Metabolic syndrome: what is it and what are the implications?

Obesity and overweight are linked with a cluster of metabolic and vascular disorders that have been termed the metabolic syndrome. Although there is not yet a universally-accepted set of diagnostic criteria, most expert groups agree that the syndrome is characterised by impaired insulin sensitivity and hyperglycaemia, dyslipidaemia (elevated blood triacyglycerols with depressed HDL-cholesterol), abdominal obesity and hypertension. Based on existing published criteria estimates suggest that the syndrome affects a substantial percentage of the middle-aged and elderly populations of most European countries (10-20%) and confers increased risk of type 2 diabetes (2-8(.)8-fold) and CVD (1(.)5-6-fold), as well as having a marked effect on morbidity. Although the pathophysiology is incompletely understood, insulin resistance and abdominal obesity are central to subsequent abnormalities in circulating glucose and lipoproteins, and vascular function that lead to type 2 diabetes, atherosclerosis and CVD. The link between metabolic syndrome, type 2 diabetes and CVD, as well as inability to reverse the present rising rates of obesity, will lead to economically-unsustainable costs of health care in the next 10-20 years. Preventative strategies for metabolic syndrome are required to slow rates of progression and to reduce dependence on costly medical management. A notable development is recent evidence that shows that diet and exercise are more effective than drug treatment in preventing the development of type-2 diabetes in high-risk individuals. The LIPGENE project will investigate dietary fat quality as a strategy for the prevention of metabolic syndrome and identify food chain approaches that can support consumer attempts to alter their dietary patterns.

The D2 antagonist sulpiride modulates the neural processing of both rewarding and aversive stimuli in healthy volunteers.

Rationale: Animal studies indicate that dopamine pathways in the ventral striatum code for the motivational salience of both rewarding and aversive stimuli, but evidence for this mechanism in humans is less established. We have developed a functional magnetic resonance imaging (fMRI) model which permits examination of the neural processing of both rewarding and aversive stimuli. Objectives: The aim of the study was to determine the effect of the dopamine receptor antagonist, sulpiride, on the neural processing of rewarding and aversive stimuli in healthy volunteers. Methods: We studied 30 healthy participants who were randomly allocated to receive a single dose of sulpiride (400 mg) or placebo, in a double-blind, parallel-group design. We used fMRI to measure the neural response to rewarding (taste or sight of chocolate) and aversive stimuli (sight of mouldy strawberries or unpleasant strawberry taste) 4 h after drug treatment. Results: Relative to placebo, sulpiride reduced blood oxygenation level-dependent responses to chocolate stimuli in the striatum (ventral striatum) and anterior cingulate cortex. Sulpiride also reduced lateral orbitofrontal cortex and insula activations to the taste and sight of the aversive condition. Conclusions: These results suggest that acute dopamine receptor blockade modulates mesolimbic and mesocortical neural activations in response to both rewarding and aversive stimuli in healthy volunteers. This effect may be relevant to the effects of dopamine receptor antagonists in the treatment of psychosis and may also have implications for the possible antidepressant properties of sulpiride.

Additive effect of P10 immunization and chemotherapy in anergic mice challenged intratracheally with virulent yeasts of Paracoccidioides brasiliensis

Paracoccidioidomycosis is a systemic granulomatous disease manifested in the acute/subacute or chronic forms. The anergic cases of the acute/subacute form are most severe, leading to death threatening conditions. Drug treatment is required to control the disease but the response in anergic patients is generally poor. A 15-mer peptide from the major diagnostic antigen gp43, named P10, induces a T-CD4(+) helper-1 immune response in mice of different haplotypes and protects against intratracheal challenge with virulent P. brasiliensis. Presently, P10 immunization and chemotherapy were associated in an attempt to improve antifungal treatment in Balb/c mice made anergic by adding dexamethasone to the drinking water. The combined drug/peptide treatment significantly reduced the lung CFUs in infected anergic mice, largely preserved lung alveolar structure and prevented fungal dissemination to liver and spleen. Results recommend that a P10-based vaccine should be associated to chemotherapy for improved treatment of paracoccidioidomycosis aiming especially at anergic cases. (C) 2008 Elsevier Masson SAS. All rights reserved.

