Disrupting inositol 1,4,5-trisphosphate (IP 3 ) receptor (IP 3 R)/B-cell lymphoma 2 (Bcl-2) complexes using a cell-permeable peptide (stabilized TAT-fused IP 3 R-derived peptide (TAT-IDP S )) that selectively targets the BH4 domain of Bcl-2 but not that of B-cell lymphoma 2-extra large (Bcl-Xl) potentiated pro-apoptotic Ca 2+ signaling in chronic lymphocytic leukemia cells. However, the molecular mechanisms rendering cancer cells but not normal cells particularly sensitive to disrupting IP 3 R/Bcl-2 complexes are poorly understood. Therefore, we studied the effect of TAT-IDP S in a more heterogeneous Bcl-2-dependent cancer model using a set of ‘primed to death’ diffuse large B-cell lymphoma (DL-BCL) cell lines containing elevated Bcl-2 levels. We discovered a large heterogeneity in the apoptotic responses of these cells to TAT-IDP S with SU-DHL-4 being most sensitive and OCI-LY-1 being most resistant. This sensitivity strongly correlated with the ability of TAT-IDP S to promote IP 3 R-mediated Ca 2+ release. Although total IP 3 R-expression levels were very similar among SU-DHL-4 and OCI-LY-1, we discovered that the IP 3 R2-protein level was the highest for SU-DHL-4 and the lowest for OCI-LY-1. Strikingly, TAT-IDP S -induced Ca 2+ rise and apoptosis in the different DL-BCL cell lines strongly correlated with their IP 3 R2-protein level, but not with IP 3 R1-, IP 3 R3- or total IP 3 R-expression levels. Inhibiting or knocking down IP 3 R2 activity in SU-DHL-4-reduced TAT-IDP S -induced apoptosis, which is compatible with its ability to dissociate Bcl-2 from IP 3 R2 and to promote IP 3 -induced pro-apoptotic Ca 2+ signaling. Thus, certain chronically activated B-cell lymphoma cells are addicted to high Bcl-2 levels for their survival not only to neutralize pro-apoptotic Bcl-2-family members but also to suppress IP 3 R hyperactivity. In particular, cancer cells expressing high levels of IP 3 R2 are addicted to IP 3 R/Bcl-2 complex formation and disruption of these complexes using peptide tools results in pro-apoptotic Ca 2+ signaling and cell death.

The effects of a hypobaric, hypoxic environment and exercise performed under extreme conditions, such as at high altitudes, are intriguing physiological aspects that need to be investigated directly on human climbers. Their skeletal muscle is one of the main tissues that can suffer from hypoxia and physical challenges, which will both define the muscle adaptation and the molecular signature of regenerative capacity. We investigated the muscle regenerative capacity characterizing satellite cells. Our study shows that satellite cells are altered by hypobaric, hypoxic environments and exercise performed at high altitudes. Of note, in human skeletal muscle after this 5,000 m a.s.l. expedition, SCs showed a significantly lower ability to regenerate skeletal muscle, in respect to before this high-altitude expedition. This impairment appears to be due to reduced satellite cell activity, consistent with their decreased myogenicity and fusion ability. Furthermore, at the transcriptional level several pathways, such as cell cycle, myogenesis, oxidative metabolism, proteolysis and sarcomeric protein synthesis, were found dysregulated.

Plants of cranberry (Vaccinium macrocarpon) furnish edible fruits and derivates that have been used for the prevention and treatment of urinary tract infections. In the present work we compare two commercial extracts that contain proanthocyanins (PACs) at 4 percent and 20 percent for antimicrobial, antiproliferative, antiradical and protective properties against oxidative stress on cell lines. Both extracts showed antimicrobial activity (MIC values range 3-100 microg/ml). Extract at 20 percent PACs showed higher antiproliferative activity against HepG2 and MCF7 cells, but not against C2C12 cells. Both extracts showed a dose-dependent free-radical scavenging capacity, and a protective effect on the cell damage was also revealed by reduction of intracellular active oxygen species release. Cranberry extracts confirmed antioxidative properties and efficacy in reduction of cell viability that resulted stronger against tumor cells. The pretreatment with cranberry extracts, furthermore, reveal an increase of cell resistance against oxidative stress, suggesting a potential role as a dietary supplement in preventing free-radical damage. The proanthocyanidin content is critical to determine the extract efficacy. In cellular experiments the extracts resulted clearly differentiated in their activity, and the activity was strongly influenced by PACs content. Only in DPPH test the free radical scavenging activity seemed to be directly related to proanthocyanidins content.

