The aim of the present study was to develop an experimental paradigm for the study of serotonergic neurotransmission in humans using positron emission tomography and the 5-HT2A selective radioligand [18F]altanserin. [18F]altanserin studies were conducted in seven subjects using the bolus/infusion approach designed for attaining steady state in blood and brain 2 hours after the initial [18F]altanserin administration. Three hours after commencement of radiotracer administration, 0.25 mg/kg of the selective serotonin reuptake inhibitor, citalopram (Lundbeck, Valby, Denmark), was administered to all subjects as a constant infusion for 20 minutes. To reduce 5-HT1A-mediated autoinhibition of cortical 5-HT release, four of the seven subjects were pretreated with the partial 5-HT1A agonist pindolol for 3 days at an increasing oral dose (25 mg on the day of scanning). In each subject, the baseline condition (120 to 180 minutes) was compared with the stimulated condition (195 to 300 minutes). Despite a pronounced increase in plasma prolactin and two subjects reporting hot flushes compatible with an 5-HT-induced adverse effect, cortical [18F]altanserin binding was insensitive to the citalopram challenge, even after pindolol pretreatment. The biochemical and cellular events possibly affecting the unsuccessful translation of the citalopram/pindolol challenge into a change in 5-HT2A receptor binding of [18F]altanserin are discussed.
In a cross-sectional study, the serum concentrations of inhibin B and prolactin of 96 male current welders were compared with the concentrations measured in 96 age-matched referents. Also, 23 patients who were all former welders diagnosed as having welding-related manganism were studied. The current welders' geometric mean (GM) airborne exposure to manganese (Mn) was 121 microg m(-3) (range 7-2320). The serum concentrations of prolactin adjusted for age and smoking habits (GM 193 mIU l(-1) vs. 166 mIU l(-1); p=0.047) and inhibin B adjusted for alcohol consumption (arithmetic mean (AM) 151 ng l(-1) vs. 123 ng l(-1); p=0.001) were higher in the welders compared with the referents. The whole blood Mn concentration was associated with the serum prolactin concentrations. Tobacco smoking resulted in lower serum prolactin concentrations. The GM serum prolactin concentrations of the patients did not significantly differ from that of the referents, but their AM serum inhibin B concentration was statistically significantly lower. The results may suggest an effect of Mn on the pituitary that is reversible upon cessation of exposure. Lower inhibin B concentrations in the patients could point to a functional impairment of the testicular Sertoli cells, that may be caused by a welding fume component or other factors in their work environment.
OBJECTIVE: To investigate the prevalence of hyperprolactinemia and common hyperprolactinemia-related symptoms and explore the association between them in patients using a modern antipsychotic drug regimen and, in addition, investigate the prevalence of the inert fraction of prolactin called macroprolactin, which, to our knowledge, has not been investigated systematically in this population before. Macroprolactin may cause misdiagnosis of hyperprolactinemia. METHOD: A cross-sectional design was applied, and 106 patients who were using antipsychotics for symptoms of psychosis were included. RESULTS: Hyperprolactinemia was found in 39% of the patients. Women were overrepresented in the group with the highest prolactin levels. Macroprolactin was not detected in any cases. Several of the second-generation antipsychotics were associated with hyperprolactinemia. Pearson correlation between prolactin level and symptoms revealed no association, and some patients did not report any symptoms despite grossly elevated levels of biologically active prolactin. CONCLUSIONS: The results suggest that hyperprolactinemia is still an important and prevalent side effect. In patients using antipsychotics with prolactin-elevating potential, prolactin levels should be routinely measured to prevent potential long-term complications of "silent" hyperprolactinemia, although we are still in the early stages of knowing what to do with the information.
