ABSTRACT Objective: To study associations between polymorphisms in the angiotensin converting enzyme (ACE I/D), actinin 3 (ACTN3 R577X) and paraoxonase 1 (PON1 T(-107)C) genes and chronic diseases (diabetes and hypertension) in women. Materials and methods: Genomic DNA was extracted from saliva samples of 78 women between 18 and 59 years old used for genetic polymorphism screening. Biochemical data were collected from the medical records in Basic Health Units from Southern Brazil. Questionnaires about food consumption, physical activity level and socioeconomic status were applied. Results: The XX genotype of ACTN3 was associated with low HDL levels and high triglycerides, total cholesterol and glucose levels. Additionally, high triglycerides and LDL levels were observed in carriers of the TT genotype of PON1, and lower total cholesterol levels were associated to the CC genotype. As expected, women with diabetes/hypertense had increased body weight, BMI (p = 0.02), waist circumference (p = 0.01), body fat percentage, blood pressure (p = 0.02), cholesterol, triglycerides (p = 0.02), and blood glucose (p = 0.01), when compared to the control group. Conclusion: Both ACTN3 R577X and PON1 T(-107)C polymorphisms are associated with nutritional status and blood glucose and lipid levels in women with diabetes/hypertense. These results contribute to genetic knowledge about predisposition to obesity-related diseases. Objective ACE I/D, ID I/D , I D I/D) ACTN (ACTN RX R X PON (PON T107C TC T 107 C diabetes hypertension methods 7 5 screening Brazil consumption applied Results Additionally expected diabeteshypertense hypertense weight p 0.02, 002 0.02 0 02 0.02) 0.01, 001 0.01 01 0.01) percentage group Conclusion obesityrelated obesity related 10 00 0.0 0.

RESUMO Objetivo Este estudo tem como objetivo descrever a distribuição dos principais alelos de risco da doença celíaca relacionados ao complexo antígeno leucocitário humano e sua associação com a gravidade da lesão intestinal, resultados de testes sorológicos, doenças associadas à doença celíaca e sintomatologia. Métodos Foi analisado o DNA de 140 pacientes com doença celíaca e identificada a distribuição dos três alelos de risco mais importantes para o desenvolvimento de doença celíaca (DQA1*05:01, DQB1*02:01 e DRB1*04, sendo este o último um marcador para o aplótipo de risco DQB1*03:02/DQA1*03/DRB1*04). Os dados de exames sorológicos, resultados de biópsia, sintomatologia e incidência de doenças associadas à doença celíaca foram coletados por meio de questionário previamente validado. Resultados Verificou-se que 98% dos pacientes apresentavam pelo menos uma cópia dos alelos estudados. Pacientes portadores simultaneamente de ambos os alelos de risco HLA-DQ2 foram altamente prevalentes (75.0%), e 20,7% dos pacientes carregavam o haplótipo HLA-DQ8. Pacientes positivos para ambos os alelos de risco HLA-DQ2 apresentaram associação positiva aos testes sorológicos anti-gliadina (p=0,037), anti-endomísio (p=0,001) e anti-transglutaminase (p=0,032), e maior prevalência de osteoporose e hipotireoidismo. Pacientes portadores de um ou nenhum desses alelos frequentemente apresentavam resultados sorológicos negativos. Além disso, foi encontrada associação entre gravidade da lesão intestinal e perfil genético (p<0,001). Conclusão Os resultados sugerem que a genotipagem do HLA-DQ está associada aos testes sorológicos e à gravidade do dano intestinal em pacientes com doença celíaca. 14 DQA1*0501, DQA10501 DQA DQA1*05 01, DQA1 05 01 (DQA1*05:01 DQB1*0201 DQB10201 DQB DQB1*02 DQB1 02 DQB1*02:0 DRB104 DRB DRB1 04 DRB1*04 DQB1*0302/DQA1*03/DRB1*04. DQB10302DQA103DRB104 DQBDQADRB DQB1*03 02/DQA1*03/DRB1*04 . 03 DQB1*03:02/DQA1*03/DRB1*04) biópsia validado Verificouse Verificou se 98 estudados HLADQ2 HLADQ HLA DQ2 DQ 75.0%, 750 75.0% , 75 0 (75.0%) 207 20 7 20,7 HLADQ8. HLADQ8 DQ8. DQ8 HLA-DQ8 antigliadina anti gliadina p=0,037, p0037 p p=0,037 037 (p=0,037) antiendomísio endomísio p=0,001 p0001 001 (p=0,001 antitransglutaminase transglutaminase p=0,032, p0032 p=0,032 032 (p=0,032) hipotireoidismo negativos disso p<0,001. p<0,001 (p<0,001) 1 0501 DQA1*0501 DQA1050 DQA105 DQA1*0 (DQA1*05:0 0201 DQB1*020 DQB1020 DQB102 DQB1*0 DQB1*02: DRB10 DRB1*0 0302 DQB1*0302/DQA1*03/DRB1*04 DQB10302DQA103DRB10 DQB103 02DQA103DRB104 DQADRB 02/DQA1*03/DRB1*0 DQB1*03:02/DQA1*03/DRB1*04 9 75.0 (75.0% 2 20, p003 p=0,03 (p=0,037 p=0,00 p000 00 (p=0,00 (p=0,032 p<0,00 (p<0,001 050 DQA1*050 DQA10 DQA1* (DQA1*05: 020 DQB10 DQB1* DRB1* 030 DQB1*0302/DQA1*03/DRB1*0 DQB10302DQA103DRB1 02DQA103DRB10 02/DQA1*03/DRB1* DQB1*03:02/DQA1*03/DRB1*0 75. (75.0 p00 p=0,0 (p=0,03 (p=0,0 p<0,0 (p<0,00 (DQA1*05 DQB1*0302/DQA1*03/DRB1* DQB10302DQA103DRB 02DQA103DRB1 02/DQA1*03/DRB1 DQB1*03:02/DQA1*03/DRB1* (75. p0 p=0, (p=0, p<0, (p<0,0 (DQA1*0 DQB1*0302/DQA1*03/DRB1 02DQA103DRB 02/DQA1*03/DRB DQB1*03:02/DQA1*03/DRB1 (75 p=0 (p=0 p<0 (p<0, (DQA1* DQB1*0302/DQA1*03/DRB DQB1*03:02/DQA1*03/DRB (7 p= (p= p< (p<0 (DQA1 ( (p (p< (DQA

