Cholesteryl ester transfer protein inhibitory oxoacetamido-benzamide derivatives: Glide docking, pharmacophore mapping, and synthesis

Abstract Dyslipidemia is an abnormal lipid profile associated with many common diseases, including coronary heart disease and atherosclerosis. Cholesteryl ester transfer protein (CETP) is a hydrophobic plasma glycoprotein that is responsible for the transfer of cholesteryl ester from high-density lipoprotein athero-protective particles to pro-atherogenic very low-density lipoprotein and low-density lipoprotein particles. The requirement for new CETP inhibitors, which block this process has driven our current work. Here, the synthesis as well as the ligand-based and structure-based design of seven oxoacetamido-benzamides 9a-g with CETP inhibitory activity is described. An in vitro study demonstrated that most of these compounds have appreciable CETP inhibitory activity. Compound 9g showed the highest inhibitory activity against CETP with an IC50 of 0.96 µM. Glide docking data for compounds 9a-g and torcetrapib provide evidence that they are accommodated in the CETP active site where hydrophobic interactions drive ligand/CETP complex formation. Furthermore, compounds 9a-g match the features of known CETP active inhibitors, providing a rationale for their high docking scores against the CETP binding domain. Therefore, these oxoacetamido-benzamides show potential for use as novel CETP inhibitors

Synthesis and In Vivo Hypolipidemic Effect of Some N-(Benzoylphenyl)-Carboxamide Derivatives in Triton WR-1339-Induced Hyperlipidemic Rats

A series of N-(benzoylphenyl)-carboxamide derivatives (2a, 2b, 3a, 3b, 4a, 4b, 5a, 5b, 6a and 6b) was prepared with good yields by reacting the corresponding carbonyl chlorides with aminobenzophenones at room temperature. This was followed by evaluating the hypotriglyceridemic and hypocholesterolemic effects of 3b, 5a and 5b. Triton WR-1339 (300 mg/kg) was intraperitoneally administered to overnight-fasted rats to induce hyperlipidemia. Rats were divided into six groups: control, hyperlipidemic, hyperlipidemic plus compounds 3b, 5a and 5b and hyperlipidemic plus bezafibrate. Results showed that after 18 h of treatment at a dose of 15 mg/kg body weight of each of the test compounds, the elevated plasma levels of triglycerides (TG) and total cholesterol (TC) were significantly lowered by compounds 5b and 3b (p < 0.001) and by 5a (p < 0.0001), compared to the hyperlipidemic control group. Compounds 3b and 5a significantly increased levels of high-density lipoprotein cholesterol (HDL-C) by 58 and 71%, respectively. In addition, compounds 3b and 5a caused significant reduction (p < 0.0001) of low-density lipoprotein cholesterol (LDL-C) levels compared to the control group. These results suggest a promising potential for compounds 3b, 5a and 5b as lipid-lowering agents, which may contribute to reducing the risk of atherosclerosis and cardiovascular disease

Vulnerabilidad cardiometabólica e indicadores bioquímicos en el momento de la captación de la embarazada y en el posparto / Cardiometabolic vulnerability and biochemical indicators during recruitment of pregnant women and in the postpartum period

Introducción: Son escasos los estudios sobre acumulaciones excesivas de tejido adiposo y su asociación con cambios en indicadores bioquímicos estudiados durante el embarazo y el posparto. Objetivo: Determinar asociaciones de la vulnerabilidad cardiometabólica por adiposidad corporal con indicadores bioquímicos en el momento de la captación de la embarazada y el posparto. Métodos: Se realizó estudio observacional prospectivo de la vulnerabilidad cardiometabólica por adiposidad corporal e indicadores bioquímicos en 773 mujeres captadas como sanas de peso adecuado, de ellas 119 al posparto, en el policlínico Chiqui Gómez Lubián. Se estudiaron por grupo de vulnerabilidad cardiometabólica indicadores bioquímicos a la captación y el posparto. Se aplicó prueba estadística de Kruskal-Wallis. Resultados: Gestantes captadas con vulnerabilidad global por adiposidad general intermedia y central alta tuvieron valores medios más bajos del ácido úrico (238,78 mmol/L), más altos de triglicéridos (1,37 mmol/L), colesterol (4,70 mmol/L) y resistencia a la insulina (8,32). Mujeres con vulnerabilidad global por adiposidad general intermedia y central alta al posparto presentaron valores medios más elevados de triglicéridos (1,18 mmol/L) y lipoproteínas de muy baja densidad (0,54 mmol/L), más bajos de lipoproteínas de alta densidad (1,06 mmol/L); mujeres con vulnerabilidad global extrema por adiposidad general y central alta, tuvieron valores medios más elevados: glicemia (4,90 mmol/L), colesterol (4,30 mmol/L), lipoproteínas de baja densidad (2,76 mmol/L), producto de acumulación de lípidos (42,63 mmol/L) e índice de adiposidad visceral (2,32 mmol/L). Conclusiones: Evaluar vulnerabilidad cardiometabólica por técnicas antropométricas, complementadas con indicadores bioquímicos, facilita orientar acciones preventivas sobre daños cardiometabólicos progresivos en la gestación y su posparto(AU)

