摘要
Malnutrition is still considered endemic in many developing countries. Malnutrition-enteric infections may cause lasting deleterious effects on lipid metabolism, especially in children living in poor settings. The regional basic diet (RBD), produced to mimic the Brazilian northeastern dietary characteristics (rich in carbohydrate and low in protein) has been used in experimental malnutrition models, but few studies have explored the effect of chronic RBD on liver function, a central organ involved in cholesterol metabolism. This study aimed to investigate whether RBD leads to liver inflammatory changes and altered reverse cholesterol metabolism in C57BL6/J mice compared to the control group, receiving a standard chow diet. To evaluate liver inflammation, ionized calcium-binding adapter protein-1 (IBA-1) positive cell counting, interleukin (IL)-1β immunohistochemistry, and tumor necrosis factor (TNF)-α and IL-10 transcription levels were analyzed. In addition, we assessed reverse cholesterol transport by measuring liver apolipoprotein (Apo)E, ApoA-I, and lecithin-cholesterol acyltransferase (LCAT) by RT-PCR. Furthermore, serum alanine aminotransferase (ALT) was measured to assess liver function. RBD markedly impaired body weight gain compared with the control group (P<0.05). Higher hepatic TNF-α (P<0.0001) and IL-10 (P=0.001) mRNA levels were found in RBD-challenged mice, although without detectable non-alcoholic fatty liver disease. Marked IBA-1 immunolabeling and increased number of positive-IBA-1 cells were found in the undernourished group. No statistical difference in serum ALT was found. There was also a significant increase in ApoA mRNA expression in the undernourished group, but not ApoE and LCAT, compared with the control. Altogether our findings suggested that chronic RBD-induced malnutrition leads to liver inflammation with increased ApoA-I activity.
Subject(s)
Humans , Animals , Male , Rabbits , Rats , Apolipoprotein A-I/blood , Malnutrition/metabolism , Diet/adverse effects , Inflammation/metabolism , Brazil , Chronic Disease , Apolipoprotein A-I/metabolism , Malnutrition/pathology , Malnutrition/blood , Inflammation/pathology , Inflammation/blood , Liver/metabolism , Mice, Inbred C57BL摘要
Abstract Objective: To investigate ApoB/ApoA1 ratio and its association with cardiovascular risk factors in children. Methods: Cross-sectional study with 258 children aged 8 and 9 years old, enrolled in all urban schools in the city of Viçosa-MG. Anthropometric and body composition assessment, as well as biochemical profile of the children was performed. Socioeconomic variables and sedentary lifestyle were evaluated through a semi-structured questionnaire. Results: Many children had excess weight (35.2%), abdominal adiposity (10.5%), and body fat (15.6%), as well as increased ApoB/ApoA1 ratio (14.7%), total cholesterol (51.8%), and triglycerides (19.8%). Children with excess weight and total and central fat had a higher prevalence of having a higher ApoB/ApoA1 ratio, as well as those with atherogenic lipid profile (increased LDL-c and triglycerides and low HDL-c). A direct association was found between the number of cardiovascular risk factors and the ApoB/ApoA1 ratio (p = 0.001), regardless of age and income. Conclusion: The increased ApoB/ApoA1 ratio was associated with excess weight, body adiposity (total and central), and altered lipid profile in children. Children with a higher number of cardiovascular risk factors had higher ApoB/ApoA1 ratio, in both genders.
Resumo Objetivo: Investigar a razão ApoB/ApoA1 e sua relação com fatores de risco cardiovascular em crianças. Métodos: Estudo transversal com 258 crianças de 8 e 9 anos, matriculadas em todas as escolas urbanas de Viçosa-MG. Foi feita avaliação antropométrica, da composição corporal e bioquímica das crianças. As variáveis socioeconômicas e o sedentarismo foram avaliados por questionário semiestruturado. Resultados: Muitas crianças apresentaram excesso de peso (35,2%), de adiposidade abdominal (10,5%) e de gordura corporal (15,6%), bem como a razão ApoB/ApoA1 (14,7%), colesterol-total (51,8%) e triglicerídeos (19,8%) aumentados. Crianças com excesso de peso e de gordura total e central apresentaram maiores prevalências de maior razão ApoB/ApoA1, bem como as com perfil lipídico aterogênico (LDL-c e triglicerídeos aumentados e baixo HDL-c). Foi encontrada associação direta entre o número de fatores de risco cardiovascular e a razão ApoB/ApoA1 (p = 0,001), independente da idade e renda. Conclusão: A razão ApoB/ApoA1 aumentada esteve associada ao excesso de peso, de adiposidade corporal (total e central) e ao perfil lipídico alterado nas crianças. As crianças com maior número de fatores de risco cardiovascular apresentaram maior razão ApoB/ApoA1, em ambos os sexos.
Subject(s)
Humans , Male , Female , Child , Arteriosclerosis/blood , Apolipoprotein A-I/blood , Apolipoprotein B-100/blood , Lipids/blood , Obesity/blood , Arteriosclerosis/etiology , Socioeconomic Factors , Urban Population , Body Composition , Biomarkers/blood , Cross-Sectional Studies , Surveys and Questionnaires , Risk Factors , Adiposity , Sedentary Behavior , Obesity/complications摘要
Abstract Background: Lipid accumulation product (LAP), a simple and low-cost tool, is a novel biomarker of central lipid accumulation and represents a potential surrogate marker for atherogenic lipoprotein profile. However, its association with lipoprotein subfractions has not been described in the literature. Objective: To determine whether LAP index could be used as a marker of low- and high-density lipoprotein (LDL and HDL) size in Brazilian individuals. Methods: This cross-sectional study included patients (n = 351) of both sexes and age between 30-74 years. Clinical and sociodemographic data and family history of diseases were evaluated. Lipoprotein size, and levels of total cholesterol (TC), lipoproteins, apolipoprotein AI and B (APO AI/APO B), glucose, insulin, insulin resistance index (HOMA-IR) and non-esterified fatty acids (NEFA) were assessed in blood samples. LAP was calculated by the formulas [(waist circumference[cm]-58) × (triglycerides[mmol/L]) for women and (waist circumference [cm]-65) × (triglycerides [mmol/L]) for men]. The association between LAP and metabolic parameters were tested by linear trend (general linear model, GLM test) before and after multiple adjustments for potential confounders (sex, age, smoking, statin, fibrate, and hypoglycemic drugs) at significant level p < 0.05. Results: LAP was positively associated with TC, APO B, NEFA, glucose, insulin and HOMA-IR values, and negatively associated with HDL-C. Higher central lipid accumulation was corelated with higher percentage of intermediate HDL and of small LDL and HDL and less amount of large HDL. LDL size was also reduced in greater LAP index values. The negative impact of LAP was maintained after adjustment for multiple variables. Conclusion: LAP was robustly associated with atherogenic profile of lipoprotein subfractions, independently of multiple confounders.
