Sex differences in the phenotypic expression of obsessive-compulsive disorder: an exploratory study from Brazil

Previous studies have shown differences in clinical features of obsessive-compulsive disorder (OCD) between men and women, including mean age at onset of obsessive-compulsive symptoms (OCS), types of OCS, comorbid disorders, course, and prognosis. The aim of this study was to compare male and female Brazilian patients with OCD on several demographic and clinical characteristics. Three hundred thirty Outpatients with OCD (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition [DSM-IV], criteria) who sought treatment at 3 Brazilian public universities and at 2 private practice clinics in the city of Sao Paulo were evaluated. The assessment instruments used were the Yale-Brown Obsessive-Compulsive Scale to evaluate OCD severity and symptoms, the Beck Depression and Anxiety Inventories, the Yale Global Tic Severity Scale, and the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Axis I Disorders to assess psychiatric comorbidity. Fifty-five percent of the patients (n = 182) were men who were significantly more likely than women to be single and to present sexual, religious, and symmetry obsessions and mental rituals. They also presented earlier onset of OCS and earlier symptom interference in functioning, and significantly more comorbid tic disorders and posttraumatic stress disorder. Women, besides showing significantly higher mean scores in the Beck Depression and Anxiety Inventories, were more likely to present comorbid simple phobias, eating disorders in general and anorexia in particular, impulse control disorders in general, and compulsive buying and skin picking in particular. No significant differences were observed between sexes concerning family history of OCS or OCD, and global symptoms severity, either in obsession or compulsive subscale. The present study confirms the presence of sex-related differences described in other countries and cultures. The fact that the OCS start earlier and probably have a worse impact in men can eventually lead to more specific and efficacious treatment approaches for these patients. (C) 2009 Elsevier Inc. All rights reserved.

Mucosal and systemic anti-GAG immunity induced by neonatal immunization with HIV LAMP/gag DNA vaccine in mice

Vaccines capable of inducing mucosal immunity in early postnatal life until adulthood, protecting early sexual initiation, should be considered as strategies to vaccination against HIV. The HIV-1 GAG protein as a chimera with the lysosome-associated membrane protein (LAMP/gag), encoded by a DNA vaccine, is targeted to the endosomal/lysosomal compartment that contains class II MHC molecules and has been shown to be immunogenic in adult mice. Assuming that one such strategy could help to overcome the immunological immaturity in the early postnatal period, we have evaluated the systemic and mucosal immunogenicity of LAMP/gag immunization in neonatal mice. Intranasal immunization with LAMP/gag vaccine induced higher levels of sIgA and IgG anti-GAG antibodies in intestinal washes than did the gag vaccine. The combination of ID injections and the IN protocol with the chimeric vaccine promoted the increase of Ab levels in sera. Both vaccines induced splenic IFN-gamma- secreting cells against GAG peptide pools, as well as in vivo cytotoxic T lymphocyte (CTL) function, and increased the percentage of CD8+ T cells to the immunodominant class I peptide in gut and spleen. However, only the chimeric vaccine was able to enhance Th1/Th2 cytokine secretion in response to class II GAG peptide and to enhance IL-4-secreting cells against GAG peptides and p24 protein stimuli. Long-lasting humoral and cellular responses were detected until adult age, following neonatal immunization with the chimeric vaccine. The LAMP/gag vaccination was able to induce potent GAG-specific T and B cell immune responses in early life which are essential to elicit sustained and long-lasting mucosal and systemic humoral response. (C) 2010 Elsevier GmbH. All rights reserved.

Immunization of neonatal mice with LAMP/p55 HIV gag DNA elicits robust immune responses that last to adulthood

Successful T cell priming in early postnatal life that can generate effective long-lasting responses until adulthood is critical in HIV vaccination strategies because it prevents early sexual initiation and breastfeeding transmission of HIV. A chimeric DNA vaccine encoding p55 HIV gag associated with lysosome-associated membrane protein 1 (LAMP-1; which drives the antigen to the MIIC compartment), has been used to enhance cellular and humoral antigen-specific responses in adult mice and macaques. Herein, we investigated LAMP-1/gag vaccine immunogenicity in the neonatal period in mice and its ability to generate long-lasting effects. Neonatal vaccination with chimeric LAMP/gag generated stronger Gag-specific immune responses, as measured by the breadth of the Gag peptide-specific IFN-gamma, proliferative responsiveness, cytokine production and antibody production, all of which revealed activation of CD4+ T cells as well as the generation of a more robust CTL response compared to gag vaccine alone. To induce long-lived T and B cell memory responses, it was necessary to immunize neonates with the chimeric IAMP/gag DNA vaccine. The LAMP/gag DNA vaccine strategy could be particularly useful for generating an anti-HIV immune response in the early postnatal period capable of inducing long-term immunological memory. (C) 2010 Elsevier Inc. All rights reserved.