Introduction: Few studies are available about excessive accumulation of adipose tissue and its association to changes in biochemical indicators in pregnancy and the postpartum period. Objective: Determine the association between cardiometabolic vulnerability due to body adiposity and biochemical indicators during recruitment of pregnant women and in the postpartum period. Methods: An observational prospective study was conducted of cardiometabolic vulnerability due to body adiposity and biochemical indicators in 773 women recruited as healthy and adequate weight, 119 of them in the postpartum period, at Chiqui Gómez Lubián polyclinic. Biochemical indicators were studied by cardiometabolic vulnerability group at recruitment and in the postpartum period. Statistical analysis was based on the Kruskal-Wallis test. Results: Pregnant women recruited with overall vulnerability due to high general intermediate and central adiposity had lower uric acid mean values (238.78 mmol/l), higher triglyceride mean values (1.37 mmol/l), cholesterol (4.70 mmol/l) and insulin resistance (8.32). Women with overall vulnerability due to high general intermediate and central adiposity in the postpartum period had higher triglyceride mean values (1.18 mmol/l), very low density lipoproteins (0.54 mmol/l), and lower high density lipoprotein mean values (1.06 mmol/l). Women with extreme overall vulnerability due to high general and central adiposity had higher mean values: glycemia (4.90 mmol/l), cholesterol (4.30 mmol/l), low density lipoproteins (2.76 mmol/l), lipid accumulation product (42.63 mmol/l) and visceral adiposity index (2.32 mmol/l). Conclusions: Evaluating cardiometabolic vulnerability using anthropometric techniques complemented with biochemical indicators, facilitates aiming preventive actions at progressive cardiometabolic damage during pregnancy and the postpartum period(AU)

Associação entre Atividade Física no Tempo Livre e HDL-C em Participantes do Elsa-Brasil: Existem Diferenças entre Homens e Mulheres no Efeito Dose-Resposta? / Association between Leisure Time Physical Activity and HDL-C in the Elsa-Brasil Study Participants: Are There Any Gender Differences in the Dose-Response Effect?

Resumo Fundamento Níveis elevados de lipoproteína de alta densidade (HDL-C) podem ter efeitos positivos para proteção de agravos cardiovasculares, e prática regular de atividade física no tempo livre (AFTL) tem sido associada ao seu aumento. Objetivo Verificar a existência de possíveis diferenças entre homens e mulheres no efeito dose-resposta na associação entre AFTL e HDL-C. Métodos Estudo transversal com dados de 13,931 participantes de ambos os sexos (7,607 mulheres) do Estudo Longitudinal da Saúde do Adulto (ELSA-Brasil). A AFTL foi mensurada por meio do International Physical Activity Questionnary (IPAQ) e classificada em quatro categorias: inativos, pouco ativos, ativos e muito ativos. O poder discriminatório da AFTL para HDL-C elevado, nas diferentes intensidades analisadas (caminhada, atividade física moderada e atividade física vigorosa) foi testado por meio das curvas ROC. As associações, ajustadas por variáveis de confundimento entre AFTL e HDL-C foram analisadas por meio de regressão logística, estimando-se a odds ratio (OR) com intervalo de confiança (IC) de 95%. Resultados Observou-se associação positiva, com efeito dose-resposta, entre AFTL e HDL-C tanto em homens quanto em mulheres. Com relação à intensidade, apenas a atividade física vigorosa discriminou o HDL-C elevado em homens, enquanto tanto a atividade física de caminhada quanto a moderada e a vigorosa discriminaram o HDL-C elevado em mulheres. Conclusão A AFTL apresenta associação positiva com gradiente dose-resposta com HDL-C; no entanto, entre os homens, a associação não é observada para aqueles classificados como pouco ativos fisicamente. Nas mulheres, tanto a intensidade da caminhada quanto a atividade física moderada ou vigorosa podem discriminar níveis de HDL-C mais altos; já nos homens, essa relação é observada apenas na intensidade vigorosa.

Abstract Background High levels of high-density lipoprotein (HDL-C) are known for their protective effect against cardiovascular diseases and the regular practice of leisure time physical activity (LTPA) may be associated with their increase. Objective To verify the existence of differences between genders in the dose-response effect regarding the association between LTPA and HDL-C in the ELSA-Brasil study cohort. Methods Cross-sectional study with data from wave 2 of 13,931 participants of both genders (7,607 women) from the Longitudinal Study of Adult Health ELSA-Brasil. The LTPA was measured using the International Physical Activity Questionnaire (IPAQ) and classified into four categories: sedentary, low active, active and very active. The discriminatory power of LTPA at different intensities analyzed for high HDL-C was tested using ROC curves. Associations, adjusted for confounders between LTPA and HDL-C were analyzed by logistic regression. A 95% confidence interval was used. Results A positive association, with a dose-response effect, was observed between LTPA and HDL-C in both men and women. With regard to intensity, only vigorous physical activity discriminated high HDL-C in men, while both walking and moderate and vigorous physical activity discriminated high HDL-C in women. Conclusions LTPA shows a positive association with gradient dose-response and HDL-C, but in men, the association is not observed for those classified as physically unfit. In women, both walking intensity and moderate or vigorous physical activity can discriminate high HDL-C levels, whereas only vigorous intensity-exercise discriminate elevated HDL-C levels in men, demonstrating that males need to do more physical activity for this benefit to be observed.

Correlation between GPR, MHR and elderly essential hypertension with unstable angina pectoris / 中南大学学报(医学版)

OBJECTIVES@#To investigate the level and significance of serum γ-glutamyl transferase-to-platelet ratio (GPR) and monocyte count to high-density lipoprotein ratio (MHR) in patients with essential hypertension (EH) and unstable angina (UA).@*METHODS@#A total of 218 patients with coronary angiography aged ≥60 years, who were admitted to the EH hospital of the Department of Cardiac Medicine, Affiliated Hospital of Chengde Medical College, were selected from September 2018 to September 2019. They were divided into an EH+UA group (@*RESULTS@#Compared with the control group, patients in the EH+UA group and the EH group had higher body mass index (BMI), tyiglyceride (TG), GPR, and MHR, and lower high-density lipoprotein-cholesterol (HDL-C) (all @*CONCLUSIONS@#There is a correlation between GPR, MHR and EH combined with UA pectoris, and the combined detection of the two indicators has adjuvant diagnostic value for elderly EH combined with UA.

