Dorotéia Rossi Silva Souza

Glutathione S-transferase variants increase susceptibility for late-onset Alzheimer's disease: association study and relationship with apolipoprotein E ɛ4 allele

Abstract Background: Several factors participate in the pathogenesis of Alzheimers disease (AD), including free radicals, which when out of balance with their antioxidant capacity contribute to the oxidative stress process and neuronal death. The glutathione S-transferase (GST) polymorphisms are associated with the organism detoxification capacity and can help with the identification of sub-groups that present susceptibility to the development of AD. The aim of this study was to analyze the association of GSTs, including GSTP1, GSTT1 and GSTM1 and apolipoprotein E (apoE) with AD and the distribution of these polymorphisms in the first-degree relatives of patients. Methods: For this, 41 patients with AD, 24 elderly without cognitive deficits (control group), 109 relatives of patients with AD and 41 relatives of controls were studied. A sample of peripheral blood was drawn for leukocyte DNA extraction. The genetic polymorphisms were analyzed by PCR-RFLP. Results: There was a significantly higher frequency of the ɛ4 allele in the patients (0.21) and in their relatives (0.25) when compared to controls (0.04; p=0.01) and their relatives (0.03; p<0.0001). The V allele of the GSTP1 polymorphism was higher in patients compared to controls (0.35 and 0.19, respectively; p=0.04). In contrast, the presence of the GSTT1 polymorphism prevailed in controls (79%) and their relatives. Conclusions: The V allele may be a risk factor for AD, mainly in the presence of the apoE ɛ4 allele, while the presence of GSTT1 may indicate protection against the disease. Clin Chem Lab Med 2008;46:439–45.

Dynamic cardiomyoplasty in chronic chagas' heart disease: Clinicopathological data

We report a 44-year-old man with chronic chagasic cardiomyopathy who underwent latissimus dorsi dynamic cardiomyoplasty and died 4 months later. The clinicopathological findings are discussed, and the literature is reviewed.

Nullity of GSTT1/GSTM1 related to pesticides is associated with Parkinson's disease

Genetic and environmental factors affect the pathogenesis of Parkinsons disease (PD). Genetic variants of the enzyme glutathione S-transferases (GST) may be related to the disease. This study aimed to evaluate the influence of genetic variants of GST (GSTT1/GSTM1) and their association with the exposure to environmental toxins in PD patients. We studied 254 patients with PD and 169 controls. The GSTM1/GSTT1 variants were analyzed by polymerase chain reaction. We applied the Fishers exact test and the χ2 test for statistical analysis (p<0.05). The present and absence for GSTT1 and GSTM1 were similar in patients and controls. The null for GSTT1 and GSTM1 (0/0) and exposure to pesticides prevailed in patients (18%) compared to controls (13%, p=0.014). This study suggests the association between PD and previous exposure to pesticides, whose effect may be enhanced in combination with null for GSTT1/GSTM1.

Mitral valve repair with a malleable bovine pericardium ring

OBJECTIVE To describe a surgical procedure utilizing a malleable bovine pericardium ring in mitral valve repair and clinical and Doppler echocardiographic results. METHODS Thirty-two (25 female and 7 male) patients, aged between 9 and 66 (M=36.4+/-17.2) years, were studied over a 16-month period, with 100% follow-up. In 23 (72%) of the patients, the mitral approach was the only one applied; 9 patients underwent associated operations. The technique applied consisted of measuring the perimeter of the anterior leaflet and implanting, according to this measurement, a flexible bovine pericardium prosthesis for reinforcement and conformation of the posterior mitral annulus, reducing it to the perimeter of the anterior leaflet with adjustment of the valve apparatus. RESULTS The patient survival ratio was 93.8%, with 2 (6.2%) fatal outcomes, one from unknown causes, the other due to left ventricular failure. Only one reoperation was performed. On Doppler echocardiography, 88% of the patients had functional recovery of the mitral valve (50% without and 38% with mild insufficiency and no hemodynamic repercussions). Of four (12%) of the remaining patients, 6% had moderate and 6% had accented insufficiency. Twenty-eight percent of class II patients and 72% of class III patients passed into classes I (65%), II (32%), and III (3%), according to NYHA classification criteria. CONCLUSION Being flexible, the bovine pericardium ring fit perfectly into the valve annulus, taking into account its geometry and contractility. Valve repair was shown to be reproducible, demonstrating significant advantages during patient evolution, which did not require anticoagulation measures.

