Analysis of clinicopathological characteristics of non-alcoholic fatty liver disease / 中华病理学杂志

Objective: To investigate the clinical and pathologic characteristics of obese adults with nonalcoholic fatty liver disease (NAFLD) and to aid the diagnosis of nonalcoholic steatohepatitis (NASH). Methods: A total of 262 patients eligible for inclusion who received volume reduction metabolism surgery and liver biopsy in the First Affiliated Hospital of Nanjing Medical University from June 2018 to September 2019 were selected. HE staining, reticular fiber staining and Masson staining were performed. Statistical analysis was performed using SPSS 20.0. Results: The patients ranged in age from 18 to 66 years. Among the 262 cases, 65 cases (65/262, 24.8%) were male and 197 cases (197/262, 75.2%) were female. Sixty-one cases (61/262, 23.3%) were non-NAFLD, 201 cases (201/262, 76.7%) were NAFLD including 27 cases (27/201, 13.4%) of nonalcoholic fatty live (NAFL) and 174 cases (174/201, 86.6%) of NASH. The main lesions of NAFLD were in hepatic acinus zone 3. There were significant differences in age, alanine aminotransferase (ALT), glutamic oxaloacetic transaminase (AST), body mass index (BMI), fasting blood-glucose (FPG) and apolipoprotein A (APOA) levels among the non-NAFLD group, NAFL group and NASH group (P<0.05). Patients with BMI≥35 m/kg2 combined with type 2 diabetes had a higher prevalence of NASH. Multiple logistic regression showed that ALT and APOA were independent predictors of NASH (P<0.001, OR=1.05, 95%CI: 1.020-1.082; P=0.027, OR=0.916, 95%CI: 0.878-0.941). Total cholesterol (CHO) and high-density lipoprotein (HDL) were independent predictors of lobular inflammation (P=0.043, 95%CI: 0.010-0.634; P=0.024, 95%CI:-3.068--0.216). AST and HDL were independent predictors of fibrosis stage (P=0.029, 95%CI: 0.001-0.021; P<0.001, 95%CI:-2.670--0.645). Conclusions: Biochemical indicators of NAFLD are closely related to its pathology. The histological lesions of NAFLD are mainly present in hepatic acinar area 3. The diagnosis of NASH is supported by extensive steatosis and high levels of CHO, ALT, AST and BMI, low levels of HDL and ApoA in biochemical markers, but pathological examination is still the gold standard for it.

Polimorfismo S19W (Ser19Ter) de la APOA5 y su relación con la hipertrigliceridemia en una población de Colombia / S19W polymorphism (Ser19Ter) of APOA5 and its relationship with hypertriglyceridemia in a Colombian population

RESUMEN Introducción: Las enfermedades cardiovasculares (ECV) son responsables del 29,69% de las muertes en Colombia. Se ha encontrado la hipertrigliceridemia, en diversos estudios como factor de riesgo independiente para la ECV. El polimorfismo S19W (Ser19Ter) de la ApoA5 se ha asociado en algunas poblaciones con la hipertrigliceridemia. Sin embargo, en Colombia esto ha sido poco estudiado. Objetivo: Estimar la asociación entre el polimorfismo S19W y la hipertrigliceridemia en población colombiana. Metodología: Estudio tipo Corte Transversal, con 400 individuos provenientes de Bucaramanga, Colombia. Se cuantificó los TAG y se genotipificaron mediante la técnica de SNaPshot y mini secuenciación. Los resultados fueron analizados utilizando el software de análisis genético Arlequín 3.5.1.2. Resultados: El polimorfismo S19W (Ser19Ter) mostró tres perfiles, CC, GG y CG. El polimorfismo S19W se caracterizó tanto en afectados como en no afectados, mostrando que no existen diferencias significativas en esta distribución cuando se comparan los dos grupos. Discusión: Diversos mecanismos se han propuesto para sustentar la hipertrigliceridemia como un factor de riesgo para ECV, entre los que se cuenta la APOA5. El estudio comprobó que la población estudiada se encuentra en equilibrio de Hardy Weinberg y al genotipo CC como el más frecuente. Los genotipos GG y el GC presentaron valores significativos en el grupo de sujetos afectados, (p<0,01 y p=0,03; respectivamente). Se demostró la existencia de una estrecha relación entre el polimorfismo Ser19Trp y la hipertrigliceridemia (p<0,01). Conclusión: Se pudo demostrar la existencia de una relación entre el polimorfismo Ser19Trp de la Apo A5 con los niveles elevados de TAG (p<0,01).

ABSTRACT Introduction: Cardiovascular diseases (CVD) are responsible for 29.69% of the deaths in Colombia. Several studies have shown that hypertriglyceridemia is an independent risk factor for CVD. ApoA5 gene S19W (Ser19Ter) polymorphism has been associated with hypertriglyceridemia in some populations; however, their influence in Colombia is unknown. Objective: To determine the relationship between S19W polymorphism and hypertriglyceridemia in Colombian population. Methodology: Transversal crossover Studio, included a total of 400 individuals. TAG was quantified and genotyped using the technique SnapShot and mini sequencing. The results were analyzed using genetic analysis software Arlequin 3.5.1.2. Results: S19W (Ser19Ter) polymorphism showed three profiles, CC, GG and CG. The S19W polymorphism was characterized both affected and not affected. There wasn´t significant differences in the distribution when the two groups are compared. Discussion: Various mechanisms have been proposed to support hypertriglyceridemia as a risk factor for CVD, including the APOA5 counted. The study found that the study population is in Hardy Weinberg and CC genotype as the most frequent. The GG and GC genotypes showed significant values in the group of affected subjects (p = 0.002 and 0.03). It demonstrated the existence of a close relationship between the Ser19Trp polymorphism and hypertriglyceridemia (p<0,01). Conclusion: It was possible to demonstrate the existence of a relationship between polymorphism Ser19Trp of ApoA5 with elevated levels of TAG (p<0,01).

