Proteomics: a tool to investigate of composition and function of HDL in hyperlipidemia / Proteômica: uma ferramenta para a investigação da composição e função da HDL em hiperlipidemia

The inverse relationship between HDL-C (high-density lipoprotein cholesterol) and cardiovascular disease is well established. However, it is consensus that the cholesterol content present in HDL does not capture its complexity, and other metrics need to be explored. HDL is a heterogeneous, protein-enriched particle with functions going beyond lipid metabolism. In this way, its protein content seems to be attractive to investigate its behavior in the face of pathologies. Many of the proteins with important function in HDL are in low abundance (<1% of total proteins), which makes their detection challenging. Quantitative proteomics allows detecting proteins with high precision and robustness in complex matrix. However, quantitative proteomics is still poorly explored in the context of HDL. In this sense, in the second chapter of this thesis, the analytical performance of two quantitative methodologies was carefully investigated. These methods achieved adequate linearity and high precision using labeled peptides in a pool HDL, in addition to comparable ability to differentiate proteins from HDL subclasses of healthy subjects. Another bottleneck that waits for a solution in proteomics is the lack of standardization in data processing and analysis after mass spectrometry acquisition. In addition, interest in the cardioprotective properties of omega-3 is growing, but little is known about its effects on the HDL proteome. Thus, in the third chapter of this thesis, we compared five protein quantification strategies using Skyline and MaxDIA software platforms in order to investigate the HDL proteome from mice submitted to a high-fat diet supplemented or not with omega-3. MaxDIA with label-free quantification (MaxLFQ) achieved high precision to show that polyunsaturated fatty acids remodel the HDL proteome to a less inflammatory profile. Therefore, the two studies presented in this thesis begin to open new paths for a deeper and more reliable understanding of HDL, both at the level of protein quantification by mass spectrometry and after data acquisition

A inversa relação entre HDL-C (do inglês, high-density lipoprotein cholesterol) e doenças cardiovasculares é bem estabelecida. No entanto, é consenso que o conteúdo de colesterol presente na HDL não captura sua complexidade, e outras métricas precisam ser exploradas. A HDL é uma partícula heterogênea, enriquecida em proteínas, com funções que vão além do metabolismo de lipídeos. Dessa forma, seu conteúdo proteico parece ser mais atrativo para exprimir seu comportamento frente às patologias. Muitas das proteínas com função importante estão em baixa abundância (<1% do total de proteínas), o que torna a detecção desafiadora. Métodos quantitativos de proteômica permitem detectar proteínas com alta precisão e robustez em matrizes complexas. No entanto, a proteômica quantitativa ainda é pouco explorada no contexto da HDL. Nesse sentido, no segundo capítulo dessa tese, a performance analítica de dois métodos quantitativos foi criteriosamente investigada, os quais alcançaram adequada linearidade e alta precisão usando peptídeos marcados em um pool de HDL, além de comparável habilidade em diferenciar as proteínas das subclasses da HDL de indivíduos saudáveis. Outro gargalo que aguarda por solução em proteômica é a falta de padronização no processamento e análise de dados após a aquisição por espectrometria de massas. Além disso, é crescente o interesse das propriedades cardioprotetivas do ômega-3, porém pouco se conhece sobre seus efeitos no proteoma da HDL. Então, no terceiro capítulo dessa tese, comparamos cinco estratégias de quantificação de proteínas utilizando os softwares Skyline e MaxDIA com o intuito de comparar o proteoma da HDL de camundongos submetidos a uma dieta hiperlipídica suplementados ou não com ômega-3. MaxDIA com quantificação label-free (MaxLFQ) apresentou alta precisão para mostrar que o ômega-3 remodela o proteoma da HDL para um perfil menos inflamatório. Portanto, os dois estudos apresentados nessa tesa começam a abrir novos caminhos para o entendimento mais profundo e confiável da HDL tanto por meio da quantificação das proteínas por espectrometria de massas quanto após à aquisição dos dados

Remodelado cardíaco en el modelo preclínico de falla cardíaca isquémica experimental por dislipidemia en el ratón SR-B1 KO/ApoER6 1h/h / Cardiac remodeling in experimental cardiac failure induced by hyperlipidemia in mice

