Butyrylcholinesterase and lipid metabolism: Possible dual role in metabolic disorders.

Butyrylcholinesterase (BChE), an enzyme primarily found in the liver, plasma, and brain, has been recognized for its role in the hydrolysis of choline esters. Recent studies have shed light on its involvement in lipid metabolism, revealing its potential as a crucial player in maintaining lipid homeostasis. However, the interactions between external factors and BChE activity in lipid metabolic pathways remain a complex subject of study. This review summarizes the current knowledge regarding BChE activity and lipid metabolism and seeks to clarify the nature of this relationship as causal or consequential. Evidence supports the role of BChE in energy homeostasis disruption, such as obesity and related metabolic disorders, where it exhibits lipolytic activity and mediates fatty acid use and storage. The unexpected functions of BChE in lipoprotein synthesis and the impact of polymorphic variants of the BCHE gene suggest a central role in lipid metabolism; however, further investigation is needed to confirm and describe these functions, especially considering the metabolic context. Furthermore, exploring therapeutic interventions in lipid metabolism disorders contributes to elucidating their implications on BChE activity, but attention to the metabolic status and genotypes as possible factors in this interaction is needed. In summary, further research in this field holds promise for improving our understanding of the complex interplay between BChE and lipid metabolism, and its potential clinical applications. However, the available data corroborate the dual role of BChE activity, both as a critical responsive element to metabolic challenges and as a predisposition factor to metabolic diseases.

Combination of vitamin D and probiotics inhibits chemically induced colorectal carcinogenesis in Wistar rats.

The modulation of inflammatory elements, cell differentiation and proliferation by vitamin D and the role of probiotics in the intestinal microbiota and immunogenic response have sparked interest in the application of both in chemotherapeutics and chemoprevention of colorectal tumors. AIMS: The present study aimed to investigate the effects of isolated and/or combined treatment of vitamin D3 and probiotics on colorectal carcinogenesis. MAIN METHODS: Pre-neoplastic lesions were induced with 1,2-dimethylhydrazine in the colon of Wistar rats, which were treated with probiotics and/or vitamin D in three different approaches (simultaneous, pre-, and post-treatment). We investigated the frequency of aberrant crypt foci (ACF) and aberrant crypt (AC) in the distal colon, fecal microbiome composition, gene and protein expression through immunohistochemical and RT-PCR assays, and general toxicity through water consumption and weight gain monitoring. KEY FINDINGS: Results confirm the systemic safety of treatments, and show a protective effect of vitamin D and probiotics in all approaches studied, as well as in combined treatments, with predominance of different bacterial phyla compared to controls. Treated groups show different levels of Nrf2, GST, COX2, iNOS, ß-catenin and PCNA expression. SIGNIFICANCE: These experimental conditions explore the combination of vitamin D and probiotics supplementation at low doses over pathways involved in distinct stages of colorectal carcinogenesis, with results supporting its application in prevention and long-term strategies.

High rate of abnormal glucose tolerance in Brazilian individuals undergoing coronary angiography.

INTRODUCTION: Undiagnosed hyperglycemia is common in high cardiovascular risk individuals, especially in those with coronary artery disease (CAD). There is no consensus about the optimal method for the screening of hyperglycemia in this population. SUBJECTS AND METHODS: Five hundred and fourteen Brazilian individuals undergoing coronary angiography, without previously known diabetes mellitus (DM), had their glycemic status evaluated by both fasting plasma glucose (FPG) and HbA1c, being classified in normal (N), prediabetes (PD), and DM according to American Diabetes Association criteria. Concordance between both methods was assessed by Cohen's κ. Accuracy of FPG and HbA1c to diagnose CAD was evaluated as proof-of-concept. RESULTS: Among individuals screened by FPG, 41.2% had PD and 6% had DM. Among those screened by HbA1c, 52.7% had PD and 12.7% had DM. Concordance for a positive screening of PD occurred in 125 individuals (κ = 0.084). Eighteen individuals had a concordant positive screening of DM (κ = 0.310). As a predictor of CAD, accuracy of FPG was 0.554 (p = 0.009) and of HbA1c 0.557 (p = 0.006). CONCLUSION: a high frequency of hyperglycemia, between 47 and 65%, was found in individuals submitted to coronary angiography without previously known glucose disturbances, using FPG and HbA1c as screening methods respectively.HbA1c detected significantly more individuals with both PD and DM than FPG. Concordance between both methods is low. The question of which is the gold-standard method to diagnose hyperglycemia in this population is still open.

