, or both. We conclude that evaluation of plasma prolactin levels and MCV may be useful as biological state markers for alcoholism and polysubstance abuse in women.

Adolescent↗
PubMed1992

Buprenorphine attenuates the effects of cocaine on adrenocorticotropin (ACTH) secretion and mood states in man.

Adrenocorticotropin (ACTH) levels in plasma increased rapidly to 105% above baseline within 5 minutes after intravenous injection of cocaine (30 mg) in cocaine-dependent men. The time course of ACTH stimulation paralleled increases in plasma cocaine levels and self-reports of salient drug effects on mood states and did not occur after placebo administration. An opioid mixed agonist-antagonist, buprenorphine (4 mg/day sublingually), suppressed the acute cocaine-induced stimulation of both ACTH and euphoria. Buprenorphine's suppression of postcocaine ACTH and euphoria were not related to differences in plasma cocaine levels or cocaine-induced alterations of cardiovascular function.

Adrenocorticotropic Hormone↗
PubMed1992

Acute effects of cocaine on plasma adrenocorticotropic hormone, luteinizing hormone and prolactin levels in cocaine-dependent men.

Acute cocaine administration alters secretion of anterior pituitary hormones in experimental animals, and cocaine abuse may compromise neuroendocrine function in humans. The goal of this study was to examine cocaine's acute effects on neuroendocrine hormones in cocaine-dependent men. Plasma adrenocorticotropic hormone (ACTH), luteinizing hormone and prolactin levels were measured in 18 men before and after i.v. administration of cocaine (30 mg) or placebo. Each subject served as his own control during the i.v. placebo and cocaine administration conditions. Plasma cocaine levels peaked at 260 ng/ml within 5 min after the i.v. injection. Plasma ACTH levels increased significantly above base-line levels at 5, 15, 30 (P < .01) and 45 min (P < .05) after i.v. cocaine. Plasma luteinizing hormone levels increased significantly above base-line levels at 5 (P < .05) and at 15 min (P < .01) after i.v. cocaine. No changes in plasma ACTH or luteinizing hormone levels were found after i.v. placebo injection. Plasma prolactin levels decreased significantly at 30, 45, 60, 90 and 120 min (P < .01) after both i.v. cocaine and placebo administration. Cocaine-induced increases in plasma ACTH levels may be due to its effects on dopaminergic systems which modulate corticotropin-releasing factor release in brain.

Adrenocorticotropic Hormone↗
PubMed1992

Effects of alcohol on E2 beta-stimulated luteinizing hormone in ovariectomized rhesus monkeys.

Anovulation is a frequent concomitant of alcohol abuse, but it has been difficult to assess the acute effects of alcohol on ovulation. Estradiol benzoate (E2 beta) can stimulate a luteinizing hormone (LH) surge in ovariectomized monkeys that appears to be associated with increased luteinizing hormone-releasing hormone (LHRH) pulse frequency and amplitude. The acute effects of alcohol (2.5 and 3.5 g/kg) and an isocaloric sucrose control solution on LH and follicle-stimulating hormone (FSH) secretory activity were studied in five ovariectomized monkeys 41 to 51 hours after administration of E2 beta (42 micrograms/kg, IM). Integrated plasma samples were collected at 20-minute intervals over 10 hours. Under sucrose control conditions, LH increased to 445 and 584 ng/ml within 46 to 49.3 hours after E2 beta administration in two monkeys and high-amplitude LH pulses were evident in three monkeys. Alcohol (2.5 and 3.5 g/kg) significantly decreased the number of LH peaks and valleys (p < 0.01). Peak blood alcohol levels averaged 195 and 291 mg/dl. After 2.5 g/kg alcohol, there was no LH surge or LH pulses in four of five monkeys. A delayed LH surge occurred in one monkey 48 to 50.6 hours after E2 beta when blood alcohol levels decreased to 62 mg/dl. After 3.5 g/kg alcohol, no monkey had an LH surge and pulsatile LH release was significantly reduced in comparison to control conditions (p < 0.01). FSH levels remained stable across alcohol and control conditions. These data suggest that alcohol attenuates pituitary release of LH in response to E2 beta stimulation. These findings are consistent with menstrual cycle disruptions observed in alcohol-dependent women, social drinkers, and in a primate model of alcoholism.