Resumo Fundamento: O produto de acumulação lipídica (LAP), um instrumento simples e de baixo custo, é um novo biomarcador de acúmulo de gordura central e representa um marcador substituto potencial para o perfil aterogênico de lipoproteínas. No entanto, sua associação com subfrações de lipoproteínas ainda não foi descrita na literatura. Objetivo: Determinar se o LAP pode ser usado como um marcador de tamanho da lipoproteína de baixa densidade (LDL) e de alta densidade (HDL) em indivíduos brasileiros. Métodos: Este estudo transversal incluiu 351 pacientes de ambos os sexos e idade entre 30 e 74 anos. Dados clínicos e sociodemográficos e história familiar de doenças foram avaliados. O tamanho das lipoproteínas, e níveis de colesterol total (CT), lipoproteínas, apolipoproteína AI e B (APO AI/APO B), glicose, ácidos graxos não esterificados (AGNEs) e insulina, e índice de resistência insulínica (HOMA-IR) foram avaliados em amostras de sangue. O LAP foi calculado utilizando-se as fórmulas (circunferência da cintura (cm]-58) × (triglicerídeos[mmol/L]) para mulheres e (circunferência da cintura[cm]-65) × (triglicerídeos [mmol/L]) para homens. Associações entre LAP e parâmetros metabólicos foram testadas por tendência linear (modelo linear generalizado, GLM) antes e após ajustes por fatores de confusão (sexo, idade, tabagismo, uso de estatinas, fibratos e hipoglicemiantes) ao nível de significância de p < 0,05). Resultados: LAP apresentou uma associação positiva com CT, APO B, AGNEs, glicose, insulina, HOMA-IR, e uma associação negativa com HDL-C. Maior acúmulo de gordura central correlacionou-se com maior porcentagem de HDL intermediária e de partículas pequenas de LDL e HDL, e menor porcentagem de HDL grande. O tamanho da LDL também era reduzido em valores de LAP mais elevados. O impacto negativo do LAP foi mantido após ajuste para múltiplas variáveis. Conclusão: o LAP esteve fortemente associado com o perfil aterogênico de subfrações de lipoproteínas, independetemente dos fatores de confusão.
Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged , Risk Assessment/methods , Atherosclerosis/blood , Lipid Accumulation Product/physiology , Cholesterol, HDL/blood , Cholesterol, LDL/blood , Apolipoproteins B/blood , Reference Values , Blood Glucose/analysis , Brazil , Insulin Resistance , Biomarkers/blood , Cardiovascular Diseases/etiology , Cardiovascular Diseases/blood , Sex Factors , Anthropometry , Epidemiologic Methods , Apolipoprotein A-I/blood , Atherosclerosis/ethnology , Fatty Acids, Nonesterified/blood , Lipid Accumulation Product/ethnology , Insulin/blood摘要
Objective: Coronary heart disease [CAD] is the most prevalent chronic disease and the main leading cause of death in the world, with more than half a million newly diagnosed CAD patients each year. The development of atherosclerosis involves the interaction of multiple metabolic and cellular processes. Central to this are disorders of lipoprotein metabolism. Apolipoprotein A-I is the major protein component of high-density lipoprotein [HDL] in plasma. Chylomicrons secreted from the intestinal enterocyte also contain Apo A-I, but it is quickly transferred to HDL in the blood stream. The aim of this study is to determine if Apo-A1 can be used as indicator to severity and extent of CAD
Methods: This study was conducted in cardiac catheterisation unit at Al Hussein Medical city from November 2014 to September 2015. It included 76 patients [49 males and 27 females] who presented with signs and symptoms of CAD and have undergone angiography. Control group consisted of 20 healthy subjects [14 males and 6 females] matched for age and BMI. Serum levels of Apo-A1 were measured in both groups. After coronary angiography was done for all patients, the extent and severity of CAD was correlated with serum levels of Apo-A1. The extent of CAD was determined by angiography, according to number of coronary arteries involved and degree of narrowing in coronary artery diameter
Results: The angiographic finding in patient group was normal in 22 patients [28.9%], single vessel involvement in 15 patients [19.7%], two vessels disease in 15 patients [19.7%] and three vessels disease in 18 patients [23.8%]. The left main stem disease [LMD] was found in 6 patients [7.9%]. There was no significant difference in the serum level of Apo-A1 between patient with CAD and control group [P = 0.147]. There was no significant correlation between serum level of Apo-A1 and the extent CAD [r = 0.004, P = 0.975]
Conclusion: There was no significant difference in serum level of Apo-A1 between the patients group and the control group. Also, there was no significant correlation between serum level of Apo-A1 and the extent of CAD
Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged , Apolipoprotein A-I/blood , Biomarkers摘要
Bipolar disorder (BD) is a common psychiatric mood disorder affecting more than 1-2% of the general population of different European countries. Unfortunately, there is no objective laboratory-based test to aid BD diagnosis or monitor its progression, and little is known about the molecular basis of BD. Here, we performed a comparative proteomic study to identify differentially expressed plasma proteins in various BD mood states (depressed BD, manic BD, and euthymic BD) relative to healthy controls. A total of 10 euthymic BD, 20 depressed BD, 15 manic BD, and 20 demographically matched healthy control subjects were recruited. Seven high-abundance proteins were immunodepleted in plasma samples from the 4 experimental groups, which were then subjected to proteome-wide expression profiling by two-dimensional electrophoresis and matrix-assisted laser desorption/ionization-time-of-flight/time-of-flight tandem mass spectrometry. Proteomic results were validated by immunoblotting and bioinformatically analyzed using MetaCore. From a total of 32 proteins identified with 1.5-fold changes in expression compared with healthy controls, 16 proteins were perturbed in BD independent of mood state, while 16 proteins were specifically associated with particular BD mood states. Two mood-independent differential proteins, apolipoprotein (Apo) A1 and Apo L1, suggest that BD pathophysiology may be associated with early perturbations in lipid metabolism. Moreover, down-regulation of one mood-dependent protein, carbonic anhydrase 1 (CA-1), suggests it may be involved in the pathophysiology of depressive episodes in BD. Thus, BD pathophysiology may be associated with early perturbations in lipid metabolism that are independent of mood state, while CA-1 may be involved in the pathophysiology of depressive episodes.