Dieta cetogênica clássica e modificada: risco cardiometabólico e potencial terapêutico em pacientes pediátricos com epilepsia refratária / Classic and modified ketogenic diet: cardiometabolic risk and therapeutic potential in pediatric patients with refractory epilepsy

A dieta cetogênica (DC) é um tratamento não farmacológico prescrito especialmente para crianças e adolescentes com epilepsia refratária. A composição da dieta cetogênica é baseada no alto teor de gorduras, baixo teor de carboidratos e teor proteico moderado, sendo a produção de corpos cetônicos o mecanismo provável envolvido no controle das crises epilépticas. Apesar dos benefícios clínicos, a relação entre DC e o risco cardiometabólico não está bem estabelecida, especialmente sob os fatores de risco não clássicos. Objetivo: comparar os efeitos da dieta cetogênica clássica com a dieta cetogênica modificada nas subfrações de LDL e HDL, nos marcadores oxidativos, no perfil de apolipoproteinas e no perfil lipídico de crianças e adolescentes com epilepsia refratária, além do efeito clínico no controle da epilepsia. Métodos: Estudo de intervenção com recrutamento de crianças e adolescentes com epilepsia refratária de 1 a 19 anos de ambos os sexos do Instituto da Criança do Hospital das Clínicas da FMUSP. O grupo controle recebeu DC clássica e o grupo caso recebeu a DC modificada com redução em pelo menos 20% de ácidos graxos saturados (AGS) e redução da relação w6/w3 em pelo menos 50% em comparação a DC clássica. Para ambos os grupos foram analisados os seguintes parâmetros bioquímicos no período basal, após 3 meses e 6 meses de DC: perfil lipídico clássico, concentração de ácidos graxos não esterificados (AGNEs), substâncias reativas ao ácido tiobarbitúrico (TBARs), subfrações de lipoproteina de baixa densidade (LDL) e lipoproteína de alta densidade (HDL), e perfil de apolipoproteínas (APOA-I e APOB). Além da avaliação clínica, antropométrica e de consumo alimentar. Resultados: A redução de crises e dos fármacos antiepilépticos foi semelhante entre os grupos. O aumento na concentração de colesterol total (CT) e LDL foi inferior no grupo caso, a Não-HDL manteve-se significativamente menor no grupo caso em comparação ao grupo controle e a relação LDL/APOB foi superior no grupo controle após 6 meses de DC. O percentual de partículas pequenas de LDL apresentou aumento superior em 208% no grupo controle comparado ao grupo caso, e consequentemente o tamanho de LDL apresentou maior redução no grupo controle. A incidência de dislipidemia foi significativamente inferior no grupo caso considerando os pontos de corte para LDL (>=130 mg/dL) e não-HDL (>=145 mg/dL). Não houve diferença entre os grupos na concentração de ácidos graxos não esterificados (AGNES) e substâncias reativas ao ácido tiobarbitúrico (TBARs). Conclusão: A mudança do perfil de gorduras 10 contribuiu para melhora das concentrações de marcadores de risco cardiometabólico (CT, LDL e LDL pequenas) e consequentemente, perfil mais cardioprotetor nos pacientes do grupo caso

The ketogenic diet (KD) is a non-pharmacological treatment especially prescribed to children and adolescentes with refractory epilepsy. The composition of the ketogenic diet is based on the high fat, low carbohydrate and moderate protein. The production of ketone bodies is the probable mechanism involved in the control of epileptic seizures. Despite the clinical benefits, the relationship between KD and cardiometabolic risk is not well established, especially under non-classical risk factors. Objective: to compare the effects of the classical KD with the modified KD on the LDL and HDL subfractions, in oxidative biomarkers, in apolipoprotein profile and lipid profile of children and adolescentes with refractory epilepsy, as well as the clinical effect on control of seizure. Methods: Dietary intervention study with recruitment of children and adolescentes with refractory epilepsy aged 1 to 19 years of both sexes from the Instituto da Criança do Hospital das Clínicas da Faculdade de Medicina da USP. The control group received classical KD and the case group received modified KD with a reduction of at least 20% saturated fatty acids (SFA) and a reduction of the w6/w3 ratio by at least 50% compared to classic KD. For both groups, the following biochemical parameters were analyzed at baseline and after 3 and 6 months of the KD: classical lipid profile, concentration of non-esterified fatty acids (NEFAs), thiobarbituric acid reactive substances (TBARs), low density lipoprotein (LDL) and high density lipoprotein (HDL) subfractions, size LDL, and apolipoprotein profile (APOA-I and APOB). In addition to clinical, anthropometric and food consumption assessment. Results: The reduction of seizures and antiepileptic drugs was similar between the groups. The increase in total cholesterol (TC) and LDL levels was lower in the case group, non-HDL remained significantly lower in the case group compared to the control group and the LDL/APOB ratio was higher in the control group after 6 months of KD. The percentage of small LDL particles showed a 208% higher in the control group than case group. Consequently, the LDL size showed a greater reduction in the control group. The incidence of dyslipidemia was significantly lower in the case group considering cut-off points for LDL (>=130 mg/dL) and non-HDL (>=145 mg/dL). There was no difference between the groups in the NEFAs and TBARs levels. Conclusion: The change in the fatty acids profile contributed to improvement the concentrations of cardiometabolic risk markers (TC, 12 LDL and small LDL), and consequently, a more cardioprotective profile in the patients of case group

Polimorfismos de los genes LEP , LDLR , APOA4 y sus relaciones con el sobrepeso, la obesidad y el riesgo de enfermedades crónicas en adultos del estado Sucre, Venezuela / LEP , LDLR and APOA4 gene polymorphisms and their relationship with the risk of overweight, obesity and chronic diseases in adults of the State of Sucre, Venezuela