Animals↗
PubMed1992

The effects of chronic buprenorphine treatment on cocaine and food self-administration by rhesus monkeys.

The goal of this study was to determine if buprenorphine continues to reduce cocaine self-administration over long periods of treatment, or if tolerance develops to this effect. The effects of 30 to 120 days of buprenorphine treatment (0.32 mg/kg/day) on cocaine and food self-administration were examined in six rhesus monkeys. Saline control treatment was studied for 15 days before and after buprenorphine treatment. Intravenous cocaine (0.05 or 0.10 mg/kg) and food (1 g banana pellet) self-administration were maintained on a FR 4 (VR 16:S) schedule of reinforcement. Cocaine self-administration decreased significantly (P less than .0001) and remained 60 to 97% below saline treatment baseline levels (52 +/- 2 injections/day) throughout 120 days of buprenorphine treatment (P less than .01). After substitution of saline for buprenorphine, cocaine self-administration resumed and averaged between 21 (+/- 3.6) and 56 (+/- 6.5) injections per day over 20 days. Buprenorphine plasma levels averaged 18 (+/- 2.84) ng/ml (range 10.9-30 ng/ml) during buprenorphine treatment. Buprenorphine plasma levels usually decreased by 50% or more within 27 hr after the last buprenorphine dose. Low levels of buprenorphine (0.10-0.19 ng/ml) were measured for 30 to 74 days after abrupt termination of daily buprenorphine treatment. Food self-administration was initially reduced (P less than .01-.05), but tolerance to buprenorphine's suppression of food-maintained responding developed over 30 to 70 days of treatment. Food self-administration returned to and significantly exceeded (P less than .05-.01) saline treatment base-line levels, whereas cocaine self-administration remained significantly suppressed.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1979

Effects of the neuropeptide DG-AVP on morphine and food self-administration by dependent rhesus monkey.

Pretreatment with the neuropeptide DG-AVP (desglycrinamide9-arginine8-vasopressin) at two dose levels (25 and 125 mcg/kg) did not reduce intravenous morphine self-administration (0.25 mg/kg/inj) by morpine dependent monkeys, in comparison to pretreatment with saline or DG-AVP vehicle placebo. Food self-administration was also unaffected by DG-AVP pretreatment in comparison to control conditions. These data do not confirm previous reports of a dose-dependent suppression of heroin self-administration in rat following DG-AVP pretreatment [14].

Animals↗
PubMed1978

Self-administration of an enkephalin analog by rhesus monkey.

Intravenous injections of a synthetic enkephalin analog, FK-33-824 were found to maintain operant responding under second-order schedule control (FR 4[VR 16:S]) in five, morphine-dependent rhesus monkeys. All monkeys self-administered enkephalin in amounts equivalent to morphine at comparable doses per injection. Each of five doses of enkephalin (0.5, 0.25, 0.125, 0.05 and 0.01 mg/kg/inj) were substituted for morphine during 10 consecutive sessions over a 56 hr period. No monkey developed opiate withdrawal signs during enkephalin substitution except at the lowest enkephalin dose (0.01 mg/kg/inj). Although the number of enkephalin injections self-administered increased as the dose per injection progressively decreased, there was a significant linear decrease (p less than 0.05) in mg/kg/enkephalin per session at doses of 0.25 mg/kg/inj and below. Reductions in morphine dose per injection, over a range of 0.5 to 0.125 mg/kg/inj produced comparable increases in number of injections per session, but no significant changes in morphine intake. The number of food pellets earned on a second order FR 4 (VR 16:S) schedule decreased during enkephalin substitution. These decreases were significant at the highest doses of enkephalin (0.5 to 0.125 mg/kg/inj). These data attest to the reinforcing characteristics of an enkephalin analog in rhesus monkey and suggest that natural polypeptides may contribute to the reinforcing properties of opiate drugs.

Animals↗