ABSTRACT Objective This study aims to describe the distribution of main celiac disease risk alleles related to human leucocyte antigen complex and their association to the severity of intestinal injury, serological test results, CD-associated diseases and symptomatology. Methods The DNA of 140 celiac disease patients was analyzed, and the distribution of the three most important risk alleles to the celiac disease development was identified (DQA1*05:01, DQB1*02:01 and DRB1*04, the last one as a DQB1*03:02/DQA1*03/DRB1*04 haplotype marker). Data on serological tests, biopsy results, symptomatology and incidence of CD-associated diseases were collected by using a previously validated questionnaire. Results It was found that 98% of patients presented at least one copy of the studied alleles. Patients carrying simultaneously both HLA-DQ2 risk alleles were highly prevalent (75%), and 20.7% patients carried the HLA-DQ8 haplotype. Positive patients for both HLA-DQ2 risk alleles presented positive association to anti-gliadin (p=0.037), anti-endomysium (p=0.001) and anti-transglutaminase (p=0.032) serological tests, and a higher prevalence of osteoporosis and hypothyroidism. Patients carrying one or none of those alleles often presented negative serological results. In addition, it was found an association between intestinal injury severity and genetic profile (No-BreakpNo-Break<0.001). Conclusion Results suggest that the HLA-DQ genotyping are associated to serological tests and the severity of intestinal damage in celiac disease patients. results CDassociated CD 14 analyzed DQA1*0501, DQA10501 DQA DQA1*05 01, DQA1 05 01 (DQA1*05:01 DQB1*0201 DQB10201 DQB DQB1*02 DQB1 02 DQB1*02:0 DRB104 DRB DRB1 04 DRB1*04 DQB1*0302/DQA1*03/DRB1*04 DQB10302DQA103DRB104 DQBDQADRB DQB1*03 02/DQA1*03/DRB1*04 03 DQB1*03:02/DQA1*03/DRB1*0 marker. marker . marker) questionnaire 98 HLADQ2 HLADQ HLA DQ2 DQ 75%, 75 75% , (75%) 207 20 7 20.7 HLADQ8 DQ8 antigliadin anti gliadin p=0.037, p0037 p p=0.037 0 037 (p=0.037) antiendomysium endomysium p=0.001 p0001 001 (p=0.001 antitransglutaminase transglutaminase p=0.032 p0032 032 (p=0.032 hypothyroidism addition NoBreakpNoBreak<0.001. NoBreakpNoBreak0001 NoBreakpNoBreak No BreakpNo Break<0.001 Break (No-BreakpNo-Break<0.001) 1 0501 DQA1*0501 DQA1050 DQA105 DQA1*0 (DQA1*05:0 0201 DQB1*020 DQB1020 DQB102 DQB1*0 DQB1*02: DRB10 DRB1*0 0302 DQB1*0302/DQA1*03/DRB1*0 DQB10302DQA103DRB10 DQB103 02DQA103DRB104 DQADRB 02/DQA1*03/DRB1*0 DQB1*03:02/DQA1*03/DRB1* 9 (75% 2 20. p003 p=0.03 (p=0.037 p=0.00 p000 00 (p=0.00 (p=0.03 NoBreakpNoBreak<0.001 NoBreakpNoBreak000 Break0001 Break<0.00 (No-BreakpNo-Break<0.001 050 DQA1*050 DQA10 DQA1* (DQA1*05: 020 DQB10 DQB1* DRB1* 030 DQB1*0302/DQA1*03/DRB1* DQB10302DQA103DRB1 02DQA103DRB10 02/DQA1*03/DRB1* DQB1*03:02/DQA1*03/DRB1 (75 p00 p=0.0 (p=0.0 NoBreakpNoBreak<0.00 NoBreakpNoBreak00 Break000 Break<0.0 (No-BreakpNo-Break<0.00 (DQA1*05 DQB1*0302/DQA1*03/DRB1 DQB10302DQA103DRB 02DQA103DRB1 02/DQA1*03/DRB1 DQB1*03:02/DQA1*03/DRB (7 p0 p=0. (p=0. NoBreakpNoBreak<0.0 NoBreakpNoBreak0 Break00 Break<0. (No-BreakpNo-Break<0.0 (DQA1*0 DQB1*0302/DQA1*03/DRB 02DQA103DRB 02/DQA1*03/DRB ( p=0 (p=0 NoBreakpNoBreak<0. Break0 Break<0 (No-BreakpNo-Break<0. (DQA1* p= (p= NoBreakpNoBreak<0 Break< (No-BreakpNo-Break<0 (DQA1 (p NoBreakpNoBreak< (No-BreakpNo-Break< (DQA (No-BreakpNo-Break

