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Biomedical subjects

N K Mello

Publications and source records attributed to N K Mello.

At least 109 records · Page 6Linked to original sources
PubMed1990

Cocaine effects on luteinizing hormone-releasing hormone-stimulated anterior pituitary hormones in female rhesus monkey.

The effects of acute cocaine administration on synthetic LHRH-stimulated anterior pituitary hormones (LH, FSH, and PRL) were studied in 6 female rhesus monkeys during the follicular phase of the menstrual cycle (days 4-7). Integrated plasma samples were collected every 10 min for 40 min before iv administration of cocaine (0.4 or 0.8 mg/kg) or an equal volume of vehicle control solution. Synthetic LHRH (100 micrograms, iv) was administered 10 min after cocaine or placebo-cocaine administration, and 10 plasma samples were collected for an additional 100 min. LHRH stimulated a significant increase in LH within 10 min after placebo-cocaine administration (P less than 0.05) and after each dose of cocaine (P less than 0.0001). Cocaine (0.4 mg/kg) significantly enhanced LHRH stimulation of LH compared to placebo or 0.8 mg/kg cocaine administration (P less than 0.01). FSH increased significantly within 20-30 min after LHRH alone (P less than 0.008) and after 0.4 mg/kg cocaine (P less than 0.0001). LHRH-stimulated FSH levels also were significantly higher after 0.4 mg/kg cocaine than after placebo or 0.8 mg/kg cocaine (P less than 0.01). These data indicate that cocaine does not suppress LHRH stimulation of pituitary gonadotropins, and low doses of cocaine significantly enhance LH and FSH release. Consequently, cocaine does not compromise anterior-pituitary function at the level of the gonadotroph and may stimulate hypothalamic release of endogenous LHRH. PRL levels were unchanged by LHRH and placebo-cocaine administration. After LHRH and cocaine administration, PRL levels decreased significantly (P less than 0.05-0.01) and remained suppressed throughout the 110-min postcocaine sampling period. These data indicate that cocaine's significant suppression of PRL is not blocked by LHRH. These findings are consistent with dopaminergic inhibitory control of PRL and suggest that cocaine's inhibition of dopamine reuptake down-regulates pituitary lactotroph activity in rhesus monkey.

Animals↗
PubMed1990

Alcohol effects on hCG-stimulated gonadal hormones in women.

Chronic alcohol abuse is associated with derangements of reproductive function in women. The mechanism of increased risk for alcohol-related abortions and fetal alcohol syndrome is unknown. The goal of this study was to determine if acute alcohol administration affected gonadal steroid hormone levels after administration of human chorionic gonadotropin (hCG) to normal healthy women. hCG was used to simulate the hormonal milieu during the first trimester of pregnancy. Ten women were studied during the mid-luteal phase (between days 17 and 23) of their menstrual cycle. Plasma estradiol, progesterone and prolactin were measured before and after simultaneous administration of 5000 I.U. of hCG (Profasi) and alcohol or placebo solution under double-blind conditions. There was a significant increase in plasma estradiol (P less than .001) and prolactin levels (P less than .01) after hCG and alcohol administration but not after hCG and placebo administration. Plasma progesterone increased significantly (P less than .001) above base line after hCG and placebo administration but this was not observed after hCG and alcohol administration. Since progesterone is essential for the maintenance of pregnancy, alcohol's attenuation of the expected progesterone response to hCG stimulation could increase the risk of spontaneous abortion. An alcohol-induced increase in estradiol after hCG administration could contribute to risk for fetal dysmorphology during the first trimester of pregnancy.

Administration, Oral↗
PubMed1990

Acute effects of cocaine on prolactin and gonadotropins in female rhesus monkey during the follicular phase of the menstrual cycle.