Compatibility studies between captopril and pharmaceutical excipients used in tablets formulations

Captopril (CAP) was the first commercially available angiotensine-converting enzyme (ACE) inhibitor. In the anti-hypertensive therapy is considered the selected drug has to be therapeutically effective together with reduced toxicity. CAP is an antihypertensive drug currently being administered in tablet form. In order to investigate the possible interactions between CAP and excipients in tablets formulations, differential scanning calorimetry (DSC) and thermogravimetric (TG) analysis completed by X-ray powder diffraction (XRPD) and Fourier transform infrared spectroscopy (FTIR) were used for compatibility studies. A possible drug-excipient interaction was observed with magnesium stearate by DSC technique.

A Graphite-Polyurethane Composite Electrode for the Analysis of Furosemide

A graphite-polyurethane composite electrode has been used for the determination of furosemide, a antihypertensive drug, in pharmaceutical samples by anodic oxidation. Cyclic voltammetry and electrochemical impedance spectroscopy were used to characterize the electrooxidation process at +1.0 V vs. SCE over a wide pH range, with the result that no adsorption of analyte or products occurs, unlike at other carbon-based electrode materials. Quantification was carried out using cyclic voltammetry, differential pulse voltammetry, and square-wave voltammetry. Linear ranges were determined (up to 21 mu mol L-1 with cyclic voltammetry) as well as limits of detection (0.15 mu mol L-1 by differential pulse voltammetry). Four different types of commercial samples were successfully analyzed. Recovery tests were performed which agreed with those obtained by spectrophotometric evaluation. The advantages of this electrode material for repetitive analyzes, due to the fact that no electrode surface renewal is needed owing to the lack of adsorption, are highlighted.

Determination of Minoxidil by Bleaching the Permanganate Carrier Solution in a Flow-Based Spectrophotometric System

The determination of minoxidil (MX) with potassium permanganate as a carrier in a flow injection method is described. The detection at 550nm was linear from 1.0x10-5 to 5.0x10-4mol L-1. The limit of detection (3 sigma/slope) was 8.92x10-6mol L-1, with an analytical frequency of 32h-1. The proposed method was applied to commercial samples, with recoveries from 104.7 to 106.4%. Comparison with the HPLC procedure reveled relative errors from 0.48 to 1.4%, and the results agreed within a 95% confidence level.

Indução de morte celular em células de adenocarcinoma cervical humano (HeLa) pela lectina da esponja Cinachyrella apion (CaL)

Cancer is a term used to represent a set of more than 100 diseases, including malignant tumors from different locations. The malignancies are the second leading cause of death in the population, representing approximately 17% of deaths of known cause. Strategies that induce differentiation have had limited success in the treatment of established cancers. In this work, a lectin purified from the marine sponge Cinachyrella apion (CaL) was evaluated due to its hemolytic, cytotoxic and antiproliferative properties, besides the ability to induce cell death via apoptosis in tumor cells. The antiproliferative activity of CaL was tested against cell lines, with the highest inhibition of tumor growth for HeLa, reducing cell growth at a dose dependent manner, with a concentration of 10 μg/mL. The hemolytic activity and toxicity against peripheral blood cells were tested using the concentration of IC50 for both trials and twice the IC50 for analysis in flow cytometry, indicating that CaL is not toxic to these cells. To assess the mechanism of cell death caused by CaL in HeLa cells, we performed flow cytometry and western blotting. The results showed the lectin probably induces cell death by apoptosis activation by pro-apoptotic protein Bax, promoting mitochondrial membrane permeabilization, cell cycle arrest in S phase, with accumulation of cells of approximately 57% in this phase, and acting as both dependent and/or independent of caspases pathway. These results suggest that CaL has the potential to be used as drug treatment against cancer.

