Positive association of the hepatic lipase gene polymorphism c.514C > T with estrogen replacement therapy response

<p>Abstract</p> <p>Background</p> <p>Hepatic lipase (HL), an enzyme present in the hepatic sinusoids, is responsible for the lipolysis of lipoproteins. Human HL contains four polymorphic sites: G-250A, T-710C, A-763G, and C-514T single-nucleotide polymorphism (SNPs). The last polymorphism is the focus of the current study. The genotypes associated with the C-514T polymorphism are CC (normal homozygous - W), CT (heterozygous - H), and TT (minor-allele homozygous - M). HL activity is significantly impaired in individuals of the TT and CT genotypes. A total of 58 post-menopausal women were studied. The subjects were hysterectomized women receiving hormone replacement therapy consisting of 0.625 mg of conjugated equine estrogen once a day. The inclusion criteria were menopause of up to three years and normal blood tests, radiographs, cervical-vaginal cytology, and densitometry. DNA was extracted from the buccal and blood cells of all 58 patients using a commercially available kit (GFX^®- Amersham-Pharmacia, USA).</p> <p>Results</p> <p>Statistically significant reductions in triglycerides (t = 2.16; n = 58; p = 0.03) but not in total cholesterol (t = 0.14; n = 58; p = 0.89) were found after treatment. This group of good responders were carriers of the T allele; the CT and TT genotypes were present significantly more frequently than in the group of non-responders (p = 0.02 or p = 0.07, respectively). However, no significant difference in HDL-C (t = 0.94; n = 58; p = 0.35) or LDL-C (t = -0.83; n = 58; p = 0.41) was found in these patients.</p> <p>Conclusions</p> <p>The variation in lipid profile associated with the C-514T polymorphism is significant, and the T allele is associated with the best response to ERT.</p

A reatividade negativa oriunda da poliquimioterapia imposta na Hanseníase

Introdução: A hanseníase é uma doença infectocontagiosa, que devido às repercussões clínicas e aos dados epidemiológicos é considerada de notificação compulsória. Contudo, esse transtorno quando é precocemente identificado e adequadamente manejado, evita consideravelmente o círculo vicioso de contágio e as manifestações clínicas que tornam a doença tão alvo de estigma. Objetivo: Descrever a reação negativa oriunda da poliquimioterapia imposta na hanseníase. Metodologia: Trata-se de uma revisão narrativa de literatura, fundamentada nas plataformas do Scielo, Pubmed, Lilacs e demais literaturas pertinentes ao tema, utilizando-se os seguintes descritores: Reação Hansênica, Efeitos Adversos e Poliquimioterapia, no período de janeiro de 2023. Resultados e Discussão:&nbsp; Atualmente, o protocolo terapêutico voltado para a Hanseníase é a poliquimioterapia e possui boa eficácia e tolerância pela maioria dos pacientes.&nbsp; No advém, a minoria destes apresenta reações adversas que variam de leve a exacerbadas e que devem ser devidamente classificados e orientados para outras opções farmacológica, objetivando impedir que o paciente abandone o tratamento, junto às enormes repercussões oriundas deste, e propiciar melhor qualidade de vida. Conclusão: Estima-se que o tratamento da Hanseníase é algo importante e indispensável para evitar problemas de saúde pública, mas este se baseia em uma alta carga associada de remédios potentes, a qual alguns portadores possuem sensibilidade e se orientados, podem continuar o tratamento até o alcance da cura.&nbsp

Analysis of polymorphisms in the QM gene in patients with premature ovarian failure and pure gonadal dysgenesis