Introducción. La prevalencia del sobrepeso, la obesidad y algunas enfermedades crónicas no transmisibles ha aumentado; sus causas pueden ser genéticas, epigenéticas o ambientales, por lo cual es importante evaluar la variabilidad en estas interacciones. Objetivo. Analizar las relaciones entre nueve polimorfismos de nucleótido simple de los genes LEP (rs2167270), LDLR (rs885765, rs688, rs5925, rs55903358, rs5742911) y APOA4 (rs5095, rs675, rs5110), y los fenotipos asociados al sobrepeso, la obesidad y otras enfermedades concomitantes. Materiales y métodos. Se evaluaron parámetros clínicos y antropométricos en 144 sujetos del estado Sucre, Venezuela, 76 hombres y 68 mujeres , con medias de edad de 29,93±8,29 y 32,49±11,15 años, respectivamente. Se hizo la genotipificación de los polimorfismos seleccionados mediante enzimas de restricción; se estudiaron las asociaciones entre genotipo y riesgo, y se compararon los promedios de las medidas antropométricas y bioquímicas previamente ajustadas a variables biológicas y ambientales. Resultados. Según el índice de masa corporal (IMC), el 38,9 % de los individuos tenía sobrepeso (25=IMC=29,9 kg/m 2 ) y el 20,1 %, obesidad (IMC=30 kg/m 2 ) . Las frecuencias genotípicas y alélicas de los grupos con un índice de masa corporal normal y uno alto (sobrepeso y obesidad) resultaron similares. Solo se encontró asociación entre el genotipo ancestral A/A del rs5742911 y el riesgo alto por los niveles de la lipoproteína de alta densidad o colesterol HDL (OR=2,944, IC 95% 1,446-5,996; p=0,003). La diferencia entre los promedios corregidos de colesterol HDL para los genotipos del rs5742911 resultó significativa (p=0,005) (A/A: 41,50±14,81 mg/dl; A/G: 45,00±12,07 mg/dl; G/G: 47,17±9,43 mg/dl). Conclusión. En la mayoría de las variantes genéticas estudiadas, se registró la asociación con el sobrepeso y la obesidad de los genotipos ancestrales, aunque sin ser significativa. El polimorfismo rs5742911 podría resultar útil como indicador del riesgo de enfermedades crónicas.

Introduction: Overweight, obesity and some chronic diseases have become more prevalent recently. It is well known that their causes may be genetic, epigenetic, environmental, or a mixture of these. Objective: To analyze the relationship between nine single nucleotide polymorphisms of genes LEP (rs2167270) , LDLR (rs885765, rs688, rs5925, rs55903358, rs5742911) and APOA4 (rs5095, rs675, rs5110) with obesity-related phenotypes and other comorbidities. Material and methods: We recruited 144 adults (76 males and 68 females, with average ages of 29.93±8.29 and 32.49±11.15 years, respectively) in the State of Sucre, Venezuela. Clinical and anthropometric parameters were obtained. Genotype-risk associations were studied. We then compared the averages registered for anthropometric and biochemical variables previously adjusted for biological and environmental factors. Results: According to the body mass index, 38.9% of the individuals in the sample were overweight (25=BMI=29.9 kg/m 2 ) and 20.1% were obese (BMI=30 kg/m 2 ). Genotype and allele frequencies did not differ statistically for groups with normal and high body mass index (overweight plus obesity). The association between LDLR rs5742911 ancestral genotype A/A and high risk condition related to HDL-cholesterol was the only one found to be significant (OR=2.944, 95% CI: 1.446-5.996; p=0.003). The difference in adjusted mean HDL-cholesterol for LDLR rs5742911 genotypes was statistically significant (p=0.005) (A/A: 41.50±14.81 mg/dL; A/G: 45.00±12.07 mg/dL; G/G: 47.17±9.43 mg/dL). Conclusions: For most of the genetic variants studied, there was an association with the presence of overweight and obesity among ancestral genotype carriers, although this was not statistically significant. The rs5742911 polymorphism may be useful as an indicator of a risk of chronic diseases.

C-reactive Protein Level, Apolipoprotein B-to-apolipoprotein A-1 Ratio, and Risks of Ischemic Stroke and Coronary Heart Disease among Inner Mongolians in China / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>We aimed to investigate the cumulative effect of high CRP level and apolipoprotein B-to-apolipoprotein A-1 (ApoB/ApoA-1) ratio on the incidence of ischemic stroke (IS) or coronary heart disease (CHD) in a Mongolian population in China.</p><p><b>METHODS</b>From June 2003 to July 2012, 2589 Mongolian participants were followed up for IS and CHD events based on baseline investigation. All the participants were divided into four subgroups according to C-reactive protein (CRP) level and ApoB/ApoA-1 ratio. Cox proportional hazard models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the IS and CHD events in all the subgroups.</p><p><b>RESULTS</b>The HRs (95% CI) for IS and CHD were 1.33 (0.84-2.12), 1.14 (0.69-1.88), and 1.91 (1.17-3.11) in the 'low CRP level with high ApoB/ApoA-1', 'high CRP level with low ApoB/ApoA-1', and 'high CRP level with high ApoB/ApoA-1' subgroups, respectively, in comparison with the 'low CRP level with low ApoB/ApoA-1' subgroup. The risks of IS and CHD events was highest in the 'high CRP level with high ApoB/ApoA-1' subgroup, with statistical significance.</p><p><b>CONCLUSION</b>High CRP level with high ApoB/ApoA-1 ratio was associated with the highest risks of IS and CHD in the Mongolian population. This study suggests that the combination of high CRP and ApoB/ApoA-1 ratio may improve the assessment of future risk of developing IS and CHD in the general population.</p>

Protective Effects of Ginger (Zingiber officinale) Extract against Diabetes-Induced Heart Abnormality in Rats

BACKGROUND: Diabetic cardiomyopathy is an important causal factor in morbidity and mortality among diabetic patients, and currently, no effective means are available to reverse its pathological progress. The purpose of the present study was to investigate the effect of ginger extract on apolipoproteins (apo) A and B, hyperhomocysteinemia, cathepsin G and leptin changes, as well as cardiac fibrosis and heart muscle cell proliferation under hyperglycemic conditions in vivo. METHODS: Twenty-four male Wistar rats were divided into three groups, namely: control, non-treated diabetic, and ginger extract-treated diabetic groups. The ginger extract-treated diabetic group received a 50 mg daily dose of ginger extract intragastrically for 6 weeks. RESULTS: The results revealed concurrent significant increases in plasma C-reactive protein (CRP), homocysteine (Hcy), cathepsin G and apoB levels and decreases in apoA and leptin levels in the non-treated diabetic group compared to the control group. Moreover, heart structural changes, including fibrosis and heart muscle cell proliferation, were observed in non-treated diabetic rats compared to the control rats. Significant amelioration of changes in the heart structure together with restoration of the elevated levels of Hcy and CRP, leptin, cathepsin G, and apoA and B were found in the ginger extract-treated diabetic group compared to the non-treated diabetic group. CONCLUSION: The findings indicated that ginger extract significantly reduces heart structural abnormalities in diabetic rats and that these effects might be associated with improvements in serum apo, leptin, cathepsin G, and Hcy levels and with the antioxidant properties of ginger extract.

