Comorbid mood and anxiety disorders in victims of violence with posttraumatic stress disorder

OBJETIVO: Buscar estudos que avaliem a comorbidade entre transtorno de estresse pós-traumático e transtornos do humor, bem como entre transtorno de estresse pós-traumático e outros transtornos de ansiedade. MÉTODO: Revisamos a base de dados do Medline em busca de estudos publicados em inglês até abril de 2009, com as seguintes palavras-chave: "transtorno de estresse pós-traumático", "TEPT", "transtorno de humor", "transtorno depressivo maior", "depressão maior", "transtorno bipolar", "distimia", "transtorno de ansiedade", "transtorno de ansiedade generalizada", agorafobia", "transtorno obsessivo-compulsivo", "transtorno de pânico", "fobia social" e "comorbidade". RESULTADOS: Depressão maior é uma das condições comórbidas mais frequentes em indivíduos com transtorno de estresse pós-traumático, mas eles também apresentam transtorno bipolar e outros transtornos ansiosos. Essas comorbidades impõem um prejuízo clínico adicional e comprometem a qualidade de vida desses indivíduos. Comportamento suicida em pacientes com transtorno de estresse pós-traumático, com ou sem depressão maior comórbida, é também uma questão relevante, e sintomas depressivos mediam a gravidade da dor em sujeitos com transtorno de estresse pós-traumático e dor crônica. CONCLUSÃO: Os estudos disponíveis sugerem que pacientes com transtorno de estresse pós-traumático têm um risco maior de desenvolver transtornos afetivos e, por outro lado, transtornos afetivos pré-existentes aumentam a propensão ao transtorno de estresse pós-traumático após eventos traumáticos. Além disso, vulnerabilidades genéticas em comum podem ajudar a explicar esse padrão de comorbidades. No entanto, diante dos poucos estudos encontrados, mais trabalhos são necessários para avaliar adequadamente essas comorbidades e suas implicações clínicas e terapêuticas.OBJECTIVE: To review studies that have evaluated the comorbidity between posttraumatic stress disorder and mood disorders, as well as between posttraumatic stress disorder and other anxiety disorders. METHOD: We searched Medline for studies, published in English through April, 2009, using the following keywords: "posttraumatic stress disorder", "PTSD", "mood disorder", "major depressive disorder", "major depression", "bipolar disorder", "dysthymia", "anxiety disorder", "generalized anxiety disorder", "agoraphobia", "obsessive-compulsive disorder", "panic disorder", "social phobia", and "comorbidity". RESULTS: Major depression is one of the most frequent comorbid conditions in posttraumatic stress disorder individuals, but individuals with posttraumatic stress disorder are also more likely to present with bipolar disorder, other anxiety disorders and suicidal behaviors. These comorbid conditions are associated with greater clinical severity, functional impairment, and impaired quality of life in already compromised individuals with posttraumatic stress disorder. Depression symptoms also mediate the association between posttraumatic stress disorder and severity of pain among patients with chronic pain. CONCLUSION: Available studies suggest that individuals with posttraumatic stress disorder are at increased risk of developing affective disorders compared with trauma-exposed individuals who do not develop posttraumatic stress disorder. Conversely, pre-existing affective disorders increase a person's vulnerability to the posttraumatic stress disorder--inducing effects of traumatic events. Also, common genetic vulnerabilities can help to explain these comorbidity patterns. However, because the studies addressing this issue are few in number, heterogeneous and based on a limited sample, more studies are needed in order to adequately evaluate these comorbidities, as well as their clinical and therapeutic implications

Serum levels of leptin and adiponectin and clinical parameters in women with fibromyalgia and overweight/obesity

ABSTRACT Objectives The objectives of this study were to evaluate the serum levels of adipokines in women with fibromyalgia with and without overweight/obesity, and to correlate the adipokines levels with clinical parameters associated with fibromyalgia and adipose tissue mass (body fat). Subjects and methods The study included 100 women divided into four groups: (a) fibromyalgia and overweight/obesity; (b) fibromyalgia and normal weight; (c) controls and overweight/obesity; and (d) controls and normal weight. Patients and controls were evaluated for clinical, anthropometric, and fibromyalgia-related parameters. Assessments included serum levels of leptin, adiponectin, monocyte chemoattractant protein-1 (MCP-1), and C-reactive protein (CRP). Levels of adipokines were further adjusted for fat mass. Results Fibromyalgia patients with overweight/obesity or normal weight had no differences in clinical parameters. Unadjusted leptin levels were lower in fibromyalgia patients than controls, a finding that was more remarkable in fibromyalgia patients with overweight/obesity. Leptin levels had no correlation with clinical parameters of fibromyalgia or inflammation markers (MCP-1 and CRP), and adiponectin levels showed no difference between groups. Conclusions No correlation was observed between adjusted leptin levels and clinical parameters of fibromyalgia. Patients with fibromyalgia and overweight/obesity presented lower levels of leptin than controls with overweight/obesity