OBJECTIVE:The aim of the present study was to evaluate the prevalence of alexithymia and its relationships with psychopathological features and suicide risk in a sample of adult patients with a DSM-IV diagnosis of paranoid schizophrenia.METHODS:A mixed male-female sample of 60 subjects (30 males and 30 females) was evaluated with the following rating scales: Toronto Alexithymia Scale (TAS-20), Scale for the Assessment of Negative Symptoms (SANS), Scale for the Assessment of Positive Symptoms (SAPS), Calgary Depression Scale for Schizophrenia (CDSS), Scale for Suicidal Ideation (SSI), State-Trait Anxiety Inventory (STAI).RESULTS:22 subjects (36.7%) were categorized as alexithymic (TAS-20 scores > or =61). Alexithymics showed more severe negative and depressive symptoms and increased suicide risk than non alexithymics. However, the results of a linear regression with SSI score as dependent variable showed that Difficulty in Identifying and Describing Feelings dimensions of TAS-20 and higher CDSS scores were significantly associated with higher scores on the Scale for Suicide Ideation.CONCLUSIONS:The presence of alexithymia in schizophrenia may be related to higher risk of suicide ideation and more severe depressive symptoms, independently by the severity of positive and negative symptoms. However, results are preliminary and limitations must be considered.

A lack of motor neurons abolishes both neurotrophic factor secretion and contractile activity in muscle, which impairs mass, contractile properties, and fibre-type characteristics of the muscle. However, the molecular pathways that can be stimulated or repressed in the scenario of spinal cord injury remain unknown. We investigated for the first time the transcriptional profile of a young male patient 8 months after spinal cord injury. Adaptive metabolic changes of complete denervated skeletal muscle were revealed. In particular, the main molecular pathways involved include metabolic and proteolitic pathways, mitochondrial and synaptic function, calcium homeostasis, sarcomere and anchorage structures. Our data depict the molecular signalling still present in complete denervated skeletal muscle fibres a few months after spinal cord injury. These data could be of interest also to design a specific therapeutic approach aimed at the electrical-stimulation of severe atrophied skeletal muscle.

