Benefits of kinesiotherapy and aquatic rehabilitation on sickle cell anemia. A case report

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Le(a-b-) phenotype: potential risk factor for infection by the RH strain of Toxoplasma gondii in pregnancy

The Lewis histo-blood group system is characterized by the expression of the Lea and Le(b) antigens in the gastrointestinal tract, whose synthesis results in interactions between alpha 2-L-fucosyltransferase (FUTII) and alpha 3/4-L-fucosyltransferase (FUTIII) enzymes coded by the FUT2 (19q. 13.3) and FUT3 (19p13.3) genes. FUTII and FUTIII fucosylate the type 1 oligosaccharide precursor (Gal beta 1 -> 3NAcGlc beta 1 -> 3-R) at distinct positions to form H type 1 (Fuc alpha 1. 2Gal beta 1. 3NAcGlc beta 1 -> 3-R) and Le(a) (Gal beta 1 -> 3[Fuc alpha 1 -> 4] NAcGlc beta 1 -> 3-R) antigens, respectively. The fucosylation of H type 1 antigens by FUTIII results in the Leb antigen (Fuc alpha 1. 2Gal beta 1. 3[Fuca1. 4] NAcGlc beta 1. 3-R). Thus, the presence of the FUTII and FUTIII enzymes leads to the expression of the Le(a+b+) phenotype, while the presence of only FUTIII allows the expression of the Le(a+b-) phenotype. The absence of the FUTIII enzyme leads to the expression of the Le(a-b-) phenotype, independent of the presence or absence of FUTII. Point mutations in FUT2 and FUT3 genes change the activity of these enzymes, impair the synthesis of Le(a) and Le(b) antigens, and contribute to the variability of Lewis phenotypes in the gastrointestinal tract. Toxoplasma gondii, an apicomplexan parasite that infects a large proportion of the world's population, utilizes the gastrointestinal tract as an infection route and seems to adhere to glycosylated molecules to invade human cells. These apparently independent events may be related. The aim of this study was to test the hypothesis that there is an association between the Lewis histo-blood group system and infection by T. gondii. Two hundred and nine serum samples collected from pregnant women were submitted to screening tests to detect anti-T. gondii antibodies, employing the indirect hemagglutination method. ELISA was utilized to identify IgG class anti-T. gondii antibodies specific for the RH strain. A hundred and ninety-five samples with concordant results for both methods were selected to form two groups: seropositive (G1) and seronegative (G2). The G428A mutation of the FUT2 gene, and T202C and C314T of the FUT3 gene, which allow inference of the gastrointestinal tract Lewis phenotypes, were identified using PCR-RFLP and PCR-SSP methods, respectively. Among the 195 samples selected, 116 (59.5%) were seropositive and 79 (40.5%) were seronegative. In G1, 68 (58.6%) were classified as Le(a+b+), 30 (25.9%) as Le(a+b-), and 18 (15.5%) as Le(a-b-), and in G2, 67 (84.8%) were classified as Le(a+b+), 12 (15.2%) as Le(a+b-), and 0 (0%) as Le(a-b-) (P < 0.0001). The Le(a-b-) phenotype is associated with a high risk of RH strain T. gondii infection when compared with the Le(a+b+) [P = 0.0001; OR = 36,460; 95%CI = 2.152-617,680] and Le(a+b-) phenotypes [P = 0.0118; OR = 15,165; 95%CI = 0.8463-271,710]. The Le(a+b-) phenotype showed a higher risk compared to the Le(a+b+) phenotype [P = 0.0206; OR = 2463; 95%CI = 2463-5214]. The results suggest that the Le(a-b-) phenotype is strongly associated with a greater risk of infection by the RH strain of T. gondii compared to the other phenotypes. It is possible that the absence of fucosylation of the type 1 oligosaccharide precursor as well as the variations in the structures of the Le(a) and Le(b) antigens influence susceptibility to infection by this parasite.