Subject(s)
Adolescent , Adult , Female , Humans , Male , Young Adult , Apolipoprotein A-I/blood , Apolipoproteins/blood , Bipolar Disorder/blood , Carbonic Anhydrase I/blood , Lipid Metabolism Disorders/metabolism , Lipoproteins, HDL/blood , Proteomics , Bipolar Disorder/complications , Bipolar Disorder/diagnosis , Databases, Protein , Diagnosis, Differential , Disease Progression , Down-Regulation , Depressive Disorder, Major/diagnosis , Electrophoresis, Gel, Two-Dimensional , Immunoblotting , Immunoprecipitation , Lipid Metabolism Disorders/complications , Mass Spectrometry/methods摘要
Objective: This study was carried out to determine whether or not Plasmodium falciparum malaria infection significantly affected apolipoprotein-A1 and cholesterol levels and if apolipoprotein-A1 correlated with the malaria severity in children younger than 5 years old
Subjects and Methods: Two hundred and fifty-five children, 170 of whom had microscopically confirmed P. falciparum infection, i.e. 85 cases of uncomplicated malaria [UM] and 85 of complicated malaria [CM], and 85 healthy controls were enrolled in this study. Serum levels of apolipoprotein-A1, total cholesterol, high-density lipoprotein [HDL], low-density lipoprotein [LDL] and triglycerides were determined. These levels were compared among the malaria and control groups, using ANOVA and post hoc analyses at p = 0.05
Results: There were significant differences in the mean serum levels of apolipoprotein-A1 [UM: 104.5 +/- 38.1 mg/dl, CM: 90.9 +/- 33.3 mg/dl and controls: 129.7 +/- 48.3 mg/dl; p < 0.001], total cholesterol [UM: 138.8 +/- 62.9 mg/dl, CM: 121.2 +/- 55.2 mg/dl and controls: 155.1 +/- 69.8 mg/dl; p = 0.002] and LDL [UM: 98.2 +/- 55.5 mg/dl, CM: 84.3 +/- 47.4 mg/dl and controls: 122.7 +/- 69.4 mg/dl; p < 0.001]. Post hoc analyses revealed that children with UM and CM had significantly lower levels of apolipoprotein-A1, cholesterol, HDL and LDL than controls but that there was no difference between the 2 malaria groups. Reductions in levels of lipids and apolipoprotein-A1 were worse in CM than in UM
Conclusion: Altered levels of serum lipids with CM were associated with a reduction in apolipoprotein-A1. These findings have potential diagnostic utility for the management of malaria
Subject(s)
Humans , Child, Preschool , Male , Female , Plasmodium falciparum , Apolipoprotein A-I/blood , Cholesterol/blood , Lipids/blood , Case-Control Studies , Child摘要
FUNDAMENTO: A prevalência das doenças cardiovasculares (DCV) tem aumentado nos últimos anos. A literatura revela que cerca de 35% dos eventos ateroscleróticos ocorrem na ausência dos fatores de risco clássicos, requerendo uma avaliação individual minuciosa para melhor caracterizar o risco. Os índices lipídicos tetravalente (LTI) e pentavalente (LPI) constituem uma nova e eficiente forma de avaliação do perfil lipídico e do risco para DCV. OBJETIVO: O presente estudo avaliou o LTI e o LPI em estudantes de graduação, estabelecendo estes índices em indivíduos saudáveis e correlacionando-os com o perfil lipídico tradicional. MÉTODOS: Participaram do estudo 110 estudantes, 48 (44%) do sexo masculino e 62 (56%) do sexo feminino, com média de idade de 20,9 ± 1,7 anos. Apolipoproteína-AI, apolipoproteína B, colesterol total, lipoproteína (a), triglicérides, HDL e LDL foram analisados usando-se métodos diagnósticos específicos. LTI e LPI foram calculados por meio das equações LTI = [colesterol total x triglicérides x lipoproteína (a) / HDL] e LPI = [colesterol total x triglicérides x lipoproteína (a) x apolipoproteína B / apolipoproteína A-I], respectivamente. RESULTADOS: Os valores de LTI e de LPI foram significativamente maiores nas mulheres quando comparados aos dos homens. Para os outros parâmetros, houve diferenças significativas entre os gêneros apenas para colesterol total, HDL e apolipoproteína A-I. Houve correlações positivas e significativas entre LDL e LTI e entre LDL e LPI. CONCLUSÃO: Os achados indicam que LTI e LPI estavam associados com LDL, um parâmetro não utilizado para calcular os índices lipídicos e amplamente usado na prática clínica para investigação do risco cardiovascular.
BACKGROUND: The prevalence of cardiovascular disease (CVD) has increased steadily in recent years. Literature data show that about 35% of atherosclerotic events occur in the absence of classic risk factors, requiring a broader assessment of the individual to better characterize the risk. Lipid Tetrad Index (LTI) and Lipid Pentad Index (LPI) constitute a new and efficient evaluation of the lipid profile and CVD risk. OBJECTIVE: This study assessed LTI and LPI in undergraduate students, seeking to establish the parameters of these indices in healthy subjects and correlate them with the conventional lipid profile. METHODS: The study included 110 students, 48 (44%) males and 62 (56%) females, mean age 20.9 ± 1.7. Apolipoprotein-AI, apolipoprotein B, total cholesterol, lipoprotein(a), triglycerides, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) were assessed, using specific diagnostic methods. LTI and LPI indices were calculated using the equations LTI = [total cholesterol x triglycerides x lipoprotein(a) / HDL] and LPI = [total cholesterol x triglycerides x lipoprotein(a) x apolipoprotein B/apolipoprotein-AI], respectively. RESULTS: LTI and LPI values were significantly higher in females compared to males. As for the other parameters, there were significant differences between males and females only regarding total cholesterol, HDL and apolipoprotein-AI. There were significant and positive correlations between LDL and LTI and between LDL and LPI. CONCLUSIONS: Findings indicate that both LTI and LPI were associated with LDL, a parameter not used to calculate lipid indices and widely used in clinical practice for cardiovascular risk assessment.
Subject(s)
Female , Humans , Male , Young Adult , Apolipoprotein A-I/blood , Apolipoproteins B/blood , Cardiovascular Diseases/diagnosis , Cholesterol/blood , Lipoprotein(a)/blood , Students/statistics & numerical data , Triglycerides/blood , Biomarkers/blood , Risk Factors , Statistics, Nonparametric摘要
Objetivo Determinar la relación del ejercicio con los niveles séricos de la apoA-I y las subpoblaciones de HDL2 y HDL3, en personas hipertensas de la Ciudad de Armenia - Quindío. Métodos La intervención fueron dos meses de ejercicio. La presión arterial se tomó con las recomendaciones del Ministerio de Salud de Colombia. Las subpoblaciones de HDL se midieron con el método del precipitado ionico y la apoA-I se midió con la técnica de nefelometría de bindig site. Resultados Los datos se analizaron con estadística descriptiva e inferencial. Se captaron 160 pacientes de los cuales 125 permanecieron hasta el final del proyecto, es decir, hubo un 78,12 % de permanencia; el 28 % hicieron ejercicio. El análisis mostró una reducción altamente significativa de la tensión arterial sistólica y diastólica mayor en las personas que hicieron que en las que no hicieron ejercicio. Las cifras de HDL estaban por debajo de lo normal antes del ejercicio aumentaron significativamente con el ejercicio pero aún se mantuvieron por debajo de los valores de referencia, las HDL2 aumentaron significativamente, mientras las HDL3 descendieroncon niveles normales de apoA-I. Conclusiones Este trabajo muestra que el ejercicio aumenta las HDL totales, pero lo más importante es que modifica la subpoblaciones de HDL en una relación que favorece aquellas que parecen tener propiedades ateroprotectivas. Y la evidencia de la interrelación entre factores protectores, aporta nuevos argumentos para las acciones en salud pública, frente al riesgo cardiovascular y la hipertensión Arterial.