Association of ADIPOQ variants, total and high molecular weight adiponectin levels with coronary artery disease in diabetic and non-diabetic Brazilian subjects.

OBJECTIVE: To investigate the association of ADIPOQ variants, total and high molecular weight adiponectin (HMW) adiponectin levels with the prevalence of diabetes mellitus and coronary artery disease (CAD) diagnosed by coronary angiography in Brazilian subjects with high cardiovascular risk. METHODS: 603 subjects undergoing coronary angiography were studied in regard to their glycemic status and presence of CAD (lesions >0%). We evaluated baseline concentrations of total and HMW adiponectin and three ADIPOQ variants: -11391G>A (rs17300539), +45T>G (rs2241766) and+276G>T (rs1501299). RESULTS: The G-allele of rs2241766 was associated with higher levels of total and HMW adiponectin, and the A-allele of rs17300539 was associated with higher levels of HMW adiponectin. Lower levels of total and HMW adiponectin were independently associated with CAD. The G-allele of rs2241766 (OR 2.45, 95% C.I. 1.05-6.04, p=0.04) and the G-allele of rs1501299 (OR 1.89, 95% C.I. 1.04-3.45, p=0.03) were associated with CAD, and these associations were independent of circulating levels of adiponectin. CONCLUSIONS: In Brazilian subjects with high cardiovascular risk, CAD was associated with lower total and HMW adiponectin levels. The rs2241766 and rs1501299 polymorphisms were associated with CAD. The rs2241766 variant was associated with total and HMW adiponectin levels, while rs17300539 was associated with HMW adiponectin levels.

ADIPOQ and adiponectin: the common ground of hyperglycemia and coronary artery disease?

Plasma adiponectin and the coding gene for adiponectin, ADIPOQ, are thought to explain part of the interaction between obesity, insulin resistance, type 2 diabetes (T2DM) and coronary artery disease (CAD). Here, we illustrate the role that adiponectin and ADIPOQ variants might play in the modulation of CAD, especially in the occurrence of hyperglycemia. Recent evidence suggests that total and high molecular weight (HMW) adiponectin levels are apparent markers of better cardiovascular prognosis in patients with low risk of CAD. However, in subjects with established or high risk of CAD, these levels are associated with poorer prognosis. We also provide recent evidences relating to the genetic control of total and HMW adiponectin levels, especially evidence regarding ADIPOQ. Accumulated data suggest that both adiponectin levels and polymorphisms in the ADIPOQ gene are linked to the risk of CAD in patients with hyperglycemia, and that these associations seem to be independent from each other, even if adiponectin levels are partly dependent on ADIPOQ.

ADIPOQ and adiponectin: the common ground of hyperglycemia and coronary artery disease? / ADIPOQ e adiponectina: base comum da hiperglicemia e doença arterial coronariana?

Plasma adiponectin and the coding gene for adiponectin, ADIPOQ, are thought to explain part of the interaction between obesity, insulin resistance, type 2 diabetes (T2DM) and coronary artery disease (CAD). Here, we illustrate the role that adiponectin and ADIPOQ variants might play in the modulation of CAD, especially in the occurrence of hyperglycemia. Recent evidence suggests that total and high molecular weight (HMW) adiponectin levels are apparent markers of better cardiovascular prognosis in patients with low risk of CAD. However, in subjects with established or high risk of CAD, these levels are associated with poorer prognosis. We also provide recent evidences relating to the genetic control of total and HMW adiponectin levels, especially evidence regarding ADIPOQ. Accumulated data suggest that both adiponectin levels and polymorphisms in the ADIPOQ gene are linked to the risk of CAD in patients with hyperglycemia, and that these associations seem to be independent from each other, even if adiponectin levels are partly dependent on ADIPOQ.