The acute effects of i.v. cocaine on basal levels of prolactin (PRL), luteinizing hormone (LH) and follicle-stimulating hormone were examined in nine female rhesus monkeys during the early follicular phase of the menstrual cycle (days 4-7). Integrated plasma samples were collected at 10-min intervals for 40 min before and 110 min after administration of cocaine (0.4 and 0.8 mg/kg i.v.). Cocaine plasma levels averaged 105 +/- 19 and 157 +/- 23 ng/ml after low- and high-dose administration. PRL decreased significantly (P less than .01) after cocaine administration and reached a nadir within 60 to 70 min. Inasmuch as cocaine blocks dopamine reuptake, PRL suppression is consistent with dopaminergic inhibitory control of PRL release from the pituitary. However, cocaine's effects on PRL were biphasic in 10 of 18 studies. PRL increased within 90 to 110 min post-cocaine and sometimes exceeded base-line levels by over 100%. The duration of PRL suppression (80 min) and the time of onset of the subsequent rebound PRL increase corresponds to the estimated half-life of i.v. cocaine in monkey plasma. PRL suppression followed by a rebound elevation also is consistent with clinical reports of hyperprolactinemia in chronic cocaine abusers. LH increased significantly (P less than .01) within 20 min after cocaine administration and remained above base-line for 40 to 50 min. Follicle-stimulating hormone did not change significantly after cocaine administration. Cocaine's stimulation of LH is consistent with cocaine's alleged enhancement of sexual arousal.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Extraosseous osteosarcoma in a nonhuman primate (Macaca mulatta).

A case of a very rare malignant bone-forming sarcoma, which was located in the soft tissue but had no anatomic attachment to bone, is presented. This tumor originated in the subcuticular tissue over the right scapula and was histologically composed of sheets of anaplastic spindle cells that produced osteoid. The tumor recurred twice before the animal was killed. The recurrent masses produced less osteoid and were generally less differentiated histologically than the initial tumor.

Animals↗
PubMed1990

Operant acquisition of alcohol by women.

Alcohol acquisition and use patterns were studied in 26 women on a clinical research ward. Women could earn alcohol (beer, wine or distilled spirits) or 50 for 30 min of performance on a second-order fixed ratio 300 (fixed interval 1 sec: S) schedule of reinforcement. Points earned for money and for alcohol were not interchangeable. A 7-day drug-free base line was followed by 21 days of alcohol availability and a postalcohol drug-free period of 7 days. Heavy, moderate and occasional drinkers differed significantly in the average number of alcohol drinks purchased (P less than .001). Five heavy drinkers purchased an average of 164 (+/- 14) drinks during the study; 12 moderate drinkers purchased an average of 80 (+/- 4) drinks; 9 occasional drinkers purchased an average of 26 (+/- 4) drinks. Individual drinking patterns fluctuated markedly from day-to-day. Daily peak blood alcohol levels (milligrams per deciliter) were significantly correlated with variations in daily drinking patterns in 22 of the 26 subjects (P less than .02-.0001). Computer analysis of daily alcohol consumption patterns (alcohol peak frequency and peak amplitude) showed that moderate drinkers had significantly more peaks in alcohol consumption than occasional drinkers (P less than .05). The average number of drinks constituting each peak was significantly greater for the heavy and moderate drinkers than for the occasional drinkers (P less than .05). The interval between successive peaks in alcohol consumption averaged 4.6 (+/- 0.8) days for the occasional drinkers, 3.2 (+/- 0.2) days for the moderate drinkers and 3.6 (+/- 0.17) days for the heavy drinkers but these differences were not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Alcohol Drinking↗
PubMed1990

Buprenorphine and naltrexone effects on cocaine self-administration by rhesus monkeys.