Assistência aos portadores de úlceras venosas: proposta de protocolo

Venous ulcers (VU), recurrent chronic wounds resulting from Chronic Venous Insufficiency (CVI), affect different age groups and would severely affect ambulation of patients. The lesions require treatment lasting and complex and are responsible for significant morbidity and mortality. Thus, this study aims to identify the important aspects covered in the scientific literature protocol for assisting patients with venous ulcers, identifying the issues to be proposed by the judges of the study (nurses, doctors and physiotherapists) to the protocol of care provided to patients venous ulcers and present the structure of protocol proposed by the judges of the study to assist patients with venous ulcers treated at a referral hospital of Rio Grande do Norte. This is a descriptive study using a quantitative approach, carried out at the dressings, located in the outpatient surgical clinic of the Hospital University Onofre Lopes (HUOL), located in East Sanitary District, Natal-RN. The sample consisted of 39 professionals, 30 nurses, seven doctors and two physical therapists, team members HUOL surgical clinic and other public and private institutions of Rio Grande do Norte and Jequié/Bahia. These professionals were the judges responsible for selecting the guidelines already proposed in the literature on VU protocols. Approved by the Ethics in Research HUOL (Report n.o 081/07), began the first stage of the study which consisted of reviewing the scientific literature about the relevant aspects to be included in a protocol for assisting patients with VU. These aspects were organized into a proposed questionnaire to the judges of the study. Following examination, held on the content validation with application of the Kappa (K), accepting a score higher than 0.80 and the Likert Scale, whereas rates from 4.0 to 5.0. The data collected were organized in Microsoft Excel and exported into Statistical Package for Social Sciences (SPSS) 15.0. The literature review included national and international scientific articles, thesis, dissertation and institutional protocols. Regarding the characterization of professional nurses predominated (76.1%), between 34 and 45 years (41.0%), female (79.5%), married/consensual union (46.2%), with specialization in VU care (61.5%), working in the hospital network (46.1%), with up to 5 years experience in VU (69.2%) and claiming to feel prepared to care for these injuries (92.3 %). With regard to aspects that had very good agreement (K ≥ 0.81), remained the items found in the literature with some modifications. In the analysis of the proposed evaluation items had very important, ranging from 4.1 (drug treatment) to 4.9 (patient assessment and care of the injury and the injured and perilesional skin). The proposition of the protocol is arranged in eleven items: A) Evaluation of patient and lesion, B) Registration and documentation, C) the wound and perilesional skin, D) an indication of coverage, E) Use of antibiotic and pain treatment, F) Surgical treatment of CVI, G) Drug treatment, H) Improving venous return and prevetion of recurrence, I) Referral of patients, J) Training and K) Reference and counter reference

Blockade of fear-induced antinociception with intra-amygdala infusion of midazolam: Influence of prior test experience

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Effect of cocaine on periadolescent rats with or without early maternal separation

Cocaine-induced behavioral sensitization and weight loss were investigated in periadolescent Wistar rats kept with their mothers or subjected to repeated maternal separation. Litters allocated to the separation procedure were placed in a temperature-controlled (33ºC) chamber for 3 h per day from postnatal day 6 (P6) to P20. Non-handled rats were left undisturbed until weaning. Treatments were started on P30-31 and the test was performed on P36-37. Animals received injections of saline or cocaine (10 mg/kg, sc) twice daily for 5 days. on day 6 all animals received saline. on day 7 animals were challenged with 10 mg/kg cocaine and their locomotion was evaluated in activity cages. A third group received saline throughout the 7-day period. Body weights were recorded on P30-31 and P36-37. Two-way ANOVA on body weights showed a main effect of treatment group (F(1,35) = 10.446, P = 0.003; N = 10-12). Non-handled rats treated with cocaine for 5 days gained significantly less weight, while no significant effect was observed in maternally separated rats. Two-way ANOVA revealed a main effect of drug treatment on locomotor activity (F(2,32) = 15.209, P<0.001; N = 6-8), but not on rearing condition (F(1,32)<0.001, P = 0.998). Animals pretreated with cocaine showed a clear behavioral sensitization relative to the saline group. No difference in the magnitude of sensitization was found between separated and non-handled animals. Only the effect of cocaine on weight gain was significantly affected by repeated episodes of early maternal separation during the pre-weaning period.