Effects of Bread with Nigella Sativa on Lipid Profiles, Apolipoproteins and Inflammatory Factor in Metabolic Syndrome Patients

Nigella sativa (N.sativa) has been used in traditional medicine and many studies have been performed in different communities in order to reveal the effects of it on medical disorders and chronic diseases. The aim of this study was to investigate the effects of bread with N. Sativa on lipid profiles, apolipoproteins, and inflammatory factors in metabolic syndrome (MetS) patients. A randomized, double-blind, cross-over and clinical trial was conducted in 51 MetS patients of both sexes with age group of 20-65 years old in Chaloos, north of Iran. Patients were randomly divided in two groups. In phase 1, intervention group (A, n = 27) received daily a bread with N. sativa and wheat bran and control group (B, n = 24) received the same bread without N. sativa for 2 months. After 2 weeks of wash out period, phase 2 was started with switch the intervention between two groups. Measuring of lipid profiles, apolipoproteins and inflammatory factor was performed for all patients before and after two phases. In this study, treatment, sequence and time effects of intervention were evaluated and revealed that consumption of bread with N. sativa has no significant treatment and time effects on triglyceride (TG), cholesterol (CHOL), low density lipoprotein (LDL), high density lipoprotein (HDL), apolipoprotein (APO)-A, APO-B and high-sensitivity C-reactive protein (p > 0.05). Sequence effect was significant on CHOL, LDL, APO-A, and APO-B (p 0.05). Consumption of bread with N. sativa has no a significant effect on lipid profiles, apolipoproteins and inflammatory factor in MetS patients.

Lipoprotein (a): Structure, Pathophysiology and Clinical Implications / Lipoproteína (a): Estrutura, Metabolismo, Fisiopatologia e Implicações Clínicas

The chemical structure of lipoprotein (a) is similar to that of LDL, from which it differs due to the presence of apolipoprotein (a) bound to apo B100 via one disulfide bridge. Lipoprotein (a) is synthesized in the liver and its plasma concentration, which can be determined by use of monoclonal antibody-based methods, ranges from < 1 mg to > 1,000 mg/dL. Lipoprotein (a) levels over 20-30 mg/dL are associated with a two-fold risk of developing coronary artery disease. Usually, black subjects have higher lipoprotein (a) levels that, differently from Caucasians and Orientals, are not related to coronary artery disease. However, the risk of black subjects must be considered. Sex and age have little influence on lipoprotein (a) levels. Lipoprotein (a) homology with plasminogen might lead to interference with the fibrinolytic cascade, accounting for an atherogenic mechanism of that lipoprotein. Nevertheless, direct deposition of lipoprotein (a) on arterial wall is also a possible mechanism, lipoprotein (a) being more prone to oxidation than LDL. Most prospective studies have confirmed lipoprotein (a) as a predisposing factor to atherosclerosis. Statin treatment does not lower lipoprotein (a) levels, differently from niacin and ezetimibe, which tend to reduce lipoprotein (a), although confirmation of ezetimibe effects is pending. The reduction in lipoprotein (a) concentrations has not been demonstrated to reduce the risk for coronary artery disease. Whenever higher lipoprotein (a) concentrations are found, and in the absence of more effective and well-tolerated drugs, a more strict and vigorous control of the other coronary artery disease risk factors should be sought.

A partícula de lipoproteína (a) apresenta estrutura semelhante à da LDL, diferenciando-se pela presença da apolipoproteína (a) ligada por uma ponte dissulfeto à apolipoproteína B. Sua síntese ocorre no fígado e sua concentração plasmática varia de < 1 mg a > 1.000 mg/dL, podendo ser dosada de rotina em laboratório clínico por método baseado em anticorpos monoclonais. Acima de 20 a 30 mg/dL o risco de desenvolvimento de doença cardiovascular aumenta em cerca de duas vezes, o que não é válido para os afrodescendentes, que já apresentam normalmente níveis mais altos dessa lipoproteína, do que caucasianos e orientais. Entretanto, o risco para indivíduos negros também deve ser levado em conta. Gênero e idade exercem pouca influência na concentração de lipoproteína (a). A homologia com o plasminogênio, que interfere na cascata fibrinolítica, pode ser um mecanismo da aterogenicidade da lipoproteína (a). Entretanto, a deposição direta na parede da artéria também é um dos mecanismos possíveis, sendo a lipoprotrína (a) mais oxidável do que a LDL. De forma geral estudos prospectivos confirmam a lipoproteína (a) como fator predisponente à aterosclerose. O uso de estatinas não interfere no nível da lipoproteína (a), diferentemente da niacina e da ezetimiba, que promovem sua diminuição, embora essa última dependa de confirmação. Não está demonstrado que a redução de lipoproteína (a) resulte em diminuição de risco de doença arterial coronária. Diante de concentrações mais elevadas de lipoproteína (a) e na falta de medicações mais efetivas e de boa tolerabilidade, deve-se, pelo menos, procurar controlar, de forma mais rigorosa, os outros fatores de risco de doença arterial coronária.