Effect of hemolysis on canine, bovine and earn e serum chemistry

Hemolysis is the main cause of biochemical analysis rejection's in veterinary laboratories, however the relative error caused by hemoglobin on serum biochemical profile has not been properly established on several species. In order to establish criteria for aproval and rejection of hemolyzed samples for serum biochemical tests, the hypothesis that hemolysis causes biochemical changes in canine, cattle and horses and that laboratorial error depends on species and hemolysis degree was tested. Thus, non-hemolyzed serum was contaminated with crescent hemoglobin levels and using commercial routine reagents, the serum concentrations of uric acid, albumin, cholesterol, triglycerides and urea, besides the activity of ALT, AST, CK and GUT were quantified in triplicate samples. The relative error was calculated by the comparison between hemolyzed and non-hemolyzed samples. Hemolys is did not cause significant error on the albumin determination in all three species, AST in canine and cattle, ALT in horses, UK and cholesterol in canine. There was a linear increase on uric acid levels in horses and cattle, triglycerides in all three species. A linear increase in serum urea in all species serum, UK and cholesterol in cattle and cholesterol in horses was observed. Serum AST activity on equine serum and ALT in cattle decreased linearly due to hemolysis. It was concluded that hemolysis promotes changes in canine, equine and bovine serum chemistry profile, however the laboratorial error not necessarily compromises the diagnosis in all cases, because the changes depends on species and degree of in vitro hemolysis.

IL-10 e TNF-α no sangue materno e nas placentas de gestações complicadas por diabete ou hiperglicemia gestacional leve - correlação com controle glicêmico e resultados perinatais

Objective - At evaluating the IL-10 production in maternal blood and placenta and correlate them with perinatal outcomes in pregnancies complicated by hyperglycemia, or with risk to developing it, differentiated by the glycemic mean (GM < or ≥ 100mg/dL). Method- 186 pregnant women were distributed into groups GM < 100 mg/dL and GM ≥ 100 mg/dL. We evaluated the GM, HbA1c levels, maternal and placental IL-10 and TNF-α and the correlation between placental cytokines and perinatal outcomes. Results - In maternal blood, the lower concentrations of IL-10 (1.01 ± 0.87 vs. 3.08 ± 5.57 pg / mL, p = 0.0019) were observed in GM ≥ 100 mg / dL group. Placental IL-10 was directly correlated with hemoglobin levels (r = 0.63, p = 0.02) and insulin (r = 0.78, p = 0.01) from umbilical cord and with Apgar scores 1 (r = 0.53, p = 0.0095) and Apgar 5 (r = 0.69, p = 0.0003). Conclusion - GM ≥ 100mg/dL was associated with decreased of maternal IL-10. Placental IL-10 was similar in both groups and correlated directly with hemoglobin and insulin and with Apgar scores of 1st. and 5th. minutes

Patogenicidade do isolado Lins de Trypanosoma vivax em bovinos natural e experimentalmente infectados

Pós-graduação em Medicina Veterinária - FCAV

Polimorfismos GSTM1, GSTT1 e GSTP1 da enzima Glutationa S-transferase como fatores moduladores do fenótipo na anemia falciforme

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Hematological and biochemical changes in a Phrynops geoffroanus (Schweigger, 1812) population in response to environmental stressors

Turtles are among the most endangered vertebrate groups, and the main threats to populations are environmental pollution and habitat degradation. The species Phrynops geoffroanus, popularly known as “Geoffroy’s side-necked turtle”, has proliferated in polluted environments, where adverse conditions could influence their living habits and physiological condition. Studies that monitor the effects of environmental pollution are key to understanding the species’ biology and designing effective conservation strategies. Thus, the analysis of hematological and biochemical parameters has been shown to be important in assessing the health of wild animals and risks for the animal and ecosystem. This study aimed to assess the environmental influence on the physiology of a P. geoffroanus population through the evaluation of antioxidant status and responses to environmental stressors, compared to specimens from a place under controlled conditions. Blood samples of 60 specimens were collected, 30 from the Felicidade Stream, polluted environment, within the city of São José do Rio Preto, and 30 from the “Reginaldo Uvo Leone” breeding farm, Tabapuã, SP, a place under controlled conditions, whose samples constituted the control group. They were evaluated by hemogram and by determining thiobarbituric acid reactive species (TBARS), Trolox-equivalent antioxidant capacity (TEAC) and the activities of the antioxidant enzymes catalase and glucose-6-phosphate dehydrogenase (G6PDH). There was a wide variation in hematological parameters of P. geoffroanus from the urban environment. The red blood cell count and hemoglobin values were significantly less than those observed in animals from the breeding farm (P = 0.0004; P = 0.0371, respectively). There was a significant increase in the number of thrombocytes (P < 0.0001) and leukocytes (P < 0.0001) in the animals from Felicidade Stream. The stress indices were similar between the two groups (P = 0.4077). TBARS levels showed the cytotoxic potential of compounds in the urban environment, whose animals had elevated levels of lipid peroxidation (P < 0.0001), despite showing a response to environmental damages with increase in antioxidant capacity, as demonstrated by the TEAC assay (P = 0.0207). The lower catalase enzyme activity noted in individuals from the urban environment (P = 0.000184) could be due to the presence of inhibitory compounds. On the other hand, G6PDH activity was higher (P = 0.002962), where this enzyme acts in the generation of NADPH, which is used in several detoxification pathways. We conclude that environmental contamination can increase oxidative damages and generate physiological changes in this species. These data are very useful for the conservation of P. geoffroanus and turtles in general, and confirm that these techniques are effective in monitoring natural regions and that P. geoffroanus can serve as an environmental contamination bioindicator.

