Advances in drug design based on the amino acid approach: Taurine analogues for the treatment of CNS diseases

Amino acids are well known to be an important class of compounds for the maintenance of body homeostasis and their deficit, even for the polar neuroactive aminoacids, can be controlled by supplementation. However, for the amino acid taurine (2-aminoethanesulfonic acid) this is not true. Due its special physicochemical properties, taurine is unable to cross the blood-brain barrier. In addition of injured taurine transport systems under pathological conditions, CNS supplementation of taurine is almost null. Taurine is a potent antioxidant and anti-inflammatory semi-essential amino acid extensively involved in neurological activities, acting as neurotrophic factor, binding to GABA A/glycine receptors and blocking the excitotoxicity glutamate-induced pathway leading to be a neuroprotective effect and neuromodulation. Taurine deficits have been implicated in several CNS diseases, such as Alzheimer's, Parkinson's, epilepsy and in the damage of retinal neurons. This review describes the CNS physiological functions of taurine and the development of new derivatives based on its structure useful in CNS disease treatment.&; 2012 by the authors; licensee MDPI, Basel, Switzerland.

Dietary intake and blood lipid profile in overweight and obese schoolchildren

Abstract. Background: The high blood lipid levels and obesity are one of the main risk factors for cardiovascular diseases, and the atherosclerotic process begins in childhood. Some environmental factors are supposed to be involved in this relationship, such as dietary factors. This study aimed to investigate the relationship between dietary intake and blood lipids levels in overweight and obese schoolchildren. Methods. This is a cross-sectional study with 147 overweight and obese schoolchildren in Botucatu city, Brazil. The anthropometric measurements (body weight, height, body mass index, waist circumference and skinfolds), pubertal staging evaluation and biochemical tests were taken in all children. Three 24h-recall were applied in order to estimate the dietary intake and its relationship with blood lipid levels. The Student t test and multiple linear regression analysis were used for statistical analysis. Statistical significance was assessed at the level of 0.05. The data were processed in SAS software (version 9.1.3; SAS Institute). Results: At this study, 63% of children were obese (body mass index higher than 95§ssup§th§esup§ percentile) and 80% showed high body fat percentage. The percentage of children with abnormal total cholesterol and triglycerides was 12% and 10%, respectively, and 28% presented at least one abnormal lipid levels. The average values of anthropometric measurements were higher in children with elevated lipid levels. Total cholesterol levels were positively related to full-fat dairy products and triglycerides levels to saturated fat percentage. Conclusions: Saturated fat was positively associated with elevated lipid levels in overweight and obese schoolchildren. These results reinforce the importance of healthy dietary habits since childhood in order to reduce the risks of cardiovascular diseases in adulthood. © 2012 Rinaldi et al.; licensee BioMed Central Ltd.

An optimised electrochemical biosensor for the label-free detection of C-reactive protein in blood

C-reactive protein (CRP) is an acute phase protein whose levels are increased in many disorders. There exists, in particular, a great deal of interest in the correlation between blood serum levels and the severity of risk for cardiovascular disease. A sensitive, label-free, non-amplified and reusable electrochemical impedimetric biosensor for the detection of CRP in blood serum was developed herein based on controlled and coverage optimised antibody immobilization on standard polycrystalline gold electrodes. Charge transfer resistance changes were highly target specific, linear with log. CRP. concentration across a 0.5-50. nM range and associated with a limit of detection of 176. pM. Significantly, the detection limits are better than those of current CRP clinical methods and the assays are potentially cheap, relatively automated, reusable, multiplexed and highly portable. The generated interfaces were capable not only of comfortably quantifying CRP across a clinically relevant range of concentrations but also of doing this in whole blood serum with interfaces that were, subsequently, reusable. The importance of optimising receptor layer resistance in maximising assay sensitivity is also detailed. © 2012.