Os níveis plasmáticos de adiponectina e o gene codante desta proteína, ADIPOQ, parecem explicar parte da interação de doenças como obesidade, resistência à insulina, diabetes melito tipo 2 (DM2) e doença arterial coronariana (DAC). Apresentamos as evidências do papel tanto dos níveis de adiponectina quanto das variantes no ADIPOQ na modulação da DAC, sobretudo na presença de hiperglicemia. Estudos recentes sugerem que níveis de adiponectina total e de alto peso molecular (HMW) são marcadores de bom prognóstico DAC, sobretudo em pacientes de baixo risco cardiovascular, enquanto nos pacientes de alto risco ou com doença já estabelecida podem se associar com pior prognóstico. Apresentamos também as evidências em relação ao possível controle genético dos níveis circulantes de adiponectina, tanto total quanto da isoforma de alto peso molecular, sobretudo em relação ao ADIPOQ. A análise global dos dados sugere que tanto os níveis circulantes de adiponectina quanto polimorfismos no gene ADIPOQ estão implicados na evolução de DAC em pacientes com hiperglicemia e que essas associações podem existir de forma independente.

Visfatin, glucose metabolism and vascular disease: a review of evidence.

The adipose tissue is an endocrine organ producing substances called adipocytokines that have different effects on lipid metabolism, metabolic syndrome, and cardiovascular risk. Visfatin was recently described as an adipocytokine with potentially important effects on glucose metabolism and atherosclerosis. Visfatin has been linked to several inflammatory conditions, beta cell function, and cardiovascular disease. The growing number of publications on the subject shall bring further evidence about this adipocytokine. Its findings may contribute in the identification of higher risk individuals for diabetes and cardiovascular disease with a better comprehension about the complex intercorrelation between adiposity, glucose metabolism and vascular disease.

A importância da prática de alimentação, higiene bucal e fatores sócio-econômicos na prevalência da cárie precoce da infância em pré-escolares de Itatiba-SP / The importance of feeding practices, oral hygiene and socioeconomic factors in the early childhood caries prevalence in preschool children from Itatiba-SP

Objetivo: Verificar se a dieta, incluindo hábitos de aleitamento, a higiene bucal e os fatores sócio-econômicos podem ser considerados indicadores de risco para a cárie precoce da infância (CPI) em pré-escolares de Itatiba-SP. Material e método: A amostra foi constituída por 288 crianças, de 3 a 4 anos, que freqüentavam pré-escolas públicas do município de Itatiba-SP. Uma cirurgiã-dentista calibrada (Kappa=0,78) realizou exame físico para a determinação da presença de biofilme dentário e do índice de cárie. Para a avaliação da dieta foi empregado um diário alimentar, enquanto hábitos de aleitamento, higiene bucal, etnia, renda familiar e escolaridade materna foram avaliados por um questionário. Os dados foram analisados pelo teste qui-quadrado/exato de Fisher, seguido de regressão logística múltipla (alfa=0,05) expressa por razão de chances (odds ratio -OR). Resultados: A ingestão de açúcar na forma sólida 3 ou mais vezes ao dia (OR=4,5), a amamentação não exclusiva no peito por 12 meses ou mais (OR=2,0), a presença de biofilme dentário nos incisivos superiores (OR=3,1) e o fato de levar lanche para consumir na escola (OR=2,1), além da merenda, apresentaram associação significativa com a CPI (<0,05). Já os fatores etnia, escolaridade, renda familiar e freqüência de higiene bucal não se mostraram estatisticamente significativos (p>0,05). Conclusão: Os resultados sugerem que a exposição frequente aos açúcares na forma sólida, a presença de biofilme dentário e o fato de levar lanche para escola, principalmente os cariogênicos, são indicadores de risco expressivos para a cárie precoce da infância na população estudada.

