Effects of antipsychotics on bone mineral density and prolactin levels in patients with schizophrenia: a 12-month prospective study

Objective: Effects of conventional and atypical antipsychotics on bone mineral density (BMD) and serum prolactin levels (PRL) were examined in patients with schizophrenia.Methods: One hundred and sixty-three first-episode inpatients with schizophrenia were recruited, to whom one of three conventional antipsychotics (perphenazine, sulpiride, and chlorpromazine) or one of three atypical antipsychotics (clozapine, quetiapine, and aripiprazole)was prescribed for 12 months as appropriate. BMD and PRL were tested before and after treatment. Same measures were conducted in 90 matched healthy controls.Results Baseline BMD of postero-anterior L1–L4 range from 1.04 ± 0.17 to 1.42 ± 1.23, and there was no significant difference between the patients group and healthy control group. However, post-treatment BMD values in patients (ranging from 1.02 ± 0.15 to 1.23 ± 0.10) were significantly lower than that in healthy controls (ranging from 1.15 ± 0.12 to 1.42 ± 1.36). The BMD values after conventional antipsychotics were significantly lower than that after atypical antipsychotics. The PRL level after conventional antipsychotics (53.05 ± 30.25 ng/ml) was significantly higher than that after atypical antipsychotics (32.81 ± 17.42 ng/ml). Conditioned relevance analysis revealed significant negative correlations between the PRL level and the BMD values after conventional antipsychotics.Conclusion The increase of PRL might be an important risk factor leading to a high prevalence of osteoporosis in patients with schizophrenia on long-term conventional antipsychotic medication.<br/

Inside-out Ca2+ signalling prompted by STIM1 conformational switch

Store-operated Ca(2+) entry mediated by STIM1 and ORAI1 constitutes one of the major Ca(2+) entry routes in mammalian cells. The molecular choreography of STIM1–ORAI1 coupling is initiated by endoplasmic reticulum (ER) Ca(2+) store depletion with subsequent oligomerization of the STIM1 ER-luminal domain, followed by its redistribution towards the plasma membrane to gate ORAI1 channels. The mechanistic underpinnings of this inside-out Ca(2+) signalling were largely undefined. By taking advantage of a unique gain-of-function mutation within the STIM1 transmembrane domain (STIM1-TM), here we show that local rearrangement, rather than alteration in the oligomeric state of STIM1-TM, prompts conformational changes in the cytosolic juxtamembrane coiled-coil region. Importantly, we further identify critical residues within the cytoplasmic domain of STIM1 (STIM1-CT) that entail autoinhibition. On the basis of these findings, we propose a model in which STIM1-TM reorganization switches STIM1-CT into an extended conformation, thereby projecting the ORAI-activating domain to gate ORAI1 channels

Prevalence of depressive disorders and associated demographic characteristics in Shandong: An epidemiological investigation

BackgroundDepression is characterized by debilitating symptoms and high recurrence rates, and there are relatively few large-scale epidemiological surveys of depressive disorders conducted in Shandong since 2005. Data from the largest Epidemiological Survey of Mental Disorders conducted in 2015 in Shandong were collected to investigate the prevalence of depressive disorders and associated demographic characteristics in general adult population.MethodsA multi-stage stratified cluster sampling method was adopted to select residents and a two-stage screening and assessment process was used to define the prevalence and characteristics of depressive disorders. Respondents were initially screened using the General Health Questionnaire followed by a structured clinical interview using the DSM-IV criteria.ResultsAmong 27,489 respondents who completed the survey, 1277 respondents met the diagnostic criteria for depressive disorders. The adjusted prevalence in the last month was 4.86%, among which the prevalence of major depressive disorder, dysthymia, and unspecified depressive disorder were 2.32%, 1.78%, and 0.75%, respectively. 40.35% of depression patients had moderate or severe functional impairment and only 10.65% of patients had visited a psychiatric service. Univariate and multivariate analyses revealed that age, gender, occupation, education, marital status, and urban/rural living were associated with the prevalence.LimitationsThe key limitation is that this is a cross-sectional survey therefore cannot draw any causal relationship between risk factors and disease progression.ConclusionsFindings from this largest epidemiological study reveal current prevalence of depressive disorders and associated demographic factors and offers opportunities for policy makers and health-care professionals to improve mental health provision in Shandong.</p

Exploitation and Application of a Highly Sensitive Ru(II) Complex-Based Phosphorescent Chemodosimeter for Hg²⁺ in Aqueous Solutions and Living Cells

A novel Ru­(II) complex-based phosphorescent probe <b>Rubpy-1</b> was designed and synthesized conveniently by incorporating of chemodosimeter into the luminophor, which exhibits good water solubility, longer excitation wavelength, and rapid turn-on phosphorescent response only toward Hg²⁺ in aqueous system under physiological pH. The spectral response mechanism and Hg²⁺-promoted structure change of the chemodosimeter were analyzed in detail by theoretical calculations and electrospray ionization mass spectrometry. When time-resolved photoluminescence techniques were used, the <b>Rubpy-1</b> could eliminate effectively the signal interference from the short-lived background fluorescence in complicated media, accompanied by the significant improvement of the signal-to-noise ratio and the accuracy of the detection. Furthermore, <b>Rubpy-1</b> showed low cytotoxicity and excellent membrane permeability toward living cells, which was successfully applied to monitor intracellular Hg²⁺ effectively by confocal luminescence imaging

Phenolic Derivatives from Hypericum japonicum

Three new acylphloroglucinol glycosides, hypericumols A - C, together with fifteen known phenolic derivatives, were isolated from the total phenolic extract of Hypericum japonicum. Hypericumols A, B, and C were characterized as 4,6-dimethyl-2-methylpropanoylphloroglucinol-1-O-beta-D-glucopyranoside (1), 4-methyl-2-methylpropanoylphloroglucinol-1-O-beta-D-glucopyranoside (2), and (2'S)-4,6-dimethyl-2-methylbutyrylphloroglucihol-1-O-beta-D-glucopyranoside (3), respectively, on the basis of spectroscopic data interpretation and chemical degradation reaction