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Journal Article 2005; 26(5): 575-580 PubMed PMID: 16264398 Citation  Keywords:  Acetylserotonin O-Methyltransferase:metabolism, Animals, Arylalkylamine N-Acetyltransferase:metabolism, Female, Melatonin:blood, Microscopy, Electron, Pineal Gland:metabolism, Pregnancy, Pregnancy, Animal:metabolism, Rabbits, Radioimmunoassay,.   

OBJECTIVES: The morphological and biochemical aspects of the pineal gland of pregnant and non-pregnant female vizcachas were investigated to examine whether there is a relationship between the pregnancy and this gland.

METHODS: Pregnant and non-pregnant adult female vizcachas were used. The ultrastructure of type I cell (dark and light pinealocytes) was studied. Pineal and serum melatonin were investigated by radioimmunoassay. Radiometric methods were applied to investigate the arylalkylamine-N-acetyltransferase (AA-NAT) and hydroxyindole-O-methyltransferase (HIOMT) activities.

RESULTS: The morphological study showed the existence of dark and light pinealocytes. The differences between both cells are slight. However, the appearance of dark pinealocytes suggests that they have a high activity. These cells were more abundant in the pineal gland of pregnant females. The pineal melatonin levels and the AA-NAT activity were higher in the pregnant females. Serum melatonin and HIOMT activity did not show significant differences.

CONCLUSION: Our results suggest that the morphological and biochemical changes in the pineal gland of pregnant vizcachas are associated with the gestation. However, the relation between the pineal gland and the pregnancy is complex and further studies are necessaries to clearly establish it....

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Journal Article 2003; 24(6): 420-424 PubMed PMID: 15073568 Citation  Keywords:  Adult, Analysis of Variance, Cells, Cultured, Corticotropin-Releasing Hormone:immunology, Female, Humans, Interferon-gamma:metabolism, Interleukin-10:metabolism, Leukocytes:cytology, Male, Neuroimmunomodulation:drug effects, Serotonin:immunology, Tumor Ne.   

: Both corticotropin releasing hormone (CRH) and serotonin (5-HT) participate in the stress response and are known to modulate cytokine release by human immune cells. Extracellular 5-HT concentrations at or above the serum values have negative immunoregulatory effects by inhibiting the production of interferon-gamma (IFNgamma), a pro-inflammatory cytokine produced by Th-1-like lymphocytes, whereas 5-HT has no significant effects on the production of interleukin-10 (IL-10), an anti-inflammatory cytokine. In one study, CRH significantly decreases IFNgamma production by cultured human peripheral blood immunocytes, whereas in other studies CRH increases the production of cytokines, such as IL-1, IL-2 and IL-6. The aims of the present study were to examine i) the effects of CRH, 10-9 M, 10(-8) M and 10(-7) M, on the stimulated production of IFNgamma, IL-10 and tumor necrosis factor-alpha (TNFalpha) by human whole blood; and ii) whether CRH, 10(-9) M, 10(-8) M and 10(-7) M, may antagonize some of the negative immunoregulatory effects of 5-HT, 1.5 microg/mL or 15 microg/mL. We found that CRH, 10(-9) M, 10(-8) M and 10(-7) M, had no significant effects either on the stimulated production of IFNgamma, IL-10 or TNFalpha or on the IFNg/IL-10 production ratio, which reflects the pro-inflammatory capacity of the culture. 5-HT, 1,5 microg/dL and 15 microg/dL, significantly suppressed the production of IFNgamma and TNFalpha and the IFNg/IL-10 production ratio. CRH, 10(-7) M, significantly reversed the 5-HT (1.5 microg/mL and 15 microg/mL)-induced suppression of IFNg production. CRH at all concentrations significantly blocked the 5-HT (1.5 microg/mL and 15 microg/mL)-induced suppression of TNFalpha production. The results suggest that CRH has no significant direct effects on the production of IFNgamma, IL-10 and TNFalpha, but antagonizes the negative immunoregulatory effects of 5-HT on the production of IFNgamma and TNFalpha and on the IFNgamma/IL-10 production ratio....

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Journal Article 2002; 23(3): 259-261 PubMed PMID: 12080289 Citation  Keywords:  Biogenic Monoamines:blood, Dopamine:blood, Epinephrine:blood, Hallucinogens:adverse effects, Humans, Hydroxyindoleacetic Acid:blood, N-Methyl-3,4-methylenedioxyamphetamine:adverse effects, Norepinephrine:blood, Psychoses, Substance-Induced, Serotonin:bloo.   