Objetive Determine the relationship of exercise with serum levels of apoA-I and HDL2 and HDL3, subpopulations in hypertensive individuals from the city of Armenia - Quindío. Methods The interventions were two months of exercise. Blood pressure was taken with the recommendations of the Ministry of Health of Colombia. HDL subpopulations were measured with the method of precipitate ionicand the apoA-I was measured using nephelometry of Bindig site. Results Descriptive and inferential statistics were used for data analysis. A total of 160 patients of whom 125 remained until the end of the project were gathered, that is, there was a 78.12 % retention, 28 % did the exercise. The analysis showed a highly significant reduction of systolic and diastolic blood pressure, higher in people who did exercise. The HDL were below normal before exercise, significantly increased with exercise but still remained below the reference values, the HDL2 increased significantly, while HDL3 decreased with normal levels of apoA-I. Conclusion This study shows that exercise increases the total HDL, but the most important is that exercise modified the HDL subpopulations in a relationship that favors those which seem to have ateroprotective properties. The evidence of the interrelationship between protective factors provides new arguments for public health actions against the cardiovascular risk and hypertension.
Subject(s)
Female , Humans , Male , Middle Aged , Apolipoprotein A-I/blood , Blood Pressure , Exercise/physiology , /blood , /blood摘要
PURPOSE: This study was conducted to determine the association between intake of milk and dairy products as well as calcium and biomarkers related to lipid metabolism in Korean female patients with type 2 diabetes. MATERIALS AND METHODS: A cohort of 509 female subjects (mean age: 59.0 years; range: 35-80 years) was recruited from Huh's Diabetes Clinic in Seoul between 2005 and 2010. Dietary intake was assessed using a validated food-frequency questionnaire. Subjects were divided into three groups on the basis of their daily intake of milk and dairy products [200 g/day (>200-1201 g/day)] and then further divided into two groups according to their daily calcium intake: below and above the estimated average requirement (EAR). RESULTS: After adjustment for age, body mass index, energy intake, exercise, use of nutritional supplements and cholesterol medication, the level of serum high-density lipoprotein (HDL)-cholesterol was significantly higher in subjects with milk and dairy products consumption of >200 g/day than in subjects in the other two groups. Those subjects with a milk and dairy products consumption of >200 g/day had significantly higher levels of apolipoprotein A-1 and a significantly lower atherogenic index than the other two groups. Patients with a calcium intake above the EAR exhibited a significantly greater serum HDL-cholesterol level than those with a calcium intake below the EAR. CONCLUSION: Milk and dairy products, good sources of calcium, play a positive role in lipid profiles in female patients with type 2 diabetes.
Subject(s)
Adult , Aged , Aged, 80 and over , Animals , Female , Humans , Middle Aged , Apolipoprotein A-I/blood , Biomarkers/metabolism , Calcium, Dietary , Cholesterol, HDL/blood , Diabetes Mellitus, Type 2/metabolism , Diet , Lipid Metabolism , Milk摘要
Despite the noninvasiveness and accuracy of multidetector computed tomography (MDCT), its use as a routine screening tool for occult coronary atherosclerosis is unclear. We investigated whether the ratio of apolipoprotein B (apoB) to apolipoprotein A1 (apoA1), an indicator of the balance between atherogenic and atheroprotective cholesterol transport could predict occult coronary atherosclerosis detected by MDCT. We collected the data of 1,401 subjects (877 men and 524 women) who participated in a routine health screening examination of Asan Medical Center. Significant coronary artery stenosis defined as > 50% stenosis was detected in 114 subjects (8.1%). An increase in apoB/A1 quartiles was associated with increased percentages of subjects with significant coronary stenosis and noncalcified plaques (NCAP). After adjustment for confounding variables, each 0.1 increase in serum apoB/A1 was significantly associated with increased odds ratios (ORs) for coronary stenosis and NCAP of 1.23 and 1.18, respectively. The optimal apoB/A1 ratio cut off value for MDCT detection of significant coronary stenosis was 0.58, which had a sensitivity of 70.2% and a specificity of 48.2% (area under the curve, 0.61; 95% CI, 0.58-0.63, P < 0.001). Our results indicate that apoB/A1 ratio is a good indicator of occult coronary atherosclerosis detected by coronary MDCT.
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Apolipoprotein A-I/blood , Apolipoproteins B/blood , Area Under Curve , Carotid Stenosis/diagnostic imaging , Coronary Stenosis/diagnostic imaging , Odds Ratio , ROC Curve , Tomography, X-Ray Computed摘要
Both genetic background and diet have profound effects on plasma lipid profiles. We hypothesized that a high-carbohydrate (high-CHO) diet may affect the ratios of serum lipids and apolipoproteins (apo) differently in subjects with different genotypes of the SstI polymorphism in the apoCIII gene (APOC3). Fifty-six healthy university students (27 males and 29 females, 22.89 ± 1.80 years) were given a washout diet of 54 percent carbohydrate for 7 days, followed by a high-CHO diet of 70 percent carbohydrate for 6 days without total energy restriction. Serum triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apoB100, apoAI, and the APOC3 SstI polymorphism were analyzed. The ratios of serum lipids and apoB100/apoAI were calculated. At baseline, the TG/HDL-C ratio was significantly higher in females, but not in males, with the S2 allele. The differences in the TG/HDL-C ratio between genotypes remained the same after the washout and the high-CHO diet in females. When compared with those before the high-CHO diet, the TC/HDL-C (male S2 carriers: 3.13 ± 1.00 vs 2.36 ± 0.65, P = 0.000; male subjects with the S1S1 genotype: 2.97 ± 0.74 vs 2.09 ± 0.55, P = 0.000; female S2 carriers: 2.68 ± 0.36 vs 2.24 ± 0.37, P = 0.004; female subjects with the S1S1 genotype: 2.69 ± 0.41 vs 2.09 ± 0.31, P = 0.000) and LDL-C/HDL-C (male S2 carriers: 1.44 ± 0.71 vs 1.06 ± 0.26, P = 0.012; male subjects with the S1S1 genotype: 1.35 ± 0.61 vs 1.01 ± 0.29, P = 0.005; female S2 carriers: 1.18 ± 0.33 vs 1.00 ± 0.18, P = 0.049; female subjects with the S1S1 genotype: 1.18 ± 0.35 vs 1.04 ± 0.19, P = 0.026) ratios were significantly decreased after the high-CHO diet regardless of gender and of genotype of the APOC3 SstI polymorphism. However, in female S2 carriers, the TG/HDL-C (1.38 ± 0.46 vs 1.63 ± 0.70, P = 0.039) ratio was significantly increased after the high-CHO diet. In conclusion, the high-CHO diet has favorable effects on the TC/HDL-C and LDL-C/HDL-C ratios regardless of gender and of genotype of the APOC3 SstI polymorphism. Somehow, it enhanced the adverse effect of the S2 allele on the TG/HDL-C ratio only in females.