Effect of dietary sodium restriction on body water, blood pressure, and inflammation in hemodialysis patients: a prospective randomized controlled study

Purpose: Accumulating evidence suggests an association between body volume overload and inflammation in chronic kidney diseases. The purpose of this study was to evaluate the effect of dietary sodium reduction in body fluid volume, blood pressure (BP), and inflammatory state in hemodialysis (HD) patients. Methods: In this prospective controlled study, adult patients on HD for at least 90 days and those with C-reactive protein (CRP) levels ≥0.7 mg/dl were randomly allocated into two groups: group A, which included 21 patients treated with 2 g of sodium restriction on their habitual diet; and group B, which included 18 controls. Clinical, inflammatory, biochemical, hematological, and nutritional markers were assessed at baseline and after 8 and 16 weeks. Results: Baseline characteristics were not significantly different between the groups. Group A showed a significant reduction in serum concentrations of CRP, tumor necrosis factor-α, and interleukin-6 during the study period, while BP and extracellular water (ECW) did not change. In group B, there were no changes in serum concentrations of inflammatory markers, BP, and ECW. Conclusions: Dietary sodium restriction is associated with the attenuation of the inflammatory state, without changes in BP and ECW, suggesting inhibition of a salt-induced inflammatory response. © 2013 Springer Science+Business Media Dordrecht.

Effect of dialysate sodium reduction on body water volume, blood pressure, and inflammatory markers in hemodialysis patients - A prospective randomized controlled study

Accumulating evidence suggests an association between body volume overload and inflammation in chronic kidney diseases. The purpose of this study was to evaluate the effect of dialysate sodium concentration reduction on extracellular water volume, blood pressure (BP), and inflammatory state in hemodialysis (HD) patients. In this prospective controlled study, adult patients on HD for at least 90 days and those with C-reactive protein (CRP) levels ≥ 0.7 mg/dL were randomly allocated into two groups: group A, which included 29 patients treated with reduction of dialysate sodium concentration from 138 to 135 mEq/L; and group B, which included 23 HD patients not receiving dialysate sodium reduction (controls). Of these, 20 patients in group A and 18 in group B completed the protocol study. Inflammatory, biochemical, hematological, and nutritional markers were assessed at baseline and after 8 and 16 weeks. Baseline characteristics were not significantly different between the two groups. Group A showed a significant reduction in serum concentrations of tumor necrosis factor-α, and interleukin-6 over the study period, while the BP and extracellular water (ECW) did not change. In Group B, there were no changes in serum concentrations of inflammatory markers, BP, and ECW. Dialysate sodium reduction is associated with attenuation of the inflammatory state, without changes in the BP and ECW, suggesting inhibition of a salt-induced inflammatory response. Copyright © 2013 Informa Healthcare USA, Inc.

Tissue-engineered blood vessel substitute by reconstruction of endothelium using mesenchymal stem cells induced by platelet growth factors

Background: Cardiovascular diseases remain leaders as the major causes of mortality in Western society. Restoration of the circulation through construction of bypass surgical treatment is regarded as the gold standard treatment of peripheral vascular diseases, and grafts are necessary for this purpose. The great saphenous vein is often not available and synthetic grafts have their limitations. Therefore, new techniques to produce alternative grafts have been developed and, in this sense, tissue engineering is a promising alternative to provide biocompatible grafts. This study objective was to reconstruct the endothelium layer of decellularized vein scaffolds, using mesenchymal stem cells (MSCs) and growth factors obtained from platelets. Methods: Fifteen nonpregnant female adult rabbits were used for all experiments. Adipose tissue and vena cava were obtained and subjected to MSCs isolation and tissue decellularization, respectively. MSCs were subjected to differentiation using endothelial inductor growth factor (EIGF) obtained from human platelet lysates. Immunofluorescence, histological and immunohistochemical analyses were employed for the final characterization of the obtained blood vessel substitute. Results: The scaffolds were successfully decellularized with sodium dodecyl sulfate. MSCs actively adhered at the scaffolds, and through stimulation with EIGF were differentiated into functional endothelial cells, secreting significantly higher quantities of von Willebrand factor (0.85 μg/mL; P < .05) than cells cultivated under the same conditions, without EIGF (0.085 μg/mL). Cells with evident morphologic characteristics of endothelium were seen at the lumen of the scaffolds. These cells also stained positive for fascin protein, which is highly expressed by differentiated endothelial cells. Conclusions: Taken together, the use of decellularized bioscaffold and subcutaneous MSCs seems to be a potential approach to obtain bioengineered blood vessels, in the presence of EIGF supplementation. © 2013 Society for Vascular Surgery.