ObjectiveTo our knowledge, there are very limited data on suicidal ideation in obsessive- compulsive disorder, despite it is a common psychiatric condition that often runs a chronic course with high rates of comorbidity and treatment nonresponse. Moreover, no studies have, to date, evaluated the role of alexithymia and insight in determining suicidal ideation among these patients. Therefore, the aim of our study was to evaluate suicidal ideation and the relationships with alexithymia and insight in a sample of adult outpatients with obsessive-compulsive disorder.MethodsA sample of 86 adult outpatients with DSM-IV diagnosis of obsessive-compulsive disorder (44 women and 42 men with a mean age of 36.2+/-13.0 years), has been evaluated with a series of rating scales such as the YaleBrown Obsessive Compulsive Scale, the Toronto Alexithymia Scale, the Scale for Suicide Ideation and the Montgomery-Asberg Depression Rating Scale. The score of item #11 on the Yale-Brown Obsessive Compulsive Scale was considered as a measure of insight and scores of >= 3 were considered to mark the boundary between illness awareness and no awareness. Scores of >= 61 on the Toronto Alexithymia Scale were considered to be within the alexithymic range. As made in previous studies, scores > 5 on the SSI were used to define a person with current suicide risk.ResultsThere were no significant gender differences concerning demographic and clinical variables. 30 subjects (34.9%) were categorized as alexithymic and showed earlier onset, longer duration of illness and more likelihood to have a chronic course than nonalexithymics; they also scored higher on the Montgomery-Asberg Depression Rating Scale and the Scale for Suicide Ideation (Table I). Alexithymics without insight (n = 21) scored higher on the Scale for Suicide Ideation than alexithymics with insight (n = 9), nonalexythimics without insight (n = 5) and nonalexithymics with insight (n = 51) (Fig. 1). Partial correlations between the Toronto Alexithymia Scale (and its subscales) and other dimensional variables, controlling for gender, age, illness duration and age at onset, showed that the Toronto Alexithymia Scale total score and Difficulty in Identifying Feelings/Difficulty in Describing Feelings subscales correlated with all study variables, whereas Externally Oriented Thinking correlated with the Yale-Brown Obsessive Compulsive Scale and its subscales (including item# 11) but not with scores on the Scale for Suicide Ideation and on the Montgomery-Asberg Depression Rating Scale (Table II). Results of a linear regression showed that chronic obsessive-compulsive disorder course together with Difficulty in Identifying Feelings dimension of Toronto Alexithymia Scale and higher MontgomeryAsberg Depression Rating Scale scores were significantly associated with higher scores on the Scale for Suicide Ideation (Table III).ConclusionsSuicidal ideation is frequent among adult outpatients with obsessivecompulsive disorder and similar to that reported in affective disorders, schizophrenia and substance abuse. Alexithymia and depressive symptoms were highly correlated in obsessive-compulsive disorder patients and were significantly associated with higher suicide risk. The Difficulty in Identifying Feelings dimension of Toronto Alexithymia Scale appears to be significantly associated with presence of suicidal ideation as well as chronic course of the disorder. The Externally Oriented Thinking dimension of Toronto Alexithymia Scale appeared to be a variable fairly independent from depressive symptoms and suicidal ideation but was closely related to the severity of the disorder. Insight alone seems not to play a direct role in increasing suicide risk, but may have some relevance when associated with alexithymia. However, further longitudinal studies on larger samples are needed to definitely clarify this topic.

The aim of the present study is to evaluate the role of CRP and Total Cholesterol (TC) in patients suffering from type I Bipolar Disorder (BD-I). Moreover, the goal is to elucidate possible CRP and TC differences in different phases of BD-I: acute mania, euthymia and bipolar depression. Medical records of 90 BD-I patients (30 patients with acute mania, 30 in euthymic state, full remission, and 30 in depressive phase) were reviewed to evaluate serum CRP and TC levels. Laboratory data of 30 healthy controls were also obtained. The scores of Young Mania Rating Scale (YMRS), Bech-Rafaelsen Manic Rating Scale (BRMRS) and Hamilton Rating Scale for Depression (HAM-D) were evaluated. CRP levels were higher in acute mania and depressive phase subgroups when compared to healthy controls. CRP was positively associated with BRMRS and YMRS scores in acute mania and with HAM-D in depressive phase subgroups. TC levels were lower in all clinical groups compared to controls. TC levels were negatively correlated to BRMRS, YMRS and HAM-D. In conclusion, the results of the present study support the notion that CRP and TC may be altered in patients with BP-I.

Recently, a possible relationship between C-Reactive Protein (CRP), a marker of underlying low-grade inflammation, and mood disorders has been proposed by some researchers. The aim of this review is to elucidate the current facts and views about CRP in mood disorders such as Depressive and Bipolar Disorders. Several studies have examined the relationship between affective disorders and CRP, but the majority of the studies in literature have been limited by retrospective, case-controlled study design, and very few studies have examined the relationship between depression and CRP in large study samples. In conclusion, the role of CRP in mood disorders is, to date, intriguing but somewhat unclear. Further prospective studies are needed to introduce the CRP in clinical settings as a marker of affective states and suicidability.

