Lithium limits trimethyltin-induced cytotoxicity and proinflammatory response in microglia without affecting the concurrent autophagy impairment

Trimethyltin (TMT) is a highly toxic molecule present as an environmental contaminant causing neurodegeneration particularly of the limbic system both in humans and in rodents. We recently described the occurrence of impairment in the late stages of autophagy in TMT-intoxicated astrocytes. Here we show that similarly to astrocytes also in microglia, TMT induces the precocious block of autophagy indicated by the accumulation of the autophagosome marker, microtubule associated protein light chain 3. Consistent with autophagy impairment we observe in TMT-treated microglia the accumulation of p62/SQSTM1, a protein specifically degraded through this pathway. Lithium has been proved effective in limiting neurodegenerations and, in particular, in ameliorating symptoms of TMT intoxication in rodents. In our in vitro model, lithium displays a pro-survival and anti-inflammatory action reducing both cell death and the proinflammatory response of TMT-treated microglia. In particular, lithium exerts these activities without reducing TMT-induced accumulation of light chain 3 protein. In fact, the autophagic block imposed by TMT is unaffected by lithium administration. These results are of interest as defects in the execution of autophagy are frequently observed in neurodegenerative diseases and lithium is considered a promising therapeutic agent for these pathologies. Thus, it is relevant that this cation can still maintain its pro-survival and anti-inflammatory role in conditions of autophagy bloc

An MMPI-2 hopelessness scale: Construction, initial validation and implication for suicide risk

This study documents the development of a new MMPI-2 scale, Hopelessness (Hp), designed to identify suicide risk in examinees who, for whatever reason, may be reluctant to endorse items reflecting explicit suicide content. The psychometric and empirical validity characteristics were examined in a sample of 153 Italian psychiatric inpatients, all of whom were administered the MMPI-2, the Beck Hopelessness Scale (BHS), and the Mini International Neuropsychiatric Interview (MINI) shortly following admission.Item analysis suggested that the removal of one of the twelve original Hp items enhanced homogeneity of the scale and Bayesian confirmatory factor analysis (BCFA) indicated the fit of a unidimensional model (PPPs = 0.50 [PPC = -36.42/37.07]) for the 11-item version, with adequate reliability (ordinal alpha = 0.86). A regression analysis, with the MINI scores as criterion, and Hp and BHS scores as independent variables, indicated that only Hp scores (beta = 0.25, t = 2.32, p < 0.05) were independently associated with the MINI suicide risk. These findings indicate that the MMPI-2 Hp scale may be considered a valid and potentially useful measure of pessimistic attitudes toward the future and of potential suicide risk

Partial Androgen Deficiency, Depression, and Testosterone Supplementation in Aging Men

The aim of this review was to summarize current knowledge on the correlation between depressive symptoms with a syndrome called partial androgen deficiency of the aging male (PADAM) and on the potential benefits of testosterone (T) treatment on mood. Despite, the causative nature of the relationship between low T levels and depression is uncertain, many hypogonadal men suffer from depression and vice versa several depressed patients are affected by hypogonadism. Supplementation with testosterone failed to show sound evidence of effectiveness in the treatment of depression. Nevertheless, testosterone supplementation has proved to be effective on some domains significant for the quality of life of aged patients with PADAM (sexual function and cognitive functions, muscular strengths)

Short-Term Psychodynamic Psychotherapy in Patients with “Male Depression” Syndrome, Hopelessness, and Suicide Risk: A Pilot Study