Birth size has been positively associated with age at menarche and height in adolescence and adulthood, but the relevant biological mechanisms remain unclear. Among 262 Norwegian term-born singleton girls, birth size measures (weight, length, ponderal index, head circumference and subscapular skin-fold thickness) were analysed in relation to adolescent hormone levels (oestradiol, prolactin, dehydroepiandrosterone sulphate, androstenedione and free testosterone index), age at menarche and adolescent (ages 12.7-15.5 years) and body size (height, weight, body mass index and waist-to-hip ratio) using survival analysis and general linear modelling. The results were adjusted for gestational age at birth, age and menarcheal status at measurement in adolescence and maternal age at menarche. Birth weight, birth length and head circumference were positively associated with adolescent weight and height, and small birth size was associated with earlier age at menarche. Subscapular skin-fold thickness at birth was not associated with adolescent body size, but low fold-thickness was associated with earlier age at menarche. Measures of birth size were inversely related to circulating levels of dehydroepiandrosterone sulphate in adolescence, but there was no clear association with other hormones. These results suggest that physical and sexual development in puberty and adolescence is influenced by prenatal factors, and in combination, these factors may influence health and disease later in life.
The aim of this study was to assess the specific biomedico-social effects of participating in cultural events and gentle physical exercise effects apart from the general effect of participating in group activities. This was a randomized controlled investigation using a factorial design, where attending cultural events and taking easy physical exercise were tested simultaneously. The 21 participants, aged between 18 and 74 y were from a simple random sample of people registered as residents in Umeå, a town in northern Sweden. Among the 1000 in the sample, 21 individuals (11 men, 10 women) were recruited into the experiment. Two out of the 21 subjects dropped out and were discounted from our analysis. Nine people were encouraged to engage in cultural activity for a two-month period. Diastolic blood pressure in eight of these nine was significantly reduced following the experiment. There were no marked changes observed in either systolic or diastolic blood pressure in those not required to engage in any form of extra-cultural activity. A decrease in the levels of both adrenocorticotropical hormone (ACTH) and s-prolactin was observed in culturally stimulated subjects, whereas the average baseline s-prolactin level of 7 ng/l for the non-culturally stimulated group was unchanged after the experiment. Physical exercise produced an increase in the high density lipoprotein (HDL) cholesterol level and in the ratio of HDL to LDL (low density lipoprotein). It was concluded that cultural stimulation may have specific effects on health related determinants.
Ayahuasca is an Amazonian psychotropic plant tea combining the 5-HT2A agonist N,N-dimethyltryptamine (DMT) and monoamine oxidase-inhibiting ß-carboline alkaloids that render DMT orally active. The tea, obtained from Banisteriopsis caapi and Psychotria viridis, has traditionally been used for religious, ritual, and medicinal purposes by the indigenous peoples of the region. More recently, the syncretistic religious use of ayahuasca has expanded to the United States and Europe. Here we conducted a double-blind randomized crossover clinical trial to investigate the physiological impact of ayahuasca in terms of autonomic, neuroendocrine, and immunomodulatory effects. An oral dose of encapsulated freeze-dried ayahuasca (1.0 mg DMT/kg body weight) was compared versus a placebo and versus a positive control (20 mg d-amphetamine) in a group of 10 healthy volunteers. Ayahuasca led to measurable DMT plasma levels and distinct subjective and neurophysiological effects that were absent after amphetamine. Both drugs increased pupillary diameter, with ayahuasca showing milder effects. Prolactin levels were significantly increased by ayahuasca but not by amphetamine, and cortisol was increased by both, with ayahuasca leading to the higher peak values. Ayahuasca and amphetamine induced similar time-dependent modifications in lymphocyte subpopulations. Percent CD4 and CD3 were decreased, whereas natural killer cells were increased. Maximum changes occurred around 2 hours, returning to baseline levels at 24 hours. In conclusion, ayahuasca displayed moderate sympathomimetic effects, significant neuroendocrine stimulation, and a time-dependent modulatory effect on cell-mediated immunity. Future studies on the health impact of long-term ayahuasca consumption should consider the assessment of immunological status in regular users.
