Antiserotonergic inhibition of calcitonin-induced increase of β-endorphin,ACTH, and cortisol secretion

Summary In a previous study we observed that calcitonin increases -endorphin, ACTH, and cortisol secretion. We assumed that calcitonin might have a modulatory role on the pituitary function. The present study was initiated to clarify whether this effect is due to a direct pituitary stimulation or to an indirect stimulation through CRF (corticotropin releasing factor).Fourteen healthy subjects, aged 30–60 years were investigated. All the subjects received 100IU Salmon calcitonin Sandoz i.v. at 8a.m. (time 0). Plasma -endorphin, ACTH and cortisol were estimated every 30min from – 30 to 120 min by specific radioimmunoassay. The same parameters were estimated a second time, at the same intervals, when cyproheptadine 8 mg (7 subjects) and 40 mg propranolol (7 subjects) were given per os at – 30 min and calcitonin i.v. at time 0. -endorphin, ACTH and cortisol levels (Mean ±SEM) rose significantly after calcitonin (peak value at 30–90 min) from 5.2 ±0.7 to 15.1±2.6 pmol/l; from 43.0±2.7 to 70.7±4.1 pg/ml and from 10.6±1.5 to 19.6 ±2.1 g/100 ml respectively (p< 0.0001 by analysis of variance and covariance and repeated measures). Propranolol 40 mg (per os) administered at time – 30 did not alter the response of -endorphin, ACTH and cortisol to calcitonin (infused at time 0).Cyproheptadine, the antiserotonergic substance that inhibits the synthesis and release of CRF completely inhibited the stimulatory effect of calcitonin.We conclude that probably calcitonin has a modulatory role on the hypothalamo-pituitary adrenal axis and that it acts at the hypothalamic level probably by stimulating CRF secretion.     

The field-stimulated vas deferens of the streptozotocin-diabetic mouse: effects of prazosin, α,β-methylene ATP,and variation of stimulation parameters

Summary The question of diabetic neuropathy was studied in the field-stimulated isolated vas deferens of the mouse. The animals were treated with either buffer or streptozotocin (170 mg/kg i.v.) 2 or 4 weeks, respectively, beforehand. Stimulus-response relationships were tested by variation of frequency (VF) at constant pulse width and by variation of pulse width (VP) at constant frequency. The adrenergic twitch component was eliminated by prazosin (1 M) and the purinergic component by ,-methylene ATP (MeATP, 10 M). The diabetes did not alter the muscular contractility (tested with KCl) and left the twitch-inhibiting effects of prazosin and MeATP unchanged, thereby revealing no difference in susceptibility between noradrenergic and purinergic mechanisms. However, in diabetic vasa, the maximal effectiveness of stimulation was decreased with VF but not VP, whereas the sensitivity of intramural neurons (50% effective frequency or pulse width, respectively) was unchanged with VF and reduced with VP. This may suggest that the diabetic neuron releases less transmitter (VF), which can be compensated for by the activation of less sensitive neurons (VP). Actually, the uptake of³H-noradrenaline into the (4 weeks-) diabetic vas was normal but the stimulation-induced fractional release of tritium was decreased by 26%. It is concluded that a sympathetic neuropathy occurred in the vas deferens of the streptozotocin-diabetic mouse.     

Variety of Self-Injury: Is the Number of Different Methods of Non-Suicidal Self-Injury Related to Personality,Psychopathology, or Functions of Self-Injury?

This study explored the association between number of methods of Nonsuicidal Self-Injury (NSSI) and personality, psychopathology, and functions of NSSI. Two combined undergraduate samples reporting a history of NSSI (n = 149) completed measures of personality, psychopathology, and NSSI. A series of regression analyses indicated that Conscientiousness, Openness, and two functions of NSSI (i.e., Automatic Negative Reinforcement and Social Negative Reinforcement) shared significant relationships with the number of NSSI methods participants engaged in. These findings demonstrate that, after accounting for NSSI frequency, a relationship exists among specific personality factors, NSSI functions, and engagement in additional methods of NSSI.     

Do knowledge of, perception of, and attitudes toward epilepsy affect the quality of life of Turkish children with epilepsy and their parents?

The main goal of this study was to evaluate knowledge of, perceptions of, and attitudes toward epilepsy and then to correlate knowledge with quality of life and stigmatization of children with epilepsy and their families. Specific questionnaires were administered to children aged 8 to 17 with epilepsy (n=220) and their parents (n=313). Poor school performance, less social support, less self-esteem, higher anxiety, greater stigmatization, and more depressive symptoms were documented in children who were less knowledgeable (P<0.05). Parents were found to be more knowledgeable about the antiepileptic drugs used, understanding both the effects and the side effects of the medications (P<0.05). Family activities were less restricted if they were more knowledgeable and these parents reported worrying less about their children (P<0.05). Knowledge about epilepsy is associated with less perceived stigmatization and social isolation, as well as fewer depressive symptoms and misperceptions.     