INTRODUCCIÓN: Los ratones SR-B1 KO/ApoER6 1h/h que son alimentados con una dieta rica en grasas saturadas, desarrollan enfermedad coronaria aterosclerótica severa, complicaciones isquémicas e insuficiencia cardíaca, con alta mortalidad. Los estudios con este modelo se han enfocado fundamentalmente en la enfermedad coronaria y menos en el remodelado cardíaco. El OBJETIVO del trabajo ha sido caracterizar el remodelado miocárdico, evaluar la evolución temporal de la función ventricular izquierda y la sobrevida asociada a enfermedad cardíaca por ateromatosis. MÉTODO: Ratones homocigotos SR-B1 KO/ApoER6 1h/h fueron alimentados por 8 semanas con dieta aterogénica o dieta normal y se comparó la sobrevida en ambos grupos. A las 4 semanas se realizó un ecocardiograma bidimensional. En los ratones eutanasiados se evaluó en la pared cardíaca fibrosis miocárdica y tamaño de los cardiomiocitos por morfometría, apoptosis con técnica de TUNEL e infiltración por células inflamatorias mononucleares (ED1) por inmunohistoquímica. RESULTADOS: En el grupo que recibió dieta aterogénica la sobrevida se redujo en 46,7% (p < 0.001), debido a muerte súbita y a falla cardíaca progresiva. En este grupo, a las 4 semanas se observó dilatación de cavidades izquierdas y disminución de la fracción de eyección del ventrículo izquierdo en comparación con el grupo control (79,3 ± 1,3% vs 66 ± 3,7%, p<0,01). También se observó aumento de la masa cardíaca relativa de 2.1 veces (p<0,001) y del peso pulmonar relativo en 80% (p<0,001), sin cambios en las dimensiones de los cardiomiocitos. En el miocardio de los ratones que recibieron dieta aterogénica hubo un aumento de la fibrosis cardíaca de 7.9 veces (p < 0.01) y del número de cardiomiocitos apoptóticos en 55.9 veces (p < 0.01), junto a un aumento del número de células inflamatorias mononucleares ED1. CONCLUSIONES: En el modelo de falla cardíaca severa de etiología isquémica con alta mortalidad en el ratón homocigoto SR-B1 KO/ApoER6 1h/h sometido a una dieta aterogénica, con falla cardíaca izquierda por disfunción sistólica, el remodelado patológico del miocardio está dado fundamentalmente por apoptosis y fibrosis. También se observa un aumento discreto de macrófagos en la pared cardíaca. Es posible que el edema parietal también pueda ser un mecanismo de remodelado relevante en este modelo.

Abstract: SR-B1 KO/ApoER6 1h/h mice fed a high saturated fat diet develop severe coronary atheromatosis, and cardiac failure with a high mortality rate. Cardiac remodeling under these conditions has not been well studied. AIM: To evaluate the time course of left ventricular function, cardiac remodeling and survival associated to the administration of an atherogenic diet. METHOD: Homozygote SR-B1 KO/ApoER6 1h/h mice received an atherogenic diet for 8 weeks. Mice receiving a normal diet served as controls. Survival rate, myocardial fibrosis, cardiomyocyte size, apoptosis and infiltration by inflammatory or mononuclear cells were compared between groups. A TUNEL technique was used to evaluate apoptosis. RESULTS: A 46.7% survival reduction compared to controls was observed in the experimental group (p<0.01), due to left ventricular and atrial dilatation associated to a decrease in ejection fraction (79,3 ± 1,3% vs 66 ± 3,7%, p<0,01, respectively). Also, an increased cardiac weight, 2.6 times greater was observed in the experimental group, compared to controls. Mice receiving the atherogenic diet showed an 80% increased lung weight. There was no evident change in cardiomyocytes, but there was more (7.9 times) cardiac fibrosis (p<0.01) and 55.9 times more apoptotic cells. (p<0.01), along with a greater number of inflammatory cells and ED1 mononuclear cells. CONCLUSION: Mice receiving an atherogenic diet develop heart failure and reduced survival rate. This is associated with cardiac remodeling with underlying apoptosis an ventricular wall fibrosis. It is posible that wall edema might contribute to the observed cardiac remodeling.

