Clinical and nutritional profile of individuals with Chagas disease

Chagas disease (CD), caused by the protozoan Trypanossoma cruzi, affects approximately 18 million individuals in the Americas, 5 million of which five in Brazil. Most chronic sufferers have either the indeterminate form of the disease, without organic compromise, or the cardiac or digestive forms. Despite the importance of this disease, there is no information on the effect of nutrition on CD evolution. We evaluated the clinical-nutritional profile of individuals with CD treated at the Tropical Diseases Nutrition Out-Patient Clinic of the Botucatu School of Medicine, UNESP.A retrospective cohort study was performed between 2002 and 2006, on 66 patients with serum and parasitological diagnosis of CD. Epidemiological, clinical, nutritional, and biochemical data were collected, including gender, age, skin color, smoking, alcoholism, physical activity, weight, stature, body mass index, abdominal circumference, glycemia, and lipid profile. Fifty-three percent were mate and 47% female; 96% were white skinned. Mean age was 49.6±6.36 years. The predominant form was indeterminate in 71 %; smoking and drinking were recorded in 23% and 17%, respectively. Sedentariness predominated in 83%, and 55% presented increased abdominal circumference. Most, 94%, were overweight or obese. The biochemical exam revealed hyperglycemia in 12% and dyslipidemia in 74%. These findings suggest that the Chagas population presents co-morbidities and risk factors for developing chronic non-transmissible diseases, including cardiovascular diseases, making CD evolution even worse. © 2007 by The Brazilian Journal of Infectious Diseases and Contexto Publishing. All rights reserved.

Fatores de risco para doenças cardiovasculares em idosos com diabetes mellitus tipo 2

The aim of this study was to analyze the risk factors related to the cardiovascular diseases (CVRF) in elderly type 2 diabetics. A cross-sectional observational study was carried out on 100 elderly patients attending the Rehabilitation Center of Araraquara (CRRA), São Paulo State, Brazil, from March to December, 2004. The majority were married, female, white, with a low income and low educational level. Regarding habits and style of life, the subjects had an adequate diet, were sedentary, non-smoking and non-drinking. In the population of 100, 42% were overweight, 42% obese, 71% had above-normal waist measurements and 84% high waist-to-hip ratios. Concerning the CVRF, it was observed that more than half had hypertension, hypercholesterolaemia and hypertriglyceridaemia. 84% had high values of LDL-cholesterol and 59% HDL-cholesterol levels below the reference values, 78% high levels of fasting glycemia, 76% glycohemoglobin and 57% fibrinogen and thus subject to cardiovascular risk. The results showed a high frequency of cardiovascular risk factors, differing according to sex and the age.

Autoimmunity does not contribute to the highly prevalent glucose metabolism disturbances in a Japanese Brazilian population

The Japanese Brazilian population has one of the highest prevalences of diabetes worldwide. Despite being non-obese according to standard definitions, their body fat distribution is typically central. We investigated whether a subset of these subjects had autoantibodies that would suggest a slowly progressive form of type 1 diabetes. A total of 721 Japanese Brazilians (386 men) in the 30- to 60-year age group underwent clinical examination and laboratory procedures, including a 75-g oral glucose tolerance test and determinations of serum autoantibodies. Antibodies to glutamic acid decarboxylase (GADab) were determined by radioimmunoassay and to thyroglobulin (TGab) and thyroperoxidase (TPOab) by flow-cytometry assays. Mean body mass index was 25.2 ± 3.8 kg/m2, but waist circumference was elevated according to the Asian standards. Diabetes, impaired glucose tolerance, and impaired fasting glycemia were found in 31%, 22%, and 22%, respectively, and 53% of the subjects had metabolic syndrome. Glutamic acid decarboxylase (GADab) was positive in 4.72%, TGab in 9.6%, and TPOab in 10% of the whole sample. When participants were stratified according to the presence of thyroid antibodies, similar frequencies of GADab were found in positive and negative groups. The prevalence rates of glucose metabolism disturbances did not differ between GADab positive and negative groups. Our data did not support the view that autoimmune injury could contribute to the high prevalence of diabetes seen in Japanese Brazilians, and the presence of co-morbidities included in the spectrum of metabolic syndrome favors the classification as type 2 diabetes.

