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Biomedical subjects

E M Dax

Publications and source records attributed to E M Dax.

At least 37 records · Page 2Linked to original sources
PubMed1991

Chronic cocaine administration and withdrawal of cocaine modify neurotensin binding in rat brain.

Neurotensin (NT) is a peptide colocalized with dopamine (DA) within some mesocorticolimbic DA neurons that are affected by cocaine. We assessed whether chronic treatment with cocaine and withdrawal from cocaine would alter NT binding within these and other areas in the brain. Rats were given infusions repeatedly of isotonic saline or cocaine (1 mg/kg i.v. every 12 min for 2 hr over 10 days) and then were killed within 15 min of the last treatment session ("cocaine" or "saline") or 10 days later ("withdrawal"). Brains were processed for NT receptor autoradiography. Cocaine affected NT binding in the mesocortical regions differently from other areas. Within the mesocorticolimbic system, NT binding in the parabrachial pigmented nucleus of the ventral tegmental area (VTA) was 67% lower in cocaine-treated rats killed immediately after or 10 days after their final infusion than in rats given saline. In contrast to the perikaryal region, significantly more NT binding occurred postsynaptically in the terminal areas of the VTA (prefrontal cortex [PFC] and substantia nigra, pars compacta) 10 days after withdrawal of cocaine than in the saline controls. NT binding in the nucleus accumbens was unaffected by cocaine or its withdrawal. Cocaine also decreased NT binding in non-mesocorticolimbic areas, including the dorsal hypothalamic area and the zona incerta, but binding returned toward control levels 10 days after withdrawal from cocaine. These data suggest that in central areas poor in DA uptake sites such as the PFC, NT may be a critical element in the inactivation of DA. Chronic cocaine treatment and its withdrawal appear to uncouple the normal NT-DA interaction at both the cell bodies and terminals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Amyl nitrite alters human in vitro immune function.

Effects on the human immune system of volatile nitrite inhalation were studied in 18 male volunteers. While nitrite inhalation decreased the absolute number of CD3+ T lymphocytes during the period of inhalation, cell numbers returned to pre-treatment levels within one week after cessation of the drug. Nitrite inhalation did not alter the percentage of CD3+, CD4+, CD8+ or CD19+ lymphocytes. Natural killer (NK) cell activity against K562 target cells was depressed by nitrite administration but returned to pre-inhalation or greater levels after nitrite discontinuation. Cell proliferation following cell activation by PHA, ConA and PWM was unaffected by amyl nitrite inhalation. We conclude that in humans inhalation of volatile nitrites causes cycles of modest immunosuppression, particularly in NK activity, followed by gradual recovery when the drug is not inhaled for several days.

Adult↗
PubMed1990

Multiple, but not acute, infusions of cocaine alter the release of prolactin in male rats.

Hypothalamic dopamine tonically inhibits the release of prolactin (PRL) from the anterior pituitary gland. Cocaine, in turn, alters dopaminergic transmission. We compared the effects of acute and repeated injections of cocaine on the release of PRL in male rats to assess whether cocaine could affect dopaminergically mediated hormonal responses. We found that the concentration of PRL in plasma was not affected by single i.v. injections of 1, 3 or 10 mg/kg of cocaine. However, in rats infused repeatedly with 1 mg/kg of cocaine for 5 s every 12 min for 2 h over 10 days, the pre-infusion concentrations of PRL increased in a time-dependent manner whereas cocaine uniformly decreased post-infusion levels of PRL. Repeated administration of cocaine may produce long-term changes in either the tuberoinfundibular dopaminergic neurons or the adenohypophysial dopamine D2-receptors, or both. Changes in the peripheral concentration of PRL after multiple injections of cocaine and during cocaine withdrawal may reflect dopaminergic activity in the hypothalamus. In contrast, single injections of cocaine increased adrenocorticotropin (ACTH) in a dose-dependent manner whereas repeated infusions did not increase peripheral concentrations of ACTH or corticosterone. It seems that repeated injections of cocaine do not result in persistent changes in the hypothalamo-pituitary-adrenal axis.

Adrenocorticotropic Hormone↗
PubMed1990

Changes in mood, craving, and sleep during short-term abstinence reported by male cocaine addicts. A controlled, residential study.

We examined changes over 28 days in mood states, craving for cocaine, and sleep during short-term abstinence reported by 12 male, predominantly intravenous-using, cocaine-addicted subjects residing in a research facility. For comparison, we examined 10 nonaddicted control subjects. There were no significant differences between cocaine addicts and controls regarding demographics and selected DSM-III-R diagnoses other than psychoactive substance use disorder and antisocial personality disorder. There were significantly higher scores of psychiatric symptoms reported by cocaine addicts 1 week before admission. Mood-distress and depression scores recorded at admission and during short-term abstinence were significantly greater than those reported by controls. Addicts' mood-distress scores and craving for cocaine were greatest at admission and decreased gradually and steadily during the 28-day study. There were no significant differences between groups regarding reports of sleep other than difficulty falling asleep and clearheadedness on arising. Although there were significant differences in resting heart rate at admission and over time, there were no significant differences in weight gain or blood pressure. Given the absence of a classic "withdrawal" pattern, "short-term abstinence" may be a more appropriate classification of psychological and physical phenomena experienced by cocaine addicts who initiate abstinence in a controlled environment.