Effects of Fluoride on Submandibular Glands of Mice: Changes in Oxidative Biochemistry, Proteomic Profile, and Genotoxicity

Although fluoride (F) is well-known to prevent dental caries, changes in cell processes in different tissues have been associated with its excessive exposure. Thus, this study aimed to evaluate the effects of F exposure on biochemical, proteomic, and genotoxic parameters of submandibular glands. Twenty one old rats (n = 30) were allocated into three groups: 60 days administration of drinking water containing 10 mgF/L, 50 mgF/L, or only deionized water (control). The submandibular glands were collected for oxidative biochemistry, protein expression profile, and genotoxic potential analyses. The results showed that both F concentrations increased the levels of thiobarbituric acid–reactive substances (TBARS) and reduced glutathione (GSH) and changed the proteomic profile, mainly regarding the cytoskeleton and cellular activity. Only the exposure to 50 mgF/L induced significant changes in DNA integrity. These findings reinforce the importance of continuous monitoring of F concentration in drinking water and the need for strategies to minimize F intake from other sources to obtain maximum preventive/therapeutic effects and avoid potential adverse effects

Blockade of mGluR5 in astrocytes derived from human iPSCs modulates astrocytic function and increases phagocytosis

TNF-α is essential for induction and maintenance of inflammatory responses and its dysregulation is associated with susceptibility to various pathogens that infect the central nervous system. Activation of both microglia and astrocytes leads to TNF-α production, which in turn triggers further activation of these cells. Astrocytes have been implicated in the pathophysiology of a wide range of neurodegenerative diseases with either harmful or protective roles, as these cells are capable of secreting several inflammatory factors and also promote synapse elimination and remodeling. These responses are possible because they sense their surroundings via several receptors, including the metabotropic glutamate receptor 5 (mGluR5). Under neuroinflammatory conditions, mGluR5 activation in astrocytes can be neuroprotective or have the opposite effect. In the current study, we investigated the role of mGluR5 in hiPSC-derived astrocytes subjected to pro-inflammatory stimulation by recombinant TNF-α (rTNF-α). Our results show that mGluR5 blockade by CTEP decreases the secreted levels of pro-inflammatory cytokines (IL-6 and IL-8) following short rTNF-α stimulation, although this effect subsides with time. Additionally, CTEP enhances synaptoneurosome phagocytosis by astrocytes in both non-stimulated and rTNF-α-stimulated conditions, indicating that mGluR5 blockade alone is enough to drive synaptic material engulfment. Finally, mGluR5 antagonism as well as rTNF-α stimulation augment the expression of the reactivity marker SERPINA3 and reduces the expression of synaptogenic molecules. Altogether, these data suggest a complex role for mGluR5 in human astrocytes, since its blockade may have beneficial and detrimental effects under inflammatory conditions

Impacto de um programa para profilaxia de tromboembolismo venoso em pacientes clínicos em quatro hospitais de Salvador

OBJETIVO: Implementar um programa hospitalar de profilaxia de TEV através da criação de uma comissão, da realização de palestras e da distribuição de algoritmos baseados na Diretriz Brasileira para Profilaxia de TEV em Pacientes Clínicos e avaliar seu impacto na adequação da utilização de profilaxia em quatro hospitais de Salvador, Bahia. MÉTODOS: Foram realizados dois estudos de corte-transversal, um antes e um depois da implementação do programa, e comparadas as proporções de pacientes em risco de TEV e as mudanças na adequação da profilaxia. RESULTADOS: Foram avaliados 219 pacientes clínicos antes e 292 depois do programa. As taxas daqueles com pelo menos um fator de risco para TEV e daqueles com contra indicação (CI) para heparina foram semelhantes nos dois grupos: 95% vs. 98% (p=0,13) e 42% vs. 34% (p=0,08), respectivamente. Nos dois estudos, 75% vs. 82% (p=0,06) eram candidates para profilaxia, e 44% vs. 55% (p =0,02) eram candidatos sem qualquer CI para heparina. Após o programa, utilizou-se mais profilaxia mecânica, 0,9% vs. 4,5% (p=0,03) e menos profilaxia farmacológica, 55,3% vs. 47,9% (p=0,04), embora tenha havido um aumento significativo na utilização das doses corretas das heparinas, 53% vs. 75% (pThere is a discrepancy between guideline recommendations and practice of venous thromboembolism (VTE) prophylaxis in hospitals worldwide. OBJECTIVE: To implement a program using a risk-assessment tool (RAT) for VTE and educational lectures based on the Brazilian Guidelines for VTE Prophylaxis for Medical Patients and to evaluate the impact of these tools on adequacy of VTE prophylaxis in 4 hospitals in Salvador, Bahia. METHODS: We performed two cross-sectional surveys before and after the implementation of the program to compare the proportion of patients at-risk of VTE and the changes in the adequacy of VTE prophylaxis. RESULTS: We compared the data of 219 medical patients before with 292 patients after the program. The rates of patients with at least one risk factor for VTE and with contraindications (CI) for heparins were similar: 95% vs. 98% (p=0.13), and 42% vs. 34% (p=0.08), respectively. In both studies, 75% vs. 82% (p=0.06) were candidates for prophylaxis, and 44% vs. 55% (p =0.02) were candidates for prophylaxis and had no CI for heparin. After the program there was an increase in the use of mechanical prophylaxis 0.9% vs. 4.5% (p=0.03) and a decrease in pharmacological prophylaxis, 55.3% vs. 47.9% (p=0.04). However, there was a significant increase of use of the recommended doses of heparins, 53% vs. 75 (p<0.001). CONCLUSION: There is underutilization of VTE prophylaxis in Brazilian hospitals. Strategies based on passive distribution of RAT and educational lectures were not sufficient to improve the practice of prophylaxis, but improved the adequacy of VTE prophylaxis in hospitalized patients