Effects of R219K polymorphism of ATP-binding cassette transporter 1 gene on serum lipids ratios induced by a high-carbohydrate and low-fat diet in healthy youth

BACKGROUND: Diets are the important players in regulating plasma lipid profiles. And the R219K polymorphism at the gene of ATP-binding cassette transporter 1(ABCA1) was reported to be associated with the profiles. However, no efforts have been made to investigate the changes of lipid profiles after a high-carbohydrate and low-fat diet in different subjects with different genotypes of this polymorphism. This study was to evaluate the effects of ABCA1 R219K polymorphism on serum lipid and apolipoprotein (apo) ratios induced by a high-carbohydrate/low-fat (high-CHO) diet. After a washout diet of 54.1% carbohydrate for 7 days, 56 healthy young subjects (22.89 ± 1.80 years old) were given a high-CHO diet of 70.1% carbohydrate for 6 days. Height, weight, waist circumference, hip circumference, glucose (Glu), triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), apoA-1 and apoB-100 were measured on the 1st, 8th and 14th days of this study. Body mass index (BMI), waist-to-hip ratios (WHR), log(TG/HDL-C), TC/HDL-C, LDL-C/HDL-C and apoA-1/apoB-100 were calculated. ABCA1 R219K was analyzed by a PCR-RFLP method. RESULTS: The results indicate that the male subjects of all the genotypes had higher WHR than their female counterparts on the 1st, 8th and 14th days of this study. The male K carriers had higher log(TG/HDL-C) and TC/HDL-C than the female carriers on the 1st and 14th days, and higher LDL-C/HDL-C on the 14th day. When compared with that on the 8th day, TC/HDL-C was decreased regardless of the genotypes and genders on the 14th day. Log(TG/HDL-C) was increased in the males with the RR genotype and the female K carriers. Lowered BMI, Glu and LDL-C/HDL-C were found in the male K carriers, but only lowered BMI in the female K carriers and only lowered LDL-C/HDL-C in the females with the RR genotype. CONCLUSIONS: These results suggest that ABCA1 R219K polymorphism is associated differently in males and females with elevated log(TG/HDL-C) and decreased LDL-C/HDL-C induced by the high-CHO diet.

Clinicopathological characteristics and imaging features of pulmonary adenocarcinoma with micropapillary pattern / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To explore the clinicopathological characteristics and imaging features of lung adenocarcinoma with a micropapillary pattern (MPP).</p><p><b>METHODS</b>Eighty cases of pulmonary adenocarcinoma with a micropapillary pattern treated in our hospital from July 2011 to December 2012 were selected to retrospectively analyze their clinicopathological characteristics and imaging features.</p><p><b>RESULTS</b>Among the 80 cases of lung adenocarcinoma with MPP, there were 38 cases of stage I (47.5%), 12 cases of stage II (15.0%), 25 cases of stage III (31.3%) and 5 cases of stage IV (6.2%). There were 14 cases of moderately differentiated (17.5%) and moderately/poorly differentiated (82.5%) tumors. Sixty-three cases had pleural involvement, vascular invasion, involving the bronchial wall, invasion of large vessels, nerve invasion, and lymph node metastasis (at least one of them) (78.8%). Immunohistochemical staining revealed that both positive rates of TTF-1 and CK7 were 100%, and that of pulmonary surfactant apolipoprotein-A (SPA) was 84.0%. Imaging examination revealed hilar or mediastinal lymph node enlargement in 15 cases (18.8%). but the pathology confirmed hilar or mediastinal lymph node metastasis in 36 cases (45.0%). Lung CT imaging showed that the majority of the cases were peripheral type, and only a few of central type, and most cases were solid lesions, with lobulation, spiculation, pleural indentation, and vascular convergence sign, while there were few ground-glass opacity sign and vacuole sign.</p><p><b>CONCLUSIONS</b>Lung adenocarcinoma with MPP component often presents with early invasions of pleura, blood vessels, lymphatic vessels, and lymph nodes. Imaging manifestation of this cancer mainly shows as peripheral and solid lesions, often with lobulation, spiculation, pleural indentation, vascular convergence sign, but GGO and vacuole signs are unusual. Overexpression of TTF-1, CK7 and SPA, and elevated CEA level are associated with clinical staging of the disease.</p>

Poliformismo das apoE a apoA5: efeitos no perfil lipídico de pacientes ambulatoriais soropositivos / ApoE and apoA5 polymorphism: effects on the lipid profile of ambulatory seropositive patients

Introdução: Pacientes soropositivos tratados com antirretrovirais(ARV) apresentam alterações do perfil lipídico. Polimorfismos dasapolipoproteínas A5 (-1131T/C) e E estão associados à dislipidemia,ocasionando aumento dos triglicerídios e resistência aos hipolipemiantes.Objetivo: Avaliar os efeitos da infecção pelo vírus da imunodeficiência humana (VIH) e dos polimorfismos das apos A5 e E sobre o perfil lipídico em pacientes ambulatoriais infectados, pré e pós-uso de ARV. Método: Estudo de coorte, observacional, prospectivo, analítico, com grupo controle, realizado entre agosto de 2008 e dezembro de 2011. Incluídos, do diagnóstico de VIH aos dias atuais, 89 pacientes de ambos os sexos, faixa etária entre 12 anos e 68 anos,sob uso ou não de terapia antirretroviral altamente ativa (HAART),atendidos no ambulatório de Cardiologia Preventiva-VIH do Hospital Universitário Antônio Pedro (Huap), UFF. Resultados: Dentre os parâmetros bioquímicos, a elevação dos triglicerídios relacionada à infecção pelo VIH e à HAART foi a mais evidente durante o estudo. Considerando o polimorfismo da apoA5, 22,4% (n = 20) dos pacientes analisados apresentaram o alelo C no seu genótipo, em comparação com 4,5% (n = 9) do grupo controle de soronegativos. Não houve diferenças significativas entre os perfis metabólicos de VIH+ que continham ou não o alelo C. Conclusão: Não houve diferença entre VIH+ carreadores do alelo C em relação àqueles não carreadoresquanto à necessidade de substituir a HAART devido à dislipidemia resistente aos hipolipemiantes. Os papéis inflamatório e aterogênico da infecção pelo VIH sobrepõem-se ou têm efeito maior do que o polimorfismo -1131T/C da apoA5 no desenvolvimento de distúrbios metabólicos.