The effects of daily treatment with buprenorphine (0.237-0.70 mg/kg/day), naltrexone (0.32-3.20 mg/kg/day) and saline on cocaine self-administration were compared in rhesus monkeys. Cocaine (0.05 or 0.10 mg/kg/injection) and food (1-g banana pellets) self-administration were maintained on a fixed-ratio 4 (variable ratio 16:S) schedule of reinforcement. Buprenorphine, naltrexone or an equal volume saline control solution were infused slowly over 1 hr through one lumen of a double lumen i.v. catheter at the same time each day. Saline and each dose of buprenorphine (0.237, 0.40 and 0.70 mg/kg/day) or naltrexone (0.32 and 3.20 mg/kg/day) were studied for 60 sessions over 15 consecutive days. Buprenorphine significantly suppressed cocaine self-administration (P less than .001-.0001) in comparison to saline in all monkeys. Cocaine self-administration decreased by 49 to 95% in five of six monkeys on the 1st day of buprenorphine administration (0.237 and 0.40 mg/kg/day) and remained suppressed by an average of 72 to 93% during buprenorphine treatment. After abrupt termination of buprenorphine treatment (0.237 and 0.70 mg/kg/day), cocaine self-administration remained suppressed for an average of 16 +/- 4.4 and 28 +/- 6.6 days, respectively. Buprenorphine (0.237 and 0.40 mg/kg/day) initially suppressed food self-administration in some monkeys (P less than .01), but tolerance developed to buprenorphine's effects on food-maintained responding whereas cocaine self-administration remained significantly suppressed. During treatment with 0.70 mg/kg/day of buprenorphine, food self-administration returned to or significantly exceeded (P less than .01) base-line levels in three animals. Daily patterns of food self-administration were not disrupted by buprenorphine treatment. Naltrexone (0.32 mg/kg/day) initially suppressed cocaine self-administration by an average of 28% over 15 days (P less than .0009). During high-dose naltrexone treatment (3.20 mg/kg/day), cocaine-maintained responding was suppressed by 25% over 15 days (P less than .01). Cocaine-maintained responding was not significantly changed by naltrexone in one of the five subjects. Food self-administration decreased by 24% (P less than .05) after 5 days of 0.32 mg/kg of naltrexone administration, then exceeded baseline levels during 3.20 mg/kg of naltrexone administration. These data suggest that buprenorphine decreases cocaine's reinforcing properties more effectively than naltrexone across the dose-range studied. Buprenorphine may be an effective pharmacotherapy for treatment of cocaine abuse as well as dual abuse of cocaine plus heroin.

Animals↗
PubMed1989

Buprenorphine suppresses cocaine self-administration by rhesus monkeys.

Cocaine abuse has reached epidemic proportions in the United States, and the search for an effective pharmacotherapy continues. Because primates self-administer most of the drugs abused by humans, they can be used to predict the abuse liability of new drugs and for preclinical evaluation of new pharmacotherapies for drug abuse treatment. Daily administration of buprenorphine (an opioid mixed agonist-antagonist) significantly suppressed cocaine self-administration by rhesus monkeys for 30 consecutive days. The effects of buprenorphine were dose-dependent. The suppression of cocaine self-administration by buprenorphine did not reflect a generalized suppression of behavior. These data suggest that buprenorphine would be a useful pharmacotherapy for treatment of cocaine abuse. Because buprenorphine is a safe and effective pharmacotherapy for heroin dependence, buprenorphine treatment may also attenuate dual abuse of cocaine and heroin.

Animals↗
PubMed1989

Naloxone suppresses buprenorphine stimulation of plasma prolactin.

The effects of parenterally-administered buprenorphine and simultaneous injection of naloxone was evaluated in six healthy adult males. Each subject was studied on six occasions, an average of 10 days apart, and received either two simultaneous intramuscular injections of saline, buprenorphine 0.3 mg and saline, or buprenorphine 0.3 mg and 0.6 mg, 0.45 mg, 0.3 mg, or 0.15 mg of naloxone. Simultaneous injection of buprenorphine 0.3 mg and saline resulted in an average increase in plasma prolactin above baseline levels of approximately 10 and 25 ng/ml, 30 and 55 minutes after injection. Buprenorphine-induced stimulation of plasma prolactin levels was statistically significantly greater than basal prolactin values (p less than 0.01). When 0.6 mg of naloxone was simultaneously injected with 0.3 mg buprenorphine, peak plasma prolactin levels were significantly lower (p less than 0.05) than prolactin values after administration of 0.3 mg buprenorphine and saline. Simultaneous injection of 0.45 mg naloxone and 0.3 mg buprenorphine also resulted in a significant attenuation (p less than 0.05) of buprenorphine-stimulated prolactin levels. Injection of 0.3 mg or 0.15 mg of naloxone did not inhibit prolactin stimulation produced by buprenorphine 0.3 mg. These findings demonstrate a dose-effect relationship between naloxone concentration and suppression of the increase in plasma prolactin levels produced by administration of buprenorphine 0.3 mg. As prolactin stimulation occurs shortly after opioid agonist administration and is temporally concordant with the rapid induction of pharmacologic reinforcement associated with opiate abuse, naloxone added to buprenorphine parenteral preparations may reduce the abuse potential of buprenorphine.

Adolescent↗
PubMed1989

Neuroendocrine consequences of alcohol abuse in women.