Objectives and Methods. This was an observational study of the efficacy of short-term psychodynamic psychotherapy (STPP) in a sample of 35 (30 women and 5 men) patients with moderate-to-severe “male depression” (Gotland Scale for Male Depression (GSMD) ≥ 13) comorbid with unipolar mood disorder (dysthymia and major depression) or anxiety disorder. Outcome measures were GSMD and BHS (Beck Hopelessness Scale) score changes from baseline. Results:. Patients had a strong response to STPP on the GSMD (estimated mean score change (± SE) = −9.08 ± 2.74; P < 0.01; partial eta squared = 0.50), but not on the BHS (estimated mean score change (± SE) = −0.92 ± 1.55; P = 0.57; partial eta squared = 0.03). BHS score changes were significantly associated with GSMD score changes (Pearson's r = 0.56; P < 0.001), even when controlling for the severity of hopelessness at the baseline (partial r = 0.62; P < 0.001). Conclusions:. STPP proved to be effective in patients suffering from “male depression” although hopelessness was only marginally reduced by this treatment which points to the need to better understand how STPP can be involved in the reduction of suicide risk

Suicide among Italian adolescents: 1970–2002

The purpose of the present study was to analyze sex and regional differences in the suicide rate of adolescents and the methods they used for suicide in Italy during the period 1970–2002. Temporal trends and regional variations in suicide for Italian adolescents were retrieved from the Italian database on mortality for the period 1970–2002, collected by the Italian Census Bureau and processed by the Italian National Institute of Health-Statistics Unit. In the period 1970–2002, 3,069 adolescent suicides were monitored in Italy. Analyses of these suicides identified significant differences by region of residence and sex. Males were 2.1 times more likely than females to kill themselves. Male and female suicides had inverse trends in the years analyzed, so that the sex difference at the present time is the result of a continuous increase in male suicides and a decrease in female suicides since 1970. The dramatic peaks observed over the time period studied cannot be attributed to a single cause, indicating that further studies are needed to better understand the phenomenon

Prenatal genetic counselling: issues and perspectives for pre-conceptional health care in Emilia Romagna (Northern Italy)

Background: there are many reasons why a couple may seek specialist genetic counselling about foetal risk. The referral for prenatal genetic counselling of women with a known risk factor during pregnancy has many disadvantages. Despite this, 10-20% of women seek counselling when already pregnant. Methods: data on 804 pregnant women out of 2 158 (37.3%) referred for genetic counselling in 2010 to three Clinical Genetic Services were retrospectively analysed. Patients referred only for advanced maternal age were analysed in a separate study. Results: the 804 pregnant women were referred for 932 counselling issues. 325 issues (34.9%) were identified during pregnancy and 607 (65.1%) were pre-existing. 81.2% of Italians compared to 41.8% of the non-Italians (P&lt;0.01) had access to counselling before 13 weeks of gestation for risk factors present before pregnancy. An accurate genetic diagnosis was available in 25.0% of cases. In 21.7% of the cases an elevated a priori risk of &gt;10% for the unborn child was established. Conclusions: genetic services provide 37.3% of counselling to pregnant women. Referral for genetic counselling during pregnancy can require considerable resources and pose significant ethical and organizational challenges. New models of pregnancy care in the community need to be developed. General practitioners and gynaecologists have an important role in the referral and in the defence of equity of access and a more structured approach to the participation of medical geneticists to primary practice should be considered

Acute hepatitis caused by a natural lipid-lowering product: When "alternative" medicine is no "alternative" at all

Background/Aims The general public's growing mistrust of the pharmaceutical industry and its perception of the lack of adverse effects of "natural" therapy have lead to the increasing use of "alternative drugs" for hypercholesterolemia. Methods A sixty-three year old woman presented with severe hypertransaminasemia that had developed progressively over a few weeks. For six months she had been taking Equisterol ® , an over-the-counter lipid-lowering product containing guggulsterol and red yeast rice extract. The product had been prescribed for hypercholesterolemia because the patient had developed hepatotoxicity while on lovastatin. Results Liver biopsy revealed severe lobular necroinflammatory changes with an eosinophilic infiltrate. The episode was regarded as an adverse drug reaction after exclusion of other possible causes of acute liver disease and the prompt normalization of liver function tests after Equisterol ® had been discontinued. Red yeast rice extract's cholesterol-lowering properties are largely due to fungal metabolites known as monacolins, one of which – monacolin K – is identical to lovastatin. Conclusions The choice of an alternative medicine approach in this case subjected the patient to "re-challenge" with the official medicine agent that had previously caused mild hepatotoxicity. Physicians should keep in mind that "alternative" medicine is not always the safest alternative and sometimes it is not even "alternative.

