Functional Genomics Unique to Week 20 Post Wounding in the Deep Cone/Fat Dome of the Duroc/Yorkshire Porcine Model of Fibroproliferative Scarring

Background: Hypertrophic scar was first described over 100 years ago; PubMed has more than 1,000 references on the topic. Nevertheless prevention and treatment remains poor, because 1) there has been no validated animal model; 2) human scar tissue, which is impossible to obtain in a controlled manner, has been the only source for study; 3) tissues typically have been homogenized, mixing cell populations; and 4) gene-by-gene studies are incomplete.Methodology/Principal Findings: We have assembled a system that overcomes these barriers and permits the study of genome-wide gene expression in microanatomical locations, in shallow and deep partial-thickness wounds, and pigmented and non-pigmented skin, using the Duroc( pigmented fibroproliferative)/Yorkshire( non-pigmented non-fibroproliferative) porcine model. We used this system to obtain the differential transcriptome at 1, 2, 3, 12 and 20 weeks post wounding. It is not clear when fibroproliferation begins, but it is fully developed in humans and the Duroc breed at 20 weeks. Therefore we obtained the derivative functional genomics unique to 20 weeks post wounding. We also obtained long-term, forty-six week follow-up with the model.Conclusions/Significance: 1) the scars are still thick at forty-six weeks post wounding further validating the model. 2) the differential transcriptome provides new insights into the fibroproliferative process as several genes thought fundamental to fibroproliferation are absent and others differentially expressed are newly implicated. 3) the findings in the derivative functional genomics support old concepts, which further validates the model, and suggests new avenues for reductionist exploration. in the future, these findings will be searched for directed networks likely involved in cutaneous fibroproliferation. These clues may lead to a better understanding of the systems biology of cutaneous fibroproliferation, and ultimately prevention and treatment of hypertrophic scarring.The National Institute on Disability and Rehabilitation ResearchThe National Institutes of HealthThe Washington State Council of Fire Fighters Burn FoundationThe Northwest Burn FoundationUniv Washington, Dept Surg, Div Plast Surg, Seattle, WA 98195 USAIowa State Univ, Dept Anim Sci, Ames, IA USAUniv Washington, Dept Biostat, Seattle, WA 98195 USAMahidol Univ, Ramathibodi Hosp, Dept Surg, Bangkok 10700, ThailandUniv Washington, Dept Environm & Occupat Hlth Sci, Seattle, WA 98195 USAUniversidade Federal de São Paulo, Div Plast Surg, Dept Surg, São Paulo, BrazilUniversidade Federal de São Paulo, Div Plast Surg, Dept Surg, São Paulo, BrazilThe National Institute on Disability and Rehabilitation Research: H133G050022The National Institutes of Health: 1R21GM074673The National Institutes of Health: 5U54GM062119-09Web of Scienc

Parity Is Not Related to Autoimmune Thyroid Disease in a Population-Based Study of Japanese-Brazilians

Background: It has been suggested that the female preponderance for autoimmune thyroid disease might be associated with hormonal differences, abortion, and fetal microchimerism. Findings emerging from the few epidemiological studies on this matter, however, are controversial. in this study, we investigated the hypothesis whether parity, abortion, and the use of estrogens are associated with a higher risk for thyroid autoimmunity.Methods: This cross-sectional population-based study examined 675 women from a Japanese-Brazilian population aged above 30 years. Thyroid peroxidase antibodies (TPOAbs), thyroglobulin antibodies (TgAbs), thyrotropin, and free T(4) were measured by immunofluorimetric assays. Urinary iodine concentration was measured using a colorimetric method. Data were analyzed in logistical regression models to obtain the odds ratio (OR) and 95% confidence intervals.Results: TPOAbs and TgAbs were present in 11.6% and 13.6% of women, respectively. After adjustment for age, smoking, and urinary iodine concentration, the OR for positive TPOAb (OR, 1.22 [95% confidence interval, 0.73-2.02]) and for positive TgAb (OR, 1.01 [0.63-1.62]) among women who had one or more parities did not differ from those who had never given birth. in addition, we found no association between the presence of thyroid antibodies and previous abortions or the use of estrogens.Conclusions: Parity, abortion, and the use of estrogens are not associated with thyroid autoimmunity in this population. These findings reinforce previous reports that advocated against a key role of fetal microchimerism in the pathogenesis of autoimmune thyroid disease.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Universidade Federal de São Paulo, Escola Paulista Med, Dept Med, Mol Endocrinol Lab,Div Endocrinol, BR-04029032 São Paulo, BrazilFac Med Marilia, Dept Med, Div Endocrinol, Marilia, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Dept Med, Mol Endocrinol Lab,Div Endocrinol, BR-04029032 São Paulo, BrazilFAPESP: 06/59737-9Web of Scienc