Biochemical evaluation of glycemic levels of long-term tacrolimus therapy in rats

One of the more serious complications following transplantation is the development of post-transplantation diabetes mellitus (PTDM), which has a major impact on the quality of life, with effects ranging from the control of glycemia times to increased susceptibility to infections and cardiovascular complications. It has been suggested that immunosuppressive therapy, mainly tacrolimus therapy, may be an important factor in the development of PTDM. There is a lack of studies that explore the effects of long-term tacrolimus on PTDM in animal protocols. The objective of this study was therefore to evaluate the effects of long-term therapy with tacrolimus in rats. One group was treated with tacrolimus, injected subcutaneously, in a daily dose of 1 mg/kg of body weight. The chosen dose was sufficient to achieve therapeutic tacrolimus serum levels. The experimental periods were 60, 120, 180 and 240 days. One group was used as control and received daily subcutaneous injections of saline solution during all periods. A tendency towards increased glycemia levels during the initial periods (60 and 120 days) was observed. However, at 180 and 240 days, the glycemia levels were not statistically different from that of the control group of the same period. It may thus be concluded that the deleterious effects of tacrolimus therapy on glycemia may be a time-related side effect.

Efeito hipocolesterolêmico dos ácidos caféicos da própolis

Natural products have been used in tratamed of hypercholesterolemia. The bee products have been promoting up the man's interest, among them it stands out the propolis, coleted by bees, rich in polyphenols. The biggest polyphenols of propolis was flavonoids and caffeic acids, which have antioxidant power, presenting the protective action to the lipoprotein LDL-cholesterol against the lipid peroxidation. Therefore, the present work was evaluated whether the caffeic acids of the Botucatu's propolis (Botucatu-SP) affect the levels of plasma cholesterol, in rabbits submitted to the rich diet in cholesterol. The animals were divided in three groups: C (n=2) they received commercial ration and water for the whole period; S (n=2) they received normal ration and water in the first period and supplemented ration and water in the second and third periods; S+T (n=5) they received normal ration and water in the first period, supplemented ration and water in the second period and supplemented ration and extract rich in caffeic acids in the third period. The caffeic acids were administered diluted in water, being in the concentration of 0.05g caffeic acid mL -1 kg -1 of animal. Weekly, after fast of 14 hours, the samples of blood were collected from the marginal vein of the ear for determination of the plasma levels of total cholesterol and their fractions. The caffeic acids of the propolis reduced the plasma concentration of total cholesterol in 30% (280 for 199 mg dL -1) in the rabbits treated with flavonoids, while in the animals of the group S those levels were reduced discreetly (380 for 400 mg dL -1). The animals of the group C maintained this biochemical parameter in the normality range during the whole period (50 mg dL -1). Therefore, we concluded that the caffeic acids exert inhibititory activity in the metabolism of the cholesterol, being considered as a substance of action against the hypercholesterolemia.

Evaluation of IFA, MAT, ELISAs and immunoblotting for the detection of anti-Toxoplasma gondii antibodies in paired serum and aqueous humour samples from experimentally infected pigs

The study evaluated the efficiency of diagnostic laboratory methods to detect anti-Toxoplasma gondii antibodies in paired serum and aqueous humour samples from experimentally infected pigs. 18-mixed breed pigs were used during the experiment; these were divided into two groups, G1 (infected group, n = 10) and G2 (uninfected group, n = 8). Infection was performed with 4 × 10 4 VEG strain oocysts at day 0 by the oral route in G1 animals. All pigs were euthanized at day 60, when retina, aqueous humour, and blood samples were collected. Anti-T. gondii antibody levels were assessed in serum (s) and aqueous humour (ah) by indirect immunofluorescence assay (IFA), modified agglutination test (MAT), m-ELISA (using crude membranes from T. gondii tachyzoites as antigen) and r-ELISA (using rhoptries from T. gondii tachyzoites as antigen). Polymerase chain reactions (PCR) of samples from the retina were performed by using Tox4 and Tox5 primers. Antibody titers of G1 animals ranged from 128 to 1024 and from 16 to 256 in serum and aqueous humour, respectively. There were differences in the correlation coefficients between IFA(s) × IFA (ah) (r = 0.62, P = 0.05), MAT(s) × MAT (ah) (r = 0.97, P < 0.0001); however, there was no significant difference between r-ELISA(s) × r-ELISA (ah) (r = 0.14, P = 0.7). Antibodies present in serum and aqueous humour recognized similar antigens. Samples of retina were positive by PCR in 30% (3/10) of infected pigs. G2 animals remained without antibody levels and were PCR negative throughout the experiment. These results suggest that the use of a combination of tests and immunoblotting for paired aqueous humour and serum samples could improve the sensitivity and specificity for the diagnosis of ocular toxoplasmosis. © 2007 Elsevier Ltd. All rights reserved.