Increased platelet GSK3B activity in patients with mild cognitive impairment and Alzheimer`s disease

The disruption of glycogen synthase kinase 3-beta (GSK3B) homeostasis has implications in the pathophysiology of neuropsychiatric disorders, namely Alzheimer`s disease (AD). GSK3B activity is increased within the AD brain, favoring the hyperphosphorylation of microtubule-associated protein Tau and the formation of neurofibrillary tangles. Such abnormality has also been detected in leukocytes of patients with cognitive disorders. The aim of the present study was to determine the expression of total and phosphorylated GSK3B at protein level in platelets of older adults with varying degrees of cognitive impairment, and to compare GSK3B activity in patients with AD, mild cognitive impairment (MCI) and healthy controls. Sixty-nine older adults were included (24 patients with mild to moderate AD, 22 patients with amnestic MCI and 23 elderly controls). The expression of platelet GSK3B (total- and Ser-9 phosphorylated GSK3B) was determined by Western blot. GSK3B activity was indirectly assessed by means of the proportion between phospho-GSK3B to total GSK3B (GSK3B ratio), the former representing the inactive form of the enzyme. Ser-9 phosphorylated GSK3B was significantly reduced in patients with MCI and AD as compared to controls (p = 0.04). Platelet GSK3B ratio was significantly decreased in patients with MCI and AD (p = 0.04), and positively correlated with scores on memory tests (r = 0.298, p = 0.01). In conclusion, we corroborate previous evidence of increased GSK activity in peripheral tissues of patients with MCI and AD, and further propose that platelet GSK may be an alternative peripheral biomarker of this abnormality, provided samples are adequately handled in order to preclude platelet activation. (C) 2010 Elsevier Ltd. All rights reserved.

Body dysmorphic disorder among dermatologic patients: Prevalence and clinical features

Background: An impairing preoccupation with a nonexistent or slight defect in appearance is the core symptom of body dysmorphic disorder (ODD), a psychiatric condition common in dermatology settings. Objective: We sought to determine the prevalence of ODD in dermatologic patients, comparing general and cosmetic settings, and describing some demographic and clinical characteristics. Methods: In all, 300 patients were consecutively assessed. Screening and diagnoses were performed with validated instruments plus a best estimate diagnosis procedure. The final sample comprised 150 patients in the cosmetic group, 150 patients in the general dermatology group, and 50 control subjects. Standard statistical analyses were performed (chi(2), nonparametric tests, logistic regression). Results: The current prevalence was higher in the cosmetic group (14.0%) compared with general (6.7%) and control (2.0%) groups. No patient had a previous diagnosis. Frequently the reason for seeking dermatologic treatment was not the main ODD preoccupation. Patients with ODD from the cosmetic group were in general unsatisfied with the results of dermatologic treatments. Limitations: Cross-sectional study conducted in a university hospital is a limitation. It is uncertain if the findings can be generalized. Retrospective data regarding previous treatments are not free from bias. Conclusions: BUD is relatively common in a dermatologic setting, especially among patients seeking cosmetic treatments. These patients have some different features compared with general dermatology patients. Dermatologists should be aware of the clinical characteristics of ODD to identify and refer these patients to mental health professionals. (J Am Acad Dermatol 2010;63:235-43.)

The Versatile Adani`s Flap for Fingertip Coverage Indications and Case Reports

Heterodigital pedicle flaps have 2 possible patters of vascularization: anterograde flow (Littler) or reverse flow (Adani). The Adani`s flap uses the Y-V pedicle lengthening principle. The flap is raised from the adjacent uninjured finger based on the digital artery. The common digital artery is ligated and a long pedicle is formed from the 2 converging digital arteries to supply a reverse flow flap. Four patients with severe fingertips injuries were submitted to surgical treatment with the Adani`s flap. All flaps integrated and provided skin coverage. The Adani`s flap has a long vascular pedicle that allows a wide arch of transposition. An easier vascular dissection in a site distant from the trauma which evolves a higher diameter digital artery and proximal interphalangeal arterial system promotes a high survival rate and good functional results. Adani`s flap is a reliable technique for severe fingertip injuries.

Fluid Replacement With Hypertonic or Isotonic Solutions Guided by Mixed Venous Oxygen Saturation in Experimental Hypodynamic Sepsis

Background: Splanchnic perfusion is prone to early injury and persists despite normalization of global hemodynamic variables in sepsis. Volume replacement guided by oxygen derived variables has been recommended in the management of septic patients. Our hypothesis was that a hypertonic isoneotic solution Would improve the benefits of crystalloids replacement guided by mixed venous oxygen saturation. Methods: Seventeen anesthetized and mechanically ventilated mongrel dogs received an intravenous infusion of live E. coli in 30 minutes. They were then randomized into three groups: control group (n = 3) bacterial infusion without treatment; normal saline (n = 7), initial fluid replacement with 32 mL/kg of normal saline during 20 minutes; hypertonic solution (n = 7), initial fluid replacement with 4 mL/kg of hypertonic solution during 5 minutes. After 30 and 60 Minutes, additional boluses of normal saline were administered when mixed venous oxygen saturation remained below 70%. Mean arterial pressure, cardiac output; regional blood flows, systemic and regional oxygen-derived variables, and lactate levels were assessed. Animals were observed for 90 minutes and then killed. Hystopathological analysis including apoptosis detection using terminal deoxynucleotidil transferase mediated dUTP-biotin nick end labeling was performed. Results: A hypodynamic septic shock was observed after bacterial infusion. Both the fluid-treated groups presented similar transient benefits in systemic and regional variables. A greater degree of gut epithelial cells apoptosis was observed in normal saline-treated animals. Conclusions: Although normalization of mixed venous oxygen saturation was not associated with restoration of markers of splanchnic or other systemic perfusion variables, the initial fluid savings with hypertonic saline and its latter effect on gut apoptosis may be of interest in sepsis management.