Subclinical thyroid dysfunctions are independent risk factors for mortality in a 7.5-year follow-up: the Japanese-Brazilian thyroid study

Objective: The currently available data concerning the influence of subclinical thyroid disease (STD) on morbidity and mortality are conflicting. Our objective was to investigate the relationships between STD and cardiometabolic profile and cardiovascular disease at baseline, as well as with all-cause and cardiovascular mortality in a 7.5-year follow-up. Design: Prospective, observational study. Methods: An overall of 1110 Japanese-Brazilians aged above 30 years, free of thyroid disease, and not taking thyroid medication at baseline were studied. In a cross-sectional analysis, we investigated the prevalence of STD and its relationship with cardiometabolic profile and cardiovascular disease. All-cause and cardiovascular mortality rates were assessed for participants followed for up to 7.5 years. Association between STD and mortality was drawn using multivariate analysis, adjusting for potential confounders. Results: A total of 913 (82.3%) participants had euthyroidism, 99 (8.7%) had subclinical hypothyroidism, and 69 (6.2%) had subclinical hyperthyroidism. At baseline, no association was found between STD and cardiometabolic profile or cardiovascular disease. Multivariate-adjusted hazard ratios (HRs (95% confidence interval)) for all-cause mortality were significantly higher for individuals with both subclinical hyperthyroidism (HR, 3.0 (1.5-5.9); n=14) and subclinical hypothyroidism (HR, 2.3 (1.2-4.4); n=13) than for euthyroid subjects. Cardiovascular mortality was significantly associated with subclinical hyperthyroidism (HR, 3.3 (1.4-7.5); n=8), but not with subclinical hypothyroidism (HR, 1.6 (0.6-4.2); n=5). Conclusion: In the Japanese-Brazilian population, subclinical hyperthyroidism is an independent risk factor for all-cause and cardiovascular mortality, while subclinical hypothyroidism is associated with all-cause mortality.Sao Paulo State Research Foundation (Fundacao de Amparoa Pesquisa do Estado de Sao Paulo, FAPESP)[06/59737-9

Macrovascular disease in a Japanese-Brazilian population of high prevalence of metabolic syndrome: Associations with classical and non-classical risk factors

Background: the Japanese-Brazilian Diabetes Study detected high prevalence of metabolic syndrome (MS) in a population of Japanese ancestry living in Brazil. We describe the prevalence of macrovascular disease (MVD) and its association with classical and non-classical cardiovascular risk factors in this population.Methods: An overall of 1163 individuals were studied; diagnosis of MVD was based on a score obtained from medical history, ankle-brachial pressure index and electrocardiogram, defining three groups: no MVD, possible MVD and definite MVD.Results: Prevalence of MVD was 14.3% (possible MVD: 11.2%; definite MVD: 3.1%). Individuals with MS had higher rates of MVD (16.9% versus 11.2%; p < 0.05). Comparing to no MVD, age, 2 It plasma glucose, anti-LDL(+) and anti-LDL(-) levels, and urinary albumin-to-creatinine ratio were higher in both categories with MVD; waist-to-hip ratio, fasting plasma glucose, HbAlc, total-to-HDL cholesterol ratio and triglycerides were higher in that with definite MVD; systolic blood pressure and homocysteine were higher in that with possible MVD. Using logistic regression, systolic blood pressure, smoking habit and anti-LDL(+) were independently associated with MVD.Conclusion: MVD is highly prevalent in Japanese-Brazilians and its association with MS was confirmed. A novel marker of lipoprotein modifications-anti-LDL(+) antibody-could be useful in identifying individuals at higher risk. (c) 2006 Elsevier Ireland Ltd. All rights reserved.Universidade Federal de São Paulo, Dept Internal Med, Div Endocrinol, BR-05508 São Paulo, BrazilUniv São Paulo, Ribeirao Preto Med Sch, Dept Social & Prevent Med, BR-05508 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Prevent Med, São Paulo, BrazilUniv São Paulo, Dept Clin & Toxicol Anal, BR-05508 São Paulo, BrazilUniv São Paulo, Sch Publ Hlth, Dept Nutr, BR-05508 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Surg, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Internal Med, Div Endocrinol, BR-05508 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Prevent Med, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Surg, São Paulo, BrazilWeb of Scienc

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