Introduction: HIV - positive patients treated with antiretroviral(ARV) drugs have changes on lipid profile. Apolipoproteins A5(-1131TC) and E polymorphisms are associated with dyslipidemia,causing increased triglycerides and resistance to lipid-lowering drugs.Objective: Evaluate the effects of human immunodeficiency virus(HIV) infection and apoA5 and apoE polymorphisms on the lipid profileof infected outpatients, pre and post-use of ARV. Method: Cohort,observational, prospective, analytical study, with control group,between August 2008 and December 2011. Since the HIV diagnosisto the present day, 89 patients of both sexes were included, agedbetween 12 years and 68 years, under use or nonuse of highly activeantiretroviral therapy (HAART), all of them attended at PreventiveCardiology Clinic-HIV Antônio Pedro University Hospital (Huap),UFF. Results: Among the biochemical parameters, the elevation oftriglycerides related to HIV infection and to HAART was the most evidentduring the study. Considering the apoA5 polymorphism, 22.4% (n= 20) of the patients examined presented the C allele in their genotype,compared to 4.5% (n = 9) of the seronegative control group. Therewere no significant differences between the HIV metabolic profilesthat contained the C allele or not. Conclusion: There was no differencebetween HIV+ C allele carriers in relation to non-carriers on the needto replace the HAART due to lipid-lowering resistance dyslipidemia.The inflammatory and atherogenic roles of HIV infection overlap orhave greater effect than the ApoA5 -1131T/C polymorphism in thedevelopment of metabolic disorders.

Association between lipoprotein [A] and small apo [A] phenotypes and coronary heart disease in Sudanese diabetic patients

Recent studies indicate an independent association of apolipoprotein [a] small phenotypes with the diabetes and the onset of coronary heart disease. Apolipoprotein [a] small phenotypes when used together with Lipoprotein [a] levels make powerful markers in assessing the actual risk of developing coronary heart disease in diabetic patients. Evaluation of clinical and diagnostic significant of Lipoprotein [a] levels and apolipoprotein [a] small phenotypes and its relation to coronary heart disease in Sudanese diabetic patients. Diabetic patients attending hospitals and medical centers from May 2011-December 2012, in Khartoum, Sudan. This was a case control, hospital based study done on 138 Sudanese diabetic patients attending hospitals and medical centers in Khartoum. Patients were divided into 2 groups. One group had diabetic cases with coronary heart disease and the other were diabetic patients without coronary heart disease. Controls were age and gender matched. Blood samples were collected from both groups [patients and controls] and were run for apolipoproteins, lipoproteins and apolipoprotein [a] small phenotype, low-density lipoprotein, high-density lipoprotein and trigeminal ganglia. The levels of Lipoprotein [a] of patients were significantly higher than controls [p<0.05]. Apolipoprotein[a] small phenotype distribution showed a significant difference when compared between patients of both groups [diabetics with and without coronary heart disease] and controls [p<0.05]. Both low-density lipoprotein and high-density lipoprotein cholesterol showed significant difference in both patient groups and controls [p<0.05]. Total cholesterol and triglyceride levels showed no significant difference between patients and controls. Apolipoprotein[a] small phenotypes showed significant distribution in diabetic patients when compared with coronary heart disease patients [more than one low molecular weight isoform] and [low molecular weight isoforms more than 600 kd]. There were significant association between apolipoprotein [a] low molecular weight isoforms and coronary heart disease in diabetes specially diabetes with history of coronary heart disease. Apolipoprotein [a] low molecular weight isoforms and Lipoprotein [a] levels are useful markers in assessing the risk of developing coronary heart disease in diabetic patients

Bone mineral changes and cardiovascular effects among female athletes with chronic menstrual dysfunction

Oligo/amenorrhea, as a part of the Female Athlete Triad has adverse effects on the athlete's bone mineral density [BMD] and cardiovascular system. Hypoestrogenism, due to suppression of hypothalamus-pituitary axis [HPA] as a result of energy imbalance, is the possible cause of the Triad. This study was designed based on following up and reassessment of elite female athletes who were diagnosed as menstrual dysfunction about two years ago. This study was conducted in three phase sections: 1] Reassess the pattern of menstrual cycle among athletes who reported menstrual dysfunction about two years ago; 2] Bone mineral density was measured twice in the same machine and same center with a two-year interval; 3] The laboratory data including blood glucose, lipid profile and inflammatory markers was assessed in phase 3. BMD of athletes did not change significantly after 25.5 months of oligomenorrhea P [spine] = 0.2, P [femur]=0.9. Mean of all cardiovascular factors was in the normal range except for high density lipoprotein [HDL] which was 49.28 [SD=9.18], however, most of the athletes had abnormalities in their lipid profile. Inverse relationship between the increase in the BMD of spine and total cholesterol [r =-0.49, P=0.04], Apolipoprotein A [r = -0.51 P=0.04], and very low density lipoprotein [VLDL] [r =-0.66, P=0.009]. Also correlation between BMD of spine and HbA1C [r =-0.70, P=0.003] were significant. Findings of this study show that negative changes in BMD and cardiovascular biomarkers of female athletes with functional hypothalamic menstrual dysfunction could occur if proper therapeutic intervention [including increase in calorie intake, decrease in exercise load or hormonal replacement] will not consider

[Association of apolipoprotein A-IV Gene G360T polymorphism with metabolic syndrome: Tehran lipid and glucose study]

Metabolic syndrome [MetS] is one of the most important risk factors for cardiovascular diseases. The aim of this study was to determine the association between the G360T polymorphism of apolipoprotein A-IV gene and MetS. For this cross sectional study, 782 individuals, aged >19 years, were selected randomly from among TLGS participants; these included 325 men [61 with MetS and 264 controls], and 457 women [131 with MetS and 326 controls]. Anthropometric and biochemical parameters were measured. The Apo A-IV gene polymorphism was studied using the PCR-RFLP method by Fnh4HI restriction enzyme. Frequencies of the G and T alleles in men with MetS and those without were 85.2, 14.8, and 83.3, 16.7%, respectively, and in women with and without MetS these were 82.4, 17.6, and 85.9, 14.1%, respectively, values not significant. The GG and TT genotypes had the highest and lowest frequency, respectively [84.4% and 0.3%]. Analyses of data showed that presence of T allele was significantly associated with lower levels of HDL-C [p<0.05] in women with MetS, and with lower apolipoprotein CIII levels [p <0.05] in normal women, and higher diastolic blood pressure [p <0.05] in men without MetS. The findings of the current study showed significant effects on HDL-C levels in women with MetS. Considering the association observed between the G360T polymorphism of Apo A-IV gene and lipid factors in women with MetS and the high prevalence of this syndrome in Iranian women, further studies recommended to assess the association of Apo AIV gene variation with lipids factors for prevention and treatment of the syndrome

