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

Tempo de aceleração na via de saída do ventrículo direito: correlação com a função diastólica do ventrículo esquerdo, sexo e idade / Right ventricular outflow tract acceleration time: correlation with left ventricular diastolic function, sex, and age

Fundamento: O tempo de aceleração na artéria pulmonar (TAP) pode ser utilizado para avaliação da hipertensão pulmonar na análise da função diastólica do ventrículo esquerdo. Objetivo: Avaliar se existe correlação entre o valor do tempo de aceleração na artéria pulmonar e parâmetros da função diastólica do ventrículo esquerdo em indivíduos com função sistólica do ventrículo esquerdo preservada e de acordo com sexo, idade e fatores de risco cardiovasculares. Métodos: Estudo observacional, transversal. Foram selecionados 119 pacientes (59 mulheres; 49,6%). Os indivíduos foram submetidos ao ecocardiograma transtorácico incluindo os valores de tempo de aceleração na artéria pulmonar; ondas E e A e relação E/A ao Doppler espectral do influxo mitral; ondas e' septal, e' lateral e relação E/e' ao Doppler tecidual do anel mitral; pressão sistólica na artéria pulmonar e volume atrial esquerdo. Resultados: No sexo feminino, foi encontrada correlação positiva (coeficiente de correlação de Spearman) entre o valor do tempo de aceleração na artéria pulmonar e e' lateral (coeficiente de correlação de Spearman de 0,47; p=0,002), relação E/A (coeficiente de correlação de Spearman de 0,32; p=0,04) e e' septal (coeficiente de correlação de Spearman de 0,36; p=0,023) e uma correlação negativa entre o valor do tempo de aceleração na artéria pulmonar e pressão sistólica na artéria pulmonar (coeficiente de correlação de Spearman de -0,43; p=0,034). No sexo masculino, não foi encontrada correlação significativa. Foram encontrados menores valores de tempo de aceleração na artéria pulmonar em mulheres com hipertensão arterial sistêmica quando comparadas a mulheres sem hipertensão arterial sistêmica (0,13±0,03 segundos versus 0,16±0,03 segundos; p = 0,015). Conclusão: O presente estudo mostrou correlação significativa dos valores do TAP com alguns parâmetros da função diastólica do ventrículo esquerdo apenas no sexo feminino, sendo que mulheres hipertensas apresentaram menores valores de TAP. (AU)

Background: Pulmonary artery acceleration time (PAAT) can be used as a parameter in the evaluation of pulmonary hypertension and aids left ventricular diastolic function (LVDF) analyses. Objective: To assess whether there is a correlation between PAAT and LVDF parameters in individuals with a preserved left ventricular systolic function and by sex, age, and cardiovascular risk factors. Method: Observational cross-sectional study. One hundred nineteen patients were selected (59 women [49.6%]). The subjects underwent transthoracic echocardiography including measurements of PAAT, E and A waves and E/A ratio, e' septal and e' lateral waves and E/e' ratio, pulmonary artery systolic pressure (PASP), and left atrial volume. Results: In female patients, a positive correlation (Spearman's correlation coefficient ­ Spearman correlation coefficient [SCC]) was found between the PAAT value and the lateral e' (SCC, 0.47; p = 0.002), with the E/A ratio (SCC, 0.32; p = 0.04), and with septal e' (SCC, 0.36; p = 0.023), and a negative correlation between PAAT and PASP (SCC, -0.43; p = 0.034). In men, no correlation was found between PAAT. and any parameters. Lower PAAT values were found in women with systemic arterial hypertension (hypertension) than in women without hypertension (0.13 ± 0.03 s versus 0.16 ± 0.03 s; p = 0.015). Conclusion: The present study showed a significant correlation between PAAT and some LVDF parameters in female patients only. Hypertension was correlated with lower PAAT values in women. (AU)

Fatores associados a anormalidades na cintilografia de perfusão miocárdica de pacientes diabéticos / Factors associated with abnormalities on myocardial perfusion scintigraphy in diabetic patients

O diabetes melito é o maior fator de risco para doença arterial coronariana. Além da longa duração de diabetes, outros fatores, como presença de doença arterial periférica e tabagismo são fortes preditores para anormalidades na cintilografia de perfusão do miocárdio. O objetivo deste estudo foi avaliar o impacto dos fatores de risco de pacientes diabéticos nos resultados da cintilografia de perfusão do miocárdio e comparar com os resultados de pacientes não diabéticos em uma clínica de medicina nuclear. Foi realizado um estudo transversal retrospectivo por meio da análise de prontuários de pacientes que realizaram cintilografia miocárdica no período de 2010 a 2019. Foram avaliados 34.736 prontuários. Analisando a fase de estresse da cintilografia de perfusão do miocárdio, os portadores de diabetes melito precisaram receber estímulo farmacológico duas vezes mais que os não diabéticos para sua realização. Também foram avaliados fatores que tivessem impacto negativo no resultado da cintilografia de perfusão do miocárdio, e foi visto que o diabetes melito (33,6%), a insulinoterapia (18,1%), a hipertensão arterial sistêmica (69,9%), a dislipidemia (53%), o sedentarismo (83,1%), o uso de estresse farmacológico (50,6%), a dor torácica típica (8,5%) e a angina limitante durante o teste (1,7%) estiveram associados significativamente (p<0,001) a anormalidades neste exame. (AU)