Exploring the shared genes of hypertension, diabetes and hyperlipidemia based on microarray

Given their relationship with metabolic syndrome and systematic inflammatory diseases, the pathogenesis of hypertension, hyperglycemia, and hyperlipidemia is closely related. To explore the common genes among these three conditions, spontaneous hypertensive rats (SHR), spontaneous diabetic Goto-Kakizaki rats (GK) and hyperlipidemia rats (HMR) were reared for experiments. Gene array was used to identify the genes of SHR, GK and HMR compared with normal Wistar rats using TBtools software. First, real-time PCR was applied to verify these genes, and Cytoscape software was used to construct networks based on the National Center for Biotechnology Information (NCBI) database. Second, Kyoto Encyclopedia of Genes and Genomes (KEGG) database analysis was performed to classify the genes. Visualization and Integrated Discovery (DAVID) database and Gene Ontology database were used to explore the biological function. Finally, Onto-tools Pathway Express was used to analyze the pathways of shared genes. Importantly, upregulated common genes, such as Bad, Orm1, Arntl and Zbtb7a, were used to construct a network of 150 genes, while downregulated genes, such as Mif and Gpx1, formed a network of 29 genes. Interestingly, the networks were involved in various pathways, such as insulin signal pathway, endometrial cancer pathway, circadian rhythm pathway, and pancreatic cancer pathway. We discovered common genes of SHR, GK and HMR compared with normal Wistar rats, and the association of these genes together with biological function were preliminarily revealed.

Large Accumulation of Collagen and Increased Activation of Mast Cells in Hearts of Mice with Hyperlipidemia / Grande Acúmulo de Colágeno e Aumento da Ativação de Mastócitos nos Corações de Ratos com Hiperlipidemia

Abstract Background: Hyperlipidemia, which is characterized by an elevation of lipids in the bloodstream, is a major risk factor for cardiac disease. Objectives: The present study investigated the role of fibrosis in the progression of hyperlipidemia in the mice heart, and whether mast cell activation was associated with the fibrosis process. Methods: Hyperlipidemia was produced in C57BL / 6 mice by feeding them on a high-fat diet for 8 weeks.To assess tissue fibrosis, picrosirius red staining was performed. Hematoxylin & eosin (H&E) staining was performed to identify the histopathological changes in the hearts. Immunohistochemistry was also accomplished to determine the localization of transforming growth factor (TGF)-β and α-smooth muscle actin (α-SMA). Western blotting was performed to analyze the expression of chymase, tryptase, TGF-β, α-SMA and activity of Wnt/β-catenin pathway. At the end, serum total cholesterol (TC) and triglycerides (TG) levels were measured. All the values were expressed as means ± SD, the statistical significance level adopted was 5%. Results: Hyperlipidemia mice showed significantly increased collagen deposition in the hearts compared with normal mice. In addition, H&E staining showed significant cellular degeneration. Cardiac muscle was arranged in disorder with fracture in mice of the model group. Immunohistochemistry and western blot analysis revealed that expression levels of tryptase, chymase, β-catenin, TGF-β and α-SMA were significantly increased in the hyperlipidemia mice compared with the control group. Conclusions: The results indicated that mast cell activation might induce cardiac fibrosis by tryptase and chymase in hyperlipidemia, which had a close relationship with the increased activity of TGF-β/Wnt/β-catenin pathway.

Resumo Fundamentos: A hiperlipidemia, que se caracteriza por uma elevação dos lipídeos na corrente sanguínea, é um importante fator de risco para a doença cardíaca. Objetivos: O presente estudo investigou o papel da fibrose na progressão da hiperlipidemia no coração do rato e se a ativação dos mastócitos estava associada ao processo de fibrose. Método: A hiperlipidemia foi produzida em ratos C57BL/6 alimentando-os com uma dieta rica em gordura durante 8 semanas. Para avaliar a fibrose tecidual, foi realizada coloração vermelha picro-Sirius. A coloração com hematoxilina e eosina (H & E) foi feita para identificar as alterações histopatológicas nos corações. A imuno-histoquímica também foi levada a cabo para determinar a localização do fator de crescimento transformante (TGF) -β e α-actina do músculo liso (α-SMA). O Western Blot foi realizado para analisar as expressões de quimase, triptase, TGF-β, α-SMA e a atividade da via Wnt / β-catenina. Finalmente, se mediram os níveis séricos de colesterol total (TC) e triglicerídeos (TG). Todos os valores foram expressos como média ± DP, o nível de significância estatística adotado foi de 5%. Resultados: Os ratos hiperlipidêmicos mostraram aumento significativo da deposição de colágeno nos corações em comparação com ratos normais. Além disso, a coloração de H & E mostrou degeneração celular significativa. O músculo cardíaco estava em desordem com ruptura de fibras em ratos do grupo modelo. A análise imuno-histoquímica e o Western Blot revelaram que os níveis de expressão de triptase, quimase, β-catenina, TGF-β e α-SMA estavam significativamente aumentados nos ratos hiperlipidêmicos em comparação com o grupo controle. Conclusões: Os resultados indicaram que a ativação de mastócitos pode induzir fibrose cardíaca por triptase e quimase em hiperlipidemia, a qual teve uma relação estreita com a atividade aumentada da via TGF-β / Wnt / β-catenina.