APOA5 Polymorphism Is Associated with Metabolic Syndrome in Korean Postmenopausal Women

BACKGROUND: Menopause is an independent risk factor in metabolic syndrome which induced an alteration of the lipid metabolism by hormonal changes. Apolipoprotein A5 gene (APOA5) was related to the regulation of triglyceride and high density lipoprotein cholesterol (HDL-C) level with biosynthesis and decomposition. This study was conducted to investigate the relationship between APOA5 polymorphism and metabolic syndrome in Korean postmenopausal women. METHODS: This study included 307 postmenopausal women with anthropometric and biochemical measurement in 2010-2011. The polymorphism of APOA5 was analyzed by polymerase chain reaction-restriction fragment length polymorphism method with MseI restriction enzyme. RESULTS: The metabolic syndrome prevalence with TT genotype was significantly lower than the frequency in those with TC/CC (27.09%, 38.46%, and 45.71% for TT, TC, and CC, respectively; P < 0.05). Multiple regression analysis of metabolic syndrome risk factors indicated that postmenopausal women with CC genotype had a higher risk with 3 times than that in TT genotype (P < 0.05). APOA5 C carriers showed an increased risk of triglyceride level (odd ratio, 2.93 and 1.85 for CC and TC+CC, respectively; P < 0.05). Interestingly, HDL-C was related to triglyceride directly in comparison to APOA5. CONCLUSION: The results of this study indicate that APOA5 has an influence on serum triglyceride and HDL-C, which contribute to metabolic syndrome in Korean postmenopausal women.

Relationship between depression and apolipoproteins A and B: a case-control study

OBJECTIVE: To investigate the relation between major depressive disorder and metabolic risk factors of coronary heart disease. INTRODUCTION: Little evidence is available indicating a relationship between major depressive disorder and metabolic risk factors of coronary heart disease such as lipoprotein and apolipoprotein. METHODS: This case-control study included 153 patients with major depressive disorder who fulfilled the criteria of the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV), and 147 healthy individuals. All participants completed a demographic questionnaire and Hamilton rating scale for depression. Anthropometric characteristics were recorded. Blood samples were taken and total cholesterol, high-and low-density lipoproteins and apolipoproteins A and B were measured. To analyze the data, t-test, χ2 test, Pearson correlation test and linear regression were applied. RESULTS: Depression was a negative predictor of apolipoprotein A (β = -0.328, p<0.01) and positive predictor of apolipoprotein B (β = 0.290, p<0.05). Apolipoprotein A was inversely predicted by total cholesterol (β = -0.269, p<0.05) and positively predicted by high-density lipoprotein (β = 0.401, p<0.01). Also, low-density lipoprotein was a predictor of apolipoprotein B (β = 0.340, p<0.01). The severity of depression was correlated with the increment in serum apolipoprotein B levels and the decrement in serum apolipoprotein A level. CONCLUSION: In view of the relationship between apolipoproteins A and B and depression, it would seem that screening of these metabolic risk factors besides psychological interventions is necessary in depressed patients.

Association of apolipoprotein A5 gene polymorphism with coronary heart disease in Uygur population of Xinjiang / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the association of the -12238T/C polymorphism of apolipoprotein A5 (APOA5) gene with coronary heart disease (CHD) and the influence of serum lipid levels in Chinese Uygur population of Xinjiang.</p><p><b>METHODS</b>The -12238T/C polymorphism of APOA5 gene in 344 patients with CHD and 408 controls was analyzed by polymerase chain reaction-restriction fragment length polymorphism; the serum lipid levels were detected as well.</p><p><b>RESULTS</b>The frequencies of CC, TC and TT genotype were 6.69%, 43.31% and 50.00% in the CHD group, while they were 14.95%, 45.10% and 39.95% in the control group. There was significant difference in the distribution of genotypes between the two groups (P < 0.01). Logistic regression analyses adjusted for age, gender, smoking, serum total cholesterol, presence of hypertension and diabetes revealed that individuals carrying CC genotype had an increased risk of CHD compared with TT genotype (OR = 0.328, 95%CI: 0.154-0.700). There was also significant difference in serum triglyceride level in genotypes between these two groups (P < 0.01). Patients in CHD group who carried CC and TC genotypes had lower serum triglyceride level than the TT genotype carriers.</p><p><b>CONCLUSION</b>The -12238T/C polymorphism of APOA5 gene has influence on the serum triglyceride level in Uygur population of Xinjianxg. This polymorphism might be associated with development of CHD, and the CC genotype might be a protective factor in the development of CHD.</p>

Impacto de la apolipoproteína A5 en el riesgo cardiovascular: Modulaciones genéticas y ambientales / Impact of apolipoprotein A5 on cardiovascular risk: Genetic and environmental modulation

Triglyceride concentrations are an independent risk factor for coronary heart disease. Apolipoprotein A5 gene (APOA5) has an important role determining triglyceride metabolism and it is a potential cardiovascular risk. However the mechanisms for these actions are not well-known. Despite the different allelic frequency of its major polymorphisms in different populations, multiple studies have shown consistent associations between these variants and fasting triglycerides. Variations in the APOA5 gene have also been associated with postprandial triglycerides, as well as with different sizes of lipoproteins and other markers. Moreover, some of the APOA5 gene variants have been associated with ischemic heart disease, stroke, and carotid intima media thickness, although the references on this issue are scanty and contradictory. This may be due to the presence of gene-environment interactions that have been poorly studied until now. Among the few studies that have examined the infuence of environmental factors on possible genetic variations, the most important are those that contemplate possible gene-diet interactions. However, the evidence is still scarce and more research is required in the feld of nutrigenomics. To understand the impact of this gene on cardiovascular disease, we review the genetic functionality and variability of APOA5, its associations with intermediate and fnal phenotypes and gene-environment interactions detected.