Diabetes mellitus (DM) is the greatest risk factor for coronary artery disease. In addition to a long duration of diabetes, the presence of peripheral arterial disease and smoking are strong predictors of abnormalities on myocardial perfusion scintigraphy (MPS). This study aimed to assess the impact of risk factors in diabetic patients on MPS results and compare them with those of non-diabetic patients in a nuclear medicine clinic. A retrospective cross-sectional study was performed through the analysis of the medical records of patients who underwent MPS in 2010­2019. A total of 34,736 medical records were evaluated. Analyzing the stress phase of MPS, DM patients required two-fold more pharmacological stimulation than non-diabetic patients for MPS. Factors that negatively impact the MPS results were also evaluated, and DM (33.6%), insulin therapy (18.1%), systemic arterial hypertension (69.9%), dyslipidemia (53%), sedentary lifestyle (83.1%), use of pharmacological stress (50.6%), typical chest pain (8.5%), and limiting angina during the test (1.7%) were significantly associated (p < 0.001) with test abnormalities. (AU)

Periodontitis, dislipidemia y obesidad. Su relación / Relationship between periodontitis and dyslipidemia and obesity

Introducción: Desde hace algunos años, se reporta en la literatura médica una posible asociación entre la periodontitis con otras enfermedades y condiciones sistémicas. Objetivo: Determinar la relación entre la periodontitis con las dislipidemia, obesidad o ambas. Material y Método: Estudio analítico transversal. Del universo de 9 350 individuos residentes en el municipio Plaza de la Revolución en edades entre 35 y 70 años, ambos sexos; se seleccionó una muestra probabilística utilizando el esquema muestreo aleatorio simple de 1 200 individuos que otorgaron su consentimiento para participar. Debían presentar, en su historia clínica médica, resultados de análisis complementarios para detectar dislipidemia en los últimos seis meses y como mínimo seis dientes en boca. Las variables estudiadas fueron: periodontitis, dislipidemia, obesidad y presencia de dislipidemia y obesidad en el mismo individuo. Los sujetos se clasificaron en tres grupos: con presencia de dislipidemia, obesos y ambas entidades (dislipidemia+obesidad). Resultados: La variable más encontrada fue dislipidemia (73,0 por ciento), seguida de periodontitis (62,2 por ciento). La periodontitis se encontró con mayor frecuencia en individuos que presentaban dislipidemia (48,1 por ciento), los obesos presentaron en su mayoría periodontitis, en los sujetos que presentaron dislipidemia + obesidad, la periodontitis fue más frecuente que en los que no presentaban ambas entidades unidas. Conclusiones: La periodontitis se relacionó con la dislipidemia, obesidad y ambas unidas, no así con la obesidad, aunque fue más frecuente en estos últimos que en los no obesos(AU)

Introduction: A possible association between periodontitis and other diseases and systemic conditions has been reported by the medical literature for many years. Objective: To determine the relationship between periodontitis and dyslipidemia and obesity or both of them. Material and Methods: An analytical cross-sectional study was conducted. The universe consisted of 9 350 individuals between the ages of 35 and 70 years, of both sexes who live in Plaza de la Revolución Municipality. From this universe, a sample composed of 1 200 individuals who gave their consent to participate in the study was selected by simple random sampling method. Their clinical records should include the results of complementary tests to determine dyslipidemia in the last six months; also, they should have at least six teeth in the mouth. The variables studies included: periodontitis, dyslipidemia, obesity and the presence of dyslipidemia and obesity in the same individual. The subjects were divided into three groups: with dyslipidemia, obese and with both entities (dyslipidemia+obesity). Results: The most common variable found was dyslipidemia (73,0 percent), followed by periodontitis (62,2 percent). Periodontitis was more frequently found in individuals with dyslipidemia (48,1 percent), and the majority of obese subjects had periodontitis. Periodontitis was more frequent in individuals with dyslipidemia + obesity than in the ones that did not present both entities at the same time. Conclusions: Periodontitis was associated with dyslipidemia, obesity and with both entities at the same time, but it was not associated with obesity only. However, it was more frequent in obese subjects than in non-obese ones(AU)

Effect of long-term consumption of oxidized polyunsaturated fatty acids on atherosclerotic lesion in LDL receptor knockout mice / Efeito do consumo crônico de ácidos graxos poliinsaturados oxidados na aterosclerose em camundongos knockout para receptor de LDL

Polyunsaturated fatty acids (PUFA) are susceptible to enzymatic and non-enzymatic oxidation, leading to the production of secondary compounds that present different physiological effects. Among the PUFA, the products formed from Omega 6 (n-6 FA) and Omega 3 (n-3 FA) fatty acids oxidation can modulate inflammation, dyslipidemia and oxidative stress preventing or reducing the atherosclerosis progression. In fact, the effect of chronic intake of edible oils containing products of polyunsaturated fatty acids oxidation (POPs) on atherosclerosis is still controversial. In general POPs from n-6 FA have a more pro-inflammatory profile than POPs from n-3 FA. Thus, the objective of this study was to compare the chronic intake of partially oxidized n-6 FA and n-3 FA rich oils on atherosclerosis biomarkers. Initially, six edible oils containing a higher amount of n-6 and n-3 FA were submitted to oxidative conditions, simulating the steps of transport, storage and consume. It was observed that oxidative reaction started in all oils since the first step and at the moment of consumption, some oxidative chemical markers were out the legal range suggested by the Official Agencies. In addition, it was possible to identify the type of secondary product formed from each precursor oil, providing a better information for oils quality control. After this step, fish and soybean oils were chosen as n-3 FA and n-6 FA rich oils, respectively. Using LDLr(-/-) mice, the effect of three oxidative levels of soybean oil was evaluated after 24 weeks of supplementation. Animals fed with the oil with the highest level of oxidation (fried and reused oil) showed no body weight gain, suggesting that POPs from soybean oil at this level could promote a browning effect on white adipose tissue by increasing UCP-1 expression. This group also showed the highest concentration of lipoproteins in plasma. However, these metabolic differences did not accelerate atherosclerosis in the animals. Finally, the effect of POPs from n-3 FA and n-6 FA oxidation were compared also using LDLr(-/-) mice as model for experimental atherosclerosis. Some alterations observed after n-3 FA supplementation, such as the increase of liver weight, IL-6, SONPC, 8-HETE and 15-F2-Isop and the decrease of BAT and glucose, were reversed by their POPs. In addition, POPs from n-6 FA caused increased of LDL and 5-HETE. As observed in the previous study, these metabolic alterations were not enough to prevent or accelerate atherosclerosis, as measured by histological analysis of the lesion size in the aorta. These results suggest that although a significant amount of POPs are being consumed by diet, their metabolic effects did not influence atherosclerotic plaques in the animal model. However, besides lesion area in the aortas, new studies should also evaluate the plaques stability

