Gender and the use of hormonal contraception in women are not associated with cerebral cortical 5-HT 2A receptor binding

Gender influences brain function including serotonergic neurotransmission, which may play a role in the well-known gender variations in vulnerability to mood and anxiety disorders. Even though hormonal replacement therapy in menopause is associated with globally increased cerebral 5-HT_2A receptor binding it is not clear if gender or use of hormonal contraception exhibits associations with 5-HT_2A receptor binding. We found no significant effect of gender on cortical 5-HT_2A receptor binding (P=0.15, n=132). When adjusting for the personality trait neuroticism, known to be positively correlated to frontolimbic 5-HT_2A receptor binding and to be more pronounced in women, again, the effect of gender was not significant (P=0.42, n=127). Also, the use of hormonal contraception (n=14) within the group of pre-menopausal women (total n=29) was not associated with cortical 5-HT_2A receptor binding (P=0.31). In conclusion, neither gender, nor the use of hormonal contraception in premenopausal women was associated with cortical 5-HT_2A receptor binding.     

The value of mucus hypersecretion as a predictor of mortality and hospitalization. An 11-year register based follow-up study of a random population sample of 876 men

The value of mucus hypersecretion as a predictor of mortality and hospitalization was studied in a random population sample of 876 men, aged 46-69 years. The cohort was examined in 1974 with the British Medical Research Council questionnaire and lung function tests. A total of 219 men had died between 1974 and 1985. Twenty-seven men died from lung cancer and 14 died from other respiratory diseases. Mucus hypersection was not found to be significantly related to overall mortality after controlling for age, smoking and FEV1. Similarly, mucus hypersection was not a predictor of lung cancer mortality after controlling for age and smoking habits. The predictive value concerning death due to respiratory disease could not be examined because of the limited number of deaths in the cohort from these diseases. Mucus hypersecretion was not significantly related to hospitalization in general. Mucus hypersecretion had a significant predictive value concerning hospitalization due to respiratory disease in general, but the value was insignificant after controlling for FEV1. In contrast to this, mucus hypersecretion was a significant predictor of hospitalization due to COPD, even after controlling for FEV1. We conclude that the predictive value of mucus hypersecretion concerning mortality is of no value. Concerning morbidity, our results show that, although secondary to airflow obstruction, mucus hypersecretion must be viewed as an indicator of severity of COPD.     

Fucoidin, but not yeast polyphosphomannan PPME, inhibits leukocyte rolling in venules of the rat mesentery

Leukocyte rolling in venules is inhibited by several sulfated polysaccharides, by antibodies to the leukocyte adhesion receptor L- selectin (LECAM-1), and by recombinant soluble L-selectin. The sulfated fucose polymer fucoidin and the polyphosphomannan PPME bind to L- selectin and inhibit L-selectin-mediated lymphocyte adhesion to lymph node high endothelial venules (LN-HEV). We investigated whether fucoidin and PPME also inhibit leukocyte rolling. Rolling leukocyte flux was determined by intravital microscopy in 47 venules (diameter 21 to 50 microns) of the rat mesentery with and without micro-infusion of each reagent through 8-microns glass micropipettes. Micro-infusion (1 mg/mL) or intravenous (IV) injection (25 mg/kg) of fucoidin, but not vehicle, reduced leukocyte rolling by greater than 90%. The half- effective concentration was approximately 2.5 micrograms/mL. Stroboscopic fluorescence video microscopy showed that fucoidin decreased the fraction of rolling leukocytes from 44% of all leukocytes passing the venules in control to less than 1%. PPME micro-infusion (1 mg/mL) or IV injection (14 mg/kg) did not reduce leukocyte rolling. Hence, leukocyte rolling differs from lymphocyte homing with respect to the effect of PPME. This may be related to fucoidin binding to L- selectin with greater affinity than PPME. Alternatively, inflamed venular endothelium may express a ligand for L-selectin different from that constitutively expressed on LN-HEV.     

Bedside Coagulometry During Intravenous Heparin Therapy after Coronary Angioplasty