Genetic & epigenetic approach to human obesity.

Obesity is an important clinical and public health challenge, epitomized by excess adipose tissue accumulation resulting from an imbalance in energy intake and energy expenditure. It is a forerunner for a variety of other diseases such as type-2-diabetes (T2D), cardiovascular diseases, some types of cancer, stroke, hyperlipidaemia and can be fatal leading to premature death. Obesity is highly heritable and arises from the interplay of multiple genes and environmental factors. Recent advancements in Genome-wide association studies (GWAS) have shown important steps towards identifying genetic risks and identification of genetic markers for lifestyle diseases, especially for a metabolic disorder like obesity. According to the 12th update of Human Obesity Gene Map there are 253 quantity trait loci (QTL) for obesity related phenotypes from 61 genome wide scan studies. Contribution of genetic propensity of individual ethnic and racial variations in obesity is an active area of research. Further, understanding its complexity as to how these variations could influence ones susceptibility to become or remain obese will lead us to a greater understanding of how obesity occurs and hopefully, how to prevent and treat this condition. In this review, various strategies adapted for such an analysis based on the recent advances in genome wide and functional variations in human obesity are discussed.

Hypolipidemic and antioxidant activity of ethanolic extract of Symplocos racemosa Roxb. in hyperlipidemic rats: An evidence of participation of oxidative stress in hyperlipidemia.

Hypolipidemic and antioxidant activity profiles of ethanolic extracts of Symplocos racemosa (EESR) were studied by triton-WR1339 (acute) and high fat diet induced (chronic) hyperlipidemic rat models. In both the models, a significant increase in total cholesterol (TC), triglycerides (TG), very low density lipoproteins (VLDL), low density lipoproteins (LDL) and decrease in high density lipoproteins (HDL) in serum were observed. EESR (200 and 400 mg/kg) and simvastatin (10 mg/kg) administered orally reduced the elevated serum lipids (TC, TG, VLDL, LDL), restored the decreased HDL and improved the atherogenic index. In high fat diet induced hyperlipidemic model, EESR treatment prevented the increased formation of malondialdehyde (MDA) in liver, restored the depleted liver antioxidants, glutathione, superoxide dismutase, catalase significantly. The increased liver cholesterol, HMG-CoA reductase activity and body weight of hyperlipidemic rats were significantly reduced by EESR treatment. The EESR inhibited HMG-CoA reductase, a rate limiting enzyme in cholesterol biosynthesis, thereby causing hypolipidemic effects. EESR treatment also improved histoarchitecture of hepatocytes in hyperlipidemic rats. Experimental findings demonstrated anti-hyperlipidemic and antioxidant activity of EESR, which may be directly or indirectly related to its antioxidant activity. The hypolipidemic activity of EESR may be due to the presence of flavonoids phenolic compounds, phenolic glycosides and steroids.

Association between Nutrition Label Use and Chronic Disease in Korean Adults: The Fourth Korea National Health and Nutrition Examination Survey 2008-2009