Abstract: This study aimed to analyze the effects of Goji Berry extract (GB, Lycium barbarum) gavage administration on liver tissue oxidative stress in Wistar rats as well as to identify and quantify the content of the major bioactive compounds of the fruit. Four diets were applied: SW - standard diet + water; SG - standard diet + Goji Berry extract (125 mg/kg of animal); PW - palatable diet + water; PG - palatable diet + Goji Berry extract (125 mg/kg of animal). Results showed a significant increase in catalase enzyme activity in the liver of rats treated with GB and also in those intaking the palatable diet without GB when compared to the SW group. An increased mRNA expression of this enzyme in the same tissue and groups was also verified. Regarding lipid peroxidation, the GB extract produced a significant decrease in the oxidation state in the SG and PG groups. The results also showed a significant amount of bioactive compounds in GB extract.

ABSTRACT Objective: The aim of this study was to evaluate the serum activity of PON1 in women according to SNPs L55M and T-107C and diet composition. Materials and methods: Blood and serum samples from 26 women were used. DNA extraction, PCR and digestion with restriction enzymes of the PCR fragment were performed for genotyping the PON1 SNPs T-107C and L55M. Serum PON1 activity was measured in a single time point. Patients completed the semi-quantitative food frequency questionnaire and diet composition was estimated. Results: Genotypic distribution for L55M SNP was 56% for the LL genotype, 32% for LM and 12% for MM; for the PON1 C(-107)T SNP it was 28% for the TT genotype, 41% for CT and 31% for CC. Individuals with C and L alleles had higher serum PON1 activity. Combining the two SNPs, we observed that individuals carrying the LL and CC genotypes had twice the activity of carriers of the TT and MM genotypes. Considering food intake, no significant difference was observed between genotypes and intake levels. Conclusion: PON1 T(-107)C and L55M SNPs exert a strong effect on serum PON1 activity in an additive manner and are more important than diet to predict serum PON1 activity.