Alcohol abuse and alcoholism are associated with a broad spectrum of reproductive system disorders. Amenorrhea, anovulation, luteal phase dysfunction, and ovarian pathology may occur in alcohol-dependent women and alcohol abusers. Luteal phase dysfunction, anovulation and persistent hyperprolactinemia have also been observed in social drinkers studied under clinical research ward conditions. The mechanisms underlying alcohol-related disruptions of the hypothalamic-pituitary-ovarian-adrenal axis are unknown. The reproductive consequences of alcohol abuse and alcoholism range from infertility and increased risk for spontaneous abortion to impaired fetal growth and development. Recent studies of alcohol's effects on pituitary gonadotropins and on gonadal, steroid and adrenal hormones in women are reviewed. Research on the acute effects of alcohol on opioid antagonist and synthetic LHRH-stimulated pituitary gonadotropins is summarized. The implications of alcohol's effects on reproductive hormones for impairment of fetal growth and development are discussed.

Alcohol Drinking↗
PubMed1989

Cocaine effects on pulsatile secretion of anterior pituitary, gonadal, and adrenal hormones.

Pulse frequency analysis of LH, PRL, testosterone, and cortisol was carried out with the Cluster Analysis Program in eight male cocaine abusers and eight aged-matched normal men. Four of the eight cocaine abusers had hyperprolactinemia (range, 22.08-44.65 micrograms/L). Cocaine users as a group had significantly higher mean peak height (P less than 0.02) than control subjects. Cocaine users with hyperprolactinemia had higher mean peak height than control subjects or cocaine users with normal PRL levels (P less than 0.01). Cocaine users with hyperprolactinemia also had higher mean amplitude increments than control subjects (P less than 0.02). Cocaine users with hyperprolactinemia had a higher mean valley than controls (P less than 0.01) and cocaine users with normal PRL levels (P less than 0.03). However, there were no significant differences in PRL peak frequency, peak duration, or interpulse intervals between cocaine users with or without hyperprolactinemia and control subjects. There were minimal differences between cocaine users and control subjects in pulse frequency analysis of LH parameters; the small differences in mean LH levels and average interpulse interval were not in the abnormal range and were probably not biologically significant. No differences between cocaine users and controls were detected for pulse frequency analysis of testosterone or cortisol. Cocaine-induced hyperprolactinemia may contribute to disorders of sexual and reproductive function in men who abuse the drug, and recent reports that PRL modulates immune function suggest that cocaine-induced derangements of PRL secretion may also contribute to cocaine-related comorbidity in infectious disease. Since cocaine users with hyperprolactinemia had a higher mean valley as well as a higher peak pulse PRL height than control subjects, but did not have greater PRL pulse frequencies, we conclude that hyperprolactinemia in these men may be due to a cocaine-induced derangement of dopaminergic inhibition of basal PRL secretion.

Activity Cycles↗
PubMed1989

Topographic distribution of EEG alpha activity during ethanol-induced intoxication in women.

Topographic maps of brain electrical activity from scalp EEG electrodes were obtained from healthy adult female volunteers using a Brain Electrical Activity Mapping (BEAM) system. Each woman received both ethanol (0.7 g/kg, p.o.) and placebo in a counterbalanced order under double-blind conditions at an interval of 1-6 days. Subjective reports of intoxication were obtained continuously via an instrumental joystick device. Subjects reported when they detected ethanol and qualitatively pleasant (i.e., euphoric) or unpleasant (i.e., dysphoric) effects. All subjects reliably discriminated ethanol from placebo. Pronounced increases in EEG alpha activity occurred during ethanol-induced intoxication in all subjects. Analysis of topographic maps revealed that the distribution of high-amplitude, fast-frequency EEG alpha activity extended further frontally to the central sulcus and temporally during ethanol intoxication than during control sessions or after placebo administration. Area analysis and significant probability mapping techniques were used to quantify the increased alpha activity and to monitor changes during the process of intoxication in each individual. One woman, with a positive family history of alcoholism, experienced only a mild degree of ethanol intoxication. This behavioral response was accompanied by a slight decrease or no change in both slow- and fast-frequency alpha activity. This finding in a single subject provides additional evidence that a possible genetic predisposition for ethanol-related effects on behavior may be reflected in measures of brain electrical activity. Overall, these data also suggest that ethanol induces rapid and widespread increases in EEG alpha activity which may be associated with the reinforcing properties of ethanol.

Adult↗