Ineraction Model Between HRSV G-Protein and Flavonoids

Background: Acute respiratory infections (ARI) are the leading cause of infant mortality in the world, and human respiratory syncytial virus (HRSV) is one of the main agents of ARI. One of the key targets of the adaptive host immune response is the RSV G-protein, which is responsible for attachment to the host cell. There is evidence that compounds such as flavonoids can inhibit viral infection in vitro. With this in mind, the main purpose of this study was to determine, using computational tools, the potential sites for interactions between G-protein and flavonoids. Results: Our study allowed the recognition of an hRSV G-protein model, as well as a model of the interaction with flavonoids. These models were composed, mainly, of -helix and random coil proteins. The docking process showed that molecular interactions are likely to occur. The flavonoid kaempferol-3-O-α-L-arabinopyranosil-(2 → 1)-α-L-apiofuranoside-7-O-α-L-rhamnopyranoside was selected as a candidate inhibitor. The main forces of the interaction were hydrophobic, hydrogen and electrostatic. Conclusions: The model of G-protein is consistent with literature expectations, since it was mostly composed of random coils (highly glycosylated sites) and -helices (lipid regions), which are common in transmembrane proteins. The docking analysis showed that flavonoids interact with G-protein in an important ectodomain region, addressing experimental studies to these sites. The determination of the G-protein structure is of great importance to elucidate the mechanism of viral infectivity, and the results obtained in this study will allow us to propose mechanisms of cellular recognition and to coordinate further experimental studies in order to discover effective inhibitors of attachment proteins.

Hydroxyurea in the sickle cell anemia: toxicity and effectiveness

Objective: to evaluate the use of hydroxyurea with regard to effectiveness and toxicity in people with sickle cell anemia. Method: this is a retrospective descriptive study, developed with 57 medical records of patients with sickle cell anemia, treated at the University Hospital Center of Campo Grande (Mato Grosso do Sul, Brazil), from 1993 to 2005. Inclusion criteria: electrophoresis of hemoglobin in medical record; regular use of drugs, for an average of 196 weeks; dosage; and hematological analyses before starting treatment. Exclusion criteria: living with other hemoglobinopathies. The variables evaluated were: neutrophils count; platelets; leukocytes; hemoglobin; time using hydroxyurea; drug response to the optimal dosage; and number and type of episodes of hospitalization. The research protocol was approved by the Ethics Committee of Universidade Federal de Mato Grosso do Sul, under the Protocol 645. Results: of the 57 medical records, 3 cases were evaluated. Comparing the hematological values, according to Portaria 872, enacted on 11/12/2002, it was found that: cases A, B, and C present an use of hydroxyurea (500 mg/day) for four years, with an average of 196 weeks. Case A, female, decreased painful episodes and frequency of hospitalization, keeping hematological values with no toxicity. In Case B, female, there was one hospitalization due to pain crises and important hemolysis. It stood out, in case C, male, neutropenia with hematological values < 2,000/mm3 . Conclusion: in the cases analyzed, we observed a drop in the number of hospitalizations with the decrease in painful crises from three to one a year, and there was no toxicity with regard to the dosage and time using hydroxyurea, in all three cases. For more comprehensive results, one suggests further study on this therapy with significant samples of this clientele.

Anemia and hemoglobinopathies in pregnant women attended in a public hospital

Objectives: to identify the demographic profile and frequency of anemia and hemoglobinopathies, as a basis for future implementation of actions aimed at pregnant women in the public health domain. Method: this is a cross-sectional study developed with pregnant women attended in a university hospital at Mato Grosso do Sul, Brazil. Blood samples were collected for the erythrogram analysis for detection of anemia and selective and specific tests for abnormal hemoglobin. The patients regarded as indigenous and mentally ill, as well as inmates, were excluded from the research, as they represent a vulnerable population which needs a cohort different from that of the sample. For data collection, a particular questionnaire was used. The research was approved by the Ethics Committee of Universidade Federal de Mato Grosso do Sul (UFMS), under the Protocol 873/2006. Results: of the 215 pregnant women under study, 20% were adolescents; 36.3% had incomplete primary education; 53.0% were non-Caucasian; 43.3% were from Campo Grande, Mato Grosso do Sul, Brazil; and 21.1% were of European descent. 17.7% had some type of anemia and, in the evaluation of hemoglobinopathies, 4.7% of patients were detected with some abnormal hemoglobin, with the following frequencies: 3.3% with HbAS; 0.9% with HbAC; and 0.5% with intermediate β-thalassemia. Conclusion: the frequencies of anemia and hemoglobinopathy found in these pregnant women showed the importance of early diagnosis, revealing indicators able to provide a basis for preventive and assistance actions for adequate clinical monitoring, reducing maternal and neonatal morbimortality in the public health services. Descriptors: pregnant women; anemia; hemoglobinopathies; public health; nursing.