Importance of ‘inflammatory molecules’, but not necessarily of inflammation,in the pathophysiology of bipolar disorder and in the mechanisms of action of anti-bipolar drugs

It is often supposed that inflammation plays a major role in the pathophysiology of bipolar disorder and that reduction of inflammation by the classical anti-bipolar drugs, the lithium ion (lithium), carbamazepine and valproic acid, partly explain their therapeutic effect. The present mini-review summarizes data for enhanced expression in bipolar patients of ‘inflammatory molecules’, i.e., cytokines and metabolites of arachidonic acid (e.g., prostaglandins) and the enzymes (e.g., COX2) that catalyze this metabolism. However, it points out that enhanced transmitter activity during manic phases may play a major part in this upregulation. It also shows that chronic treatment with any of the 3 anti-bipolar drugs, known to decrease expression of the enzyme that releases arachidonic acid (cPLA₂) in whole brain, has this effect only in neurons, whereas it upregulates cPLA₂ expression in astrocytes. Literature data are presented that this upregulation may have therapeutically beneficial effects in bipolar disorder, supporting increasing evidence for involvement of not only neurons but also astrocytes in bipolar disorder and anti-bipolar drug action.     

Plasma amyloid-β as a function of age, level of intellectual disability, and presence of dementia in Down syndrome

Adults with Down syndrome (DS) are at risk for developing Alzheimer's disease (AD). While plasma amyloid-β (Aβ) is known to be elevated in DS, its relationship to cognitive functioning is unknown. To assess this relationship, samples from two groups of subjects were used. In the first group, nondemented adults with DS were compared to: 1) a group of young and old individuals without DS and 2) to a group of patients with AD. Compared to these controls, there were significantly higher levels of plasma Aβ in nondemented adults with DS while AD patients showed lower levels of plasma Aβ. A larger second group included demented and nondemented adults with DS, in order to test the hypothesis that plasma Aβ may vary as a function of dementia and Apolipoprotein E (ApoE) genotype. Plasma Aβ levels alone did not dissociate DS adults with and without dementia. However, in demented adults with DS, ApoE4 was associated with higher Aβ40 but not Aβ42. After controlling for level of intellectual disability (mild, moderate, severe) and the presence or absence of dementia, there was an improved prediction of neuropsychological scores by plasma Aβ. In summary, plasma Aβ can help predict cognitive function in adults with DS independently of the presence or absence of dementia.     

Predictive Modeling of Quality of Life,Family Dynamics,and School Violence in Adolescent Students from Medellín,Colombia, 2014

The purpose of this study was to develop a predictive population model with respect to quality of life, school violence, and family dynamics in adolescent students from Medellín, Colombia. Cross-sectional, explanatory study was realized with 3460 adolescents using probability sampling for selection. Structural equation modeling was performed. The results of this study showed that the quality of life of adolescents is determined based on physical health, psychology, leisure time, relationship with parents, peer support, and perception of academic well-being. School violence negatively affects quality of life; bullying is the factor with the least predictive capacity, and relationship with teachers is the most predictive factor. The improvement of family dynamics is associated with an improvement in quality of life. The results show lines of action to guide the design of intersectoral and interdisciplinary policies aimed at family dynamics and the school environment as primary support networks for improving adolescents’ quality of life.     

Comparison of phenelzine and geometric isomers of its active metabolite, β-phenylethylidenehydrazine, on rat brain levels of amino acids, biogenic amine neurotransmitters and methylamine

Phenelzine is a monoamine oxidase (MAO) inhibitor used in treatment of depression and anxiety disorders. It also elevates brain levels of γ-aminobutyric acid (GABA) and inhibits primary amine oxidase (PrAO), an enzyme whose activity and/or expression has been reported to be increased in diabetes mellitus, Alzheimer’s disease and cardiovascular disorders. Phenelzine is not only an inhibitor of, but also a substrate for, MAO and it has been suggested that an active metabolite, namely β-phenylethylidenehydrazine (PEH), is responsible for phenelzine’s effects on amino acids. PEH is also a strong inhibitor of PrAO but has weak effects on MAO. PEH has a double bond and can thus exist as (E)- and (Z)-geometric isomers, but to date the two isomers have not been compared with regard to their neurochemical effects. We have investigated the effects of phenelzine, (E)- and (Z)-PEH on rat whole brain levels of amino acids, biogenic amine neurotransmitters and methylamine (an endogenous substrate of PrAO). Under the conditions used in the study, (E)- and (Z)-PEH appear to be equivalent in their neurochemical properties. Both PEH isomers and phenelzine produced marked increases in rat brain levels of GABA and alanine while decreasing brain levels of glutamine. Phenelzine increased brain levels of biogenic amine neurotransmitters (noradrenaline, dopamine and serotonin), whereas neither PEH isomer altered levels of these neurotransmitters to a considerable extent. All three drugs significantly increased rat brain levels of methylamine, with (E)- and (Z)-PEH causing a greater increase than phenelzine. These results are discussed in relation to the possible therapeutic applications of these drugs.