Alteration in Serum Lipid Profile Pattern in Oral Squamous Cell Carcinoma and Potentially Malignant Disorders

ABSTRACT Objective: To evaluate and compare lipid profile level in oral submucous fibrosis (OSMF), oral leukoplakia (OL) and oral squamous cell carcinoma (OSCC) patients. Material and Methods: Thirty histopathologically diagnosed subjects each of OL, OSMF, OSCC were recruited along with 30 healthy controls. 5ml of venous blood is collected and estimated using standard diagnostic kits. Results: The mean of Total cholesterol level in controls was 219.03 mg%, in OSCC, OL and OSMF was 142.89 ± 10.21mg%, 155.44 ± 17.63 mg% and 180.60 ± 13.25 mg%, respectively. The mean low-density lipid level in controls was 137.24 mg and in OSCC, OL and OSMF groups were 109.28 ± 2.16 mg%, 126.63 ± 0.85 mg% and 119.15 ± 0.93 mg%, respectively. The mean of high-density lipid level in controls, OSCC, OL and OSMF was 42.87 ± 0.42 mg%, 36.50 ± 2.31 mg%, 21.13 ± 0.77 mg% and 28.37 ± 1.11mg%, respectively. The mean of very low density lipids level in controls, OSCC, OL and OSMF was 30.12 ± 1.51 mg%, 17.24 ± 0.80 mg%, 22.25 ± 0.93 mg% and 25.89 ± 0.43 mg%, respectively. The mean triglyceride level in controls, OSCC, OL and OSMF was 118.80 ± 9.47 mg%, 91.2 ± 3.03 mg%, 105.05 ± 2.96 mg% and 106.19 ± 3.09 mg%, respectively. Conclusion: Lipid profile levels could be early indicators of precancer and cancer.

Associação entre a razão de monócitos por HDL e TIMI frame count e a trombose de stent em pacientes com primeiro infarto do miocárdio / Association of the monocyte to HDL ratio and TIMI frame count and stent thrombosis in patients with first myocardial infarction

Objetivo: Avaliar a associação entre marcadores de gravidade e complexidade, assim como de desfechos em 30 dias, com a razão de monócitos por HDL em pacientes com primeiro infarto agudo do miocárdio. Métodos: Foram selecionados 580 pacientes com primeiro infarto agudo do miocárdio submetidos a questionário durante a internação e seguimento em 30 dias. Os dados laboratoriais foram obtidos de 312 pacientes na entrada e de 237 em 72 horas. A gravidade e a complexidade foram avaliadas pelo TIMI frame count, pela fração de ejeção do ventrículo esquerdo e pelo escore Syntax. Resultados: O estudo evidenciou correlação positiva entre a razão de monócitos por HDL em 72 horas e o TIMI frame count, com r de 0,219 (p=0,018). Também evidenciou maior mediana de razão de monócitos por HDL nos pacientes que apresentaram trombose de stent em até 30 dias da internação ­ 35,8 (30,0-43,9) ­ comparados àqueles que não apresentaram, com 18,27 (12,98-26,74), p=0,038. Não houve correlação significativa entre a razão de monócitos por HDL da entrada com TIMI frame count, escore SYNTAX ou fração de ejeção do ventrículo esquerdo. Conclusão: Houve correlação positiva entre a razão de monócitos por HDL em 72 horas e o TIMI frame count em pacientes com primeiro infarto agudo do miocárdio submetidos à angioplastia primária. Verificou-se, também, associação entre maiores níveis de razão de monócitos por HDL na entrada com trombose de stent em 30 dias.

Objective: To investigate the association between complexity and severity markers, as well as 30-day outcomes with the monocytes to HDL-cholesterol ratio in patients with first myocardial infarction. Methods: A total of 580 patients with first myocardial infarction was selected and answered a questionnaire during hospitalization and 30-day follow up. Laboratory data were obtained at admission for 312 patients and for 237 in 72 hours. Severity and complexity were assessed by TIMI frame count, left ventricular ejection fraction, and Syntax score. Results: The study showed that the monocyte to HDL ratio in 72 hours was significantly positively correlated with TIMI frame count, with r of 0.219 (p=0.018). It also showed higher monocyte to HDL ratio median in patients presenting stent thrombosis within 30 days of hospitalization ­ 35,8 (30,0-43,9) ­ compared to those who did not develop it 18,27 (12,98-26,74), p=0.038. No correlation was found between admission monocytes to HDL ratio and TIMI frame count, Syntax score, or left ventricular ejection fraction. Conclusion: There was a positive correlation between Monocytes to HDL ratio in 72 hours and TIMI frame count in patients with first myocardial infarction undergoing primary percutaneous coronary intervention. An association between higher levels of admission monocyte to HDL ratio and stent thrombosis in 30 days was also observed.

Influence of weight gain on the lipid profile of adolescents / Influencia de la ganancia de peso sobre el perfil lipídico en adolescentes

The objective of this study was to assess the influence of weight gain on the lipid profile of 135 adolescents between 10 - 14 years at baseline and 15 - 19 years at follow-up, enrolled in public schools in Recife, Brazil. The results showed that a BMI z-score correlated with triglycerides (TG) and with high density trigliceride lipopoteine ratio (TG/HDL-c) in males. In females, high z-score correlated with total cholesterol (TC) and low density lipoprotein (LDL-c). In males, for each unit increase in z-score, TG increased by 14.7 mg/dL and the TG/HDL-c ratio increased by 0.4. Among females, TC increased by 9.4 mg/dL, LDL-c increased by 11.6 mg/dL, non-HDL cholesterol increased by 11.8 mg/dL, and HDL-c decreased by 2.3 mg/dL. In males, excessive weight gain was associated with an increase in TG and TG/HDL-c; in females, it was associated with a higher increase in TG/HDL-c and non-HDL cholesterol. However, z-score variation can be a good predictor of lipid profile changes, even in those that are within the normal range.