Estudos mais detalhados do cromossomo X vem sendo realizados e algumas alteracoes, como translocacoes e delecoes, foram detectadas e estariam associadas a perda da funcao endocrina das gonadas antes dos 40 anos. Inumeros genes passaram a ser avaliados, principalmente aqueles que se encontravam no cromossomo X, mais precisamente em seu braco longo, nas regioes entao denominadas POF1 (Xq26-ter) e POF2 (Xq13.3-21.3). O gene QM pertence ao segmento POF1. Pesquisas com celulas animais mostraram ser um importante gene supressor de tumor. A associacao dessas duas caracteristicas e a possibilidade de ocorrerem alteracoes estruturais nesse gene, despertou nosso interesse em analisa-lo em pacientes com a falencia ovariana prematura e disgenesia gonadal pura. Propusemo-nos, pois, a analisar, por meio de tecnicas biomoleculares, a presenca de mutacoes na regiao codificadora do gene QM em pacientes com diagnostico de falencia ovariana prematura e disgenesia gonadal pura Estudaram-se 37 pacientes, atendidas no Setor de Ginecologia Endocrina do Departamento de Ginecologia da Universidade Federal de São Paulo - Escola Paulista de Medicina (UNIFESP-EPM), das quais 23 tinham diagnostico de falencia ovariana prematura e 14 de disgenesia gonadal pura. Todas possuiam idade inferior a 40 anosa fenotipo feminino; amenorreia primaria ou secundaria (de, no minimo, seis meses de duracao); cariotipo 46, XX e niveis sericos de hormonio foliculo-estimulante (FSH) superiores a 30 UIImL. As pacientes autorizaram a coleta de 10mL de sangue que foi acondicionado em freezer a -80°C. A seguir, realizamos extracao de DNA, reacao da polimerase em cadeia (PCR) para o gene QM e analise de single strand conformation polymorphism (SSCP). Uma paciente, a de numero 4, apresentou padrao de migracao eletroforetica diferente das demais. Nessa amostra foi realizado o sequenciamento automatico do DNA. Todas as amostras das pacientes com falencia ovariana prematura sofreram analise do gene da sindrome do X fragil realizada no J. C. Self Research Institute of Human Genetics (1 Gregor Mendel Circle - Greenwood - South Carolina 29646), pelo Dr. Charles E. Schwartz. Encontramos total de cinco pontos de mutacao na regiao codificadora do gene QM em paciente com falencia ovariana prematura. Em quatro dessas mutacoes, as alteracoes de nucleotideos levou tambem a troca de aminoacidos na proteina QM propriamente ditaa(au)BV UNIFESP: Teses e dissertaçõe

Three year seroepidemiological study of varicella-zoster virus in São Paulo, Brazil

A serosurvey of varicella has been carried out in children attending the public school network of São Paulo city, Brazil, from 1992 to 1994. This study was performed in order to establish the age related prevalence of antibodies against varicella-zoster virus (VZV) and its age specific transmission dynamics pattern in these children. Among 2500 schools in the city of São Paulo public network, 304 were randomly selected; 7 children of a given age (ranging from 1 to 15 years) were randomly selected in each school, and blood samples were obtained by fingerprick into filter paper. Blood eluates were analyzed for the presence of antibodies to VZV by ELISA. Proportion of seropositivity were calculated for each age group. Samples consisted of 1768 individuals in 1992, 1758 in 1993, and 1817 in 1994, resulting in 5343 eluates. A high proportion of seropositive children from 1 to 3 years of age was observed, ascending until 10 years of age and reaching a plateau around 90% afterwards. VZV transmission in this community was similar along the three years of the study. In children attending public schools in the city of São Paulo, contact with VZV occurs in early childhood. If immunization against VZV is considered it should be introduced as soon as possible.Um estudo sorológico para varicela foi realizado em crianças matriculadas na rede pública de ensino da cidade de São Paulo, Brasil, entre 1992 e 1994. O objetivo deste estudo foi determinar a soroprevalência idade-dependente de anticorpos contra o vírus varicela-zoster (VVZ) e definir sua dinâmica de transmissão nestas crianças. Foram selecionadas, ao acaso, 304 escolas entre os 2500 equipamentos da Rede Pública de Educação e Bem Estar Social na cidade de São Paulo; foram sorteadas em cada escola 7 crianças de determinada idade (de 1 a 15 anos), e o sangue colhido em papel de filtro. Os eluatos foram avaliados para anticorpos contra o vírus varicela zoster através de técnica de ELISA. A proporção de soropositivos para cada faixa etária foi calculada. Foram obtidas 1768 amostras em 1992, 1758 em 1993 e 1817 em 1994, resultando em 5343 eluatos. Observou-se alta proporção de soropositivos no intervalo etário de 1 a 3 anos de idade, ascendendo até os 10 anos, mantendo-se ao redor de 90% a partir desta idade. O padrão de transmissão do VVZ nesta comunidade é semelhante ao longo dos 3 anos estudados. Nas crianças frequentadoras das escolas públicas da cidade de São Paulo, o contacto com o VVZ ocorre no início da infância. Considerando-se a possibilidade de introdução da imunização contra a varicela, ela deve ocorrer o mais cedo possível