Subject(s)
Female , Humans , Male , Young Adult , Apolipoprotein C-III/genetics , Cholesterol, HDL/blood , Dietary Carbohydrates/adverse effects , Polymorphism, Genetic , Triglycerides/blood , Alleles , Asian People , Apolipoprotein A-I/blood , Apolipoprotein A-I/genetics , /blood , /genetics , Apolipoprotein C-III/blood , Cholesterol, HDL/genetics , Cholesterol, LDL/blood , Cholesterol, LDL/genetics , Cholesterol/blood , Cholesterol/genetics , Dietary Carbohydrates/administration & dosage , Genotype , Genotyping Techniques , Heterozygote , Sex Factors摘要
OBJECTIVE: To evaluate whether lipid profile (LP), apolipoprotein A-1 (apo A-I) and malondialdehyde (MDA) have any relationship with physical exercise by comparing the groups of footballers (FG) with sedentary individuals (CG) and their relatives (RFG and RCG). SUBJECTS AND METHODS: Twenty individuals from FG and CG, 60 from RFG, and 57 from RCG were studied. RESULTS: FG showed lower levels of total cholesterol (119.5 ± 37.9 mg/dL), LDL-cholesterol fraction (53.6 ± 30.3), apo A-I (116.7 ± 11.9), and higher level of HDL-cholesterol fraction (HDLc) (49.7 ± 8.5) compared to RFG (148.3 ± 36.9, P = 0.02; 82.4 ± 37.7, P < 0.01; 124.6 ± 10.2, P = 0.03; and 42.7 ± 7.7, P < 0.01; respectively). Moreover, FG had reduced levels of MDA (101.0 ± 77.0 ng/mL) compared to CG (290.0 ± 341.0, P = 0.03) and RFG (209.9 ± 197.5, P = 0.04). CONCLUSIONS: These results suggest an association between physical exercise and lower levels of MDA in FG. Physical activity seems to promote beneficial effects on the LP regardless of the genetic influence considering HDLc levels.
OBJETIVO: Avaliar se perfil lipídico (PL), apolipoproteína A-1 (apo A-I) e malondialdeído (MDA) têm relação com atividade física comparando os grupos: jogadores de futebol (FG) com indivíduos sedentários (CG) e seus familiares. SUJEITOS E MÉTODOS: Foram avaliados 20 indivíduos de FG e CG, além de 60 familiares de FG (RFG) e 57 de CG (RCG). RESULTADOS: FG mostrou menores níveis (média ± DP [mg/dL]) de colesterol total (119.5 ± 37.9), LDL colesterol (53.6 ± 30.3), e apo A-I (116.7 ± 11.9), e maiores níveis de HDL colesterol (HDLc) (49.7 ± 8.5) comparado ao RFG (148.3 ± 36.9, P = 0.02; 82.4 ± 37.7, P < 0.01; 124.6 ± 10.2, P = 0.03; e 42.7 ± 7.7, P < 0.01; respectivamente). Além disso, o FG mostrou níveis reduzidos de MDA (101.0 ± 77.0 [ng/mL]) comparado a CG (290.0 ± 341.0, P = 0.03) e RFG (209.9 ± 197.5, P = 0.04). CONCLUSÕES: Esses resultados sugerem que existe uma associação entre atividade física e níveis reduzidos de MDA em FG. O exercício físico parece promover efeitos benéficos no PL independente da influência genética considerando os níveis de HDLc.
Subject(s)
Adolescent , Adult , Aged , Aged, 80 and over , Child , Female , Humans , Male , Middle Aged , Young Adult , Apolipoprotein A-I/blood , Lipids/blood , Malondialdehyde/blood , Oxidative Stress/physiology , Physical Endurance/physiology , Sedentary Behavior , Soccer/physiology , Case-Control Studies , Exercise Test/methods , Family摘要
FUNDAMENTO: Recentes pesquisas tem se concentrado no uso de biomarcadores inflamatórios na previsão de risco cardiovascular. Entretanto, a informação é escassa em relação à associação entre esses marcadores inflamatórios com outros fatores de risco cardiovasculares em indianos asiáticos, particularmente em mulheres. OBJETIVO: Explorar a associação entre marcadores inflamatórios tais como proteína C-reativa de alta sensibilidade (PCR-as) e contagem de leucócitos (LEU) e fatores de risco cardiovascular tais como adiposidade geral e central, pressão arterial, variáveis lipídicas e lipoproteicas e glicemia de jejum. MÉTODOS: Conduzimos uma análise transversal de 100 mulheres com idade entre 35-80 anos. As participantes foram selecionadas através da metodologia de amostragem por cluster, de 12 distritos urbanos selecionadas ao acaso na Corporação Municipal de Kolkata, Índia. RESULTADOS: A PCR-as apresentou uma associação significante com o índice de massa corporal (IMC) (p < 0,001) e circunferência da cintura (CC) (p = 0,002). Associações significantes inversas foram observadas entre a lipoproteína de alta densidade colesterol (HDL-c) e ambos marcadores inflamatórios PCR-as (p = 0,031) e LEU (p = 0,014). A apo-lipoproteína A1 (Apo A1) também estava negativamente associada com a PCR-as. A contagem de leucócitos apresentou uma correlação significante com a glicemia de jejum e a razão colesterol total (CT) /HDL-C. Usando regressão logística ajustada para idade, IMC (odds ratio/OR, 1,186; intervalo de confiança/IC, 1,046-1,345; p=0,008) e LEU (OR, 1,045; IC, 1,005-1,087; p=0,027) foram as covariantes significantemente associadas com a PCR-as. CONCLUSÃO: No presente estudo, os fatores de risco tais como IMC, CC e HDL-c e Apo-A1 mostraram uma associação significante com PCR-as. A contagem de leucócitos estava significantemente associada com os níveis de HDL-c, glicemia de jejum, razão CT/HDL-c em mulheres.