The purpose of our study was to evaluate the efficacy and tolerability of low-dose olanzapine augmentation in selective serotonin reuptake inhibitor (SSRI)-resistant panic disorder (PD) with or without agoraphobia. In this 12-week, open-label study, 31 adult outpatients with treatment-resistant PD who had previously failed to respond to SSRI treatment were treated with fixed dose of olanzapine (5 mg/d) in addition to SSRI. Efficacy was assessed using the Panic Attack and Anticipatory Anxiety Scale (PAAAS), the Agoraphobic Cognitions Questionnaire (ACQ), the Hamilton Rating Scale for Anxiety (HAM-A), the Hamilton Rating Scale for Depression (HAM-D), the Global Assessment of Functioning Scale (GAF), and the Clinical Global Impression of Improvement (CGI-I). Twenty-six patients completed the trial period with a dropout rate of 16.1%. At week 12, 21 patients were responders (81.8%), and an overall improvement on all rating scales was observed in all patients both with or without agoraphobia. Fifteen patients (57.7%) achieved remission. Olanzapine was well tolerated and the most frequent adverse effects were mild-to-moderate weight gain and drowsiness. No extrapyramidal symptoms were reported. Olanzapine appears to be effective as augmentation strategy in the treatment of SSRI-resistant PD, but study limitations must be considered and placebo-controlled studies are needed.

OBJECTIVEThe current study elucidates the relations between alexithymia and body image in patients with binge eating disorder (BED).METHODOne hundred one patients with BED were evaluated. Alexithymia was measured with the Toronto Alexithymia Scale (TAS-20). The severity of BED was measured with the Binge Eating Scale (BES). Body concerns were assessed with the Body Shape Questionnaire-Short Version (BSQ-S), the Body Uneasiness Test (BUT), and the Body Attitude Test (BAT). Additional measures were the Rosenberg Self-Esteem Scale (RSES) and the Beck Depression Inventory (BDI).RESULTSThe prevalence of alexithymia in our sample was 39.6% (n = 40) and individuals with alexithymia showed higher scores on all rating scales. Higher body dissatisfaction, lower self-esteem, depressive symptoms, and the Difficulty in Identifying Feelings/Difficulty in Describing Feelings subscales of the TAS-20 were predictors of the severity of BED in the linear regression analysis.CONCLUSIONAlexithymia was associated with more severe BED. Individuals with alexithymia and BED exhibited significantly poorer appearance evaluation and body satisfaction as well as higher depressive symptoms than individuals without alexithymia.

Hypothalamic pituitary thyroid (HPT) axis abnormalities and alterations in major depression are reported in literature. The aim of our study was to evaluate the effect of mirtazapine on thyroid hormones after 6 months of therapy in a sample of adult outpatients with Major Depression (MD). 17 adult outpatients (7 men, 10 women) with MD according to DSM-IV criteria, were included in the study. All participants had to have met criteria for a major depressive episode with a score of at least 15 on the Hamilton Depression Rating Scale (HAM-D). Fasting venous blood samples were obtained for determination of serum Thyroid Stimulating Hrmone (TSH), Free T3 (FT3) and Free T4 (FT4) concentrations both at baseline and after 6 months of therapy. HAM-D scores decreased significantly from the first day of treatment to the end of the treatment period (p<0.001) and twelve patients (70.6%) were classified as responders. A significant increase in FT3 concentrations was found between baseline and the end of treatment period (P=0.015) whereas FT4 concentrations decreased (P=0.046). No significant changes were found in TSH levels. Higher FT4 concentrations at baseline predicted higher HAM-D scorers both at baseline and at the end of the treatment period. Furthermore, higher FT3 concentrations at endpoint were found to be predictors of lower HAM-D scores. Long-term treatment with mirtazapine increases FT3 levels and decreases FT4 maybe involving the deiodination process of T4 into T3.

Objective. To elucidate the relationships between insight and perceived expressed emotion (EE) in a sample of adult outpatients with obsessive-compulsive disorder (OCD). Methods. The study involved 75 subjects with OCD. Subjects were assessed with the Yale-Brown Obsessive Compulsive Scale (Y-BOCS), with the score on item 11 used as a measure of insight level. Perceived EE was evaluated using the Family Emotional Involvement and Criticism Scale (FEICS). The Montgomery Asberg Depression Rating Scale (MADRS) was used to evaluate depressive symptoms. Results. Poor or absent insight was found to be associated with higher perceived EE and significantly higher OCD severity, as well higher familial perceived criticism and more compulsions and depressive symptoms.