Cortisol response to acute stress in jundiá Rhamdia quelen acutely exposed to sub-lethal concentrations of agrichemicals

Exposure to agrichemicals can have deleterious effects on fish, such as disruption of the hypothalamus-pituitary-inter-renal axis (HPI) that could impair the ability of fish to respond to stressors. In this study, fingerlings of the teleost jundiá (Rhamdia quelen) were used to investigate the effects of the commonly used agrichemicals on the fish response to stress. Five common agrichemicals were tested: the fungicide - tebuconazole, the insecticide - methyl-parathion, and the herbicides - atrazine, atrazine + simazine, and glyphosate. Control fishes were not exposed to agrichemicals and standard stressors. In treatments 2-4, the fishes were exposed to sub-lethal concentrations (16.6%, 33.3%, and 50% of the LC50) of each agrichemical for 96 h, and at the end of this period, were subjected to an acute stress-handling stimulus by chasing them with a pen net. In treatments 5-7 (16.6%, 33.3%, and 50% of the LC50), the fishes were exposed to the same concentrations of the agrichemicals without stress stimulus. Treatment 8 consisted of jundiás not exposed to agrichemicals, but was subjected to an acute stress-handling stimulus. Jundiás exposed to methyl-parathion, atrazine + simazine, and glyphosate presented a decreased capacity in exhibiting an adequate response to cope with stress and in maintaining the homeostasis, with cortisol level lower than that in the control fish (P < 0.01). In conclusion, the results of this study clearly demonstrate that the acute exposure to sub-lethal concentrations of methyl-parathion, atrazine + simazine, and glyphosate exert a deleterious effect on the cortisol response to an additional acute stressor in the jundiá fingerlings. © 2008 Elsevier Inc. All rights reserved.

Influence of lower cutoff values for 100-g oral glucose tolerance test and glycemic profile for identification of pregnant women at excessive fetal growth risk

Objective: To evaluate data from patients with normal oral glucose tolerance test (OGTT) results and a normal or impaired glycemic profile (GP) to determine whether lower cutoff values for the OGTT and GP (alone or combined) could identify pregnant women at risk for excessive fetal growth. Methods: We classified 701 pregnant women with positive screening for gestational diabetes mellitus (GDM) into 2 categories - (1) normal 100-g OGTT and normal GP and (2) normal 100-g OGTT and impaired GP - to evaluate the influence of lower cutoff points in a 100-g OGTT and GP (alone or in combination) for identification of pregnant women at excessive fetal growth risk. The OGTT is considered impaired if 2 or more values are above the normal range, and the GP is impaired if the fasting glucose level or at least 1 postprandial glucose value is above the normal range. To establish the criteria for the OGTT (for fasting and 1, 2, and 3 hours after an oral glucose load, respectively), we considered the mean (75 mg/dL, 120 mg/dL, 113 mg/dL, and 97 mg/dL), mean plus 1 SD (85 mg/dL, 151 mg/dL, 133 mg/dL, and 118 mg/dL), and mean plus 2 SD (95 mg/dL, 182 mg/dL, 153 mg/dL, and 139 mg/dL); and for the GP, we considered the mean and mean plus 1 SD (78 mg/dL and 92 mg/dL for fasting glucose levels and 90 mg/dL and 130 mg/dL for 1- or 2-hour postprandial glucose levels, respectively). Results: Subsequently, the women were reclassified according to the new cutoff points for both tests (OGTT and GP). Consideration of values, in isolation or combination, yielded 6 new diagnostic criteria. Excessive fetal growth was the response variable for analysis of the new cutoff points. Odds ratios and their respective confidence intervals were estimated, as were the sensitivity and specificity related to diagnosis of excessive fetal growth for each criterion. The new cutoff points for the tests, when used independently rather than collectively, did not help to predict excessive fetal growth in the presence of mild hyperglycemia. Conclusion: Decreasing the cutoff point for the 100-g OGTT (for fasting and 1, 2, and 3 hours) to the mean (75 mg/dL, 120 mg/dL, 113 mg/dL, and 97 mg/dL) in association with the GP (mean or mean plus 1 SD-78 mg/dL and 92 mg/dL for the fasting state and 90 mg/dL and 130 mg/dL for 1- or 2-hour postprandial values-increased the sensitivity and specificity, and both criteria had statistically significant predictive power for detection of excessive fetal growth. © 2008 AACE.