BACKGROUND: Recent research has focused on the use of inflammatory biomarkers in the prediction of cardiovascular risk. However, information is scant regarding the association between these inflammatory markers with other cardiovascular risk factors in Asian Indians, particularly in women. OBJECTIVE: To explore the association between inflammatory markers such as high-sensitivity C-reactive protein (hs-CRP) and white blood cell (WBC) count and cardiovascular risk factors such as overall and central adiposity, blood pressure, lipid and lipoprotein variables and fasting glucose. METHODS: We conducted a cross-sectional analysis on 100 women aged 35-80 years. Participants were selected following cluster sampling methodology from 12 different randomly selected urban wards of Kolkata Municipal Corporation. RESULTS: Hs-CRP has a significant association with body mass index (BMI) ( p < 0.001) and waist circumference (WC) (p = 0.002). Significant inverse associations were observed between high-density lipoprotein cholesterol (HDL-C) and both inflammatory markers, hs-CRP (p = 0.031) and WBC count, (p = 0.014). Apolipoprotein A1 (Apo A1) was also negatively associated with hs-CRP. WBC count has significant correlation with fasting glucose and total cholesterol (TC) /HDL-C ratio. Using logistic regression, adjusting for age, BMI (odds ratio/OR, 1.186; confidence interval/CI, 1.046-1.345; p=0.008) and WC (OR, 1.045; CI, 1.005-1.087; p=0.027) were the covariates significantly associated with hs-CRP. CONCLUSION: In the present study, risk factors like BMI, WC, and HDL-C and apo A1 show significant association with hs-CRP. WBC count was significantly correlated with HDL-C, fasting glucose, TC/HDL-C ratio in women.
FUNDAMENTO: Recientes investigaciones se han concentrado en el uso de biomarcadores inflamatorios en la previsión de riesgo cardiovascular. Entre tanto, la información es escasa en relación a la asociación entre esos marcadores inflamatorios con otros factores de riesgo cardiovasculares en indios asiáticos, particularmente en mujeres. OBJETIVO: Explorar la asociación entre marcadores inflamatorios tales como proteína C-reactiva de alta sensibilidad (PCR-as) y recuento de leucocitos (LEU) y factores de riesgo cardiovascular tales como adiposidad general y central, presión arterial, variables lipídicas y lipoproteicas y glucemia de ayuno. MÉTODOS: Condujimos un análisis transversal de 100 mujeres con edad entre 35-80 años. Las participantes fueron seleccionadas a través de la metodología de muestreo por cluster, de 12 distritos urbanos seleccionadas al azar en la Corporación Municipal de Kolkata, India. RESULTADOS: La PCR-as presentó una asociación significativa con el índice de masa corporal (IMC) (r=0,373, p<0,001) y circunferencia de la cintura (CCI) (r=0,301, p=0,002). Asociaciones significativas inversas fueron observadas entre la lipoproteína de alta densidad colesterol (HDL-c) y ambos marcadores inflamatorios (r= -0,220, p=0,031 y r= -0,247, p=0,014 para PCR-as y LEU, respectivamente). La apo-lipoproteína A1 (Apo A1) también estaba negativamente asociada con la PCR-as (r= -0,237, p=0,031). El recuento de leucocitos presentó una correlación significativa con la glucemia de ayuno (r=0,253, p=0,011) y la razón colesterol total (CT) /HDL-C (r=0,284, p=0,004). Usando regresión logística ajustada para edad, IMC (odds ratio/OR, 1,186; intervalo de confianza/IC, 1,046-1,345; p=0,008) y LEU (OR, 1,045; IC, 1,005-1,087; p=0,027) fueron las covariantes significativamente asociadas con la PCR-as. CONCLUSIÓN: En el presente estudio, los factores de riesgo tales como IMC, CCI y HDL-c y Apo-A1 mostraron una asociación significativa con PCR-as. El recuento de leucocitos estaba significativamente asociado a los niveles de HDL-c, glucemia de ayuno, razón CT/HDL-c en mujeres.
Subject(s)
Adult , Aged , Aged, 80 and over , Female , Humans , Middle Aged , Apolipoprotein A-I/blood , C-Reactive Protein/analysis , Cardiovascular Diseases/blood , Cholesterol, HDL/blood , Body Mass Index , Biomarkers/blood , Cross-Sectional Studies , Cholesterol/blood , White People , India , Leukocyte Count , Prevalence , Risk Factors , Waist Circumference摘要
Hepatitis B virus initiates a complicated cascade process leading to chronic hepatitis B, cirrhosis, and hepatocellular carcinoma. In inflammatory situations, myeloperoxidase is released in plasma and binds to apolipoprotein A-1 in high-density lipoproteins. This study aims to evaluate the level of plasma myeloperoxidase as well as the pattern of plasma proteins in patients with chronic hepatitis B. Included in this study were 30 male subjects: 19 chronic hepatitis B patients, 6 HBV-related cirrhotic patients, and 5 healthy controls. Plasma myeloperoxidase was measured using enzyme-linked immunosorbent assay. Proteomic analysis of plasma proteins was performed by two-dimensional gel electrophoresis [2-DE] and mass spectrometry. One way ANOVAwas used for data analysis. Mean plasma myeloperoxidase levels were higher in patients with liver cirrhosis [65.5 +/- 12.5; P=0.007] and chronic hepatitis B [53.7 +/- 10.6; P=0.18] when compared with healthy subjects [45 +/- 7.6]. Moreover, a positive correlation was found between plasma myeloperoxidase levels and hepatic fibrosis stage [r=0.53, P=0.002; r=0.63, P=0.000]. Proteomic analysis showed an altered plasma protein pattern in progressive hepatitis B and down-regulation of the major apolipoprotein A-1 along with the appearance of a variety of spots noted to be apolipoprotein A-1isoforms with different molecular masses. In this study, progressive liver injury due to HBV infection correlated with higher plasma myeloperoxidase and an altered plasma apolipoprotein A-1 pattern
Subject(s)
Humans , Adult , Middle Aged , Male , Apolipoprotein A-I/blood , Hepatitis B, Chronic/enzymology , Liver Cirrhosis/enzymology , Liver Cirrhosis/virology , Liver Cirrhosis/metabolism , Hepatitis B virus , Hepatitis B, Chronic/metabolism , Analysis of Variance , Down-Regulation , Proteome/metabolism摘要
La enfermedad renal crónica (ERC) se asocia estrechamente con un estado pro-inflamatorio, aumento de lipoproteínas ricas en triglicéridos y disminución de HDL. La HDL contiene enzimas antioxidantes asociadas como la paraoxonasa (PON), cuya actividad en ERC se encuentra disminuida. Nuestro objetivo fue evaluar la relación entre la actividad de PON, apoA1, colesterol(col)-HDL y Proteína C reactiva-altamente sensible (PCR-as) como marcador de inflamación en pacientes en hemodiálisis. Se estudiaron n = 42 pacientes; edad, mediana (rango) = 50 (25-67) años; sexo M/F = 22/20; antigüedad de hemodiálisis = 4.4 ± 0.5 años; índice de masa corporal (IMC) = 23 ± 0.5 kg/m². Se obtuvo una muestra de sangre después de 12 h de ayuno y se determinaron los parámetros clásicos del perfil lipídico, se midieron los valores de apoproteínas A1 y B, PON a través de su actividad arilesterasa y PCR-as, la cual permitió dividir a los pacientes con PCR-as ≤ 1 (bajo riesgo, rango: 0.1 a 1.0 mg/l) y > 1 mg/l (moderado y alto riesgo, 1.1 a 10.7 mg/l). Los niveles de triglicéridos, col-LDL y apoB no fueron diferentes entre los grupos. Los pacientes con PCR-as > 1 presentaron menor col-HDL (40 ± 2 mg/dl) y apoA1 (118 ± 4 mg/dl) que los pacientes con PCR-as ≤ 1 (50 ± 4 y 133 ± 5, respectivamente); p < 0.05. La PON fue menor en PCR-as > 1: 90.5 ± 24.0 μmol/ml.min que en PCR-as ≤ 1: 105.2 ± 18.0. Consecuentemente, se obtuvieron correlaciones inversas entre apoA1 y PCR-as, r = -0.381 p = 0.013 y entre PON y PCR-as, r = -0.32, p = 0.042. Además, el aumento de PCR-as correlacionó positivamente con el IMC, r = 0.318, p = 0.042. La disminución de col-HDL, apoA1 y PON en los individuos con mayor estado inflamatorio explicaría, en parte, el aumento de riesgo cardiovascular de estos pacientes, dado los efectos antiinflamatorios de la apoA1 y antioxidantes de la PON.