Screening disease-associated proteins from sera of patients with rheumatoid arthritis: a comparative proteomic study / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation at the synovial membrane. Although great progress has been made recently in exploring the etiology and pathogenesis of RA, its molecular pathological mechanism remains to be further defined and it is still a great challenge in determining the diagnosis and in choosing the appropriate therapy in early patients. This study was performed to screen candidate RA-associated serum proteins by comparative proteomics to provide research clues to early diagnosis and treatment of RA.</p><p><b>METHODS</b>Sera isolated from 6 RA patients and 6 healthy volunteers were pooled respectively and high-abundance proteins were depleted by Plasma 7 Multiple Affinity Removal System. The protein expression profiles between the two groups were then compared by two-dimensional gel electrophoresis (2-DE) and the proteins over/under-expressed by more than 3-fold were identified by mass spectrometry analysis. To validate the differential expression levels of the identified proteins between the two groups, ELISA was performed in two of the identified proteins in individual sera from 32 RA patients and 32 volunteers.</p><p><b>RESULTS</b>Eight proteins which over/under-expressed in sera of RA patients were identified. Among them, chain A of transthyretin (TTR) was under-expressed, while serum amyloid A protein, apolipoprotein A (ApoA)-IV, ApoA-IV precursor, haptoglobin 2, ceruloplasmin (Cp), immunoglobulin superfamily 22 and HT016 were over-expressed. ELISA test confirmed that Cp expressed remarkably higher while TTR obviously lower in RA group compared with volunteer group.</p><p><b>CONCLUSION</b>There were 8 identified proteins differentially expressed between RA group and volunteer group, which might be candidate RA-associated proteins and might be promising diagnostic indicators or therapeutic targets for RA.</p>

Polimorfismos genéticos de APOA5 se asocian a hipertrigliceridemia e hiperglicemia en individuos chilenos con enfermedad coronaria y controles / Genetic polymorphisms of APOA5 are associated with hypertriglyceridemia and hyperglycemia in Chilean subjects with coronary artery disease and controls

Introducción: Diversas variantes genéticas han sido relacionadas al desarrollo de enfermedad coronaria y/o sus factores de riesgo; entre ellas, los polimorfismos S19W y -1131T>C del gen que codifica para la apolipoproteína A5 (APOA5). Así, el objetivo del presente estudio fue investigar la posible asociación entre las variantes S19W y -1131T>C del gen APOA5 y enfermedad coronaria en individuos chilenos. Métodos: Se evaluaron 425 sujetos adultos, no relacionados; 209 pacientes con enfermedad coronaria (EC) comprobada por angiografía (estenosis→ 70 por ciento), con edades entre 33 y 74 años, y 216 individuos controles (30 a 68 años). La genotipificación de los polimorfismos S19Wy -1131T>C del gen APOA5 fue realizada mediante la técnica de PCR-RFLP Resultados: La distribución de los genotipos para el polimorfismo S19W del gen APOA5 en el grupo casos (SS: 80 por ciento, SW: 19 por ciento y WW: 1 por ciento) y en el grupo control (SS: 82 por ciento, SW: 17 por ciento y WW: 1 por ciento) fue semejante (p=NS). La distribución genotípica para el polimorfismo -1131T>C en pacientes con EC (TT: 56 por ciento, TC: 37 por ciento, y CC: 7 por ciento) y controles (TT: 63 por ciento, TC: 30 por ciento y CC: 7 por ciento) fue similar (p=NS). Las ORs relacionadas a los alelos mutados 19W (1.12; I.C.95 por ciento, 0.72- 1.74, p=NS)y-1131C (1.19; I.C.95 por ciento,, 0.87- 1.63, p=NS), confirman la ausencia de asociación. Por otro lado, las concentraciones de triglicéridos y glucosa en ayunas fueron significativamente más elevadas en los sujetos portadores de los alelos 19Wy -1131C, tanto en casos como en controles (p<0.05). Conclusión: La asociación observada entre las variantes genéticas de APOA5 y las altas concentraciones séricas de triglicéridos y glucosa, en ambos grupos, sugiere que estos polimorfismos podrían contribuir al desarrollo de la dislipidemia diabética; un reconocido factor de riesgo para enfermedad arterial coronaria.

Background: Several genetic variants have been linked to the development of coronary heart disease and/or their risk factors, including the S19Wand-1131T> C polymorphisms of the gene that encodes apolipoprotein A5 (APOA5). Thus, the objective of this study was to investigate the possible association between S19W and -1131T>C genetic variants ofAPOA5 and coronary disease in Chilean individuals. Methods: We evaluated 425 not related subjects; 209 patients with coronary artery disease (CAD) confirmed by angiography (stenosis→ 70 percent,), aged between 33 and 74 years, and 216 control individuals (30 to 68 years). The genotyping of S19W and -1131T>C polymorphisms of APOA5 gene was evaluated by PCR-RFLP. Results: The genotype distribution of S19W polymorphism of APOA5 gene in CAD patients (SS: 80 percent,, SW: 19 percent, WW: 1 percent>) and controls (SS: 82 percent,, SW: 17 percent, WW: 1 percent>) was similar (p = NS). In the same way the genotype distribution of-1131T>C genetic variant in CAD subjects (TT: 56 percent,, TC: 37 percent,, and CC: 7 percent>) and controls (TT: 63 percent,, TC: 30 percent, and CC: 7 percent) was equivalent (p = NS). The Odds ratios related to the mutant alleles 19W (1.12, 95 percent, Cl, 0.72 - 1.74, p = NS) and -1131C (1.19, 95 percent, Cl, 0.87 -1.63, p = NS) confirms the absence of association. On the other hand, the triglycerides and fasting glucose concentrations were significantly higher in subjects carrying the alleles 19W and -1131C, in both groups, CAD patients and controls (p <0.05). Conclusion: The observed association between genetic variants of APOA5 and higher serum levels of triglycerides and glucose, in both groups, suggesting that these polymorphisms could be contribute to the development of diabetic dyslipidemia, a known risk factor for coronary artery disease.