Purpose: This study aimed to verify if the cariogenic diet, including nursing habits, the oral hygiene and the socioeconomic factors could be considered risk indicators for early childhood caries (ECC) in preschool children from Itatiba-SP. Methods: The sample was composed of 288 children, 3 to 4 years old, who attended public preschools from Itatiba-SP. Clinical examinations were conducted by one calibrated dentist (Kappa=0.78) for biofilm presence and caries index determination. For the diet evaluation, a diet chart was used, whereas the nursing habits, oral hygiene, ethnicity, family income and mothers´ level of education were evaluated by a questionnaire. Data were analyzed by chi-square/fisher´s exact test and multiple logistic regression (alfa=0.05) expressed by odds ratios (OR). Results: Sugar consumption in the solid form three or more times a day (OR=4.5), non-exclusive breast-feeding for 12 months or more (OR=2.0), presence of biofilm on the maxillary incisors (OR=3.1) and intake of snacks or drinks at school (OR=2.1), in addition to school meals were significantly associated with ECC (p<0.05). Besides, the factors ethnicity, level of education, family income and oral hygiene frequency did not show statistical significance (p>0.05). Conclusion: The results suggest that frequent exposure to solid sugar, biofilm presence and snacks as complement to school meals, particularly the cariogenic ones, are expressive risk indicators for early childhood caries in the population studied.

Laparoscopic versus open splenectomy in dogs

In the last few years, the use of laparoscopy in veterinary medicine has expanded and consequently so was the need for studies that establish the advantages, disadvantages and possible complications of each procedure. The purpose of the current study was to describe a laparoscopic splenectomy technique and the alterations due to this access, and compare it to the open procedure in dogs. A total of 15 healthy female mongrel dogs were used, with mean weight of 17.4±2.5kg. The animals were distributed into three groups: Group IA of open splenectomy (laparotomy) using double ligation of the vessels of the splenic hilum with poliglicolic acid, Group IB of open splenectomy (laparotomy) with bipolar electrocoagulation of the splenic hilum, and Group II of laparoscopic access with bipolar electrocoagulation of the splenic hilum. Operative time, blood loss, size of incisions, complications during and after surgery were evaluated. Other parameters included pain scores, white blood cell (WBC) counts and postoperative serum concentrations of alanine aminotransferase (ALT), alkaline phosphatase (ALP), creatine kinase (CK), C-reactive protein (CRP), glucose and cortisol. No differences were found in the evaluation of parameters between both open splenectomy techniques employed. Laparoscopic access presented significant differences (p<0,05) when compared with open surgery: Longer operative time, smaller abdominal access, decrease in blood loss, lower concentrations of CRP, higher levels of CK and ALP, and lower scores in the pain scale. Laparoscopic surgery showed fewer complications of the surgical wound. No significant differences were observed between groups in the postoperative temperature, WBC, ALT, cortisol and glucose concentrations. In conclusion, the laparoscopic technique is useful for splenectomy in dogs, being advantageous in terms of blood loss, surgical stress and surgical wounds. However, it expends more operative time and causes transitory...

Nos últimos anos, a utilização da laparoscopia em Medicina Veterinária vem expandindo e, conseqüentemente, a necessidade de pesquisas que determinem as vantagens, desvantagens e possíveis complicações de cada procedimento. Este estudo teve como objetivo descrever uma técnica de esplenectomia laparoscópica, assim como as alterações decorrentes deste acesso, e compará-la ao procedimento convencional em cães. Foram utilizadas 15 cadelas hígidas, sem raça definida, com peso médio de 17,4 ±2,5kg. Os animais foram distribuídos em três grupos: Grupo IA de acesso convencional (por laparotomia) utilizando ligadura com ácido poliglicólico no selamento vascular do hilo esplênico, Grupo IB de acesso convencional (por laparotomia) com eletrocoagulador bipolar do hilo esplênico, e Grupo II de acesso laparoscópico com eletrocoagulador bipolar para selamento vascular dos ramos esplênicos. Estes grupos foram avaliados em relação ao tempo cirúrgico, à perda de sangue, ao tamanho das incisões e às complicações durante e após a cirurgia. Também foram comparadas as avaliações da escala de dor e as alterações no leucograma e nas concentrações séricas da alanina aminotransferase (ALT), da fosfatase alcalina (FA), da creatina quinase (CK), da proteína C-reativa (CRP), da glicose e do cortisol no pós-operatório. Os acessos convencionais não diferiram entre si nos parâmetros avaliados. O acesso laparoscópico apresentou diferenças significativas (p<0,05) quando comparado ao convencional: maior tempo cirúrgico, menor acesso abdominal, diminuição na perda de sangue, menores concentrações de CRP, maiores níveis de CK e FA, além de pontuação menor na escala de dor. A cirurgia laparoscópica apresentou menor número de complicações das feridas cirúrgicas. A ALT, o cortisol, a glicemia, o leucograma e a temperatura retal pós-operatórias não diferiram significativamente entre os acessos convencional e laparoscópico. Conclui-se que a cirurgia laparoscópica é viável para...