: Recreational use of the synthetic methamphetamine derivative MDMA (3,4-methylenedioxymethamphetamine), the main constituent of the illegal drug "ecstasy", has increased dramatically in recent years. The reasons for ecstasy-associated cardiovascular complications like tachycardia, arrhythmias and hypertensive crises and psychiatric symptoms like psychotic episodes are not well understood. We have measured the plasma concentrations of 5-HIAA, 5-HT, norepinephrine, epinephrine and dopamine in 159 ecstasy users and controls. Ecstasy users showed elevated resting sympathetic activity, reflected in increased norepinephrine, epinephrine and dopamine levels. The levels of these catecholamines correlated positively with the cumulative dose and also with consumption during the last 30 days and 12 months. Although it is known that significant changes in 5-HT and 5-HIAA appear in the cerebrospinal fluid in ecstasy users, we could not detect alterations in serotonergic neurotransmitters in plasma in this large sample of subjects. Thus, in the drug-free interval, ecstasy users show lowered central serotonergic activity (lowered 5-HT and 5-HIAA concentrations in CSF) along with unchanged central noradrenergic and dopaminergic activity (HVA and MHPG unchanged in CSF) and elevated peripheral noradrenergic, dopaminergic and adrenergic activity along with unchanged peripheral serotonergic activity (plasma levels). We conclude, that the data presented here could argue for a noradrenergic hyperreactivity in the drug-free interval in ecstasy users resulting from previous ecstasy consumption. Also for an association with psychotic episodes and cardiovascular complications like tachycardia, arrhythmias....

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Journal Article 2002; 23(1): 49-53 PubMed PMID: 11880862 Citation  Keywords:  Aging:physiology, Animals, Circadian Rhythm, Freund's Adjuvant:administration & dosage, Hydroxyindoleacetic Acid:metabolism, Injections, Subcutaneous, Male, Melatonin:metabolism, Norepinephrine:metabolism, Pineal Gland:metabolism, Rats, Rats, Wistar, Sero.   

OBJECTIVES: This study was performed to search for changes in rat pineal function attributed to age and immunization with Freund's adjuvant.

METHODS: Young (2 months) and old (18-20 months) Wistar rats were injected s.c. with Freund's adjuvant or its vehicle. Eighteen days later, at the acute phase of arthritis, pineal concentration of serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), norepinephrine (NE) and melatonin was measured by high pressure liquid chromatography at 4 different time intervals throughout the nocturnal activity span.

RESULTS: Old rats had the lowest pineal 5-HT and 5-HIAA content, the decrease in 5-HIAA exceeding that of 5-HT; consequently, old rats had the lowest 5-HIAA/5-HT ratio, an index of pineal 5-HT turnover. Although immunization did not affect globally pineal 5-HT or 5-HIAA levels, significant interactions "immunization x age" and "immunization x time" were found, i.e., immunization augmented pineal 5-HT content at the beginning of the activity span in young rats and at second half of the activity span in young and old rats, and increased pineal 5-HIAA concentration in young rats at the second part of the activity span only. Freund's adjuvant treatment increased pineal 5-HT turnover exclusively in old rats, an effect mainly seen during the second part of the activity span. Old rats exhibited the lowest pineal NE and melatonin levels, immunization further depressing them.

CONCLUSION: The effect of immunization with Freund's adjuvant on a number of pineal pre- and postsynaptic parameters are age-dependent....

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Journal Article 2018; 39(3): 205-208 PubMed PMID: 30431739 Citation  Keywords:  Adult, Aged, Bipolar Disorder:complications, Female, Humans, Injections, Intramuscular, Injections, Intravenous, Logistic Models, Male, Middle Aged, Multivariate Analysis, Psychomotor Agitation:drug therapy, Retrospective Studies, Serotonin Uptake Inhibit.   

OBJECTIVES: Trazodone is a multifunctional triazolopyridine drug with antidepressant, anxiolytic, sedative, and hypnotic properties. The current retrospective study was designed to investigate the effectiveness of trazodone for reducing acute psychomotor activation (PA) in patients with bipolar disorder (BD). We specifically reasoned that a parenteral route of administration could offer potential advantages in this clinical setting. METHODS: We assessed the effectiveness and safety of parenteral trazodone in a retrospective study conducted in 64 inpatients with BD and acute PA. The effectiveness assessment was the Clinical Global Impression Scale - Severity Of Illness (CGI-S) rated before the administration of parenteral trazodone (baseline) and at the end of treatment. A post-treatment reduction in CGI-S score ≥ 20% compared with baseline was considered as the primary outcome measure. RESULTS: Administration of parenteral trazodone was associated with significant improvements in CGI-S scores from baseline (5.4 ± 0.9) to the end of the study (4.2 ± 1.0; p < 0.001, Wilcoxon matched-pairs signed-ranks test). A total of 34 patients (53.1%) showed a post-treatment reduction in CGI-S score ≥ 20% compared to baseline. Multivariable binary logistic regression analysis using a forward selection procedure identified treatment duration (in days) as the only independent predictor of post-treatment reduction in CGI-S score ≥ 20% (odds ratio: 1.28; 95% confidence interval: 1.02-1.60, p <0.05). Adverse effects occurred in 13 (20.3%) patients. CONCLUSIONS: Parenteral trazodone is well-tolerated and effective in 53.1% of patients with BP and acute PA. Treatment duration was identified as an independent predictor of response in our sample....

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