Adult↗
PubMed1990

Safety and side-effects of buprenorphine in the clinical management of heroin addiction.

Sublingual buprenorphine (8 mg) was administered to heroin-dependent addicts daily for 18 days and continued from day 19-day 36 either daily or on alternate days. Final data are reported on 18 subjects. The number of self-reported symptoms reviewed as potential adverse drug reactions ranged from 1 to 88 per participant. None was considered to be related definitely to the study medication, and there were no reporting differences between the two dosing regimens. Forty-five reactions were considered probably related to buprenorphine: sedation/drowsiness (three reports) and constipation (42 reports). It was concluded that these were anticipated drug effects rather than adverse reactions. Although some participants showed increases in serum aminotransferase levels, those increases could not be directly attributed to buprenorphine. We conclude that buprenorphine was well tolerated, but further study is needed in this population to delineate the possible attributable risk of the drug to hepatic dysfunction in this population.

Administration, Sublingual↗
PubMed1990

Use of buprenorphine in the treatment of opioid addiction. II. Physiologic and behavioral effects of daily and alternate-day administration and abrupt withdrawal.

Nineteen heroin-dependent male volunteers were administered buprenorphine sublingually, in ascending daily doses of 2, 4, and 8 mg. They were maintained on 8 mg daily through study day 18. On study days 19 through 36, subjects in group 1 continued to receive burprenorphine daily; subjects in group 2 received buprenorphine or placebo on alternate days. On days 37 through 52, all subjects received placebo. Subjects receiving buprenorphine on alternate days reported significantly greater urge for an opioid, increased dysphoria scores, and pupillary dilation on placebo days. After abrupt termination of buprenorphine, no withdrawal signs were detected with the Himmelsbach scale. However, subjects reported mild-to-moderate opioid withdrawal symptoms, peaking at 3 to 5 and lasting for 8 to 10 days. Daily administration of buprenorphine provided greater control of subtle opioid withdrawal symptoms, but subjects could tolerate a between-dose interval of 48 hours.

Adult↗
PubMed1990

Endurance training, not acute exercise, differentially alters beta-receptors and cyclase in skeletal fiber types.

beta-Adrenergic receptor binding characteristics and adenylate cyclase activity were examined in rat skeletal muscle membranes to determine if acute exercise or endurance training altered beta-receptors or adenylate cyclase activity in different muscle fiber types. Binding characteristics and adenylate cyclase activity were examined in type IIA [red fast-twitch, red vastus (RV)], type IIB [white fast-twitch, white vastus (WV)], and type I [red slow-twitch, soleus (S)] muscles. Acute exercise involved a 20-min run on a treadmill at 20 m/min and did not alter beta-receptor density or adenylate cyclase activity in any of the fiber types examined. Endurance training consisted of a progressive treadmill protocol that involved increasing intensity and duration of exercise for 18 wk. beta-Adrenergic receptor density increased in skeletal muscle fiber types primarily recruited during submaximal training (types I and IIA), whereas nonreceptor-mediated adenylate cyclase activity was altered in the three fiber types. Endurance training significantly increased beta-receptor density in RV by 25% and in S by 19% (P less than 0.05), whereas in WV beta-receptor density was not altered. Basal adenylate cyclase activity in RV was increased approximately 2.5 fold by endurance training. Nonreceptor-mediated adenylate cyclase activity, stimulated by NaF and forskolin, increased by approximately twofold in both RV and WV as a result of endurance training. The data support and extend previous observations to show greater effects of endurance training in types I and IIA fibers with respect to alterations in beta-receptor density and alterations in adenylate cyclase activity in each fiber type. Acute exercise did not alter these parameters either in trained or untrained rats.

Adenylyl Cyclases↗
PubMed1990

Altered glucagon- and catecholamine hormone-sensitive adenylyl cyclase responsiveness in rat liver membranes induced by manipulation of dietary fatty acid intake.