Nutrition labels are helpful for chronic disease management in patients requiring balanced nutritional intake. This study aimed to investigate the association between the use of nutrition labels and chronic diseases (hypertension, diabetes mellitus, and hyperlipidemia) by using the 2008-2009 Korea National Health and Nutrition Examination Survey data. A total of 10,695 individuals aged 20 and over was included in the analysis. Using multiple logistic regressions, there was no difference in nutrition label use between the chronic disease and normal groups (men with hypertension OR, 0.97; 95% CI, 0.75-1.27; women with hypertension OR, 0.83; 95% CI, 0.67-1.03; men with diabetes OR, 0.70; 95% CI, 0.45-1.08; women with diabetes OR, 1.13; 95% CI, 0.84-1.53; men with hyperlipidemia OR, 0.85; 95% CI, 0.59-1.23; women with hyperlipidemia OR, 1.14; 95% CI, 0.91-1.44). In hyperlipidemia patients, awareness (OR, 1.55; 95% CI, 1.03-2.35) and control (OR, 2.19; 95% CI, 2.32-3.63) of disease were related to nutrition label use; however, no significant associations were found for the hypertension and diabetes mellitus patients. Considering the importance of dietary habits in the management of chronic diseases, an improvement in nutrition label use by patients with these diseases is required.

Co-administration of trientine and flaxseed oil on oxidative stress, serum lipids and heart structure in diabetic rats.

The administration of flaxseed oil or flaxseed oil plus trientine in diabetic rats reduced triglyceride, very low density lipoprotein, and total cholesterol. Furthermore, the combined treatment significantly increased superoxide dismutase activity and attenuated serum Cu2+. The results suggest that the administration of flaxseed oil plus trientine is useful in controlling serum lipid abnormalities, oxidative stress, restoring heart structure, and reducing serum Cu2+ in diabetic rats.

Preclinical immunohistochemical biomarkers for testicular changes in hyperlipidemic rats and the role of Ocimum fratissimum

High plasma levels of cholesterol or triglycerides were accompanied by testicular dysfunction, besides being a high risk factor for coronary and cerebrovascular diseases. The aim of the study was to investigate the histological effect of Ocimum gratissimum on the testes of rats with tyloxapol-induced hyperlipidemia as well as investigate its effect on androgen receptor [AR] and proliferating cell nuclear antigen [PCNA] distribution as a molecular biomarker for spermatogenesis. Twenty-four adult male albino rats were used and divided into four equal groups: the control group [group I]; the group treated with crude aqueous extract of O. gratissimum [group II]; the tyloxapol-injected group [group III]; and the group injected with tyloxapol followed by treatment with O. gratissimum [group IV]. The rats were anesthetized at the time of sacrifice; thereafter, blood samples were collected to estimate the lipid profile levels, and the testis specimens were examined histologically and immunohistochemically for AR and PCNA. The present results showed a significant increase in the levels of total cholesterol, triglycerides, and low-density lipoprotein and a decrease in the levels of high-density lipoprotein in the tyloxapol-injected group [hyperlipidemic rats] with histological changes in the form of loss of normal distribution of spermatogenic cells, vacuolation, diminution of germinal epithelium, and sloughing of germ cells into the tubular lumen with acidophilic material in the interstitial tissues when compared with the control group. Immunohistochemical study showed a significant decrease in the intensity of AR immunostaining in Sertoli, Leydig, and peritubular myoid cells and in the number of PCNA immunopositive germ cells; the index PCNA values were also significantly decreased in tyloxapol-injected rats in comparison with controls. O. gratissimum administration after tyloxapol injection induced a significant reduction in lipid profile with marked improvement in testicular histological changes as well as increase in the number of AR and PCNA immunopositive cells. This study revealed that AR and PCNA indexing can be used as a preclinical biomarker for testicular changes in hyperlipidemic states. The extract of O. gratissimum leaves provides effective hypolipidemic activity and exerts significant improvement in combating the harmful effects of hyperlipidemia on the rat testes

Hypolipidemic activity of Hibiscus rosa sinensis root in rats.

The hypolipidemic activity of Hibiscus rosa sinensis (family Malvaceae) root extract was studied on triton and cholesterol-rich high fat diet (HFD) induced models of hyperlipidemia in rats. In triton WR-1339-induced hyperlipidemia, feeding with root extract (500 mg/kg body wt/day p.o.) exerted lipid-lowering effect, as assessed by reversal of plasma levels of total cholesterol (TC), phospholipids (PL) and triglycerides (TG) and reactivation of post-heparin lipolytic activity (PHLA) of plasma. The other model was fed with cholesterol-rich HFD and root extract (500 mg/kg body wt/ day p.o.) simultaneously for 30 days. This also caused lowering of lipid levels in plasma and liver homogenate and reactivation of plasma PHLA and hepatic total lipoprotein lipase activity. The hypolipidemic activity of Hibiscus rosa sinensis root was compared with a standard drug guggulipid (200 mg/kg body wt/day p.o.), a known lipid- lowering agent in both models. Histopathological findings in rat liver supported the protective role of H. rosa sinensis root extract in preventing cholesterol-rich HFD-induced hepatic steatosis.