Impact of Genetic Variants of Apolipoprotein E on Lipid Profile in Patients with Parkinson's Disease

The pathogenesis of Parkinsons disease (PD) seems to involve genetic susceptibility to neurodegeneration. APOE gene has been considered a risk factor for PD. This study aimed to evaluate the association of APOE polymorphism with PD and its influence on lipid profile. We studied 232 PD patients (PD) and 169 individuals without the disease. The studied polymorphism was analyzed by PCR/RFLP. The Fishers exact test, chi-square, ANOVA, and t-test (P < 0.05) were applied. The APOE3/3 genotype was prevalent in PD patients and Controls (P = 0.713) followed by APOE3/4 (P = 0.772). Both groups showed recommended values for lipid profile, with increase in the values of total cholesterol and LDLc, as well as decreased values of triglycerides in PD patients compared with Controls (P < 0.05 for all of them). Increased levels of HDLc, in PD patients, were associated with the APOE3/3 versus APOE-/4 genotypes (P = 0.012). The APOE polymorphism does not distinguish PD patients from Controls, as opposed to the lipid profile alone or in association with APOE. Furthermore, a relationship between increase of HDLc levels and APOE3 in homozygous was found in PD patients only.

Oxidative stress and antioxidant status in beta-thalassemia heterozygotes

Background Several studies have evaluated the oxidant and antioxidant status of thalassemia patients but most focused mainly on the severe and intermediate states of the disease. Moreover, the oxidative status has not been evaluated for the different beta-thalassemia mutations. Objective To evaluate lipid peroxidation and Trolox equivalent antioxidant capacity in relation to serum iron and ferritin in beta thalassemia resulting from two different mutations (CD39 and IVS-I-110) compared to individuals without beta-thalassemia. Methods One hundred and thirty subjects were studied, including 49 who were heterozygous for beta-thalassemia and 81 controls. Blood samples were subjected to screening tests for hemoglobin. Allele-specific polymerase chain reaction was used to confirm mutations for beta-thalassemia, an analysis of thiobarbituric acid reactive species was used to determine lipid peroxidation, and Trolox equivalent antioxidant capacity evaluations were performed. The heterozygous beta-thalassemia group was also evaluated for serum iron and ferritin status. Results Thiobarbituric acid reactive species (486.24 ± 119.64 ng/mL) and Trolox equivalent antioxidant capacity values (2.23 ± 0.11 mM/L) were higher in beta-thalassemia heterozygotes compared to controls (260.86 ± 92.40 ng/mL and 2.12 ± 0.10 mM/L, respectively; p-value < 0.01). Increased thiobarbituric acid reactive species values were observed in subjects with the CD39 mutation compared with those with the IVS-I-110 mutation (529.94 ± 115.60 ng/mL and 453.39 ± 121.10 ng/mL, respectively; p-value = 0.04). However, average Trolox equivalent antioxidant capacity values were similar for both mutations (2.20 ± 0.08 mM/L and 2.23 ± 0.12 mM/L, respectively; p-value = 0.39). There was no influence of serum iron and ferritin levels on thiobarbituric acid reactive species and Trolox equivalent antioxidant capacity values. Conclusion This study shows an increase of oxidative stress and antioxidant capacity in beta-thalassemia heterozygotes, mainly in carriers of the CD39 mutation.