El objetivo de este estudio fue evaluar la influencia del aumento de peso en el perfil lipídico de 135 adolescentes de edades entre 10 y 14 años de edad al inicio del estudio y de 15 a 19 años en el seguimiento. Los adolescentes pertenecían a escuelas públicas de Recife, Brasil. Los resultados mostraron que el alto puntaje z de indice de masa corporase (IMC) correlacionaba con triglicéridos (TG) y con relación de triglicéridos con lipoproteínas de alta densidad (TG/HDL-c) en los hombres. En las mujeres, puntaje z de IMC se correlacionó con CT y lipoproteína de baja densidad (LDL-c). En los hombres, por cada unidad de aumento en el puntaje z, los TG aumentaron en 14,7 mg/dL y la relación TG / HDL-c aumentó en 0,4; en las mujeres, el CT aumentó en 9,4 mg/dL, el LDL-c aumentó en 11,6 mg/dL, el colesterol no HDL aumentó en 11,8 mg / dL y el HDL-c disminuyó en 2,3 mg/dL. En los hombres, el aumento de peso excesivo se asoció con un aumento de TG y TG/HDL-c; en las mujeres, con un aumento mayor en TG/HDL-c y colesterol no HDL. Sin embargo, la variación z-score puede ser un buen predictor de cambios en el perfil lipídico, incluso en aquellos que se encuentran dentro del rango normal.

Prevalencia de dislipidemias en pacientes obesos / Dylispidemia prevalence in obese patients

Introducción: Las dislipidemias asociadas a la obesidad constituyen factores de riesgo de varias enfermedades especialmente del sistema cardiovascular. Objetivo: Determinar la prevalencia de dislipidemias en pacientes obesos. Métodos: Se realizó un estudio correlacional, retrospectivo y transversal de150 pacientes obesos, quienes acudieron a la consulta externa de la Clínica Medina del Hospital Básico de Guayaquil, desde el 2018 hasta el 2019. Las variables analizadas fueron edad, sexo, índice de masa corporal y resultados de laboratorio, tales como colesterol total, triglicéridos, colesterol LDL y dislipidemia mixta (colesterol HDL y VLDL). Resultados: En la serie predominaron el sexo masculino (62,6%), los pacientes con más de 65 años de edad (42,0 %), los niveles entre rango crítico y alto riesgo (66 pacientes); 16,0 % se clasificaron de alto riesgo con niveles de colesterol superior a 240 mg/dL. Mostraron resultados anormales en cuanto a los triglicéridos 62 afectados, en un rango mayor de 150 con niveles y limítrofe altos. Conclusiones: Se observó una correspondencia entre las dislipidemias y la obesidad, pues todos los pacientes presentaron algún tipo de alteración en los lípidos.

Introduction: Dyslipidemias associated to obesity constitute risk factors of several diseases specially from the cardiovascular system. Objective: To determine the prevalence of dyslipidemias in obese patients Methods: A correlational restrospective and cross-sectional study of 150 obese patients, who visited the outpatients department of Medina Clinic from Hospital Básico in Guayaquil, from 2018 to 2019. Variables used were age, sex, body mass index and laboratory results such as total cholesterol, triglycerids. LDL colesterol and mixed dyslipidemias (cholesterol HDL and VLDL). Results: In the serie, male sex (62.6 %), patients over 65 years (42.0 %), levels between critical and high risk (66 patients) prevailed, 16.0 % were classified as high risk patients with cholesterol level over 240 mg/dL. Sixty two patients showed subnormal results regarding triglycerids, in a rank higher than 150 with high limits and levels. Conclusions: A correspondance between dyslipidemias and obesity was observed, as all patients presented some type of change in lipids.

Perfil lipídico e consumo de bebida alcoólica: estudo longitudinal de saúde do adulto (ELSA-BRASIL) / Lipid profile and alcohol consumption: longitudinal study on adults' health (ELSA-BRASIL) / Perfil lipídico y consumo de bebida alcohólica: Estudio Longitudinal de Salude do Adulto

OBJETIVO: investigar o efeito do consumo de álcool em geral e do tipo de bebida alcoólica consumida, em diferentes medidas lipídicas. MÉTODO: o efeito do consumo de álcool foi investigado, bem como do tipo de bebida alcoólica, em diferentes medidas lipídicas, em ambos os sexos de população do Estudo Longitudinal de Saúde do Adulto. RESULTADOS: foram realizadas análises em relação ao tipo e quantidade de consumo de bebida alcoólica por sexo. O consumo baixo-a-moderado de álcool, independentemente do tipo de bebida alcoólica consumida, resultou em níveis mais elevados de HDL-colesterol, HDL2-colesterol e HDL3-colesterol em homens e mulheres. Não houve participantes da pesquisa que consumiam quantidade baixa a moderada de bebidas alcoólicas destiladas. Os triglicerídeos tiveram efeitos inversos para homens e mulheres no perfil lipídico. Para homens, bebidas destiladas contribuíram para melhor perfil dos triglicerídeos, enquanto para mulheres foi o contrário. Homens que consumiam bebidas alcoólicas destiladas tiveram níveis menores de triglicerídeos e mulheres que consumiam bebidas alcóolicas destiladas tiveram níveis maiores. Nossos resultados estão de acordo com os de estudos anteriores. CONCLUSÃO: o consumo de álcool resultou em níveis diferentes de medidas lipídicas séricas em homens e mulheres. Dessa forma, conclui-se que a resposta ao álcool tem diferenças biológicas.

