Differential diagnoses and management strategies in patients with schizophrenia and bipolar disorder

Successful treatment of psychiatric disorders, including bipolar disorder and schizophrenia, is complicated and is affected by a broad range of factors associated with the diagnosis, choice of treatment and social factors. In these patients, treatment management must focus on accurate and early diagnosis, to ensure that correct treatment is administered as soon as possible. In both disorders, the treatment of the disease in the acute phase must be maintained long term to provide continuous relief and normal function; the treatment choice in the early stages of the disease may impact on long-term outcomes. In schizophrenia, treatment non-compliance is an important issue, with up to 50% of patients discontinuing treatment for reasons as diverse as efficacy failure, social barriers, and more commonly, adverse events. Treatment non-compliance also remains an issue in bipolar disorder, as tolerability of mood stabilizers, especially lithium, is not always good, and combination treatments are frequent. In order to achieve an optimal outcome in which the patient continues with their medication life-long, treatment should be tailored to each individual, taking into account treatment and family history, and balancing efficacy with tolerability to maximize patient benefit and minimize the risk of discontinuation. These case studies illustrate how treatment should be monitored, tailored and often changed over time to meet these needs

Transcranial Brain Stimulation Techniques For Major Depression : Should We Extend TMS Lessons to tDCS?

Transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) are non-invasive brain stimulation techniques that, by means of magnetic fields and low intensity electrical current, respectively, aim to interefere with and modulate cortical excitability, at the level of dorsolateral prefrontal cortex, in patients with major depression and poor response to standard antidepressants. While the clinical efficacy of TMS in major depression has been extensively investigated over the last 10 years, tDCS has attracted research interest only in the last years, with fewer randomized clinical trials (RCTs) in the field. Nevertheless, in spite of the different rationale and mechanism of action of the two techniques, tDCS recent acquisitions, in relation to the treatment of major depression, seem to parallel those previously obtained with TMS, in terms of treatment duration to achieve optimal benefit and patient's history of drug-resistance. After briefly introducing the two techniques, the article examines possible common pathways of clinical use for TMS and tDCS, emerging from recent RCTs and likely orienting future investigation with non invasive brain stimulation for the treatment of major depression

Fluorescence and Morphology of Self-Assembled Nucleobases and Their Diphenylalanine Hybrid Aggregates

Studies carried out in recent decades have revealed that the ability to self-assemble is a widespread property among biomolecules. Small nucleic acid moieties or very short peptides are able to generate intricate assemblies endowed with remarkable structural and spectroscopic properties. Herein, the structural/spectroscopic characterization of aggregates formed by nucleobases and peptide nucleic acid (PNA)-peptide conjugates are reported. At high concentration, all studied nucleobases form aggregates characterized by previously unreported fluorescence properties. The conjugation of these bases, as PNA derivatives, to the dipeptide Phe-Phe leads to the formation of novel hybrid assemblies, which are characterized by an amyloid-like association of the monomers. Although these compounds share the same basic cross-\u3b2 motif, the nature and number of PNA units have an important impact on both the level of structural order and the intrinsic fluorescence of the self-assembled nanostructure

Do patients with hallucinations imagine speech right?

A direct relationship between auditory verbal hallucinations (AVHs) and decreased left-hemispheric lateralization in speech perception has been often described, although it has not been conclusively proven. The specific lateralization of AVHs has been poorly explored. However, patients with verbal hallucinations show a weak Right Ear Advantage (REA) in verbal perception compared to non AVHs listeners suggesting that left-hemispheric language area are involved in AVHs. In the present study, 29 schizophrenia patients with AVHs, 31 patients with psychotic bipolar disorder who experienced frequent AVHs, 27 patients with schizophrenia who had never experienced AVHs and 57 healthy controls were required to imagine hearing a voice in one ear alone. In line with previous evidence healthy controls confirmed the expected REA for auditory imagery, and the same REA was also found in non-hallucinator patients. However, in line with our hypothesis, patients with schizophrenia and psychotic bipolar disorder with AVHs showed no lateral bias. Results extend the relationship between abnormal asymmetry for verbal stimuli and AVHs to verbal imagery, suggesting that atypical verbal imagery may reflect a disruption of inter-hemispheric connectivity between areas implicated in the generation and monitoring of verbal imagery and may be predictive of a predisposition for AVHs. Results also indicate that the relationship between AVHs and hemispheric lateralization for auditory verbal imagery is not specific to schizophrenia but may extend to other disorders as well

Nitric oxide cooperates with auxin to mitigate the alterations in the root system caused by cadmium and arsenic