The aim of this study was to retrospectively evaluate the role of C-reactive protein, total cholesterol and high-density lipoprotein cholesterol in patients suffering from Major Depression (MD). Data of C-reactive protein, total cholesterol (TC) and high-density lipoprotein cholesterol of 37 adult outpatients (17 men, 20 women) with a DSM-IV diagnosis of MD were analyzed. Depression was measured with the 17-item Hamilton Depression Rating Scale (HAM-D) and with the Beck Depression Inventory (BDI). Suicide risk was evaluated with the Scale of Suicide Ideation (SSI). Patients with a lifetime history of attempted suicide were categorized as having higher suicide risk. Higher suicide risk patients showed higher C-reactive protein levels and lower high-density lipoprotein cholesterol levels than lower suicide risk patients whereas total cholesterol levels were not statistically different. C-reactive protein positively correlated with BDI, HAM-D, SSI scores and with number of previous depressive episodes. High-density lipoprotein cholesterol correlated inversely with BDI, HAM-D and SSI scores, whereas, no significant correlations were found between Total Cholesterol and other variables including C-reactive protein. In linear regression models, C-reactive protein was predictor of more severe depression and increased suicide risk. Lower high-density lipoprotein cholesterol levels were significantly predictive of increased suicide risk.

Background. To evaluate alexithymia and body image in women with Premenstrual Dysphoric Disorder and test whether alexithymic traits influence severity of Premenstrual Dysphoric Disorder or body distress.Methods. Sixty-four consecutive women with a DSM-IV diagnosis of Premenstrual Dysphoric Disorder and age range of 18-45 were recruited. Alexithymia was measured with the Italian version 20-items Toronto Alexithymia Scale. Severity of premenstrual mood symptoms was measured through the use of Visual Analogue Scales. Body concerns were assessed with the Body Uneasiness Test, Body Shape Questionnaire and Body Attitude Test. Additional measures were Rosenberg Self-Esteem Scale and Sheehan Disability Scale.Results. Prevalence of alexithymia in our sample was 31.3% (n = 20). Alexithymics showed higher scores on all rating scales (p range 0.001-< 0.001). Difficulty in Identifying Feelings and Difficulty in Describing Feelings subscales of Toronto Alexithymia Scale were predictors of severity of Premenstrual Dysphoric Disorder in the multiple linear regression analysis.Conclusions. Alexithymia was associated with more severe Premenstrual Dysphoric Disorder. Alexithymic women with Premenstrual Dysphoric Disorder exhibited significantly poorer appearance evaluation and body satisfaction than nonalexithymic women.

Background To evaluate whether valproic acid (VPA) can cause thrombocytopenia and impaired platelet function in young patients with new-onset bipolar disorder. Methods The authors studied 25 new-onset young bipolar patients. Platelet count, platelet aggregation, platelet release, and bleeding time were evaluated before beginning VPA treatment and at least after 10 months of treatment. The control group consisted of 20 sex-matched and age-matched subjects. Patients were started on VPA at a dose of 250 to 750 mg/d, given in divided doses. Mean dosage of VPA was 1137.5 ± 241.1 mg/d. Mean VPA total plasma concentration was 61.1 ± 20 g/mL. Results At baseline, no significant differences were observed for platelet count and function between the bipolar group and the control subjects. After 10 months, at the second evaluation, the platelet count was significantly lower in the bipolar patients than in the control subjects: 192.7 ± 21.4/μL versus 289.8 ± 23.9/μL; P < 0.0001. An important observation was that platelet counts were negatively correlated with VPA dose (r = −0.47; P = 0.05) and its plasma concentration (r = −0.50; P = 0.05). In the present study, the authors observed impairment in platelet release of ATP and aggregation that correlated with both VPA dosage and plasma levels. Bleeding times were also significantly longer in patients taking VPA compared with control subjects (P < 0.0001). Conclusion Thrombocytopenia can appear after a few months of therapy and with plasma VPA levels within the therapeutic range.