MET Is Highly Expressed in Advanced Stages of Colorectal Cancer and Indicates Worse Prognosis and Mortality

The aim of the present study was to evaluate by immunohistochemistry the prognostic meaning of the tumor marker MET (hepatocyte growth factor) in patients submitted to surgical resection due to primary colorectal adenocarcinoma. Patients and Methods: A retrospective study was carried out that included 286 consecutive patients with colorectal adenocarcinoma, submitted to surgical resection at Barretos Cancer Hospital, from 1993 to 2002. The histopathological expression of the MET tumor marker was evaluated using an anti-protein monoclonal antibody against MET by the streptavidin-biotin-peroxidase technique. The expression of the tumor marker was semi-quantitative, and the slide samples were independently analyzed by three pathologists unaware of patient clinical and histopathological data. Results: The tumor marker expression was positive in 236 (79%) out of a total of 286 patients. This expression was statistically significantly different between stages I and IV (p=0.004), for overall survival (p=0.009), and for cancer-related mortality rates (p=0.022). However, no association between the tumor marker and recurrence (p=0.89) or disease-free interval (p=0.91) was observed. Conclusion: MET has shown significant expression at advanced stages of the disease, as well as for overall survival and cancer-related mortality rates demonstrating to be a valuable marker for poor prognosis in colorectal cancer patients.

Comorbid major depression in obsessive-compulsive disorder patients

Although major depressive disorder (MDD) has been consistently considered the most frequent complication of obsessive-compulsive disorder (OCD), little is known about the clinical characteristics of patients with both disorders. This study assessed 815 Brazilian OCD patients using a comprehensive psychiatric evaluation. Clinical and demographic variables, including OCD symptom dimensions, were compared among OCD patients with and without MDD. Our findings showed that prevalence rates of current MDD (32%) and lifetime MDD (67.5%) were similar for both sexes in this study. In addition, patients with comorbid MDD had higher severity scores of OCD symptoms. There was no preferential association of MDD with any particular OCD symptom dimension. This study supports the notion that depressed OCD patients present more severe general psychopathology. (C) 2011 Elsevier Inc. All rights reserved.

Human apolipoprotein A-I binds amyloid-beta and prevents A beta-induced neurotoxicity

Aggregates of the amyloid-P peptide (A beta) play a central role in the pathogenesis of Alzheimer`s disease (AD). Identification of proteins that physiologically bind A beta and modulate its aggregation and neurotoxicity could lead to the development of novel disease-modifying approaches in AD. By screening a phage display peptide library for high affinity ligands of aggregated A beta(1-42), We isolated a peptide homologous to a highly conserved amino acid sequence present in the N-terminus of apolipoprotein A-I (apoA-I). We show that purified human apoA-I and A beta form non-covalent complexes and that interaction with apoA-I affects the morphology of amyloid aggregates formed by A beta. Significantly, A beta/apoA-I complexes were also detected in cerebrospinal fluid from AD patients. Interestingly, apoA-I and apoA-I-containing reconstituted high density lipoprotein particles protect hippocampal neuronal cultures from A beta-induced oxidative stress and neurodegeneration. These results suggest that human apoA-I modulates A beta aggregation and A beta-induced neuronal damage and that the A beta-binding domain in apoA-I may constitute a novel framework for the design of inhibitors of A beta toxicity. (C) 2009 Published by Elsevier Ltd.

Higher prevalence of obsessive-compulsive spectrum disorders in rheumatic fever

Objective: This study aims to compare the prevalence of obsessive-compulsive spectrum disorders (OCSD) in psychiatric outpatients with and without a history of rheumatic fever (RF). Methods: An analytical cross-sectional study assessing a large sample of consecutive psychiatric outpatients at a Brazilian private practice was conducted during a 10-year period. Psychiatric diagnoses were made by a senior psychiatrist based on Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Best-estimate diagnosis procedure was also performed. Results: The total sample comprised 678 subjects, 13 of whom (1.92%) presented with a previous history of RF. This group showed a higher prevalence of subclinical obsessive-compulsive disorder (P=.025) and OCSD (P=.007) when compared to individuals with no such history. Conclusions: A previous history of RF was associated with OCSD. These results suggest that clinicians should be encouraged to actively investigate obsessive-compulsive symptoms and related disorders in patients with a positive history of RF. (C) 2009 Published by Elsevier Inc.