RESUMO Objetivo Determinar a frequência dos alelos do Human leukocyte antigen e verificar a associação da presença desses alelos com sintomas e outras doenças relacionados à doença celíaca em portadores de doenças autoimunes da tireoide. Métodos Aplicou-se um questionário relacionado aos sintomas e doenças associados à doença celíaca. O ácido desoxirribonucleico genômico foi extraído por meio da coleta das células da mucosa bucal. Os alelos (DQA1*0501; DQB1*0201; DRB1*04) foram identificados por meio da reação em cadeia da polimerase. Resultados Participaram deste estudo 110 portadores de doenças autoimunes da tireoide. Observou-se que 66,4% dos indivíduos carregavam pelo menos um dos alelos estudados e que 58,2% dos indivíduos eram positivos para pelo menos um dos alelos DQ2 (DQA1*0501; DQB1*0201) e destes 18,2% foram positivos para ambos alelos do DQ2(DQA1*0501; DQB1*0201). Com relação ao DQ8 (DRB1*04), 21,8% da população estudada eram positivos para esse alelo e 3,6% eram positivos tanto para o DQ2 (DQA1*0501; DQB1*0201) quanto para o DQ8 (DRB1*04). Foi encontrada associação significativa da presença do alelo DRB1*04 com os sintomas gastrointestinais (p=0,02). Houve associação significativa do alelo DRB1*04 com diabetes mellitus tipo 1 (p=0,02). Conclusão O perfil genético mais fortemente associado à doença celíaca, tais como DQ2 (DQA1*0501; DQB1*0201) e DQ8 (DRB1*04) estavam presentes em torno de 20,0% da população estudada, estes são haplótipos de risco para doença celíaca e principalmente na presença de sintomas e doenças relacionadas à doença celíaca. Sendo assim, é importante realizar o rastreamento para investigar um possível diagnóstico para doença celíaca.

ABSTRACT Objective To determine the frequency of Human leukocyte antigen alleles and to verify the association of the presence of these alleles with symptoms and other diseases related to celiac disease in patients with autoimmune thyroid diseases. Methods A questionnaire on the symptoms and diseases associated with celiac disease was applied. Genomic deoxyribonucleic acid was extracted by collecting cells from the oral mucosa. The alleles (DQA1*0501; DQB1*0201; DRB1*04) were identified by means of the polymerase chain reaction. Results A total of 110 patients with autoimmune thyroid diseases participated in this study. It was observed that 66.4% of the individuals carried at least one of the alleles assessed and that 58.2% of the individuals were positive for at least one of the DQ2 alleles (DQA1*0501; DQB1*0201) and out of these 18.2% were positive for both DQ2 alleles (DQA1*0501; DQB1*0201). With regard to DQ8 (DRB1*04), 21.8% of the studied population was positive for this allele and 3.6% was positive for both DQ2 (DQA1*0501; DQB1*0201) and DQ8 (DRB1*04). A significant association was found between the presence of the DRB1*04 allele and gastrointestinal symptoms (p=0.02). A significant association of the DRB1*04 allele with type 1 diabetes mellitus (p=0.02) was observed. Conclusion The genetic profiles most commonly associated with celiac disease, such as DQ2 (DQA1*0501; DQB1*0201) and DQ8 (DRB1*04) were around 20.0% prevalent in the studied population. These are risk haplotypes for celiac disease especially when symptoms and diseases related to celiac disease are present. Therefore, it is important to screen patients to investigate a potential diagnosis for celiac disease.