Os ácidos graxos poliinsaturados (PUFA) são suscetíveis à oxidação enzimática e não enzimática, levando à produção de compostos secundários que apresentam diferentes efeitos fisiológicos. Entre os PUFA, os produtos formados a partir da oxidação dos ácidos graxos ômega 6 (n-6 FA) e ômega 3 (n-3 FA) podem modular a inflamação, dislipidemia e estresse oxidativo, impedindo ou reduzindo a progressão da aterosclerose. De fato, o efeito da ingestão crônica de óleos contendo produtos da oxidação de ácidos graxos poliinsaturados (POPs) na aterosclerose ainda é controverso. Em geral, os POPs dos n-6 FA têm um perfil mais pró-inflamatório do que os POPs dos n-3 FA. Assim, o objetivo deste estudo foi comparar a ingestão crônica de POPs provenientes de óleos ricos em n-6 FA e n-3 FA em biomarcadores de aterosclerose. Inicialmente, seis óleos ricos em n-6 FA e n-3 FA foram submetidos a condições oxidativas, simulando as etapas de transporte, armazenamento e consumo. Observou-se que a reação oxidativa iniciou-se em todos os óleos desde a primeira etapa e, no momento do consumo, alguns marcadores oxidativos estavam fora da faixa legal sugerida pelas agências reguladoras. Além disso, foi possível identificar o tipo de produto secundário formado a partir de cada óleo precursor, fornecendo melhores informações para o controle de qualidade dos óleos. Após esta etapa, os óleos de peixe e soja foram escolhidos como óleos ricos em n-3 FA e n-6 FA, respectivamente. Utilizando camundongos LDLr(-/-), o efeito de três níveis oxidativos de óleo de soja foi avaliado após 24 semanas de suplementação. Os animais alimentados com o óleo com maior nível de oxidação (óleo frito e de reuso) não apresentaram ganho de peso corporal, sugerindo que os POPs do óleo de soja nesse nível de oxidação pudessem promover um efeito de Browning no tecido adiposo branco, aumentando a expressão de UCP-1. Este grupo também mostrou a maior concentração de lipoproteínas no plasma. No entanto, essas diferenças metabólicas não aceleraram a aterosclerose nos animais. Finalmente, o efeito de POPs da oxidação de óleos ricos em n-3 FA e n-6 FA foi comparado também usando camundongos LDLr(-/-), como modelo para aterosclerose experimental. Algumas alterações observadas após a suplementação com óleo de peixe fresco, como aumento do peso hepático, IL-6, SONPC, 8-HETE e 15-F2-IsoP e diminuição da BAT e glicose, foram revertidas por seus POPs. Além disso, os POPs do óleo de soja causaram aumento de LDL e 5-HETE. Como observado no estudo anterior, essas alterações metabólicas não foram suficientes para prevenir ou acelerar a aterosclerose, medida pela análise histológica do tamanho da lesão na aorta. Esses resultados sugerem que, embora uma quantidade significativa de POPs esteja sendo consumida pela dieta, seus efeitos metabólicos não influenciaram as placas ateroscleróticas no modelo animal. Porém, além da área de lesão nas aortas, novos estudos também devem avaliar a estabilidade das placas

Lipid profile and response to statin therapy in patients with hypopituitarism

ABSTRACT Objective: Dyslipidemia is prevalent among patients with hypopituitarism, especially in those with growth hormone (GH) deficiency. This study aimed to evaluate the response to statin therapy among adult patients with dyslipidemia and hypopituitarism. Subjects and methods: A total of 113 patients with hypopituitarism following up at a neuroendocrinology unit were evaluated for serum lipid levels. Dyslipidemia was diagnosed in 72 (63.7%) of these patients. A control group included 57 patients with dyslipidemia and normal pituitary function. The distribution of gender, age, weight, and dyslipidemia type was well balanced across both groups, and all participants were treated with simvastatin at doses adjusted to obtain normal lipid levels. Results: Patients with hypopituitarism and dyslipidemia presented deficiency of TSH (69%), gonadotropins (69%), ACTH (64%), and GH (55%) and had a similar number of deficient pituitary axes compared with patients with hypopituitarism but without dyslipidemia. All patients with dyslipidemia (with and without hypopituitarism) had lipid levels well controlled with doses of simvastatin ranging from 20-40 mg/day. The mean daily dose of simvastatin was not significantly different between patients with and without hypopituitarism (26.7 versus 23.5 mg, p = 0.10). Similarly, no significant variation in simvastatin dose was observed between patients with different causes of hypopituitarism, presence or absence of GH deficiency, number of deficient pituitary axes, prior pituitary radiation therapy or not, and presence or absence of obesity. Conclusions: Patients with GH deficiency without GH replacement showed good response to simvastatin at a mean dose equivalent to that used in individuals with dyslipidemia and normal pituitary function.