In order to assess the applicability of a bedside coagulometer for measurement of b-APTT, serial blood samples were obtained from 20 patients receiving intravenous heparin treatment following PTCA, and from 5 healthy volunteers. B-APTT was analysed bedside on the Hemochron® coagulometer; p-APTT and p-heparin, measured asfactor anti-Xa activity, were analysed ex-vivo in the laboratory. B-APTT values, determined by the Hemochron coagulometer, were closely correlated to p-heparin (r=0.83, p<0.001, SD=52 seconds (sec), n=89), and duplicate determinations of b-APTT on the Hemochron coagulometer showed an acceptable repeatability. However, an APTT ratio of 1.5–2.5 was not related to a therapeutic p-heparin level, neither as measured by the Hemochron device nor in the laboratory. Abstract. Background: When administering intravenous heparin during angioplasty procedures, a quick and reliable method for safe and effective monitoring of anticoagulation is necessary. Objective: To assess the applicability of a bedside coagulometer, measuring the activated partial thromboplastin time (APTT) in patients receiving intravenous heparin treatment after percutaneous transluminal coronary angioplasty (PTCA). Methods: In patients with stable angina pectoris, receiving intravenous heparin treatment following PTCA, serial blood samples were obtained by venipuncture and from the arterial sheath for analysis of whole blood APTT (b-APTT), and plasma heparin concentration (p-heparin). Additionally, in healthy volunteers blood samples were obtained after a single bolus injection of heparin. B-APTT was analysed bedside on the Hemochron® coagulometer; p-APTT and p-heparin, measured as factor anti-Xa activity, were analysed ex-vivo in the laboratory using conventional analytical methods. Results: In 20 patients a total of 94 venous and 69 arterial blood samples were analysed, and in five healthy volunteers analyses were performed in 20 venous blood samples. B-APTT values, determined by the Hemochron coagulometer, were closely correlated to p-heparin (r=0.83, p<0.001, SD=52 seconds (sec), n=89). An APTT ratio of 1.5–2.5 was not related to a therapeutic p-heparin level, however, neither when using APTT assessed by the Hemochron device nor APTT measured in the laboratory. Duplicate determinations of b-APTT on the Hemochron coagulometer showed an acceptable repeatability; the mean difference between duplicate measurements was 4[emsp4 ] sec (coefficient of variation (c.v.)=6%, p<0.05, n=163). Conclusions: In patients receiving intravenous heparin after PTCA treatment, b-APTT values measured by the Hemochron method showed an acceptable repeatability and were significantly correlated to p-heparin.     

Hypothalamic-Pituitary and Thyroid Function in Chronic Alcoholics with Neurological Complications

Endocrinological tests were performed in 14 chronic alcoholic men with signs of intellectual impairment and/or peripheral neuropathy. All had been abstinent from alcohol for at least 1 month. Basal serum growth hormone (GH) was consistently increased in only one patient whereas the GH responses to insulin hypoglycemia stimulation was normal in all patients. Thyroid function values (T4, T3, rT3, TSH) were normal in all patients whereas baseline serum prolactin values were significantly increased in alcoholics as compared with a control group. In a combined TRH- and GnRH-stimulation tests, GH-responses were also normal whereas TSH and prolactin responses were blunted or absent in about half of the patients, the responses correlating significantly (p less than 0.01). It is concluded that disturbances in the hypothalamic-pituitary axis may occur in chronic alcoholics with nervous impairment independently of the physical deterioration, which often is associated with chronic alcoholism.     

The 5‐HT4 receptor levels in hippocampus correlates inversely with memory test performance in humans

The cerebral serotonin (5‐HT) system is involved in cognitive functions such as memory and learning and animal studies have repeatedly shown that stimulation of the 5‐HT type 4 receptor (5‐HT₄R) facilitates memory and learning and further that the 5‐HT₄R modulates cellular memory processes in hippocampus. However, any associations between memory functions and the expression of the 5‐HT₄R in the human hippocampus have not been investigated. Using positron emission tomography with the tracer [¹¹C]SB207145 and Reys Auditory Verbal Learning Test we aimed to examine the individual variation of the 5‐HT4R binding in hippocampus in relation to memory acquisition and consolidation in healthy young volunteers. We found significant, negative associations between the immediate recall scores and left and right hippocampal BP_ND, (p = 0.009 and p = 0.010 respectively) and between the right hippocampal BP_ND and delayed recall (p = 0.014). These findings provide evidence that the 5‐HT₄R is associated with memory functions in the human hippocampus and potentially pharmacological stimulation of the receptor may improve episodic memory. Hum Brain Mapp 34:3066–3074, 2013. © 2012 Wiley Periodicals, Inc.     

Stimulation of the subthalamic nucleus at an earlier disease stage of Parkinson's disease: Concept and standards of the EARLYSTIM-study

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an established treatment for advanced Parkinson's disease (PD) with disabling motor complications. However, stimulation may be beneficial at an earlier stage of PD when motor fluctuations and dyskinesia are only mild and psychosocial competence is still maintained. The EARLYSTIM trial was conducted in patients with recent onset of levodopa-induced motor complications (≤3 years) whose social and occupational functioning remained preserved. This is called ‘early’ here. The study was a randomized, multicenter, bi–national pivotal trial with a 2 year observation period. Quality of life was the main outcome measure, and a video-based motor score was a blinded secondary outcome of the study. Motor, neuropsychological, psychiatric and psychosocial aspects were captured by established scales and questionnaires. The patient group randomized here is the earliest in the disease course and the youngest recruited in controlled DBS trials so far. The methodological innovation for DBS-studies of this study lies in novel procedures developed and used for monitoring best medical treatment, neurosurgical consistency, best management of stimulation programming, blinded video assessment of motor disability, and prevention of suicidal behaviors.