Exercise training in the aerobic/anaerobic metabolic transition prevents glucose intolerance in alloxan-treated rats

Background: Ninety percent of cases of diabetes are of the slowly evolving non-insulin-dependent type, or Type 2 diabetes. Lack of exercise is regarded as one of the main causes of this disorder. In this study we analyzed the effects of physical exercise on glucose homeostasis in adult rats with type 2 diabetes induced by a neonatal injection of alloxan. Methods: Female Wistar rats aged 6 days were injected with either 250 mg/ kg of body weight of alloxan or citrate buffer 0.01 M (controls). After weaning, half of the animals in each group were subjected to physical training adjusted to meet the aerobic-anaerobic metabolic transition by swimming 1 h/day for 5 days a week with weight overloads. The necessary overload used was set and periodically readjusted for each rat through effort tests based on the maximal lactate steady state procedure. When aged 28, 60, 90, and 120 days, the rats underwent glucose tolerance tests (GTT) and their peripheral insulin sensitivity was evaluated using the HOMA index. Results: The area under the serum glucose curve obtained through GTT was always higher in alloxan-treated animals than in controls. A decrease in this area was observed in trained alloxan-treated rats at 90 and 120 days old compared with non-trained animals. At 90 days old the trained controls showed lower HOMA indices than the non-trained controls. Conclusion: Neonatal administration of alloxan induced a persistent glucose intolerance in all injected rats, which was successfully counteracted by physical training in the aerobic/anaerobic metabolic transition. © 2008 Mota et al; licensee BioMed Central Ltd.

Determinação de cetamina em plasma por HPLC: Aplicação em um estudo de farmacocinética de associação medicamentosa em cães

A S(+) cetamina é um fármaco amplamente utilizado na medicina para induzir anestesia e a associação com midazolam é empregada para minimizar seus efeitos adversos. Associações medicamentosas podem resultar em interações farmacocinéticas e a disponibilidade de métodos bioanalíticos para a determinação da cetamina em plasma constitui ferramenta útil para a avaliação do perfil cinético do fármaco administrado isoladamente ou em associação. O presente estudo teve como objetivo o desenvolvimento e validação de um método analítico para determinação da cetamina em plasma por cromatografia líquida de alta eficiência (HPLC) e a investigação do perfil farmacocinético da cetamina em quatro cães hígidos da raça Beagle. A S(+) cetamina (10mg/kg) foi administrada pela veia cefálica em dose única isoladamente (protocolo I) ou associada ao midazolam (0.2mg/kg) (protocolo II) em estudo cruzado com intervalo de uma semana para washout. Amostras seriadas de sangue foram coletadas no intervalo de oito horas e analisadas por HPLC para a avaliação do perfil farmacocinético utilizando modelo bicompartimental. O método bioanalítico apresentou limites de confiança aceitáveis para sua aplicação em estudos de farmacocinética e os parâmetros área sob a curva (ASC0-8), volume de distribuição (Vd), clearance total (Clt), meia vida de eliminação (t/12 ß), constante de eliminação (ß), meia vida de distribuição (t1/2α) e constante de distribuição (α) não mostraram diferenças estatísticas significativas entre os grupos (p < 0.05, Wilcoxon). Os resultados obtidos sugerem que a redução dos efeitos colaterais da cetamina decorrente do uso da associação cetamina-midazolam não está relacionada a alterações no perfil farmacocinético da cetamina.