Prevalencia de hipertrigliceridemia en adultos jóvenes en el Ambulatorio Militar La Rosaleda: durante el período 2003-2005

Recientemente se ha demostrado la importancia de las alteraciones en los valores séricos lipídicos como factor de riesgo de mortalidad por enfermedad cardiovascular en población aparentemente sana, asimismo de una relación significativa entre la hiperlipidemia y la extensión de la aterosclerosis. Con el objetivo de conocer la prevalencia de hipertrigliceridemia en adultos jóvenes se realizó un estudio en 122 pacientes con edades comprendidas entre los 20 y 24 años de edad que asistieron al Ambulatorio Militar La Rosaleda durante los años 2003-2005. El valor máximo encontrado fue de 858 mg/dL correspondiente al sexo masculino, y el valor menor fue de 25 mg/dL también del sexo masculino. El promedio de los niveles séricos para el sexo femenino fue de 114 mg/dL y para el sexo masculino fue de 134 mg/dL. La prevalencia general fue del 24,6 por ciento. El 13,94 por ciento corresponde al sexo femenino y el 10,66 por ciento corresponde al sexo masculino

It has been recently proven that changes in lipid serum levels are a significant risk factor for cardiovascular disease-related mortality in apparently healthy population, and show a close relation between hyperlipidemia and atherosclerosis extension. In order to know the prevalence of hyper-tryglyceridemia among young adults, 122 patients aged 20 to 24 and visiting the La Rosaleda Military Ambulatory Hospital between 2003 and 2005 were studied. Among male patients, the highest level found was 858 mg/dL, and the lowest 25 mg/dL. The average serum level for female patients was 114 mg/dL,and 134 mg/dL for male patients. Overall prevalence was 24.6%. The 13.94% among females and 10.66% among males

Frecuencia de dislipidemia en una población de adultos jóvenes / Frequency of dislipidemia in a population young-adult

Analizar la frecuencia de dislipidemias en una población hospitalaria y ambulatoria sin enfermedad predisponente. La muestra estuvo conformada por 200 pacientes, 100 hospitalizados y 100 ambulatorios en los Servicios de Medicina Interna del Hospital Universitario de Caracas de 15 a 45 años. Se determinaron los valores de lípidos en sangre de dichas poblaciones y se realizó una encuesta conformada por antecedentes, hábitos y examén físico que incluyó la evolución de los parámetros del síndrome metabólico. De 200 pacientes estudiados (121 mujeres y 79 hombres 30,19 años, la dislipidemia prevalente fue el HDL colesterol bajo (41 por ciento) predominantemente en los masculinos. El 21,5 por ciento de la muestra fue diagnósticada como síndrome metabólico. El 47,5 por ciento resultó con sobrepeso y al 14,5 por ciento con algún grado de obesidad. No se encontró relación entre los resultados obtenidos con los antecedentes familiares. Se encontró relación entre sedentarismo y hábito tabáquico con colesterol total elevado, LDL colesterol elevado y dislipidemia mixta. La pesquisa de dislipidemia en la población joven asintóm tica es de gran utilidad para realizar prevención. La frecuencia encontrada en este grupo fue elevada en comparación con la obtenida en otros trabajos. Se sugiere continuar el estudio de prevalencia en todo el país.