OBJECTIVE: to investigate the effect of general alcohol consumption and of the type of alcoholic beverage consumed, in different lipid measurements. METHOD: the effect of alcohol consumption as well as that of the type of alcoholic beverage consumed were investigated, in different lipid measurements, for the participants in the Longitudinal Study on Adults' Health for both sexes. RESULTS: analyses were conducted on the type and amount of alcoholic beverage consumed by sex. Low-to-moderate alcohol consumption, regardless of the type of alcoholic beverage, resulted in higher levels of HDL-cholesterol, HDL2- cholesterol and HDL3-cholesterol in males and females. No participants in the study consumed low-to-moderate amounts of spirits. Triglycerides showed inverse effects for men and women according to the lipid profile. For men, spirits contributed to a better triglyceride profile while for women it was the opposite. Men who consumed spirits showed lower triglyceride levels, and women who consumed that beverage type had higher levels. Our results are in agreement with those of previous studies. CONCLUSION: alcohol consumption resulted in different levels of serum lipid measurements in men and women. Thus, it is concluded that response to alcohol has biological differences.

OBJETIVO: investigar el efecto del consumo de alcohol general, así como el tipo de bebida alcohólica consumida, en diferentes medidas lipídicas. MÉTODO: el efecto del consumo de alcohol fue investigado, así como el tipo de bebida alcohólica, en diferentes medidas lipídicas en ambos sexos de población del Estudio Longitudinal de Salud del Adulto. RESULTADOS: se realizaron análisis en relación al tipo y cantidad de consumo de bebida alcohólica por sexo. El consumo bajo a moderado de alcohol, independientemente del tipo de bebida alcohólica consumida, resultó en niveles más altos de HDL-colesterol, HDL2-colesterol y HDL3-coleseterol en hombres y mujeres. No hubo participantes de investigación que consumían en cantidad baja a moderada de bebidas alcohólicas destiladas. Los triglicéridos tuvieron efectos inversos para hombres y mujeres en el perfil lipídico. Para los hombres, las bebidas destiladas contribuyeron a un mejor perfil de los triglicéridos, mientras que para las mujeres fue lo contrario. Los hombres que consumían bebidas alcohólicas destiladas tenían niveles más pequeños de triglicéridos y las mujeres que consumían bebidas alcohólicas destiladas tuvieron niveles más altos. Nuestros resultados están de acuerdo con estudios anteriores. CONCLUSIÓN: el consumo de alcohol resultó en niveles significativamente mayores de HDL-colesterol, HDL2-colesterol y HDL3-colesterol, tanto en mujeres como en hombres. De esta forma, se concluye que la respuesta al alcohol tiene diferencias biológicas.

Evaluation of monocyte to high-density lipoprotein ratio, lymphocytes, monocytes, and platelets in psoriasis,

Abstract Background: Psoriasis is a chronic immune-mediated inflammatory skin disease that is associated with cardiovascular comorbidities. Objectives: The objective of this retrospective study is to assess the C-reactive protein, monocyte-to-high-density-lipoprotein ratio, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and monocyte-to-lymphocyte ratio as inflammatory markers in patients with psoriasis and to search for a relationship between these parameters and psoriasis severity, as defined by the psoriasis area and severity index. Methods: There were 94 patients with psoriasis and 118 healthy controls enrolled in the study. The C-reactive protein, monocyte-to-high-density-lipoprotein ratio, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and monocyte-to-lymphocyte ratio values of two groups were retrospectively evaluated. Results: Statistically significant differences were observed in terms of C-reactive protein, monocyte-to-high-density-lipoprotein ratio, neutrophil-to-lymphocyte ratio and monocyte-to-lymphocyte ratio between the patient and control groups (p = 0.001, p = 0.003, p = 0.038, and p = 0.007, respectively). Positive correlations were found between the psoriasis area and severity index and the values of C-reactive protein, monocyte-to-high-density-lipoprotein ratio, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and monocyte-to-lymphocyte ratio (r: 0.381; p < 0.01, r: 0.203; p < 0.05, r: 0.268; p < 0.01, r: 0.374; p < 0.01, r: 0.294; p < 0.01, respectively). Study limitations: The small sample size and the retrospective design of the study are limitations. Conclusion: Elevated C-reactive protein, monocyte-to-high-density-lipoprotein ratio, neutrophil-to-lymphocyte ratio, and monocyte-to-lymphocyte ratio were significantly associated with psoriasis. A positive correlation between C-reactive protein and monocyte-to-high-density-lipoprotein ratio leads to the suggestion that monocyte-to-high-density-lipoprotein ratio might be a reliable parameter in psoriasis during the follow-up. The relationship between the diasease and inflammatory parameters might provide early detection of cardiovascular morbidities in psoriasis patients.

Fibroblast Growth Factor-23 is associated with High-density lipoprotein in Systemic sclerosis Female patients

@#INTRODUCTION: Fibroblast growth factor-23 (FGF23) is a circulating regulator of phosphate and vitamin D metabolism and has been implicated as a putative pathogenic factor in cardiovascular disease. The objectives of this study were: to compare serum FGF23 levels between systemic sclerosis (SSc) patients and healthy controls and to investigate possible associations between FGF23 and serum lipid profile in SSc patients. METHODS: This cross-sectional study was performed in San Cecilio Hospital, Granada (Spain) from November 2017 to May 2019. We enrolled 62 consecutive female patients affected by SSc and 62 healthy women who served as controls. Cardiovascular risk factors and related biochemical parameters were collected. Serum FGF23 was analyzed using enzyme- linked immunosorbent assay (ELISA). Linear regression was used to examine the cross-sectional associations of serum FGF23 concentrations with high density lipoprotein-cholesterol (HDL-c). RESULTS: There was no significant differences in FGF23 levels between the patients and controls (78.2 ± 60.5 vs. 80.3 ± 56.3 pg/mL, p= 0.662), but we found a statistically significant inverse relationship between FGF23 and HDL-c measurements (r= -0.27; p= 0.03) in women with SSc. In addition, in the linear regression model, higher FGF23 concentrations were associated with lower HDL-c [β = -1.45 95% CI (-2.81, -0.08); p < 0.05]. CONCLUSIONS: We report an association between circulating FGF23 and HDL-c in SSc female patients, representing a novel pathway linking high FGF23 to an increased cardiovascular risk.