Factores pronósticos de aterosclerosis subclínica en pacientes dislipidémicos / Prognostic factors subclinical atherosclerosis in dyslipidemic patients

Introducción: La aterosclerosis subclínica es predictora de eventos vasculares futuros y es diagnosticada por imágenes y biomarcadores sin que existan manifestaciones clínicas. Objetivo: Identificar los factores pronósticos asociados con la aterosclerosis subclínica en pacientes dislipidémicos. Método: Se realizó un estudio de cohorte en el Hospital Hermanos Ameijeiras en 1028 pacientes en el periodo de 2016 al 2019. Resultados: La existencia de placa de ateroma fue de 26,9 por ciento. Existieron diferencias significativas relacionadas al tabaquismo (30,0 por ciento vs 23,7 por ciento). En las variables lipídicas, el promedio de los valores de la LDLc fue superior en los pacientes con placa de ateroma y la relación CT/LDL fue mayor en los que no tienen esta alteración. La frecuencia de engrosamiento del complejo íntima-media mayor de 1,0 mm fue de 37,1 por ciento. Existieron diferencias significativas relacionadas al tabaquismo (30,4 por ciento vs 22,4 por ciento) y la presencia de HTA (56,7 por ciento vs 48,8 por ciento ) en las variables lipídicas el promedio de los valores de la HDLc fue superior en los pacientes sin aumento del grosor del complejo íntima-media y la elevación CT/HDL fue mayor en los que presentan dicha alteración. Conclusiones: Los factores que influyen de manera independiente en la probabilidad de formación de las placas de ateroma son la LDLc (elevada), la edad, los triglicéridos y el sexo masculino y los que influyen en la probabilidad para el engrosamiento del complejo íntima-media son la HDLc (baja), el tabaquismo, y la hipertensión arterial(AU)

Introduction: Subclinical atherosclerosis is a predictor of future vascular events and is diagnosed by imaging and biomarkers without any clinical manifestations. Objective: To identify the prognostic factors that are associated with subclinical atherosclerosis in dyslipidemic patients. Method: A cohort study was carried out at the Hermanos Ameijeiras Hospital in 1028 patients in the period from 2016 to 2019. Results: The existence of atheroma plaque was 26.9 percent. There were significant differences related to smoking (30.0 percent vs 23.7 percent). In the lipid variables, the average of the LDLc values ​​is higher in patients with atheroma plaque and the CT/LDL ratio is higher in those without this alteration. Regarding the frequency of thickening of the intima-media complex greater than 1.0 mm, it was 37.1 percent. There were significant differences related to smoking (30.4 percent vs 22.4 percent) and the presence of HTA (56.7 percent vs 48.8 percent in the lipid variables, the average of the HDLc values ​​is higher in the patients without an increase in the thickness of the intima-media complex and the CT/HDL elevation is greater in those with said alteration. Conclusions: The factors that independently influence the probability of atheroma plaque formation are LDLc (elevated), age, triglycerides and male sex, and those that influence the probability of thickening of the intima-media complex. They are HDLc (low), smoking, and high blood pressure(AU)

Associação entre o índice de massa corporal e a gravidade e complexidade das lesões coronarianas em pacientes pós-infarto / Association of body mass index and coronary lesions severity and complexity in post-myocardial infarction patients

Objetivo: Avaliar a associação entre o índice de massa corporal e a gravidade das lesões coronarianas em pacientes com infarto agudo do miocárdio. Métodos: Coorte aninhada ao Catarina Heart Study que avaliou 350 indivíduos durante o primeiro evento de infarto agudo do miocárdio e o 30º dia pós-infarto. As variáveis qualitativas foram analisadas pelo teste do qui-quadrado. Após o resultado da distribuição, a avaliação de variáveis quantitativas foi feita pelo teste de t de Student, pela correlação de Pearson, pelo teste de Mann-Whitney e pela correlação de Spearman. Resultados: Indivíduos com obesidade G2 (15,4%) tiveram maior probabilidade de trombose em 30 dias em comparação a indivíduos com índice de massa corporal normal (1,1%), com p=0,005. Indivíduos com obesidade grau 1 (6,0%) e obesidade grau 2 (7,7%) tiveram mais eventos de infarto agudo do miocárdio em 30 dias em comparação a indivíduos com índice de massa corporal normal (0,0%), com p=0,019 e p=0,009, respectivamente. Nenhuma associação significativa foi encontrada em termos de fração de ejeção do ventrículo esquerdo, mortalidade e complexidade das lesões coronarianas (escore SYNTAX e TIMI frame count). Conclusão: A obesidade em diversos graus está diretamente associada a fatores de risco para doença cardiovascular, como hipertensão arterial sistêmica, dislipidemia e tabagismo. Não houve associação entre o índice de massa corporal com a gravidade das lesões coronarianas ou a fração de ejeção do ventrículo esquerdo. Não houve diferença na mortalidade comparando-se indivíduos com índice de massa corporal elevado a pacientes com índice de massa corporal normal. Pacientes com obesidade tiveram mais desfechos cardiovasculares, como trombose e novo evento de infarto agudo do miocárdio em 30 dias, ao serem comparados a pacientes com índice de massa corporal normal. Outros desfechos de seguimento em 30 dias não estiveram associados ao índice de massa corporal.

Objective: To evaluate the association between body mass index and severity of coronary lesions in patients with acute myocardial infarction. Methods: A cohort nested to Catarina Heart Study, which evaluated 350 individuals during the first event of myocardial infarction and the 30th day post-infarction. Qualitative variables were analyzed using the Chi-square test. After the distribution result, the evaluation of quantitative variables was done through Student's t-test, Pearson's correlation, Mann Whitney's test, and Spearman's correlation. Results: Individuals with G2 obesity (15.4%) had a greater probability of having thrombosis in 30 days compared to individuals with normal body mass index (1.1%), p=0.005. Individuals with G1 obesity (6.0%) and G2 obesity (7.7%) had more events of myocardial infarction in 30 days compared to individuals with normal body mass index (0.0%), with p=0.019 and p=0.009, respectively. No significant association was found in terms of left ventricle ejection fraction, mortality, and complexity of coronary lesions (SYNTAX score and TIMI frame count). Conclusion: Obesity in several degrees is directly associated with risk factors for cardiovascular disease, such as hypertension, dyslipidemia, and smoking. There was no association between the body mass index and the severity of coronary lesions or left ventricle ejection fraction. There was no difference in mortality comparing individuals with high body mass index to patients with normal body mass index. Patients with obesity had more cardiovascular outcomes, such as thrombosis and a new event of myocardial infarction in 30 days when compared to patients with normal body mass index. Other follow-up outcomes in 30 days were not associated with body mass index