Glucagon-stimulated adenylyl cyclase activity has been shown to change in liver membranes manipulated to alter either their fatty acid composition or fluidity. We examined whether membrane alterations induced by dietary manipulation affected receptor function. Glucagon- and beta-adrenergic-stimulated receptor-adenylyl cyclase systems were examined in liver membranes of rats fed diets containing 10% corn oil, 10% coconut oil (essential FFA deficient), or 8.5% coconut oil with 1.5% corn oil (essential FFA repleat). Basal and maximal nonreceptor-mediated adenylyl cyclase activity (stimulated by NaF, guanylylimidodiphosphate, and forskolin) was the same in membranes of each of the dietary groups, suggesting that Gs-protein and the catalytic unit activity per se were unaltered by the manipulations. Glucagon-stimulated adenylyl cyclase activity increased with increasing unsaturation of dietary fatty acids; activity in coconut oil-fed rats was 527 +/- 30 (mean +/- SEM) pmol/mg.10 min, that in coconut/corn oil-fed rats was 752 +/- 74 pmol/mg.10 min, and that in corn oil-fed rats was 981 +/- 94 pmol cAMP/mg.10 min. [125I]Monoiodoglucagon binding did not increase in parallel to the adenylyl cyclase alterations; coconut oil-fed animals (614 fmol/mg) differed from the other groups (450 and 430 fmol/mg). Isoproterenol (beta-adrenergic)-stimulated adenylyl cyclase activity was also highest in the corn oil-fed animals, but was similar in the other dietary groups, with no difference in other characteristics of [125I]iodopindolol binding between the groups. The results demonstrate that alterations in the glucagon-stimulated adenylyl cyclase response are different from those in the beta-adrenergic adenylyl cyclase response. Further, they suggest that although direct activations of the catalytic unit or its interaction with the guanine nucleotide-sensitive protein are apparently not affected, hormone receptor-mediated adenylyl cyclase activity may be altered by these dietary manipulations.

Adenylyl Cyclases↗
PubMed1989

The effects of 9-ene-tetrahydrocannabinol on hormone release and immune function.

We investigated effects of 9-ene-tetrahydrocannabinol (THC) on endocrine and immunological function. Seventeen male volunteers entered into a double blind, randomized study to receive oral THC (10 mg t.i.d. for 3 days and on the morning of the fourth day) or placebo, after at least 2 weeks of abstinence. Plasma prolactin, ACTH, cortisol, luteinizing hormone and testosterone were not altered during or after THC, compared with baseline concentrations. Tests of lymphocyte function showed no differences compared to baseline between THC and placebo groups. As the relatively low dosing regimen of THC (10 mg t.i.d.) resulted in no alterations, another group of 6 men were administered higher doses of THC by inhalation (18 mg/marijuana cigarette) following the same dosing regimen. No endocrine or immunological alterations were observed. When the subjects were grouped according to their history of THC use prior to admission, heavy THC users had lower prolactin concentrations than light users. No differences were observed in concentrations of other hormones or in tests of immune function.

Adult↗
PubMed1989

Food restriction prevents an age-associated increase in rat liver beta-adrenergic receptors.

In male Wistar rats fed ad libitum (24% protein, 4.5 Kcal/gm), the [125I]iodopindolol binding capacity of the beta-adrenergic receptors in liver of 24-month-old animals is 3-4 times greater than that of 6-month-old counterparts. In rats fed the same diet, on alternate days from weaning, the receptor capacity did not increase significantly between 6 and 24 months (10.20 +/- 0.55 vs 9.20 +/- 0.72 fmol/mg) or between 24 and 30 months. This was not due to acute dietary deprivation, as rats food-restricted for only 2 weeks, at 23.5 months of age, also showed elevated receptor capacities compared to 6-month-old ad libitum fed animals. Moreover, intermittent feeding produced no significant effects among 6-month-old animals, whether restricted since weaning or for two weeks prior to sacrifice. Many biochemical parameters that decrease with aging in rats fed ad libitum are prevented by dietary restriction. Our results demonstrate that a reproducible biochemical process that increases with aging is also prevented with dietary restriction. The age-related, liver beta-receptor increase may be a potentially reliable marker for studying biochemical perturbations that modify life span.

Adrenergic beta-Antagonists↗
PubMed1989

Are missionaries at risk for AIDS? Evaluation for HIV antibodies in 3,207 protestant missionaries.

Serum specimens (n = 6,045) obtained from 3,207 Protestant missionaries serving in 57 countries, including 28 African nations, between 1967 and 1984 were assayed for antibodies to the human immunodeficiency virus (HIV) by enzyme-linked immunosorbent assay (ELISA) screening and Western blot confirmatory testing. Seventy sera (1.2%) from 51 missionaries (1.6%) were ELISA positive; however, on Western blot confirmatory testing none was diagnostic of HIV infection. Twenty-two (43%) of the Western blot tests were read as indeterminate, with band p17 occurring with the greatest frequency (57%), followed by p24 (23%), either alone or in combination. The significance of these equivocal results is unclear, but they do not appear to be a consequence of exposure to either HIV or the related retrovirus HTLV-I. Based on this seroprevalence survey, we conclude that missionary staff and their families were not at high risk of HIV infection between 1967 and 1984, even when serving in regions of high HIV endemicity.

Adult↗