Renoprotective Effects of Gallic Acid Against Gentamicin Nephrotoxicity Through Amelioration of Oxidative Stress in Rats

Abstract Gallic acid (GA), as a strong antioxidant, was selected in this study to investigate its possible nephroprotective effects against gentamicin (GM)-induced nephrotoxicity. Twenty-four rats were separated into three groups (n=8): group 1 (control group) received saline (0.5 mL/day), group 2 (GM group) received GM (100 mg/kg/day), and group 3 (treated group) received GM (100 mg/kg/day) and GA (100mg/kg/day). All treatments were performed intraperitoneally for 12 days. After 12 days, the rats were euthanized, and kidneys were removed immediately. For serum preparation, blood samples were collected before killing. Kidney paraffin sections were prepared from one of the kidneys and stained by the periodic acid-Schiff process. GA significantly decreased GM-induced renal histopathological injuries, including tubular necrosis, tubular cast, and leucocyte infiltration compared with the GM group. Additionally, GA significantly improved proteinuria, serum levels of urea and creatinine, and serum activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) compared with nephrotoxic animals. Furthermore, GA caused a significant improvement in the levels of cholesterol (Chol), low-density lipoprotein (LDL), high-density lipoprotein (HDL), and cardiac risk ratios 1 and 2 in comparison with nephrotoxic animals. GA administration was observed to significantly improve the levels of lipid peroxidation, nitric oxide (NO), and glutathione (GSH) compared with the GM group. Finally, the activities and gene expression levels of catalase (CAT) and glutathione peroxidase (GPX) significantly increased following GA administration compared with the GM group. Our results indicated that GA has potential protective effects against GM nephrotoxicity by reducing oxidative stress in rats.

Metabolic syndrome in pregnancy and postpartum: prevalence and associated factors

SUMMARY OBJECTIVE Evaluate the prevalence of metabolic syndrome (MS) and the main associated maternal factors in women without pre-gestational conditions, in early pregnancy and in the immediate postpartum. METHODS Two hundred pregnant women were evaluated at the 16th week of pregnancy, and 187 were reassessed postpartum. MS was diagnosed according to the criteria by the National Cholesterol Education Program Adult Treatment Panel III. In addition to the diagnostic criteria, anthropometric measures, blood pressure, metabolic profile, and visceral and subcutaneous fat thickness (by ultrasonography) were collected from the pregnant woman. The student's t-test was used to compare the prevalence of MS and its components in the 16th week and in the postpartum. Multiple logistic regression was performed to identify the principal factors associated with the syndrome. RESULTS The prevalence of the MS was 3.0% in early pregnancy and 9.7% postpartum (p=0.01). Following multiple logistic regression, the prepregnancy body mass index (BMI) (p=0.04) and high-density lipoprotein cholesterol (HDL-c) (p=0.02) remained associated with MS at 16 weeks, and triglyceride levels evaluated in postpartum (p<0.001) with MS in postpartum. CONCLUSION The frequency of the MS was high in the immediate postpartum. The factors associated were prepregnancy BMI and HDL-c at the 16th week, as well as triglyceride levels postpartum.

RESUMO OBJETIVO Avaliar a prevalência da SM e os principais fatores maternos associados em mulheres sem doenças pré-gestacionais, no início da gravidez e no pós-parto imediato. MÉTODOS Foram avaliadas 200 mulheres na 16a semana de gravidez, sendo 187 reavaliadas no pós-parto. A SM foi diagnosticada de acordo com os critérios do National Cholesterol Education Program Adult Treatment Panel III. Além dos critérios diagnósticos da síndrome, foram coletadas medidas antropométricas, pressão arterial, perfil metabólico e espessura de gordura visceral e subcutânea (através de ultrassonografia) da gestante. O teste t de Student foi usado para comparar a prevalência de SM e dos seus componentes nos dois momentos. Os modelos de regressão logística múltipla, para investigar os principais fatores associados à síndrome na 16a semana de gestação e no pós-parto. RESULTADOS A prevalência da SM foi de 3,0% no início da gravidez e 9,7% no pós-parto (p=0,01). O índice de massa corporal (IMC) pré-gravídico (p=0,04) e o colesterol lipoproteínas de alta densidade (HDL-c) (p=0,02) permaneceram associados à SM na 16a semana. Após o parto, os níveis de triglicerídeos permaneceram associados à SM no pós-parto (p<0,001). CONCLUSÃO A prevalência da SM foi alta no pós-parto imediato e os fatores associados à síndrome foram IMC pré-gravídico e HDL-c na 16a semana, e níveis triglicerídeos no pós-parto.

Relationship of the low-density lipoprotein (LDL)/high-density lipoprotein (HDL) index with antioxidant enzymes and with the oxLDL/HDL index

Introduction: The low-density lipoprotein (LDL)/high-density lipoprotein (HDL) index is a predictive factor for atherosclerosis, which is associated with oxidative modifications. Objective: To assess the association of the index with oxidative stress markers. Methods: 444 subjects were included and were clinically, anthropometrically and biochemically characterized; superoxide dismutase, glutathione peroxidase 3 (GPx3), magnesium and oxidized LDL (oxLDL) index (oxLDL/HDL) were quantified. Results: A decrease of 1.014 units in the LDL/HDL index was associated with a superoxide dismutase increase of 1 unit/mL (p = 0.030), while a decrease of 0.023 units was associated with a GPx3 increase of 1 nmol/min/mL (p < 0.0005). An increase of one unit in the index was associated with an increase of 0.831 in the oxLDL/HDL index (p < 0.05). After controlling for the effect of gender, age, smoking, obesity and insulin resistance, a reduction of 0.001 per index unit was associated with an increase of 1 µg/g of magnesium in the nails (p = 0.020). Conclusions: The LDL/HDL index shows an inverse relationship with the antioxidant status and a direct relationship with oxidation status, regardless of other cardiovascular and oxidative stress risk factors.