Dislipidemia e hipertensão arterial. uma relação nefasta / Dyslipidemia and arterial hypertension. a harmful relation

A relação maléfica entre hipertensão arterial sistêmica (HAS) e dislipidemia torna-se explícita a partir da análise da progressão dessas comorbidades simultaneamente, agravando diretamente o risco cardiovascular. Se observa o aumento de espécies reativas do oxigênio gerando estresse oxidativo, a diminuição da biodisponibilidade de óxido nítrico promovendo disfunção endotelial, maior concentração de moléculas LDL oxidadas o que resulta na progressão de eventos ateroscleróticos. Somado a isto, se percebe que o tratamento em conjunto das duas doenças é mais eficaz quando comparado ao tratamento de cada uma delas isoladamente, demonstrando o efeito sinérgico do tratamento em conjunto. Concluindo então, que as comorbidades estão intimamente relacionadas e agravam o estado geral do paciente

The harmful relations systemic arterial hypertension (SAH) and dyslipidemia be comes explicit from the analysis of the progression of these comorbidities simultaneously, directly aggravating cardiovascular risk. There is an increase in reactive oxygen species generating oxidative stress, a decrease in the nitric oxide bioavailability promoting endothelial dysfunction, a higher concentration of oxidized LDL molecules which results in the progression of atherosclerotic events. In addition, it is clear that the joint treatment of the two diseases is more effective when compared to the treatment of each separately, demonstrating the synergistic effect of the joint treatment. In conclusion, then, that comorbidities are closely related and aggravate the patient's general condition

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.

Granuloma anular perforante: patologia inusual / Perforating Granuloma Annulare: unusual pathology

Resumen El Granuloma Anular (GA) es una dermatosis inflamatoria crónica, benigna, auto limitada, de etiología desconocida. Existen numerosas variantes clínicas dentro de las cuales se encuentra la perforante, de presentación inusual. La histopatología más característica de GA, cuenta con la presencia de histiocitos epitelioides en empalizada alrededor de áreas de degeneración focal de fibras de colágeno con depósitos de mucina. La variedad perforante evidencia eliminación transepidérmica de fibras de colágeno. Se presenta un paciente de 72 años de edad, diabético, dislipémico, con lesiones pruriginosas en dorso de ambas manos, con el diagnóstico de granuloma anular perforante. Realizó tratamiento con clobetasol tópico, más antihistamínicos por vía oral, quedando una cicatriz atrófica.

Abstract Granuloma annulare is a chronic, benign, self-limiting, inflammatory dermatosis of unknown etiology. There are numerous clinical variants within which is the perforating, unusual presentation. The most histopathology characteristic of GA is the presence of palisading epithelioid histiocytes around areas of focal degeneration of collagen with mucin deposits. The perforating variety evidences transepidermal elimination of collagen tissue. A 72 years-old, diabetes, dyslipidemic patient is presented with pruritic lessions on the dorsum of both hands, with the diagnosis of perforating granuloma annulare. I perform medical treatment with topical clobetasol, leaving an atrophic scar.

High-fat diet augments ovariectomy-induced bone resorption in rats / Dieta rica en grasas aumenta la resorción ósea inducida por ovariectomía en ratas

Menopause complications such as cardiovascular and bone diseases represent a major public health concern. We sought to determine whether a high-fat diet (HFD) can augment ovariectomy-induced bone resorption in a rat model of menopause possibly via the upregulation of the inflammatory biomarkers and dyslipidemia. Rats were either ovariectomized and fed a standard laboratory chow (model group) or were ovariectomized and fed with a HFD for 15 weeks before being sacrificed. Ovariectomy significantly (p<0.05) increased body weight, dyslipidemia, insulin resistance, pro-inflammatory cytokines tumor necrosis factor-a (TNF-α) and interleukin-6 (IL-6), and biomarker of bone resorption, nuclear factor-kB (NF-kB), which were augmented by feeding animals with a HFD. This was confirmed through immunohistochemical study, where ovariectomy induced expression of p65/NF-kB protein in tibia bone sections of the model group, which were augmented by HFD. HFD augments ovariectomy-induced bone resorption through increased inflammatory biomarkers and NF-kB in rats.

Las complicaciones de la menopausia, como las enfermedades cardiovasculares y óseas, representan un importante problema de salud pública. Intentamos determinar si una dieta alta en grasas (HFD) puede aumentar la resorción ósea inducida por ovariectomía en un modelo de menopausia en ratas, a través de la regulación positiva de los biomarcadores inflamatorios y la dislipidemia. Las ratas fueron ovariectomizadas y alimentadas con una comida estándar de laboratorio (grupo modelo) o fueron ovariectomizadas y alimentadas con un HFD durante 15 semanas antes de ser sacrificadas. La ovariectomía aumentó significativamente (p <0,05) el peso corporal, dislipidemia, resistencia a la insulina, citocinas proinflamatorias, factor de necrosis tumoral a (TNF-α) e interleucina-6 (IL-6), y el biomarcador de resorción ósea, factor nuclear-kB (NF-kB), que se aumentaron alimentando animales con un HFD. Esto se confirmó a través del estudio inmunohistoquímico, donde la ovariectomía indujo la expresión de la proteína p65 / NF-kB en secciones de hueso de tibia del grupo modelo, que fueron aumentadas por HFD. HFD aumenta la resorción ósea inducida por ovariectomía a través del aumento de biomarcadores inflamatorios y NF-kB en ratas.