Tratamento do transtorno de pânico com terapia psicodramática de grupo

INTRODUÇÃO/OBJETIVOS: Há poucos trabalhos publicados sobre psicoterapia grupal para pacientes com transtorno de pânico (TP); além disso, esses estudos geralmente são restritos a abordagens cognitivo-comportamentais. O objetivo deste trabalho é relatar uma experiência de atendimento psicoterápico psicodramático grupal para portadores de TP, iniciada em 1996 na Faculdade de Medicina de Botucatu/Unesp, e discutir aspectos psicodinâmicos desse transtorno. MÉTODOS: Atende-se uma média de oito a dez pacientes em sessões mensais de duas horas de duração, nas quais se utilizam técnicas psicodramáticas. O uso associado de psicofármacos é a regra. A temática é aberta, centrando-se tanto em aspectos próprios do TP (sintomas mais comuns; peregrinação em serviços médicos até o diagnóstico; preocupações hipocondríacas; limitações e dependência; reações dos familiares; estratégias de exposição e enfrentamento; efeitos e reações dos medicamentos) quanto em problemas individuais específicos. RESULTADOS: A abordagem psicodramática favorece a identificação e a elaboração de aspectos psicodinâmicos. Entre estes, destacaram-se os sentimentos de desamparo e seus desdobramentos: insegurança; fragilidade e medo; raiva e culpa; sentimentos de desamor e rejeição; vergonha e inferioridade; isolamento e dificuldade de pedir ajuda; dificuldade de identificar e de expressar sentimentos - manifestados somaticamente -; e dificuldade de assumir o papel de cuidador e outras responsabilidades. CONCLUSÕES: Aspectos valiosos para o tratamento do TP, como apoio mútuo, companheirismo, confiança, modelo e estímulo, são favorecidos pelo contexto grupal homogêneo. O compartilhar de experiências e sofrimentos comuns propiciou rápida coesão e suporte grupal, melhora da capacidade de expressar sentimentos e da auto-estima e o aprimoramento de papéis sociais. Além da melhora dos sintomas, possibilitou-se a melhor compreensão e elaboração destes, que passam a ser integrados significativamente no contexto existencial.

Recrudescence of Toxoplasma gondii infection in chronically infected rats (Rattus norvegicus)

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Experimental development of bisphosphonate-related osteonecrosis of the jaws in rodents

Osteonecrosis of the jaw (ONJ) following the use of bisphosphonates has become of increased interest in the scientific community, due in particular to its as-yet-unsolved pathogenesis. An experimental model of ONJ was induced in normal male rats [alendronate (ALN); 1 mg/Kg/day; n = 10] and matched controls (saline solution; n = 10). After 60 days of drug treatment, all animals were subjected to extractions of the left first lower molars and were euthanized at 3 and 28 days postsurgery. The following analyses were performed: (i) descriptive and quantitative (scores) histological evaluation, (ii) stereometry of distal sockets and (iii) biochemical measurement of C-telopeptide cross-linked collagen type I (CTX) and bone-specific alkaline phosphatase (BALP). The results showed that 28 days postsurgery the animals treated with ALN had areas of exposed and necrotic bone, associated with significant infection, especially in the interalveolar septum area and crestal regions, compared with controls. The levels of CTX, BALP and bone volume, as well as the degrees of inflammation and vascularization, were significantly reduced in these animals. Therefore, analysis of the data presented suggests that ALN therapy is associated with the development of osteonecrosis in the jaws of rodents after tooth extraction. © 2012 International Journal of Experimental Pathology.

Efeito agudo de CPAP na funçao diastólica ventricular e na capacidade funcional de pacientes com insuficiência cardíaca

Pós-graduação em Fisiopatologia em Clínica Médica - FMB

Desenvolvimento e caracterização de carreadores lipídicos nanoestruturados contendo praziquantel

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)