Waist-to-height ratio is as reliable as biochemical markers to discriminate pediatric insulin resistance / A razão cintura/estatura é tão confiável quanto marcadores bioquímicos para discriminar resistência à insulina

Abstract Objective: Given the importance of incorporating simple and low-cost tools into the pediatric clinical setting to provide screening for insulin resistance, the present study sought to investigate whether waist-to-height ratio is comparable to biochemical markers for the discrimination of insulin resistance in children and adolescents. Methods: This cross-sectional study involved students from nine public schools. In total, 296 children and adolescents of both sexes, aged 8 -14 years, composed the sample. Waist-to-height ratio, triglycerides/glucose index, and triglycerides-to-HDL-C ratio were determined according to standard protocols. Insulin resistance was defined as homeostatic model assessment for insulin resistance with cut-off point ≥ 3.16. Results: Age, body mass index, frequency of overweight, waist circumference, waist-to-height ratio, insulin, glucose, homeostatic model assessment for insulin resistance, triglycerides, triglycerides/glucose index, and triglycerides-to-HDL-C were higher among insulin resistant boys and girls. Moderate correlation of all indicators (waist-to-height ratio, triglycerides/glucose index, and triglycerides-to-HDL-C ratio) with homeostatic model assessment for insulin resistance was observed for both sexes. The areas under the receiver operational characteristic curves ware similar between waist-to-height ratio and biochemical markers. Conclusion: The indicators provided similar discriminatory power for insulin resistance. However, taking into account the cost-benefit ratio, we suggest that waist-to-height ratio may be a useful tool to provide screening for insulin resistance in pediatric populations.

Resumo Objetivo: Considerando a importância de incorporar ferramentas simples e de baixo custo no cenário clínico-pediátrico para a triagem de resistência à insulina, o presente estudo buscou investigar se a razão cintura/estatura é comparável a marcadores bioquímicos na discriminação de resistência à insulina em crianças e adolescentes. Métodos: Este estudo transversal envolveu estudantes de nove escolas públicas. No total, 296 crianças e adolescentes, de ambos os sexos, com idades entre 8 e 14 anos, compuseram a amostra. A razão cintura/estatura, o índice triglicerídeos/glicose e a razão triglicerídeos/HDL-C foram determinados de acordo com protocolos padrão. A resistência à insulina foi definida por meio do modelo de avaliação homeostática para resistência insulínica, com ponto de corte ≥ 3.16. Resultados: Idade, índice de massa corporal, frequência de excesso de peso, circunferência da cintura, razão cintura/estatura, insulina, glicemia, modelo de avaliação homeostática para resistência insulínica, triglicerídeos, índice triglicerídeos/glicose e razão triglicerídeos/HDL-C foram maiores entre meninos e meninas com resistência à insulina. Também foram observadas, em ambos os sexos, correlações moderadas de todos os indicadores (razão cintura/estatura, índice triglicerídeos/glicose e razão triglicerídeos/HDL-C) com o modelo de avaliação homeostática para resistência à insulina. As áreas sob as curvas ROC foram semelhantes entre a razão cintura/estatura e os marcadores bioquímicos. Conclusão: Os indicadores forneceram poder discriminatório similar para a resistência à insulina. No entanto, levando em conta o custo-benefício, sugerimos que a razão cintura/estatura pode ser uma ferramenta útil para a triagem de resistência à insulina em populações pediátricas.

Intraocular pressure in subjects with beta-thalassemia minor / Pressão intraocular em indivíduos com talassemia beta minor

ABSTRACT Purpose: Beta-thalassemia minor, a common hereditary blood disorder in Mediterranean countries such as Turkey, is associated with insulin resistance. Insulin resistance, in turn, can be associated with excessively high intraocular pressure and, therefore, intraocular pressure-induced blindness. This study aimed to investigate the intraocular pressure in subjects with beta-thalassemia minor. Methods: We conducted a cross-sectional study comprising of 203 subjects divided into two groups: beta-thalassemia minor (103) and healthy (100).Hemoglobin electrophoresis was performed and complete blood count, blood pressures, serum fasting glucose and insulin levels were measured. All subjects underwent ophthalmological examinations including intraocular pressure measurements. Results: Intraocular pressure in the subjects with beta-thalassemia minor was significantly lower than that in healthy subjects (p=0.007). Additionally, intraocular pressure was inversely correlated with hemoglobin A2 levels (p=0.001, r=-0.320). Serum insulin and systolic blood pressure were significantly higher in subjects with beta-thalassemia minor (p=0.03, p=0.009, respectively). Conclusion: Subjects with beta-thalassemia minor had lower intraocular pressure than healthy controls, suggesting beta-thalassemia minor may actually protect against high intraocular pressure.