Exposure to pesticides and heterozygote genotype of GSTP1-Alw26I are associated to Parkinson's disease

OBJECTIVE This study aimed to analyze the frequency of GSTP1-Alw26I polymorphism and to estimate its association with toxic substances in Parkinsons disease (PD). METHODS A study group with 154 patients - subdivided into familial and sporadic PD groups - and 158 elderly individuals without the disease (control group) were evaluated. GSTP1-Alw26I polymorphism was analyzed by polymerase chain reaction/restriction fragment length polymorphism (PCR-RFLP). RESULTS Patients were significantly more exposed to pesticides compared with the control group (p=0.0004), and the heterozygote genotype associated to exposure to pesticides also prevailed in patients (p=0.0001). Wild homozygote genotype was related to tobacco use (p=0.043) and alcoholism (p=0.033) in familial PD patients. CONCLUSION Exposure to pesticides is associated to PD, whose effect can be enhanced when combined with the heterozygote genotype of GSTP1-Alw26I. Also, large genetic and environmental studies considering tobacco use, alcoholism, GSTP1 and PD are necessary to confirm our findings.

Polimorfismo da apolipoproteína e nos familiares em primeiro grau de pacientes com doença de Alzheimer familial ou esporádica

INTRODUCTION Apolipoprotein E (apo E) has been recognized as a risk factor for Alzheimer disease (AD). OBJECTIVE To analyze apo E polymorphism in first-degree relatives of patients with familial or sporadic late-onset AD comparing with families without AD. METHOD Forty patients with familial or sporadic late-onset of AD, being both groups classified as probable, according of NINCS-ADRDAs criteria. RESULTS Allele epsilon3 was the most frequent in all of these groups. Higher frequency of epsilon4 when comparing the relatives of the probands with the relatives of the control group (p<0,0001) was observed. Allele epsilon2 showed significant difference only between relatives of familial AD and relatives of control group (p=0,026). CONCLUSION Apo E polymorphism has not differentiated familial from sporadic AD. The study of families allows to amplify the alelles epsilon2 and epsilon4 representative, revealing, their value as protecting factor and of risk for AD, respectively.

Anticardiolipin Antibodies as a Risk Factor of Atherosclerosis in Intermittent Claudication

Anticardiolipin antibodies have been associated as a risk factor of atherosclerosis. The aim of this study was to evaluate the association between anticardiolipin antibodies and intermittent claudication. Forty consecutive patients (33 men, 7 women; age range: 45-84 years, mean 65.5) who were seen in the angiology and vascular surgery department with intermittent claudication were evaluated. Exclusion criteria included prior revascularization, angioplasty, or a history of thrombosis of a lower limb. Forty individuals (23 men, 17 women; age range: 58-82 years, mean 67.1) who attended a support group for senior citizens and who were apparently healthy formed the control group. Anticardiolipin antibodies were evaluated by means of enzyme-linked immunosorbent assay (ELISA) for quantitative measurement of immunoglobulin G (IgG) and IgM antibodies against cardiolipins in serum. IgG levels were considered normal when <7, borderline from 7 to 10, and elevated at >10 GPL units/mL; IgM levels were normal when <4, borderline from 4 to 7, and elevated at >7 MPL, as recommended by the test manufacturers. Statistical analysis used the relative risk test with a confidence interval of 95%. Twenty-three patients from the study group and 6 individuals from the control group were found to have elevated levels of anticardiolipin antibodies giving a relative risk of 3.833 (ranging from 1.749 to 8.4; p value <0.0001). In conclusion, patients who have elevated levels of anticardiolipin antibodies present a 3.8 times greater risk of developing intermittent claudication.

Effects of Statin and Aerobic Physical Exercise Association in the Cardiomyocytes of the Rat: Morphometric Study

Sao Paulo State Univ, FCT Unesp, Physiotherapy Dept, BR-19060900 Presidente Prudente, SP, Brazil