Advanced Chronic Renal Disease (CKD) is closely associated with a pro-inflammatory condition, with an increase in triglyceride-rich lipoproteins and decrease in HDL level. HDL contains antioxidant enzymes such as paraoxonase (PON), whose activity is diminished in CKD. The aim of our study was to evaluate the relationship between PON activity with HDL cholesterol, apo A1 and hs-CRP levels, which are known to be inflammatory markers in hemodialyzed patients. Forty-two patients were studied; age, median (range) = 50 (25-67) years old, gender M/F = 22/20, duration of hemodialysis = 4.4 ± 0.5 years, BMI: 23 ± 0.5 kg/m². After a 12 h fast, a blood sample was obtained and classic components of lipid profile were determined, as well as apoproteins A1 and B, PON by means of its arylsterase activity and hs-CRP levels. On the basis of the latter, patients were divided into two groups: hs-CRP ≤ 1 (low risk, range: 0.1 to 1.0 mg/l) and >1 mg/l (moderate and high risk, 1.1 to 10.7 mg/l). No difference was found in triglycerides, LDL cholesterol and apo B in the groups. Patients with hs-CRP > 1 showed lower HDL cholesterol (40 ± 2 mg/dl) and apo A1 (118 ± 4 mg/dl) than patients with hs-CRP ≤ 1 (50 ± 4 and 133 ± 5, respectively); p < 0.05. PON was lower in hs-CRP > 1 = 90.5 ± 24.0 μmol/ml.min than in hs-CRP ≤ 1 = 105.2 ± 18.0. Consequently, inverse correlations were obtained between apo A1 and hs-CRP, r = -0.381, p = 0.013 and between PON and hs-CRP, r = -0.32, p = 0.042. Furthermore, increase in hs-CRP correlated positively with BMI r = 0.318, p = 0.042. Since apo A1 has an anti-inflammatory role and PON an antioxidant activity, the decrease in HDL and its components, cholesterol, apo A1 and PON, in subjects with higher chronic inflammatory condition might explain, in part, the increased cardiovascular risk in these patients.
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Apolipoprotein A-I/blood , Aryldialkylphosphatase/blood , C-Reactive Protein/analysis , Cholesterol, HDL/blood , Inflammation/blood , Renal Dialysis , Body Mass Index , Biomarkers/blood , Reference Values摘要
Coronary heart diseases (CHD) have reached epidemic proportions among Indians. The recently concluded INTWERHEART study emphasizes the role of behavioural and conventional risk factors in the prediction of CHD risk among Indians. These findings have implication for the health care providers and policy makers in the country due to the fact that all these conventional risk factors are potentially modifiable and are good starting points for prevention. The policy measures by means of legislation and regulatory approaches on agriculture and food industry or tobacco or physical activity will have large impact on CHD risk factor reduction in the population. In addition, the health system needs to focus on: (i) providing information for increasing awareness and an enabling environment for adoption of healthy living habits by the community; (ii) early detection of persons with risk factors and cost-effective interventions for reducing risk; and (iii) early detection of persons with clinical disease and cost-effective secondary prevention measures to prevent complications. The evidence from INTERHEART provides rationale for developing treatment algorithms and treatment guidelines for CHD at various levels of health care. In addition, INTERHEART provides answer for the quest for a single reliable biomarker, Apo B/ApoA 1 ratio that can predict the future CHD risk among individuals. Further to this, the INTERHEART study also opens up several unanswered questions on the pathobiology of the premature onset of myocardial infarction among Indians and calls for the need to developing capacity in clinical research in CHD in India.
Subject(s)
Apolipoprotein A-I/blood , Apolipoproteins B/blood , Biomarkers/blood , Coronary Disease/epidemiology , Coronary Disease/prevention & control , Humans , India/epidemiology , Life Style , Practice Guidelines as Topic , Primary Prevention/legislation & jurisprudence , Primary Prevention/methods , Public Policy , Risk Factors摘要
Hepatitis C virus [HCV] infection is one of the commonest chronic liver diseases worldwide. Progression to chronic disease occurs in the majority of HCV infected patients. The aim of the present work was to study serum levels of alpha2 macroglobulin [alpha2-MG], Apolipoprotein A1 [Apo-1] and Haptoglobin [HP] as non-invasive index of the presence of cirrhosis in chronic hepatitis C patients in relation to the histopathological findings. The study was carried out on 20 patients with chronic HCV and liver cirrhosis [Group I], 20 patients with chronic HCV without liver cirrhosis [Group II] and 10 healthy subjects of mathing age and sex as controls [Group III]. Quantitative estimation of alpha2-MG, HP and Apo AI in serum was done using turbidimetry. The mean serum level of alpha2-MG was significantly higher in group I than in groups II, III [F=12.8] [p=0.00]. On the other hand, Serum Apo A1 and HP were significantly lower in group I than in groups II, III [F=5.9 and 26.3] [p=0.005 and 0.00]. On the other hand, no significant difference was found between groups II and III. Significant positive correlation was observed between serum alpha2-macroglobulin and Child Pugh score, Grading and staging of liver pathology [P<0.05]. On the other hand, significant negative correlation was noticed between serum Apo-1, HP and Child Pugh score, histopathological grading and staging [P<0.05]. Elevated serum levels of alpha2 macroglobulin in addition to low levels of apolipoprotein A1 and haptoglobin might be considered as valuable non invasive parameters for predicting the occurrence of cirrhosis in chronic hepatitis C patients
Subject(s)
Humans , Male , Female , Liver Cirrhosis , Biomarkers , Apolipoprotein A-I/blood , alpha-Macroglobulins/blood , Haptoglobins/blood摘要
It has been hypothesized that blood infusion of reconstituted HDL (rHDL) is a possible therapeutic strategy for the treatment of coronary artery disese. To compare short-term anti-inflammatory activity of wildtype (WT) apoA-I and point mutants, each rHDL containing WT, V156K, or R173C was infused into apo-E deficient atherosclerotic mice. Each rHDL was injected via the tail vein at a dosage of 120 mg/kg of body weight in 0.4 ml of tris-buffered saline (TBS), and blood was then collected at 24 and 48 h post-injection. Although regression activity was observed in each of the rHDL infused groups, a 30% reduction in the lipid-stained area of the aortic sinus was observed in the V156K and R173C-rHDL groups when compared to that of the WT-rHDL group, and this reduction was well correlated with an approximately 60% reduction in the accumulation of macrophages in the lesion area. Additionally, the groups that received the V156K and R173C-rHDL treatments showed smaller increases in the GOT, GPT, interleukin-6, myeloperoxidase (MPO) and lipid hydroperoxide (LPO) serum levels than those that received the WT-rHDL treatment. In addition, the strongest serum paraoxonase and ferric reducing ability was observed in the V156K and R173C-rHDL groups. In vitro nitration and chlorination of apoA-I by MPO treatment revealed that V156K-rHDL and R173C-rHDL were less susceptible to chlorination. Furthermore, rHDL treatment inhibited cellular uptake of oxidized LDL by macrophage cells and the production of proatherogenic species in culture media. In conclusion, blood infusions of the rHDLs exerted in vivo regression activity with anti-inflammatory and antioxidant activity in apo-E deficient mice and THP-1 cells, especially in those that were treated with V156K and R173C apoA-I.