Association between the angiotensin-converting enzyme (insertion/deletion) and angiotensin II type 1 receptor (A1166C) polymorphisms and breast cancer among Brazilian women

Introduction. We evaluated the assocation between components of the renin-angiotensin system and the development of breast cancer in a case-control study by means of angiotensin-converting enzyme (ACE) insertion/deletion (I/D) and angiotensin II type I (AT(1))-receptor A1166C polymorphisms.Methods. Genotyping was performed by PCR-RFLP (restriction fragment length polymorphism) or PCR (polymerase chain reaction) using genomic DNA extracted from buccal cells of subjects with (101 cases) or without (307 controls) breast cancer.Results. the frequencies of genotypes for ACE were: DD, ID and II (in %: cases: 60; 20; 20; controls: 46; 37; 17; p=0.019, chi(2) ); and for AT(1)-receptor were: AA, AC and CC (in %; cases: 65; 30; 5; controls: 51; 44; 5; p=0.114, chi(2)). the results suggested that the A1166C polymorphism was not associated with breast cancer risk. On the other hand, for the ACE (I/D), there seemed to be different risks for cancer between cases and controls.Conclusions. the ID genotype was less frequently associated with the disease than were the DD or II; that is, women with the ID genotype were 3.1 times less likely to develop breast cancer than those with the other genotypes. the ID genotype might be protective against breast cancer and the ACE (I/D) polymorphism a possible targer for developing genetic markers for breast cancer.Universidade Federal de São Paulo, Mol Gynaecol Lab, Dept Gynaecol, BR-04039032 São Paulo, BrazilUniversidade Federal de São Paulo, Mol Gynaecol Lab, Dept Gynaecol, BR-04039032 São Paulo, BrazilWeb of Scienc

Global variation in postoperative mortality and complications after cancer surgery: a multicentre, prospective cohort study in 82 countries

© 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 licenseBackground: 80% of individuals with cancer will require a surgical procedure, yet little comparative data exist on early outcomes in low-income and middle-income countries (LMICs). We compared postoperative outcomes in breast, colorectal, and gastric cancer surgery in hospitals worldwide, focusing on the effect of disease stage and complications on postoperative mortality. Methods: This was a multicentre, international prospective cohort study of consecutive adult patients undergoing surgery for primary breast, colorectal, or gastric cancer requiring a skin incision done under general or neuraxial anaesthesia. The primary outcome was death or major complication within 30 days of surgery. Multilevel logistic regression determined relationships within three-level nested models of patients within hospitals and countries. Hospital-level infrastructure effects were explored with three-way mediation analyses. This study was registered with ClinicalTrials.gov, NCT03471494. Findings: Between April 1, 2018, and Jan 31, 2019, we enrolled 15 958 patients from 428 hospitals in 82 countries (high income 9106 patients, 31 countries; upper-middle income 2721 patients, 23 countries; or lower-middle income 4131 patients, 28 countries). Patients in LMICs presented with more advanced disease compared with patients in high-income countries. 30-day mortality was higher for gastric cancer in low-income or lower-middle-income countries (adjusted odds ratio 3·72, 95% CI 1·70–8·16) and for colorectal cancer in low-income or lower-middle-income countries (4·59, 2·39–8·80) and upper-middle-income countries (2·06, 1·11–3·83). No difference in 30-day mortality was seen in breast cancer. The proportion of patients who died after a major complication was greatest in low-income or lower-middle-income countries (6·15, 3·26–11·59) and upper-middle-income countries (3·89, 2·08–7·29). Postoperative death after complications was partly explained by patient factors (60%) and partly by hospital or country (40%). The absence of consistently available postoperative care facilities was associated with seven to 10 more deaths per 100 major complications in LMICs. Cancer stage alone explained little of the early variation in mortality or postoperative complications. Interpretation: Higher levels of mortality after cancer surgery in LMICs was not fully explained by later presentation of disease. The capacity to rescue patients from surgical complications is a tangible opportunity for meaningful intervention. Early death after cancer surgery might be reduced by policies focusing on strengthening perioperative care systems to detect and intervene in common complications. Funding: National Institute for Health Research Global Health Research Unit