Associations between post-traumatic stress symptoms and sleep/circadian parameters: Exploring the effect of chronotype as a moderator variable.

The present study aimed at evaluating how post-traumatic stress symptoms (PTSS) are associated with rest-activity circadian and sleep-related parameters, assessed both subjectively (via questionnaires) and objectively (via actigraphy). Specifically, we explored whether chronotype could moderate the association between sleep/circadian parameters and PTSS. Participants (n = 120 adults; mean age 35.6 ± 14; 48 male) were assessed through the Trauma and Loss Spectrum Self Report (TALS-SR) for lifetime PTSS, the reduced version of the Morningness-Eveningness Questionnaire (rMEQ) for chronotype, the Pittsburgh Sleep Quality Index (PSQI) for self-reported sleep quality, and wrist actigraphy for sleep and circadian parameters. Eveningness, poor self-reported sleep quality, lower sleep efficiency (SE), lower interdaily stability (IS), and higher intradaily variability (IV) were correlated with higher TALS-SR scores. Regression analyses showed that IV, SE, and PSQI remained associated with TALS symptomatic domains after adjusting for potentially confounding factors (age and gender). Moderation analysis showed that only the PSQI remained significantly associated with TALS symptomatic domains; however, the interaction with chronotype was not significant. Targeting self-reported sleep disturbances and rest-activity rhythms fragmentation could mitigate PTSS. Although the effect of chronotype as a moderator of the associations between sleep/circadian parameters and PTSS was not significant, eveningness was associated with higher TALS scores, thus confirming the vulnerability of evening types to worse stress reactions.

Deiodination in cancer growth: the role of type III deiodinase.

Thyroid hormone (TH) is a pleiotropic agent that has widespread biological functions, i.e., it controls cellular growth, tissue development and homeostasis and neoplastic transformation. Suitable TH levels are critical for the development of various types of tissues and are essential for the regulation of metabolic processes throughout life. The serum concentrations of TH affect its biological activity. Moreover, at tissue level, TH action is regulated by the expression and activity of deiodinases, i.e., the enzymes that mediate the metabolic pathways by activating and/or inactivating TH. The type I and II deiodinases (D1 and D2) initiate TH action by converting thyroxine (T4) into the active TH form (T3), whereas type III deiodinase (D3) mediates the local attenuation of TH by converting T4 and T3 into the inactive metabolites rT3 and T2, respectively. The deiodinase system is a potent mechanism of pre-receptoral control of TH action; it is often altered in such pathological conditions as cancer. D3 is widely expressed in embryonic tissues and in placenta, where it blocks excessive maternal-to-fetal transfer of TH. In contrast, during late neonatal and adult life, D3 is expressed mainly in the central nervous system and skin. Interestingly, D3 expression is re-activated in various types of human cancers. Here we review recent evidence that D3 expression plays a crucial role in human carcinogenesis, and speculate as to its complex role in the regulation of cell proliferation in several neoplastic contexts. It is conceivable that the local modulation of TH action via deiodinases is a powerful molecular tool to manipulate the intracellular TH status, thus influencing the growth and maintenance of selected hormone-dependent cancers.

Investigating the relationship between autistic traits and symptoms and Catatonia Spectrum.

BACKGROUND: In recent years, numerous studies have highlighted the overlap between autism spectrum disorder (ASD) and catatonia, both from a clinical and pathophysiological perspective. This study aimed to investigate the relationship between the autism spectrum (autistic traits and ASD signs, symptoms, and behavioral manifestation) and Catatonia Spectrum (CS). METHODS: A total sample of 376 subjects was distributed in four diagnostic groups. Subjects were assessed with the Structured Clinical Interview for DSM-5, Research Version, the Adult Autism Subthreshold Spectrum (AdAS Spectrum), and CS. In the statistical analyses, the total sample was also divided into three groups according to the degree of autism severity, based on the AdAS Spectrum total score. RESULTS: A statistically significant positive correlation was found between AdAS Spectrum and CS total score within the total sample, the gender subgroups, and the diagnostic categories. The AdAS Spectrum domains found to be significantly and strongly correlated with the total CS score were hyper-hypo reactivity to sensory input, verbal communication, nonverbal communication, restricted interests and rumination, and inflexibility and adherence to routine. The three groups of different autistic severity were found to be distributed across all diagnostic groups and the CS score increased significantly from the group without autistic traits to the group with ASD. CONCLUSIONS: Our study reports a strong correlation between autism spectrum and CS.

Tolerance to the sedative effect of lorazepam correlates with a diminution in cortical release and affinity for glutamate.

Benzodiazepines are anxiolytic, anticonvulsant, sedative and hypnotic compounds usually prescribed on a long-term basis. Chronic treatment with these compounds induces tolerance, which has been extensively attributed to modifications in the GABAergic neurotransmission. However, a compensatory increase in the excitatory response, named as an oppositional response, has also been put forward as a means for explaining such tolerance. Changes in the excitatory neurotransmission have been found in withdrawn rats after a long treatment with benzodiazepines but these modifications have not been conclusively studied during tolerance. In this work we studied several parameters of the glutamatergic neurotransmission in rats made tolerant to the sedative effect of 3 mg/kg (i.p.) of lorazepam (LZ). We found a decrease in the affinity of cortical NMDA receptors for (3)H-glutamate (K(D): 124.4 +/- 13.3 nM in tolerant rats, 71.6 +/- 10.4 nM in controls, P<0.05) together with a decrease in the in vitro 60 mM K(+)-stimulated cortical glutamate release (59+/- 12% vs. 153 +/- 38%, tolerant rats vs. controls, P<0.05). We conclude that tolerance to the sedative effect of LZ correlates with a decreased sensitivity for glutamate that may in turn diminish the cortical response to a chemical stimulus. Our findings constitute an evidence against the oppositional model of pharmacodynamic tolerance in this experimental condition.