Abstract The present study aimed to evaluate the anti-inflammatory potential of a Lycium barbarum (L. barbarum) fruit extract in Wistar rats submitted to a palatable diet presenting systemic inflammation induced by lipopolysaccharides (LPS). Forty-two Wistar female rats (Rattus Novergicus) were used with 60 days old. The animals were feed for 60 days and divided in six groups (n=7): standard diet+water; standard diet+L. barbarum; palatable diet+water; palatable diet+L. barbarum; standard diet+water+LPS; standard diet+L. barbarum+LPS. A significant difference was shown between the analyzed groups concerning C-reactive protein, with the standard diet+water+LPS group presenting the highest inflammatory response in comparison to the other groups. Decreased inflammatory response was observed in the group administered a palatable diet along with the fruit extract when compared to the group that received only a palatable diet. Significant decrease in glutamic-oxaloacetic transaminase activity was observed in the standard diet+L. barbarum+LPS group compared to the standard diet+water group, as well as in the palatable diet+L. barbarum group compared to the palatable diet+water group. A significant increase in creatinine in the standard diet+water+LPS group was observed in according to the L. barbarum administration groups. The gene expression of the inflammatory markers genes in the liver showed a significant increase in TNF-α and IL-6 genes in the group treated with standard diet+L. barbarum+LPS when compared to the standard diet+LPS group. Thus, the administered L. barbarum extract displays the potential to reduce inflammatory responses induced by LPS and a palatable diet.

ABSTRACT Studies have shown that drinks containing Ilex paraguariensis extract can promote many benefits in animals and in humans. The present study aimed to evaluate in vivo effects of Ilex paraguariensis extract on metabolic profile, obesity prevention and expression of genes related with adipogenesis and lipogenesis in Wistar female rats fed a high-fat diet. For this experiment 32 Wistar female rats with normal weight were used and randomly separated into four groups: diet (standard or high-fat) and treatment (water or Ilex paraguariensis extract) for 34 days. The rats receiving Ilex paraguariensis extract had lower body weight compared to the control group in both diets. Likewise, there was a reduction in triglycerides in the groups fed high-fat diet and treated with Ilex paraguariensis extract. The creatinine levels were lower in the groups treated with Ilex paraguariensis and in high-fat diet. It was observed an increased liver gene expression for Fas and Scd1 in the group treated with hyperlipid diet + Ilex paraguariensis. It can be concluded that Ilex paraguariensis extract decreased body weight gain in both control and high-fat diets, reduced plasma triglycerides and creatinine levels and increased liver expression of genes related to lipogenesis.

ABSTRACT Objective The aims of this study were to investigate changes in serum paraoxonase 1 (PON1) activity in women at the pre and postmenopausal stages and its association with the PON1 C(-107)T polymorphism and food intake profile. Subjects and methods A cross-sectional study with female patients aged between 35 and 59 years old was conducted. Women were divided into two groups: premenopausal (n = 40) and postmenopausal (n = 36). Women enrolled in the study had serum PON1, total cholesterol, HDL, LDL, glucose and HbA1c, as well as the BMI measured. Additionally, women were genotyped for the PON1 T(-107)C polymorphism and the food intake profile was obtained through interview. Results Glucose (p = 0.03), HbA1c (p = 0.002) and total cholesterol (p = 0.002)concentrations were higher in post than premenopausal women, however PON1 activity was not different (p > 0.05). Carriers of the C allele had higher PON1 activity (CC: 88.9 ± 6.5 U/mL and CT: 79.9 ± 4.7 U/mL) than women of the TT genotype (66.6 ± 5.9 U/mL) (p < 0.05). However, the model predicting PON1 activity was slightly better when genotype, total fat and cholesterol content in the diet were all included. Conclusion In sum, we observed that the PON1 C(-107)T genotype was the major regulator of PON1 activity, and menopause had no effect on PON1 activity. The lipid and glycemic profile were altered in postmenopausal women.

ABSTRACT This study aimed to evaluate the effect of Ilex paraguariensis infusion on redox state of Wistar rats submitted to high-fat and standard diet. Glutathione determination and lipid peroxidation in the hippocampus tissues and liver was performed, as well as the analysis of gene expression of superoxide dismutase, catalase and glutathione peroxidase by real-time polymerase chain reaction. The results from hippocampus showed that the groups fed with standard diet exhibited significant reduction of lipid peroxidation when supplemented with Ilex paraguariensis. The analysis from glutathione determination in the hippocampus showed a significant increase in glutathione activity in the group treated with high-fat diet and Ilex paraguariensis. In the liver, results showed no significant difference in both glutatione and lipid peroxidation analisys. Gene expression of superoxide dismutase, catalase and glutathione peroxidase showed that there was significant difference in the groups treated with high-fat diet and Ilex paraguariensis. In summary, the Ilex paraguariensis showed substantial potential for antioxidant activities.