Fifty-seven breast cancers were diagnosed among indigenous Greenlandic women from 1950 to 1974. An additional 22 cases registered between 1975 and 1979 represent a minimum number and were only used as basis for minimum incidence rates. Changes in age-adjusted rate, age-specific incidence pattern, and relative risk were consistent with an upward shift from a population of low risk between 1950 and 1969 to one of intermediate risk from 1970 onward, a finding that relates well to increased urbanization and westernization. The risk of breast cancer in Greenland may be associated with consumption of saturated fats but is seemingly not correlated to total fat intake which has always been on a par with high-risk Danish levels. An association with diet may in reality have been stronger than suggested but weakened by a counterbalancing effect of high fertility, especially in the youngest age groups. Evaluation of histological features and survival did not suggest differences which could favorably compare with findings in white population groups contrary to reported results from the population of Japan, also one of low risk and of mongoloid origin. Further studies should consider dietary intakes, endocrine variations, and breast fluid secretion with special attention to girls at the age of menarche.
This Canadian Society of Clinical Chemists (CSCC) sponsored position statement addresses the problem of nonuniformity of standardization of polypeptide hormone analyses. First we review the structural diversity of selected polypeptide hormones including growth hormone (GH), prolactin, follitropin (FSH), lutropin (LH), human chorionic gonadotropin (hCG), and thyrotropin (TSH) and the problem that this heterogeneity creates. The history and availability of reference materials for the analyses of these hormones are then summarized. Finally we make a list of recommendations regarding standardization, methods of measurement, and reporting of polypeptide hormone results. Implementation of the recommendations will lead to improvement in inter-laboratory comparability and more useful hormone assays.
Acute dyspnea affects a large heterogeneous patient group with high mortality and readmission rates.
To investigate if cardiometabolic biomarkers and clinical characteristics predict readmission and death in patients hospitalized for acute dyspnea.
65 dyspnea patients at a general internal medicine ward were followed for six months. The combined endpoint was readmission or death.
Cardiometabolic biomarkers at admission were related to the endpoint in Cox proportional hazard models (adjusted for sex, age, oxygen saturation, respiratory rate and C-reactive protein (CRP)). The biomarkers tissue-type plasminogen activator (tPA), prolactin (PRL), tumor necrosis factor receptor superfamily member 6 (FAS) and C-C motif chemokine 3 (CCL3) were independently and significantly related to the endpoint and combined into a biomarker risk score (BRS). Each SD increment of the BRS conferred a hazard ratio (HR) of 2.13 (1.39-3.27) P=0.001. The top vs bottom tertile of the BRS conferred a HR of 4.75 (1.93-11.68) P=0.001. Dyspnea severity was also associated with worse outcome, HR=3.43 (1.28-9.20) P=0.014. However, when mutually adjusted the BRS remained significant (P=0.004) whereas dyspnea severity was not. The BRS was related to the endpoint among patients with mild to moderate dyspnea (P=0.016) but not among those with severe dyspnea.
A score of tPA, PRL, FAS and CCL3 predicts 6-month death and readmission in patients hospitalized for acute dyspnea and may prove useful to optimize length of stay and follow-up. Although the BRS outweighs dyspnea severity in prediction of the endpoint, its prognostic role is strongest in mild-moderate dyspnea.
Thirty-two female participants in a mobilising labour market programme offering temporary, alternative employment in Sweden were followed longitudinally for one year, including a six month post participation follow-up period. It can be hypothesised that an important aspect of the physiological effects of unemployment is a change in the balance between anabolic and catabolic activities in the body and that re-employment should lead to a shift towards anabolism. An earlier study of a smaller subset of the data, however, including both men and women, showed increased prolactin and decreased dehydroepiadrosterone sulphate (DHEA-s) levels, contrary to the initial hypothesis. In the present analysis, intended to elucidate these results, psychophysiological data were summarised in two indices, one connected with anabolism (made up of testosterone and DHEA-s) and one with catabolism (prolactin, gamma-glutamyl transferase, aspartate amino transferase, alpha levuline amino transferase, and body mass index). In addition, self-rated anxiety, depression, hopelessness and personal control were analysed. The results indicate that the effect of 'better' activities within the programme was a temporary increase in anabolism, possibly indicating lower stress levels, and the effect of 'worse' activities, on the one hand, a temporary decrease in the catabolic index, probably reflecting repressed alcohol consumption, and, on the other hand, impaired anabolism. There was also a general but transient decrease in depressiveness measured by the Hospital Anxiety and Depression Scale. The results seem to imply that it is difficult to achieve lasting effects through a relatively short participation in a mobilising programme.