Subject(s)
Animals , Humans , Mice , Anti-Inflammatory Agents/immunology , Apolipoprotein A-I/blood , Apolipoproteins E/genetics , Aryldialkylphosphatase/blood , Atherosclerosis/drug therapy , Cell Line , Cell Membrane Permeability , Cholesterol/blood , Lipoproteins, HDL/genetics , Lipoproteins, LDL/metabolism , Macrophages/cytology , Mice, Inbred C57BL , Mice, Knockout , Oxidation-Reduction/drug effects , Peroxidase/blood , Point Mutation摘要
We have planned this work to evaluate the significance and prognostic values of both membrane and soluble APO-1 as markers of apoptosis in patients with acme leukaemia before and alter chemotherapy. For that, 30 patients suffering from acute leukaemia [15 patients with ALL and 15 patients with AMD and 10 apparently healthy individuals serving as control group, were selected and subjected to the following: thorough history and clinical examination, routine investigations including: complete blood picture, bone marrow examination, cytochemistry, immunopheno typing of the blast cells and specific investigations including: detection of mAPO1 [CD95] on surface of blast cells by flow cytometry, detection of DNA fragmentation by agarose gel electrophoresis and measurement of soluble APO-1 by ELISA technique before and after chemotherapy. Surface membrane CD9S was found to be expressed on the majority of ALL blast cells [86.6%] and in only 60% of AML blast cells. The degree of surface membrane expression was variable ranging from 23-86% in ALL and from 43-89%; in AML. In both ALL and AML patients, a significant relationship was detected between surface CD95 expression and response to initial induction chemotherapy. Ninety-one percent of ALL patients and 84% of AML patients who had surface CD95 expression>20% on their blast cells showed complete hematological remission after initial induction chemotherapy. This was confirmed by finding that DNA extracted from patients under chemotherapy, whose blast cells CD95 expression was>20%, showed DNA fragmentation [DNA laddering] by agarose gel electrophoresis [characteristic of apoptosis]. As regards soluble CD9S [SCD95] before starting chemotherapy, no statistically significant difference was observed between the level of soluble CD9S in both ALL and AML patients and the control group [P>0.05]. But, in AML patients, the level of soluble CD95 tended to be etevated [not significantly] in comparison with normal control. After initial induction chemotherapy, the level of soluble CD95 was found to be significantly decreased in both ALL and AML patients in comparison to its level before therapy [P<0.001 and<0.01, respectively]. By following up patients who were resistant to chemotherapy, it was observed that patients who did not achieve complete remission after induction chemotherapy had relatively higher levels of sAPO-1. From these results we can conclude that, since there is a significant relationship between surface CD95 expression in both ALL and AML patients and response to chemotherapy, the expression of surface CD95 could serve as a new prognostic marker as it is helpful in predicting the outcome of therapy. In addition, because soluble APO-1 was found to be relatively high in patients resistant to anti-leukaemic therapy, so measurement of s-APO-1 in sera of acute leukaemia patients could serve as a putative marker for an active persisting leukaemia
Subject(s)
Humans , Male , Female , Biomarkers , Apolipoprotein A-I/blood , Apoptosis , fas Receptor , Immunophenotyping , DNA Damage , Electrophoresis, Agar Gel/methods摘要
Although liver biopsy is acknowledged as the gold standard for evaluating fibrosis, it is occasionally prone to sampling error and complications. Is to correlate an index of biochemical markers with histological features of fibrosis in patients with chronic hepatitis C virus [HCV] and/or non alcoholic steatohepatitis [NASH] with or without schistosomiasis in order to reduce the use of liver biopsy. Fifty-six patients [n-56] attending tropical medicine clinics in Kasr El-Aini and Beni Suef Faculty of Medicine were enrolled and classified into 3 groups according to the histopathological findings of their liver biopsy. Stool and urine analysis were done to exclude passage of Schistosoma ova, in addition to liver biopsy, abdominal ultrasonography, and testing of their sera for fibrosis biomarkers [Apolipoprotein Al, Haptoglobin, Alpha-2-Macroglobulin, and Ganima-glutamyl transpeptidase [GGT]]. Patients with history of contact with canal water [35 patients] were screened for Schistosoma mansoni infection by detecting anti-Schistosoma IgG antibodies and circulating Schistosoma soluble egg antigen using indirect ELISA and sandwich ELISA techniques, respectively. Forty-three [43%] of group I [HCV] and 40% of group II [HCV and NASH] had advanced fibrosis [F3 and F4]. Out of the 35 patients with positive history of canal water contact 25 [71.4%] were antibody positive; Schistosoma antigen was detected in only 5 patients [14.3%], with no statistically significant differences in the level of fibrosis seromarkers from other patients. Alpha-2-macroglobulin was found to be a reliable predictor of fibrosis. Haptoglobin was negatively related to the degree of hepatic fibrosis in groups I and II and significantly directly correlated in group III [NASH]. By regression analysis, haptoglobin can be a good predictor for fibrosis in group Ill. Apolipoprotein Al had insignificant negative correlation to the stage of fibrosis in groups I and II. GGT was positively correlated to the degree of hepatic fibrosis in groups I, II and III. AST/platelet ratio index [APRI] proved significantly directly correlated with fibrosis stage and grade of inflammation of the studied patients. Co-infection with schistosomiasis in patients with HCV and/or NASH gave no statistically significant differenceinfibrosis staging in all groups.Alpha-2-macroglobulin, haptoglobin and apolipoprotein Al, besides APRI index and modified APRI index proved to be significant predictors of hepatic fibrosis