Low prevalence of MODY2 and MODY3 mutations in Brazilian individuals with clinical MODY phenotype.

Prevalence of MODY2 and MODY3 mutations has been assessed in 23 Brazilian families with MODY phenotype. Mutations in HNF-1alpha have been found in 3 families (13%) and 2 families (8.7%) had new glucokinase mutations. These genes do not explain the majority of MODY cases in Brazilian population.

[Cardiovascular assessment of diabetic patients]. / Avaliação cardiovascular de pacientes diabéticos em ambulatório universitário.

INTRODUCTION: Type 2 diabetes is a cardiovascular disease. The morbidity and mortality among these patients are primarily due to cardiovascular diseases. There are many guidelines regarding clinical evaluation of cardiovascular disease in those patients. Implementation of these guidelines has been an argued subject. Our objective in this paper is to describe what basal cardiovascular evaluation has been carried out at a specialized university Diabetes Center. SUBJECTS AND METHODS: Data were collected from February to October 2006 of 121 type 2 diabetes individuals who were enrolled at the Diabetes Center of Federal University of São Paulo. We analyzed the type of cardiovascular disease evaluation that they had been submitted in the year that preceded the consultation. RESULTS: We have observed a high prevalence of several other cardiovascular risk factors in this population. The cardiovascular evaluations during this period has shown 36% of the patients had not been submitted to any cardiovascular test, 17% had been submitted to resting electrocardiogram and 27% of the patients had been submitted to exercise test. Rest echocardiogram, pharmacologic stress echocardiogram, myocardial perfusion scintigraphy, and coronary angiography have been carried out in a much lesser ratio. CONCLUSION: Our data has shown the variability and limitations on boarding diagnosing of DAC in university environment patients and point us the necessity of constructing defined and directed directives for the peculiarities of the Brazilian population and health system.

Avaliação cardiovascular de pacientes diabéticos em ambulatório universitário / Cardiovascular assessment of diabetic patients

INTRODUÇÃO: Baseado no conhecimento atual sobre o diabetes tipo 2 (DM), considerado como um estado de doença cardiovascular, várias diretrizes surgem no intuito de sugerir uma avaliação cardiovascular rotineira nesses indivíduos, na tentativa de se detectar precocemente a doença arterial coronariana (DAC). Neste trabalho, objetivamos descrever qual avaliação cardiovascular basal fora realizada em um período de seguimento dos mesmos, dentro de um centro universitário especializado no tratamento de diabetes, adequado para a realidade brasileira. SUJEITOS E MÉTODOS: Anotamos dados clínicos do prontuário de 121 pacientes portadores de DM tipo 2 atendidos no Centro de Diabetes da Universidade Federal de São Paulo e confrontamos com o tipo de avaliação cardiovascular a que os mesmos haviam sido submetidos no ano que precedia a consulta. RESULTADOS: Observamos que na população estudada havia uma alta prevalência de outros fatores de risco cardiovasculares associados. Quanto às avaliações cardiovasculares realizadas no período, cerca de 36 por cento dos pacientes não realizaram nenhum teste cardiológico, 17 por cento foram submetidos ao eletrocardiograma de repouso e 27 por cento dos pacientes foram submetidos ao teste ergométrico. Exames como ecocardiograma em repouso ou sob stress farmacológico, cintilografia de perfusão do miocárdio e cinecoronariografia foram realizados em menor proporção. CONCLUSÃO: Nossos dados mostraram a variabilidade e limitações na forma de abordagem diagnóstica de DAC de pacientes acompanhados em ambiente universitário e nos apontam para a necessidade de construir diretrizes mais bem definidas e dirigidas para as peculiaridades da população e sistema de saúde brasileiros.