Effect of triamterene on 5-hydroxytryptamine biosynthesis in different brain areas.

Triamterene is structurally similar to the natural cofactor of tryptophan hydroxylase, (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin. The hydroxylation of tryptophan has been studied by measuring the accumulation of 5-hydroxytryptophan (5-HTP) and the concentrations of 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in brainstem, frontal cortex and hypothalamus after inhibition of L-amino acid decarboxylase with benserazide hydrochloride and administration of either the vehicle or triamterene. Triamterene (30 mg/kg i.p.) decreased 5-HTP accumulation and 5-HT concentrations in brainstem and hypothalamus after 90 min; when the diuretic was given p.o. either acutely or chronically (triamterene 30 mg/kg twice daily during 4 days), no effect either on 5-HTP accumulation or on 5-HT and 5-HIAA concentrations was observed in the three brain areas studied. These results are in accordance with the 4 to 5 times higher concentrations of triamterene plus metabolites found in brainstem and hypothalamus after the acute i.p. administration of the drug than after an acute or chronic p.o. treatment. Hence, the effect of triamterene on 5-HT biosynthesis depends on the concentration it reaches in each brain area after i.p. or p.o. administration.

Adult-type hypolactasia and calcium availability: decreased calcium intake or impaired calcium absorption?

UNLABELLED: Adult-type hypolactasia, as mediated by a widespread genetic predisposition, not only reduces calcium intake but also calcium absorption in the presence of high amounts of lactose and may, therefore, promote osteoporosis. A lactose-reduced diet and lactose-free calcium supplements may reverse this imbalance. INTRODUCTION AND HYPOTHESIS: Adult-type hypolactasia (HL) defined by the LCT(-13910) polymorphism may reduce calcium intake by reducing dairy consumption and, therefore, promote osteoporosis. This study aimed to evaluate whether lactose also decreases intestinal calcium absorption in subjects with HL and whether lactose-reduced diet and lactose-free calcium supplementation as recommended could maintain bone mineral density (BMD). METHODS: Based on LCT genotyping, 73 postmenopausal women with and without HL underwent a conventional H(2) breath test with a concomitant oral strontium absorption test lasting 150 minutes, which closely reflects intestinal calcium absorption. In addition, we compared bone-specific laboratory parameters, lumbar and femoral BMD, and spinal radiographs to a similar bone assessment 5 years earlier. RESULTS: LCT genotyping and functional lactose malabsorption tests were highly correlated. Dairy product consumption was reduced by 80% in HL individuals. During concomitant lactose application, mean strontium absorption was blunted by 54% in HL subjects after 150 minutes (1272 +/- 629 microg/L vs. 2020 +/- 1130 microg/L in lactose tolerant subjects, p=0.001). Nevertheless, BMD in HL subjects remained stable with lactose-free calcium supplements during the observation period. CONCLUSION: Both decreased calcium intake as well as lactose-associated impaired calcium absorption may predispose subjects with HL to osteoporosis. Lactose-free calcium supplementation may help to maintain BMD in HL subjects.

Chronic administration of valproic acid induces a decrease in rat striatal glutamate and taurine levels.

The effect of acute and chronic (10 days) administration of 200 mg/kg (i.p.) of valproic acid (VPA) on endogenous levels of aspartate, glutamate, alanine, glycine and taurine in the cerebral frontal cortex and corpus striatum of rats was studied. Quantification of the amino acid levels was performed by HPLC.Valproic acid (VPA) did not either induce changes on these neurotransmitters contents in corpus striatum after acute treatment. After chronic administration we found a decrease on the endogenous levels of glutamic acid (24%, p < 0.05) which was related to an increase (250%, p < 0.02) of the in vitro KCl evoked release of glutamate. We found decrements in taurine endogenous levels (22%, p < 0.05) which was not associated with an increase of its release.In cerebral frontal cortex there was not found any change neither under the acute nor under the chronic condition.Thus, it may be conclude that chronic treatment with VPA produces decreases on the endogenous levels of glutamate and taurine. However the relevance of this effect concerning it therapeutic action remains unclear.

Presence of 5-hydroxy-indolacetic acid in Diloboderus abderus larvae without monoamine-oxidase-like activity.

The authors confirmed the presence of monoamines and 5-hydroxy-indolacetic acid (5-HIAA) in the cephalic region of Diloboderus abderus larvae employing a high pressure liquid chromatography (HPLC) with electrochemical detector. An anticholinesterase insecticide produced an increase in the serotonin and 5-HIAA endogenous levels, and did not modify the catecholamines. Monoamine-oxidase activity was undetectable with a radioactive method using 3H-tyramine as substrate.