Oryza sativa L. is a worldwide food-crop frequently growing in cadmium (Cd)/arsenic (As) polluted soils, with its root-system as the first target of the pollutants. Root-system development involves the establishment of optimal indole-3-acetic acid (IAA) levels, also requiring the conversion of the IAA natural precursor indole-3-butyric acid (IBA) into IAA, causing nitric oxide (NO) formation. Nitric oxide is a stress-signaling molecule. In rice, a negative interaction of Cd or As with endogenous auxin has been demonstrated, as some NO protective effects. However, a synergism between the natural auxins (IAA and/or IBA) and NO was not yet determined and might be important for ameliorating rice metal(oid)-tolerance. With this aim, the stress caused by Cd/As toxicity in the root cells and the possible recovery by either NO or auxins (IAA/IBA) were evaluated after Cd or As (arsenate) exposure, combined or not with the NO-donor compound sodium-nitroprusside (SNP). Root fresh weight, membrane electrolyte leakage, and H2O2 production were also measured. Moreover, endogenous IAA/IBA contents, transcription-levels of OsYUCCA1 and OsASA2 IAA-biosynthetic-genes, and expression of the IAA-influx-carrier OsAUX1 and the IAA-responsive DR5::GUS construct were analyzed, and NO-epifluorescence levels were measured. Results showed that membrane injury by enhanced electrolyte leakage occurred under both pollutants and was reduced by the treatment with SNP only in Cd-presence. By contrast, no membrane injury was caused by either exogenous NO or IAA or IBA. Cd- and As-toxicity also resulted into a decreased root fresh weight, mitigated by the combination of each pollutant with either IAA or IBA. Cd and As decreased the endogenous NO-content, increased H2O2 formation, and altered auxin biosynthesis, levels and distribution in both adventitious (ARs) and mainly lateral roots (LRs). The SNP-formed NO counteracted the pollutants’ effects on auxin distribution/levels, reduced H2O2 formation in Cd-presence, and enhanced AUX1-expression, mainly in As-presence. Each exogenous auxin, but mainly IBA, combined with Cd or As at 10 µM, mitigated the pollutants’ effects by increasing LR-production and by increasing NO-content in the case of Cd. Altogether, results demonstrate that NO and auxin(s) work together in the rice root system to counteract the specific toxic-effects of each pollutant

Emerging roles for ion channels in ovarian cancer: Pathomechanisms and pharmacological treatment

Ovarian cancer (OC) is the deadliest gynecologic cancer, due to late diagnosis, development of platinum resistance, and inadequate alternative therapy. It has been demonstrated that membrane ion channels play important roles in cancer processes, including cell proliferation, apop-tosis, motility, and invasion. Here, we review the contribution of ion channels in the development and progression of OC, evaluating their potential in clinical management. Increased expression of voltage-gated and epithelial sodium channels has been detected in OC cells and tissues and shown to be involved in cancer proliferation and invasion. Potassium and calcium channels have been found to play a critical role in the control of cell cycle and in the resistance to apoptosis, promoting tumor growth and recurrence. Overexpression of chloride and transient receptor potential channels was found both in vitro and in vivo, supporting their contribution to OC. Furthermore, ion channels have been shown to influence the sensitivity of OC cells to neoplastic drugs, suggesting a critical role in chemotherapy resistance. The study of ion channels expression and function in OC can improve our understanding of pathophysiology and pave the way for identifying ion channels as potential targets for tumor diagnosis and treatment

Peroxisomal PEX7 Receptor Affects Cadmium-Induced ROS and Auxin Homeostasis in Arabidopsis Root System

Peroxisomes are important in plant physiological functions and stress responses. Through the production of reactive oxygen and nitrogen species (ROS and RNS), and antioxidant defense enzymes, peroxisomes control cellular redox homeostasis. Peroxin (PEX) proteins, such as PEX7 and PEX5, recognize peroxisome targeting signals (PTS1/PTS2) important for transporting proteins from cytosol to peroxisomal matrix. pex7-1 mutant displays reduced PTS2 protein import and altered peroxisomal metabolism. In this research we analyzed the role of PEX7 in the Arabidopsis thaliana root system exposed to 30 or 60 μM CdSO4. Cd uptake and translocation, indole-3-acetic acid (IAA) and indole-3-butyric acid (IBA) levels, and reactive oxygen species (ROS) and reactive nitrogen species (RNS) levels and catalase activity were analyzed in pex7-1 mutant primary and lateral roots in comparison with the wild type (wt). The peroxisomal defect due to PEX7 mutation did not reduce Cd-uptake but reduced its translocation to the shoot and the root cell peroxisomal signal detected by 8-(4-Nitrophenyl) Bodipy (N-BODIPY) probe. The trend of nitric oxide (NO) and peroxynitrite in pex7-1 roots, exposed/not exposed to Cd, was as in wt, with the higher Cd-concentration inducing higher levels of these RNS. By contrast, PEX7 mutation caused changes in Cd-induced hydrogen peroxide (H2O2) and superoxide anion (O2●−) levels in the roots, delaying ROS-scavenging. Results show that PEX7 is involved in counteracting Cd toxicity in Arabidopsis root system by controlling ROS metabolism and affecting auxin levels. These results add further information to the important role of peroxisomes in plant responses to Cd