Widespread use of anti-retroviral therapy elevated the prevalence of dyslipidemia in HIV-infected Chinese patients

With the widespread use of high-efficiency antiretroviral therapy (HAART), the life expectancy of HIV-infected patients has been significantly extended. However, the metabolic complications among HIV-infected patients treated with HAART have become the most common problem in the world. It is very important to explore the incidence of dyslipidaemia and studies on the role of potential risk factors in HIV-infected Chinese patients treated with HAART are sparse. Therefore, we designed current study, to investigate the effects of therapeutic intervention and continuous information support on the lifestyle of HIV/AIDS patients with dyslipidaemia. Three hundred and six HIV/AIDS patients admitted to the AIDS clinic in Beijing from January 2016 to January 2017 were recruited and assigned into two groups: the treatment group (n=64) and the control group (n=64). The median age of the participants was 38.8±11.0 years (range 20-75 years). The prevalence of dyslipidemia in control and treatment group was (59/64) 92.2% and (53/64) 82.8%, respectively. In this study, low HDL-cholesterol (HDLC) led to abnormalities 47/64 (73.3%) in the control group and 35/64 (54.7%) in HAART-treatment group. Additionally, HAART group showed higher triglyceride, total cholesterol, and low-density lipoprotein (246.1±171.8, 1.73±1.61 mmol/L, 4.46±1.1 mmol/L, 2.54±0.74 mmol/L). In multivariate analysis, gender, marital status, high BMI, dietary habits and physical activity were potential risk factors for dyslipidemia in HIV-infected Chinese patients. In this study, we reported high prevalence dyslipidemiain two HIV infected groups. We suggest that the appropriate diagnosis should be performed for analyzing the metabolic complications in HIV-infected Chinese patients. Further studies are very important to understand the role of potential risk factors in metabolic complications.

Real-world evidence of health outcomes and medication use 24 months after bariatric surgery in the public healthcare system in Brazil: a retrospective, single-center study

OBJECTIVES: The number of bariatric procedures has significantly increased in Brazil, especially in the public Unified Health System. The present study describes health outcomes and medication use in obese patients treated in a major hospital that performs publicly funded surgery in Brazil. METHODS: A retrospective, single center study was conducted to collect real-world evidence of health outcomes and medication use in 247 obese patients (female, 82.2%) who underwent open Roux-en-Y gastric bypass. Changes in weight and body mass index (BMI), presence of apnea, hypertension, and type 2 diabetes (T2D), and medication use (hypertension, diabetes, and dyslipidemia) were assessed preoperatively and up to 24 months postoperatively. The mean cost of medications was calculated for the 12-month preoperative and 24-month postoperative periods. RESULTS: During the surgery, the mean age of patients was 43.42 years (standard deviation [SD], 10.9 years), and mean BMI was 46.7 kg/m2 (SD, 6.7 kg/m2). At 24 months, significant declines were noted in weight (mean, -37.6 kg), BMI (mean, -14.3 kg/m2); presence of T2D, hypertension, and apnea (-29.6%, -50.6%, and -20.9%, respectively); and number of patients using medications (-66.67% for diabetes, -41.86% for hypertension, and -55.26% for dyslipidemia). The mean cost of medications (total costs for all medications) decreased by >50% in 12-24 postoperative months compared to that in 12 preoperative months. CONCLUSION: Roux-en-Y gastric bypass successfully reduced weight, BMI, and comorbidities and medication use and cost at 24 months in Brazilian patients treated in the public Unified Health System.

Efecto del consumo de alimentos con elevado contenido lipídico sobre el perfil lipídico de ratones sanos / Effect of the consumption of foods with high lipid content on lipid profile of healthy mice

La alteración de los lípidos en sangre o dislipidemias sobre todo el colesterol y triglicéridos, son un factor de riesgo de ateroesclerosis y enfermedades cardiovasculares. En este trabajo se analizó el efecto del consumo de huevo, clara, yema de huevo, mantequilla y maní sobre el perfil lipídico de ratones sanos. Se utilizaron seis grupos de ratones hembras sanas, el grupo control (GC) recibió balanceado comercial, mientras que en los demás grupos, 15% de su alimentación diaria consistió en huevo entero (GHE), yema (GY), clara de huevo (GCH), manteca o mantequilla (GMT) o maní (GMN), durante 28 días. Al final de este periodo, se obtuvo la muestra de suero para la determinación de los niveles de colesterol total (CT), triglicéridos (TG), colesterol HDL, colesterol LDL y colesterol VLDL, y se calcularon los índices de riesgo aterogénico y de riesgo cardiaco. Se observó un aumento estadísticamente significativo en los niveles de CT y LDL en relación al GC en los grupos GHE (p<0,0001), GY (p<0,0001), GCH (p<0,005) y GMT (p<0,001), mientras que en niveles de TG presentan un aumento los grupos GHE (p<0,0001) y GY (p<0,0001). El nivel de HDL aumentó significativamente en los grupos GHE (p<0,005) y GMT (p<0,001), y en cuanto al índice de riesgo cardiaco y aterogénico el grupo GY fue el único que reveló aumento significativo (p<0,0001). En el grupo que recibió maní (GMN), no se alteraron los niveles de lípidos, y por lo tanto tampoco el riesgo cardiaco ni aterogénico, lo que se traduce en un menor riesgo de enfermedades cardiovasculares de este grupo(AU)