Contribuição ao entendimento da patogenia da sepse

The most frequent cause of vasodilatory shockis outcome from sepsis, a systemic inflammatory response to infection, characterized by hypotension, hyporeactivity to the catecholamines and disseminated intravascular coagulation. The commonest cause of sepsis has reported to be infection with Gram-negative bacteria, typically E. coli, resulting in the release of lipopolysaccharide (endotoxin) from the bacterial outer membrane during autolysis or death of these microorganisms, with the involvement of many mediators, including nitric oxide. Later it was found that plasma levels of vasopressin in sepsis patients were abnormally low and observed that some patients with advanced septic shock were extremely sensitive to the activity actions of exogenous vasopressin.

Effects of pentoxifylline and n-acetylcysteine on injuries caused by ischemia and reperfusion of splanchnic organs in rats

Aim. Occlusion and reperfusion of splanchnic arteries cause local and systemic changes due to the release of cytotoxic substances and the interaction between neutrophils and endothelial cells. This study evaluated the role of pentoxifylline (PTX) and n-acetylcysteine (NAC) in the reduction of ischemia, reperfusion shock and associated intestinal injury. Methods. Sixty rats were divided into 6 groups of 10 animals. Rats in three groups underwent mesenteric ischemia for 30 minutes followed by 120 minutes of reperfusion, and were treated with saline (SAL-5 mL/kg/ h), pentoxifylline (PTX-50 mg/kg) or n-acetylcysteine (NAC-430 mg/kg/h). The other 3 groups underwent sham ischemia and reperfusion (I/R) and received the same treatments. Hemodynamic, biochemical and histological parameters were evaluated. Results. No significant hemodynamic or intestinal histological changes were seen in any sham group. No histological changes were found in the lung or liver of animals in the different groups. There was a progressive decrease in mean arterial blood pressure, from mean of 111.53 mmHg (30 minutes of ischemia) to 44.30±19.91 mmHg in SAL-I/R. 34.52±17.22 mmHg in PTX-I/R and 33.81±8.39 mmHg in NAC-I/R (P<0.05). In all I/R groups, there was a progressive decrease in: aortic blood flow, from median baseline of 19.00 mL/min to 2.50±5.25 mL/min in SAL-I/ R; 2.95±6.40 mL/min in PTX-I/R and 3.35±3.40 mL/min in NAC-I/R (P<0.05); in the heart rate, from mean baseline of 311.74 bpm to 233.33±83.88 bpm in SAL-I/R, 243.20±73.25 bpm in PTX-I/R and 244.92±76.05 bpm in NAC-I/R (P<0.05); and esophageal temperature, from mean baseline of 33.68°C to 30.53±2.05°C in SAL-I/R, 30.69±2.21°C in PTX-I/R and 31.43±1.03°C in NAC-I/R (P<0.05). In the other hand, there was an attenuation of mucosal damage in the small intestine of the animals receiving PTX, and only in the ileum of the animals receiving NAC. No changes were found in ileum or plasma malondialdehyde levels in any group. Conclusion. PTX was more efficient in reducing histological lesions than NAC, but neither treatment prevented hemodynamic changes during splanchnic organs I/R.

Glycogen storage and muscle glucose transporters (GLUT-4) of mice selectively bred for high voluntary wheel running

To examine the evolution of endurance-exercise behaviour, we have selectively bred four replicate lines of laboratory mice (Mus domesticus) for high voluntary wheel running ('high runner' or HR lines), while also maintaining four non-selected control (C) lines. By generation 16, HR mice ran ∼2.7-fold more than C mice, mainly by running faster (especially in females), a differential maintained through subsequent generations, suggesting an evolutionary limit of unknown origin. We hypothesized that HR mice would have higher glycogen levels before nightly running, show greater depletion of those depots during their more intense wheel running, and have increased glycogen synthase activity and GLUT-4 protein in skeletal muscle. We sampled females from generation 35 at three times (photophase 07:00 h-19:00 h) during days 5-6 of wheel access, as in the routine selection protocol: Group 1, day 5, 16:00 h-17:30 h, wheels blocked from 13:00 h; Group 2, day 6, 02:00 h-03:30 h (immediately after peak running); and Group 3, day 6, 07:00 h-08:30 h. An additional Group 4, sampled 16:00 h-17:30 h, never had wheels. HR individuals with the mini-muscle phenotype (50% reduced hindlimb muscle mass) were distinguished for statistical analyses comparing C, HR normal, and HR mini. HR mini ran more than HR normal, and at higher speeds, which might explain why they have been favored by the selective-breeding protocol. Plasma glucose was higher in Group 1 than in Group 4, indicating a training effect (phenotypic plasticity). Without wheels, no differences in gastrocnemius GLUT-4 were observed. After 5 days with wheels, all mice showed elevated GLUT-4, but HR normal and mini were 2.5-fold higher than C. At all times and irrespective of wheel access, HR mini showed approximately three-fold higher [glycogen] in gastrocnemius and altered glycogen synthase activity. HR mini also showed elevated glycogen in soleus when sampled during peak running. All mice showed some glycogen depletion during nightly wheel running, in muscles and/or liver, but the magnitude of this depletion was not large and hence does not seem to be limiting to the evolution of even-higher wheel running.