INTRODUCTION: Type 2 diabetes is a cardiovascular disease. The morbidity and mortality among these patients are primarily due to cardiovascular diseases. There are many guidelines regarding clinical evaluation of cardiovascular disease in those patients. Implementation of these guidelines has been an argued subject. Our objective in this paper is to describe what basal cardiovascular evaluation has been carried out at a specialized university Diabetes Center. SUBJECTS AND METHODS: Data were collected from February to October 2006 of 121 type 2 diabetes individuals who were enrolled at the Diabetes Center of Federal University of São Paulo. We analyzed the type of cardiovascular disease evaluation that they had been submitted in the year that preceded the consultation. RESULTS: We have observed a high prevalence of several other cardiovascular risk factors in this population. The cardiovascular evaluations during this period has shown 36 percent of the patients had not been submitted to any cardiovascular test, 17 percent had been submitted to resting electrocardiogram and 27 percent of the patients had been submitted to exercise test. Rest echocardiogram, pharmacologic stress echocardiogram, myocardial perfusion scintigraphy, and coronary angiography have been carried out in a much lesser ratio. CONCLUSION: Our data has shown the variability and limitations on boarding diagnosing of DAC in university environment patients and point us the necessity of constructing defined and directed directives for the peculiarities of the Brazilian population and health system.

Estimation of diabetes risk in Brazilian population by typing for polymorphisms in HLA-DR-DQ, INS and CTLA-4 genes.

The study aimed to further characterise HLA encoded risk factors of type 1 diabetes (T1D) in Brazilian population and test the capability of a low resolution full-house DR-DQ typing method to find subjects at diabetes risk. Insulin and CTLA-4 gene polymorphisms were also analysed. The method is based on an initial DQB1 typing supplemented by DQA1 and DR4 subtyping when informative. Increased frequencies of both (DR3)-DQA1*05-DQB1*02 and DRB1*04-DQA1*03-DQB1*0302 haplotypes were detected among patients. DRB1*0401, *0402, *0404 and *0405 alleles were all common in DQB1*0302 haplotypes and associated with T1D. (DRB1*11/12/1303)-DQA1*05-DQB1*0301, (DRB1*01/10)-DQB1*0501, (DRB1*15)-DQB1*0602 and (DRB1*1301)-*0603 haplotypes were significantly decreased among patients. Genotypes with two risk haplotypes or a combination of a susceptibility associated and a neutral haplotype were found in 78 of 126 (61.9%) T1D patients compared to 8 of 75 (10.7%) control subjects (P < 0.0001). Insulin gene -2221 C/T polymorphism was also associated with diabetes risk: CC genotype was found among 83.1% of patients compared to 69.3% of healthy controls (P=0.0369, OR 1.98) but CTLA-4 gene +49 A/G polymorphism did not significantly differ between patients and controls. Despite the diversity of the Brazilian population the screening sensitivity and specificity of the used method for T1D risk was similar to that obtained in Europe.

Diabetes mellitus do tipo MODY / Diabetes mellitus of the MODY type

Estima-se que perto de 5 por cento dos indivíduos classificados como portadores de diabetes mellitus (DM) tipo 2 e 10 por cento daqueles considerados como tipo 1 (anteriormente classificado como juvenil) sejam, na verdade, portadores de mutaçöes MODY. Nesta forma de DM ocorre uma co-segregaçäo evidente de algumas mutaçöes com a hiperglicemia, fato este reproduzido em inúmeras famílias estudadas em várias populaçöes do mundo. Caracteriza-se por ser uma das poucas causas de DM cujo modo de transmissäo da predisposiçäo genética ocorre de uma forma autossômica-dominante, compondo o grupo chamado de DM monogênicos, onde os outros representantes têm uma prevalência bastante rara. As mutaçöes nos genes MODY, mesmo no estado heterozigoto, apresentam um forte impacto no fenótipo (alta penetrância), sendo que 95 por cento dos indivíduos nascidos com alguma mutaçäo MODY seräo diabéticos ou apresentaräo alteraçöes no âmbito do metabolismo glícídico antes dos 55 anos de idade. Este trabalho objetiva a discussäo desta forma de DM, enfatizando suas características clinicas e genéticas mais relevantes. A pesquisa sistemática de mutaçöes MODY começa a ser feita de forma rotineira em vários países, havendo uma tendência de se colocar este recurso diagnóstico como um exame na prática da diabetologia.