The alteration of blood lipids or dyslipidemias, especially cholesterol and triglycerides, are a risk factor for atherosclerosis and cardiovascular diseases. In this work, the effect of consumption of egg, egg white, egg yolk, butter and peanut on the lipid profile of healthy mice was analyzed. Six groups of healthy female mice were used, the control group (GC) received commercial pellets, while for the other groups, 15% of their daily food consisted of whole egg (GHE), egg yolk (GY), egg white (GCH) ), butter (GMT) or peanut (GMN), for 28 days. At the end of this period, a serum sample was obtained for the determination of the levels of total cholesterol (CT), triglycerides (TG), HDL cholesterol, LDL cholesterol and VLDL cholesterol, and cardiac and atherogenic risk index were calculated. A statistically significant increase in TC and LDL levels was observed in relation to GC in the GHE (p <0,0001), GY (p <0,0001), GCH (p <0,005) and GMT (p <0,001) groups; whereas TG levels showed an increase in the GHE (p <0,0001) and GY (p <0,0001) groups. The HDL level increased significantly in the groups GHE (p <0,005) and GMT (p <0,001), and in terms of the cardiac and atherogenic risk index, the GY group was the only group that revealed a significant increase (p <0,0001). In the group that received peanuts (GMN), the lipid levels were not altered, and therefore neither the cardiac nor the atherogenic risk, which indicates the risk of cardiovascular diseases in this group, were affected(AU)

An atypical presentation of a severe and massive atheroembolic disease / Uma apresentação atípica de doença ateroembólica grave

ABSTRACT Atheroembolic renal disease (AERD) is a kidney manifestation of atherosclerosis as a systemic disease. AERD is defined as a renal impairment secondary to embolization of cholesterol crystals with consequent occlusion of renal vascularization. The current case report describes one patient with multiple risk factors but without any inciting event history who presents a very atypical clinical course of a severe and massive atheroembolic disease that developed spontaneously and silently.

RESUMO A doença renal ateroembólica (DRAE) é uma manifestação renal da aterosclerose enquanto patologia sistêmica. A DRAE é definida como uma disfunção renal secundária à embolização de cristais de colesterol seguida da oclusão da vascularização renal. O presente relato descreve o caso de um paciente com vários fatores de risco, porém sem um evento precipitante, que se apresentou com um curso clínico bastante atípico de doença ateroembólica grave de evolução espontânea e silenciosa.

Síndrome de Turner: nuestra experiencia en la creación del Registro Institucional y de la Unidad Interdisciplinaria en el Hospital Italiano de Buenos Aires: un primer paso para el mejor seguimiento / Turner syndrome: our experience in the creation of the Registry Institutional and Interdisciplinary Unit at the Italian Hospital of Buenos Aires: a first step to the best follow-up

El síndrome de Turner (ST) resulta de la ausencia completa o parcial del segundo cromosoma sexual en fenotipos femeninos. Tiene una incidencia de 1:2000- 2500 nacidas vivas. Recién en la última década se ha puesto atención a la salud de las adultas con ST. La mortalidad es 3 veces superior respecto de la población general debido al riesgo de disección aórtica por anomalías cardiovasculares estructurales y aterosclerosis vinculada a hipertensión arterial, diabetes, dislipidemia y obesidad. También presentan elevada prevalencia de enfermedades autoinmunitarias. Objetivo: evaluar la calidad del seguimiento clínico de pacientes adultas con ST, comparando los controles de salud preconformación y posconformación del Registro y de la Unidad Interdisciplinaria. En el año 2017 fuimos convocados para integrar el Programa de Enfermedades Raras del Hospital Italiano de Buenos Aires. A partir de la creación del Registro Institucional y del equipo multidisciplinario obtuvimos mejoría significativa en los controles por las especialidades de cardiología, endocrinología y otorrinolaringología, en los controles bioquímicos del metabolismo lipídico, hidrocarbonado, hepatograma, TSH y anticuerpos para celiaquía e imágenes cardiovasculares y densitometría ósea. En conclusión, el seguimiento sistematizado e institucional, mediante el Registro y la creación de la Unidad Interdisciplinaria de Síndrome de Turner, permitió encontrar las falencias del sistema de atención y optimizar el seguimiento de esta población. (AU)

Turner syndrome (TS) results from the complete or partial absence of the second sex chromosome in female phenotypes. It has an incidence of 1: 2000-2500 girls born alive. Only in the last decade has been paid attention to the health of adults women with TS. Mortality is 3 times higher than in the general population due to the risk of aortic dissection cause to structural cardiovascular anomalies and atherosclerosis related to hypertension, diabetes, dyslipidemia and obesity. They also have a high prevalence of autoimmune diseases. Until nowadays in Argentina do not exist a national registry of this disease that complies with the international follow-up recommendations for these patients. We proposed to develop the institutional register at 2014 and a multidisciplinary team was created to care and follow up girls and women with TS during 2015. It was indexed to Italian Hospital of Buenos Aires' Rare Diseases Program since 2017. After the creation of the institutional registry and the multidisciplinary team we obtained a significant improvement in cardiology, endocrinology and otorhinolaryngology schedule visits, in lipids and hydrocarbon metabolism, liver, thyroid and celiac diseases biochemical controls and in the performance of cardiovascular MNR and bone densitometry. In conclusion, the systematized and institutional follow-up, through the registry and the creation of the Interdisciplinary Unit of Turner Syndrome, allowed us to find the flaws of the care system and to optimize the follow up of this population. (AU)

Dyslipidemia in Adolescents Seen in a University Hospital in the city of Rio de Janeiro/Brazil: Prevalence and Association / Dislipidemia em Adolescentes Atendidos em um Hospital Universitário no Rio de Janeiro/Brasil: Prevalência e Associação