Effects of Long-Term FK 506 Therapy on the Alveolar Bone and Cementum of Rats

Cyclosporine (CsA) and tacrolimus (FK 506) exert complex, incompletely understood actions on bone. The objective of the study was to evaluate the effects of long-term tacrolimus therapy on the periodontium. Rats were treated for 60, 120, 180, and 240 days with daily subcutaneous injections of 1 mg/kg body weight of FK 506. After the experimental period, we obtained serum levels of calcium and alkaline phosphatase (ALP). After histological processing, the alveolar bone and cementum, as well as volume densities of bone (Vb) and osteoclasts (Vo), were assessed at the regions of the lower first molar. There was a tendency toward a statistically significant decrease in ALP levels with FK 506; however, serum calcium levels increased during the long periods. At 60, 180, and 240 days of treatment with FK 506, we did not observe Vb and Vo alterations. At 120 days of treatment, there was an evident decrease in Vb, but it did not show alveolar bone loss. We did not observe any alterations of cementum among rats treated with FK 506. It may be concluded that FK 506 administration did not induce side effects on the periodontium. © 2009 Elsevier Inc. All rights reserved.

Effect of 6-months of physical exercise on the nitrate/nitrite levels in hypertensive postmenopausal women

Background: Evidences have showed that the incidence of arterial hypertension is greater in postmenopausal women as compared to premenopausal. Physical inactivity has been implicated as a major contributor to weight gain and abdominal obesity in postmenopausal women and the incidence of cardiovascular disease increases dramatically after menopause. Additionally, more women than men die each year of coronary heart disease and are twice as likely as men to die within the first year after a heart attack. A healthy lifestyle has been strongly associated with the regular physical activity and evidences have shown that physically active subjects have more longevity with reduction of morbidity and mortality. Nitric oxide (NO) produced by endothelial cells has been implicated in this beneficial effect with improvement of vascular relaxing and reduction in blood pressure in both laboratory animals and human. Although the effect of exercise training in the human cardiovascular system has been largely studied, the majority of these studies were predominantly conducted in men or young volunteers. Therefore, the aim of this work was to investigate the effects of 6 months of dynamic exercise training (ET) on blood pressure and plasma nitrate/nitrite concentration (NOx-) in hypertensive postmenopausal women. Methods: Eleven volunteers were submitted to the ET consisting in 3 days a week, each session of 60 minutes during 6 months at moderate intensity (50% of heart rate reserve). Anthropometric parameters, blood pressure, NOx- concentration were measured at initial time and after ET. Results: A significant reduction in both systolic and diastolic blood pressure values was seen after ET which was accompanied by markedly increase of NOx- levels (basal: 10 ± 0.9; ET: 16 ± 2 μM). Total cholesterol was significantly reduced (basal: 220 ± 38 and ET: 178 ± 22 mg/dl), whereas triglycerides levels were not modified after ET (basal: 141 ± 89 and ET: 147 ± 8 mg/dl). Conclusion: Our study shows that changing in lifestyle promotes reducftion of arterial pressure which was accompanied by increase in nitrite/nitrate concentration. Therefore, 6-months of exercise training are an important approach in management arterial hypertension and play a protective effect in postmenopausal women. © 2009 Zaros et al; licensee BioMed Central Ltd.