Potential utility of melatonin as an antioxidant therapy in the management of sickle cell anemia

This study aimed to assess antioxidant effects of melatonintreatment compared to N-acetylcysteine (NAC) and to their combination in asickle cell suspension. Sickle erythrocytes were suspended in phosphate-buffered saline, pH 7.4, composing external control group. They were alsosuspended and incubated at 37°C either in the absence (experimental controlgroup) or in the presence of NAC, melatonin and their combination atconcentrations of 100 pM, 100 nM and 100 lM for 1 hr (treatment groups).The melatonin influences were evaluated by spectrophotometric [hemolysisdegree, catalase (CAT), glutathione S-transferase (GST), glutathioneperoxidase (GPx), glutathione reductase (GR), glucose-6-phosphatedehydrogenase (G6PDH), and superoxide dismutase (SOD) activities] andchromatographic methods [glutathione (GSH) and malondialdehyde (MDA)levels]. Incubation period was able to cause a rise about 64% on hemolysisdegree as well as practically doubled the lipid peroxidation levels (P < 0.01).However, almost all antioxidants tested treatments neutralized this incubationeffect observed in MDA levels. Among the antioxidant biomarkers evaluated,we observed a modulating effect of combined treatment on GPx and SODactivities (P < 0.01), which showed ~25% decrease in their activities. Inaddition, we found an antioxidant dose-dependent effect for melatonin onlipid peroxidation (r = 0.29; P = 0.03) and for combined antioxidanttreatments also on MDA levels (r = 0.37; P = 0.01) and on SOD activity(r = 0.54; P < 0.01). Hence, these findings contribute with important insightthat melatonin individually or in combination with NAC may be useful forsickle cell anemia management.

Efeitos da redução da concentração de sódio na solução de hemodiálise e no conteúdo de sódio da dieta sobre a resposta inflamatória de pacientes com doença renal crônica

Pós-graduação em Fisiopatologia em Clínica Médica - FMB

Eficácia da haptoglobina como marcador de hemólise no diagnóstico da síndrome HELLP

Introduction: The HELLP syndrome is a severe complication of pregnant women with preeclampsia (PE), characterized by association of hemolysis, changes in liver enzymes and thrombocytopenia. Hemolysis, defined by the presence of microangiopathic hemolytic anemia, is one of the characteristics in this syndrome. However, as hemolysis occurs in a short time there is some difficulty in its laboratory diagnosis. Therefore, the search for a more sensitive and specific method for hemolysis determination may help in the early diagnosis of the HELLP syndrome. Objectives: a) To determine the plasma concentration of haptoglobin in normotensive pregnant women and in pregnant women with PE, classified into mild PE, severe PE and HELLP/partial HELLP syndrome; b) To compare the efficacy of haptoglobin plasma concentration and serum total bilirubin as criteria for hemolysis diagnosis in HELLP/partial HELLP syndrome. Methods: We conducted a cross-sectional analytical and comparative study involving 66 pregnant women diagnosed with PE, being 25 cases with mild PE, 28 with severe PE, and 13 with HELLP/partial HELLP syndrome. Twenty-one normotensive pregnant women were included for comparison of haptoglobin plasma concentration between the groups and to determine the normal values for pregnant women. The variables studied were: maternal age, gestational age, systolic and diastolic blood pressure, proteinuria, hematocrit and hemoglobin values, platelet count, serum total bilirubin, lactate dehydrogenase (LDH), glutamic oxaloacetic transaminase (AST) and glutamic-pyruvic transaminase (ALT), urea, creatinine and uric acid, and also plasma concentrations of haptoglobin. The results were analyzed by nonparametric tests, with a significance level of 5%. Results: The values of urea, uric acid, AST, ALT and LDH were significantly higher, while the number of platelets was lower in pregnant women with HELLP/partial HELLP syndrome compared to pregnant women with mild PE and ...