Abstract Background: Early exposure to obesity favors greater risks of cardiovascular factors such as dyslipidemia. Objectives: To establish the prevalence of dyslipidemia, and to evaluate its association with nutritional status of the adolescents attended at the ambulatory of the Adolescent Health Studies Center of the University Hospital Pedro Ernesto. Methods: This is a cross-sectional, observational study, the sample of which was of convenience, consisting of adolescents from 12 to 18 years old of both genders. The lipid profile was evaluated, along with its association with the anthropometric indicators: body mass index and waist circumference. For statistical analysis, a significance level of 5% was used. Results: A total of 239 adolescents, 104 boys (43.5%) and 135 girls (56.5%) were evaluated and, of these, 52 (21.8%) were eutrophic, 60 (25.1%) overweight, and 127 (53.1%) obese. Obeseadolescents had significantly lower mean values of HDL-cholesterol (44.7 mg/dl vs 53.9 mg/dl; p < 0.001) and higher triglycerides (109.6 mg/dl vs 87.3 mg/dl; p = 0.01). The changes with higher prevalence were low HDL-cholesterol (50.6%), hypercholesterolemia (35.1%), and hypertriglyceridemia (18.4%). A negative association of HDL-cholesterol with body mass index and a positive association of triglycerides with body mass index could be observed, even after adjustment for gender and skin color. Conclusion: This study demonstrated high prevalence of dyslipidemia among adolescents. In view of the significant association between lower levels of HDL-cholesterol and increased triglycerides with overweight, the control of these factors should receive attention, with the precocious diagnosis of the dyslipidemia being important, mainly if it is associated with another cardiovascular risk, to develop effective intervention strategies.

Resumo Fundamentos: Exposição precoce à obesidade favorece maiores riscos de fatores cardiovasculares como dislipidemias. Objetivos: Estabelecer a prevalência de dislipidemia e avaliar sua associação com o estado nutricional de adolescentes atendidos no ambulatório de atenção secundária do Núcleo de Estudos da Saúde do Adolescente do Hospital Universitário Pedro Ernesto. Métodos: Estudo transversal observacional, cuja amostra foi de conveniência e compreendeu adolescentes de 12 a 18 anos de ambos os sexos. Avaliado o perfil lipídico e sua associação com os indicadores antropométricos: índice de massa corporal e circunferência da cintura. Para as análises estatísticas foi utilizado nível de significância de 5%. Resultados: Foram avaliados 239 adolescentes, 104 meninos (43,5%) e 135 meninas (56,5%) e destes, 52 (21,8%) apresentaram eutrofia, 60 (25,1%) sobrepeso e 127 (53,1%) obesidade. Os adolescentes com obesidade apresentaram valores médios de HDL-colesterol significativamente menores (44,7 mg/dl vs. 53,9 mg/dl; p < 0,001) e triglicerídeos maiores (109,6 mg/dl vs. 87,3 mg/dl; p = 0,01). As alterações com maior prevalência foram HDL-colesterol baixo (50,6%), hipercolesterolemia (35,1%) e hipertrigliceridemia (18,4%). Foi possível observar associação negativa do HDL-colesterol com o índice de massa corporal e associação positiva dos triglicerídeos com o índice de massa corporal, mesmo após ajuste para gênero e cor da pele. Conclusão: Este estudo demonstrou alta prevalência de dislipidemia entre os adolescentes. Tendo em vista a associação significativa entre baixos níveis de HDL-colesterol e triglicerídeos aumentados com excesso de peso, o controle destes fatores deve receber atenção, sendo importante o diagnóstico precoce da dislipidemia principalmente se associada a outro risco cardiovascular, para desenvolvimento de estratégias de intervenção.

Prevalence and factors associated to chronic kidney disease in older adults / Prevalência e fatores associados à doença renal crônica em idosos

ABSTRACT OBJECTIVE To verify the prevalence of chronic kidney disease and the factors associated to it in older adults (≥ 60 years). METHODS This is a population-based research conducted in 2014, involving 1,016 older adults living in urban and rural areas of the municipality of Rio Branco, Acre. Chronic kidney disease was defined by glomerular filtration rate < 60 ml/min/1.73 m 2 , estimated by the equations of the Chronic Kidney Disease Epidemiology Collaboration, and the presence of albuminuria > 29 mg/g. Association measure were estimated by gross and adjusted odds ratio (OR), with a confidence level of 95% (95%CI). RESULTS The overall prevalence of chronic kidney disease was 21.4% in older adults, with the associated factors age, diabetes (OR = 3.39; 95%CI 2.13-5.40), metabolic syndrome (OR = 2.49; 95%CI 1.71-3.63), self-assessment of poor health (OR = 1.79; 95%CI 1.10-2.91), arterial hypertension (OR = 1.82; 95%CI 1.04-3.19) and obesity (OR = 1.69; 95%CI 1.02-2.80). CONCLUSIONS The prevalence of chronic kidney disease was high in older adults, being associated with age, self-assessment of health as bad or very bad, obesity, diabetes and metabolic syndrome.

RESUMO OBJETIVO Verificar a prevalência de doença renal crônica e os fatores a ela associados em idosos (≥ 60 anos). MÉTODOS Trata-se de um inquérito de base populacional realizado em 2014, envolvendo 1.016 idosos residentes nas zonas urbana e rural do município de Rio Branco, Acre. A doença renal crônica foi definida pela taxa de filtração glomerular < 60 ml/min/1,73 m 2 , estimada pelas equações da Chronic Kidney Disease Epidemiology Collaboration , e presença de albuminúria > 29 mg/g. Medidas de associação foram estimadas por regressão logística (OR) bruta e ajustada, com grau de confiança de 95% (IC95%). RESULTADOS A prevalência geral de doença renal crônica foi de 21,4% nos idosos, com os fatores associados idade, diabetes (OR = 3,39; IC95% 2,13-5,40), síndrome metabólica (OR = 2,49; IC95% 1,71-3,63), autoavaliação de saúde ruim (OR = 1,79; IC95% 1,10-2,91), hipertensão arterial (OR = 1,82; IC95% 1,04-3,19) e obesidade (OR = 1,69; IC95% 1,02-2,80). CONCLUSÕES A prevalência de doença renal crônica foi alta entre os idosos, estando associada com idade, autoavaliação de saúde como ruim ou muito ruim, obesidade, diabetes e síndrome metabólica.