Reference range for T lymphocytes populations in blood donors from two different regions in Brazil

ABSTRACT: This study defined the normal variation range for different subsets of T-lymphocyte cells count in two different Brazilian regions. We analysed the T-lymphocytes subpopulations (CD3+, CD4+, CD8+) in blood donors of two Brazilian cities, located in North (Belem, capital state of Para, indian background) and Northeast (Salvador, capital state od Bahia, African background) regions of Brazil. Results were compared according to gender, stress level (sleep time lower than 8 hours/day), smoking, and alcohol intake. Lymphocytes subpopulations were measured by flow cytometry. Five hundred twenty-six blood donors from two Brazilians cities participated in the study: 450 samples from Bahia and 76 samples from Pará. Most (60%) were men, 59% reported alcohol intake, 12% were smokers, and 80% slept at least 8 h/day. Donors from Bahia presented with significantly higher counts for all parameters, compared with Para. Women had higher lymphocytes levels, in both states, but only CD4+ cells count was significantly higher than men's values. Smokers had higher CD4+ counts, but sleep time had effect on lymphocytes levels only for Para's donors (higher CD3+ and CD4+ counts). That state had also, a higher proportion of donors reporting sleep time <8 h/day. The values for CD3, CD4 and CD8+ cells count were significantly higher in blood donors from Bahia than among those from Pará. Female gender, alcohol intake, stress level, and smoking were associated with higher lymphocyte counts. The use of a single reference range for normal lymphocytes count is not appropriate for a country with such diversity, like Brazil is.

Evaluation of canine and feline leishmaniasis by the association of blood culture, immunofluorescent antibody test and polymerase chain reaction

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

A Reproducible Venous Thrombosis Model in Horses Induced by the Combination of an Endothelial Lesion and Blood Flow Stasis

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

Phenotypic and functional evaluations of peripheral blood monocytes from chronic-form paracoccidioidomycosis patients before and after treatment

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

Blood pressure and lipid profile in young women: the role of anthropometric measurement

Body composition has fundamental importance in the quality of life and is a powerful predictor of mortality and morbidity in humans. The identification and monitoring of the amount of body fat have been receiving special attention in aspects related to health promotion, not just for its actions in the prevention and in the control of cardiovascular diseases but also for their induction and association with risk factors, especially in the plasmatic lipid levels and arterial pressure. It was investigated the relationship between body mass index (BMI) and body fat percentage (%BF) by bioelectrical impedance analysis (BIA) with the blood pressure levels (systolic and diastolic) and serum lipids (TC, HDL-c, LDL-c, VLDL-c, TG). In a group of fifty seven women (aged 18 to 26 years old ), obesity was detected in 5 and 19 women by BMI (≥ 30 kg/m2) and %BF (≥ 30%), respectively. BMI and % BF were positively correlated with blood pressure (systolic and diastolic), and highly significant in the obese group by %BF. Moreover, BMI and % BF were significantly correlated with all lipids and lipoprotein fractions VLDL-c and triglyceride, respectively. These results suggest that %BF is a good indicator of “occult obesity” in subjects with normal body mass index. The associated use of BMI and %BF to better evaluate obesity may improve the study of blood pressure levels and serum lipid changes that are commonly associated with obesity.

High sodium intake during postnatal phases induces an increase in arterial blood pressure in adult rats

Coordenadoria de Aperfeiçoamento em Pesquisa (CAPES)

The role of HLA-G molecule and HLA-G gene polymorphisms in tumors, viral hepatitis, and parasitic diseases

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Influence of daily consumption of synbiotic soy-based product supplemented with okara soybean by-product on risk factors for cardiovascular diseases

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

Alcohol levels in cerebrospinal fluid and blood samples from patients under pathological conditions

We measured alcohol levels by the Cordebard method in 148 CSF samples from individuals who had abstained from alcohol for at least 7 days prior to the beginning of the study. Each blood sample was accompanied by a CSF sample from the same patient. CSF samples found to be normal after analysis were used as controls. Mean alcohol concentration in blood did not differ significantly between the control group and the groups with altered CSF. The group with altered CSF had statistically higher alcohol levels in CSF than in blood. CSF lactate, glucose and protein levels were not correlated with alcohol level. The results suggest the presence of endogenous alcohol in the CSF, with levels increasing in the presence of pathological processes involving the nervous system.