Effect of cholesterol diet on reproductive function in male albino rats

The present study was carried out to investigate the effect of cholesterol diet [400 mg/kg body weight] for 60 days on gonadal function in albino rats. The study was conducted in the Animal House Unit at Jordan University of Science and Technology, School of Medicine, Irbid, Jordan between October 2003 and February 2004. Adult male and female albino rats of Sprague Dawley strain were raised under controlled temperature and light. Male rats were divided into: a] control group - rats receiving vehicle [olive oil] for 60 days and treatment group - rats receiving cholesterol diet for a reproductive cycle. Animals were weighed and autopsied 24 hours after the last dose. Biochemical and histological approaches were used to assess fertility in both groups. The treatment caused significant reduction [p<0.001] in sperm motility and density in cauda epididymides and testes. A significant reduction [p<0.001] in epithelial cell height of caput, cauda and seminal vesicle was also observed. In the treated group, there was a significant reduction [p<0.001] in seminiferous tubules diameter and Leydig cell nuclear diameter. Spermatocytes [primary and secondary] were significantly decreased [p<0.01] and spermatids were significantly reduced [p<0.001] in the treatment group. Whereas, the number of degenerating Leydig cells [interstitial cells] increased significantly [p<0.001]. Serum biochemistry reveals significant increase [p<0.001] in cholesterol and triglyceride levels. The intragastric administration of cholesterol diet to male rats for 60 days significantly reduced the number of females impregnated by these males. However, the number of implantations and number of viable fetuses were significantly [p<0.01] decreased in female rats impregnated by males that ingested cholesterol. On the other hand, the number of resorptions was significantly [p<0.01] increased in females impregnated by males that ingested cholesterol. The histometry and histology of reproductive organs confirm these results. Hyperlipidemia can cause alteration in the biochemistry and histometry of reproductive organs and can cause inhibition of spermatogenesis via the Leydig cell

Does Waist Indicate Dyslipidemia better than BMI in Korean Adult Population?

Obesity is an independent and modifiable risk factor for cardiovascular disease, and known as a core of the metabolic syndrome. Obesity has been largely diagnosed based upon anthrompometric measurements like waist circumference (WC) and body mass index (BMI). We sought to determine associations between anthropometric measurements and dyslipidemia in a community adult sample composed of 1,032 community residents (356 men, 676 women) aged 50 yr and over in Namwon, Korea. Blood tests for lipid profiles, including total cholesterol (TC) and HDL cholesterol (HDL) were performed, and dyslipidemia was defined as TC/HDL greater than 4. Anthropometric measurements included WC, waist-to-height ratio (WHtR), waist-to-hip ratio, and BMI. All anthropometric measures were categorized into quartiles and evaluated for associations with dyslipidemia. TC/HDL showed the significant associations with the anthropometric measures, independently of potential confounders. In women, increases of obesity indexes by quartile analyses showed linear increases of odds ratios for dyslipidemia (p values <0.01 by trend test). In men, except BMI, same patterns of association were noted. WC and WHtR were significantly associated with dyslipidemia in Korean adult population. As a simple and non-invasive method for a detection of obesity and dyslipidemia, anthropometric measurements could be efficiently used in clinical and epidemiologic fields.

Dislipidemias / Dyslipidemia

As doenças cardiovasculares representam a principal causa de óbito em indivíduos diabéticos. Entre os fatores que contribuem para que o processo aterosclerótico se revele mais extenso e severo nesses pacientes, podemos destacar as dislipidemias. O diabete melito pode levar a uma série de alterações no metabolismo lipídico. Aumento nos níveis de triglecerídeos, diminuiçäo dos níveis de HDL-colesterol e formaçäo de partículas de LDL-colesterol de maior potencial aterogênico representam as alterações mais comuns. As atuais recomendações visam a proporcionar diagnóstico e tratamento precoces. O diagnóstico envolve näo só a identificaçäo da dislipidemia em si, como também a investigaçäo de causas secundárias. A eficácia da terapêutica hipolipemiante exige a adesäo a mudançäs no estilo de vida e uso adequado de medicações.

Estudio comparativo sobre la eficacia y tolerancia de Lovastatina Vs. Gemfibrozil, en pacientes con dislipidemias / Comparative study efficacy and toleration of Lovastatin Vs. Gemfibrozil in patients with dyslipidemies

Se evaluó el efecto de 40 mg de Lovastatina en comparación con 900 mg de Gemfibrozil en 32 pacientes con hiper-colesterolemia primaria e hipertriglicidemia, después de un período de dieta tipo I de acuerdo a la Sociedad Americana de Cardiologia. En ambos grupos se produjo un descenso en los niveles de colesterol, siendo más pronunciado en el grupo que recibió Lovastatina con un descenso promedio de 92 mg/dl Vs. 58,5 mg/dl de Gemfibrozil. En relación a los triglicéridos los descensos fueron de 99 mg/dl para el grupo de Lovastatina y de 149,9 mg/dl en el grupo de Gemfibrozil. No se reportaron efectos secundarios en el grupo que recibió Lovastatina, el grupo con Gemfibrozil (5/16) en 31 por ciento presentaron efectos en el área gastrointestinal