Intense terahertz pulses from SPARC-LAB coherent radiation source

The linac-based Terahertz source at the SPARC_LAB test facility is able to gene rate highly intense Terahertz broadband pulses via coherent transition radiation (CTR) from high brightness electron beams. The THz pulse duration is typically down to 100 fs RMS and can be tuned through the electron bunch duration and shaping. The measured stored energy in a single THz pulse has reached 40 μ J, which corresponds to a peak electric field of 1.6 MV/cm at the THz focus. Here we present the main features, in particular spatial and sp ectral distributions and energy characterizations of the SPARC_LAB THz source, which is very competitive for investigations in Condensed Matter, as well as a valid tool for electron beam longitudinal diagnostics

Antidepressants and Suicide Risk: A Comprehensive Overview

The annual worldwide suicide rate currently averages approximately 13 per 100,000 individuals per year (0.013% per year), with higher average rates for men than for women in all but a few countries, very low rates in children, and relatively high rates in elderly men. Suicide rates vary markedly between countries, reflecting in part differences in case-identification and reporting procedures. Rates of attempted suicide in the general population average 20–30 times higher than rates of completed suicide, but are probably under-reported. Research on the relationship between pharmacotherapy and suicidal behavior was rare until a decade ago. Most ecological studies and large clinical studies have found that a general reduction in suicide rates is significantly correlated with higher rates of prescribing modern antidepressants. However, ecological, cohort and case-control studies and data from brief, randomized, controlled trials in patients with acute affective disorders have found increases, particularly in young patients and particularly for the risk of suicide attempts, as well as increases in suicidal ideation in young patients. whether antidepressants are associated with specific aspects of suicidality (e.g., higher rates of completed suicide, attempted suicide and suicidal ideation) in younger patients with major affective disorders remains a highly controversial question. In light of this gap this paper analyzes research on the relationship between suicidality and antidepressant treatment

The role of asenapine in the treatment of manic or mixed states associated with bipolar I disorder

Maurizio Pompili1,2, Paola Venturini1, Marco Innamorati1, Gianluca Serafini1, Ludovica Telesforo1, David Lester3, Roberto Tatarelli1, Paolo Girardi11Department of Neurosciences, Mental Health and Sensory Functions, Suicide Prevention Center, Sant&amp;#39;Andrea Hospital, Sapienza University of Rome, Rome, Italy; 2McLean Hospital, Harvard Medical School, Boston, MA, USA; 3The Richard Stockton College of New Jersey, Pomona, NJ, USABackground: Bipolar disorders (BD) are of particular public health significance as they are prevalent, severe and disabling, and often associated with elevated risks of premature mortality. The aim of this concise overview is to investigate the role of asenapine in the treatment of manic and mixed states associated with BD type 1 disorder.Method: MedLine, Excerpta Medica and PsycINFO searches were performed to identify papers in English published over the past 7 years. Search terms were &amp;quot;asenapine&amp;quot;, &amp;quot;manic&amp;quot; OR &amp;quot;mixed states&amp;quot;, &amp;quot;bipolar I disorder&amp;quot;. Subjects included in this study suffered from BD type 1 disorder.Results: To date, only four studies of asenapine for the treatment of manic or mixed episodes associated with BD type 1 have been published.Conclusion: Research indicates that asenapine is generally well-tolerated, and that asenapine is efficacious and not inferior to olanzapine in the treatment of mixed or manic episodes associated with BD type 1 in the short-term and long-term.Keywords: asenapine, bipolar disorder, side effect