RESUMO Objetivo: Beta-talassemia menor é uma doença hereditária comum no sangue em países mediterrâneos como a Turquia e está associada à resistência à insulina. A resistência à insulina por sua vez, pode estar associada à pressão intraocular excessivamente alta e, portanto à cegueira induzida pela pressão intraocular. Este estudo teve como objetivo investigar a pressão intraocular em indivíduos com beta-talassemia menor. Métodos: Foi realizado um estudo transversal compreendendo 203 indivíduos divididos em 2 grupos: beta-talassemia menor (103) e saudável (100). Eletroforese de hemoglobina foi realizada e hemograma completo, pressão arterial, glicemia em jejum e níveis de insulina medidos. Todos os indivíduos foram submetidos foram submetidos a exames oftalmológicos, incluindo medidas de pressão intraocular. Resultados: A pressão intraocular nos indivíduos com beta-talassemia menor foi significativamente menor do que em indivíduos saudáveis (p=0,007). Além disso, a pressão intraocular foi inversamente correlacionada com os níveis de hemoglobina A2 (p=0,001, r=-0,320). Insulina sérica e pressão arterial sistólica foram significativamente maiores em indivíduos com beta-talassemia menor (p=0,03, p=0,009, respectivamente). Conclusão: Os indivíduos com beta-talassemia menor tiveram pressão intraocular menor do que os controles saudáveis, sugerindo que a beta-talassemia menor pode, na verdade, proteger contra a alta pressão intraocular.

Sex-differential effects of olanzapine vs. aripiprazole on glucose and lipid metabolism in first-episode schizophrenia

Abstract Objective To compare sex difference in metabolic effect of olanzapine versus aripiprazole on schizophrenia. Methods A twelve-week prospective open-label cohort study to compare four subgroups according to first-episode schizophrenia patients' type of drug usage and sex: female aripiprazole (n = 11), male aripiprazole (n = 11), female olanzapine (n = 10), and male olanzapine (n = 11) for body mass index, fasting serum triglyceride, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and fasting glucose. Results Aripiprazole may be associated with weight gain in female patients with low-baseline weight. Aripiprazole may have an adverse effect of weight and favorable effects of circulating glucose and lipid on female over male schizophrenia patients. The aripiprazole-induced changes in glucose and lipid may be independent of body fat storage, especially for female schizophrenia patients. Olanzapine may have adverse effects of weight, glucose and lipid profiles on female over male schizophrenic patients. Discussion Our findings fill the gap in knowledge and provide a sex-specific guidance to psychiatrist better tailoring treatment to individual sex-differential characteristics and a key clue to understand the sex-differential mechanism of antipsychotics-induced metabolic dysfunction.

Assessment of the Relationship between Monocyte to High-Density Lipoprotein Ratio and Myocardial Bridge / Avaliação da Relação entre a Razão de Monócitos para Lipoproteínas de Alta Densidade e a Ponte Miocárdica

Abstract Background: Assessing the monocyte to high-density lipoprotein ratio (MHR) is a new tool for predicting inflamation, which plays a major role in atherosclerosis. Myocardial bridge (MB) is thought to be a benign condition with development of atherosclerosis, particularly at the proximal segment of the brigde. Objective: To evaluate the relationhip between MHR and the presence of MB. Methods: We consecutively scanned patients referred for coronary angiography between January 2013- December 2016, and a total of 160 patients who had a MB and normal coronary artery were enrolled in the study. The patients' angiographic, demographic and clinic characteristics of the patients were reviewed from medical records. Monocytes and HDL-cholesterols were measured via complete blood count. MHR was calculated as the ratio of the absolute monocyte count to the HDL-cholesterol value. MHR values were divided into three tertiles as follows: lower (8.25 ± 1.61), moderate (13.11 ± 1.46), and higher (21.21 ± 4.30) tertile. A p-value of < 0.05 was considered significant. Results: MHR was significantly higher in the MB group compared to the control group with normal coronary arteries. We found the frequency of MB (p = 0.002) to increase as the MHR tertiles rose. The Monocyte-HDL ratio with a cut-point of 13.35 had 59% sensitivity and 65.0% specificity (ROC area under curve: 0.687, 95% CI: 0.606-0.769, p < 0.001) in accurately predicting a MB diagnosis. In the multivariate analysis, MHR (p = 0.013) was found to be a significant independent predictor of the presence of MB, after adjusting for other risk factors. Conclusion: The present study revealed a significant correlation between MHR and MB.

Resumo Fundamento: A avaliação da razão de monócitos para lipoproteínas de alta densidade (MHR, sigla em inglês) é uma nova ferramenta para se prever o processo inflamatório, o qual desempenha um papel importante na aterosclerose. A ponte miocárdica (PM) é considerada uma condição benigna com desenvolvimento de arteriosclerose, particularmente no segmento proximal da ponte. Objetivo: Avaliar a relação entre a MHR e a presença de PM. Métodos: Examinamos concecutivamente pacientes encaminhados para angiografia coronariana entre janeiro de 2013 e dezembro de 2016, e um total de 160 pacientes, uma parcela dos quais com PM, e outra com artérias coronárias normais, foram incluídos no estudo. As características angiográficas, demográficas e clínicas dos pacientes foram revisadas a partir de registros médicos. Monócitos e colesteróis HDL foram medidos através de hemograma completo. A MHR foi calculada como a razão entre a contagem absoluta de monócitos e o valor do colesterol HDL. Os valores de MHR foram divididos em três tercis, da seguinte forma: tercil inferior (8,25 ± 1,61); tercil moderado (13,11 ± 1,46); e tercil superior (21,21 ± 4,30). Considerou-se significativo um valor de p < 0,05. Resultados: A MHR foi significativamente maior no grupo com PM, em comparação com grupo controle com artérias coronárias normais. Verificamos que a prevalência de PM (p=0,002) aumentou à medida que se elevavam os tercis de MHR. A razão monócitos-colesterol HDL com ponto de corte de 13,35 apresentou sensibilidade de 59% e especificidade de 65,0% (área ROC sob a curva: 0,687, IC95%: 0,606-0,769, p < 0,001) na predição acurada do diagnóstico de PM. Na análise multivariada, a MHR (p = 0,013) mostrou-se um preditor independente significativo da presença de PM, após ajustes para outros fatores de risco. Conclusão: O presente estudo revelou uma correlação significativa entre MHR e PM.