Aortic Response to Strength Training and Spirulina platensis Dependent on Nitric Oxide and Antioxidants

Studies have shown that supplementation with Spirulina platensis improves vascular reactivity. However, it is unclear whether in association with strength training this effect can be enhanced. Thus, this study aimed to determine the effects of strength training and S. platensis on the reactivity of the aorta from Wistar rat and the possible mechanisms involved. The animals were supplemented with S. platensis and divided into sedentary (SG, SG50, SG150, and SG500) and trained groups (TG, TG50, TG150, and TG500). Nitrite, malondialdehyde (MDA) and antioxidant activity were determined by biochemical assays. To evaluate vascular response, cumulative concentration—response curves to phenylephrine (PHE) and acetylcholine (ACh) were constructed. L-NAME was used to assess the participation of nitric oxide (NO). It was observed that the PHE contractile potency was reduced in TG50, TG150, and TG500 groups compared to SG50, SG150, and SG500 groups, respectively. However, the presence of L-NAME increased the contractile response in all groups. Strength training potentiated the increase in relaxing activity induced by S. platensis, where the pCE50 values of ACh increased in TG150 and TG500. These responses were accompanied by increased nitrite production, MDA reduction and increased antioxidant activity in the aorta of both TG150 and TG500 groups. Thus, the present study demonstrated that combined with strength training, S. platensis potentiates vascular improvement through the participation of NO and reduction of oxidative stress

Stress-inducible phosphoprotein 1 (HOP/STI1/STIP1) regulates the accumulation and toxicity of α-synuclein in vivo

The predominantly pre-synaptic intrinsically disordered protein α-synuclein is prone to misfolding and aggregation in synucleinopathies, such as Parkinson’s disease (PD) and Dementia with Lewy bodies (DLB). Molecular chaperones play important roles in protein misfolding diseases and members of the chaperone machinery are often deposited in Lewy bodies. Here, we show that the Hsp90 co-chaperone STI1 co-immunoprecipitated α-synuclein, and co-deposited with Hsp90 and Hsp70 in insoluble protein fractions in two mouse models of α-synuclein misfolding. STI1 and Hsp90 also co-localized extensively with filamentous S129 phosphorylated α-synuclein in ubiquitin-positive inclusions. In PD human brains, STI1 transcripts were increased, and in neurologically healthy brains, STI1 and α-synuclein transcripts correlated. Nuclear Magnetic Resonance (NMR) analyses revealed direct interaction of α-synuclein with STI1 and indicated that the STI1 TPR2A, but not TPR1 or TPR2B domains, interacted with the C-terminal domain of α-synuclein. In vitro, the STI1 TPR2A domain facilitated S129 phosphorylation by Polo-like kinase 3. Moreover, mice over-expressing STI1 and Hsp90ß presented elevated α-synuclein S129 phosphorylation accompanied by inclusions when injected with α-synuclein pre-formed fibrils. In contrast, reduced STI1 function decreased protein inclusion formation, S129 α-synuclein phosphorylation, while mitigating motor and cognitive deficits as well as mesoscopic brain atrophy in α-synuclein-over-expressing mice. Our findings reveal a vicious cycle in which STI1 facilitates the generation and accumulation of toxic α-synuclein conformers, while α-synuclein-induced proteostatic stress increased insoluble STI1 and Hsp90