RESUMEN
The association between TP53 gene polymorphisms and breast cancer (BC) in Brazilian women is a controversial topic. In this cross-sectional study, we evaluated the association between clinical pathological variables and three polymorphisms (TP53*11, TP53*72, and TP53*248) in BC patients and controls. Genomic DNA was extracted from the blood cells of 393 participants; the cancer-free control subjects were 26-72 years old (41 ± 11.03) and the BC patients were 28-80 years old (51 ± 10.70). We used standard polymerase chain reaction-restriction fragment length polymorphism and confirmed the results by genetic sequencing. In TP53*11, there was 100% homozygous Glu distribution in both groups. TP53*72 showed genotypic distribution: in the control group, there was 16.10% homozygous Pro, and 42.44% heterozygous and 41.46% homozygous Arg; in the BC group, there was 15.43% homozygous Pro, and 42.55% heterozygous and 42.02% homozygous Arg. The relative frequency of each allele was 0.37% for Pro and 0.63% for Arg in the control group, and 0.37% for Pro and 0.63% for Arg in the BC group. The nuclear grade (P = 0.0084) and adapted histological grade (P = 0.0265) were associated with TP53*72. The distribution of the codon 72 genotypes did not deviate from Hardy-Weinberg equilibrium in either group. In TP53*248, there was 100% homozygous Arg distribution in both groups. In codon 72, the Arg allele is the most prevalent in Brazilian women. TP53*72 may be associated with susceptibility to BC, although more studies are required to evaluate the profile of Brazilian women with BC.
Asunto(s)
Neoplasias de la Mama/genética , Codón/genética , Polimorfismo Genético/genética , Proteína p53 Supresora de Tumor/genética , Adulto , Alelos , Brasil , Estudios Transversales , Femenino , Predisposición Genética a la Enfermedad/genética , Genotipo , Heterocigoto , Homocigoto , Humanos , Persona de Mediana EdadRESUMEN
Intermittent hypoxia seems to be a major pathomechanism of obstructive sleep apnea-associated progression of atherosclerosis. The goal of the present study was to assess the influence of hypoxia on endothelial function depending on the initial stage of vasculopathy. We used 16 ApoE-/- mice were exposed to a 6-week-intermittent hypoxia either immediately (early preatherosclerosis) or after 5 weeks of high-cholesterol diet (advanced preatherosclerosis). Another 16 ApoE-/- mice under normoxia served as corresponding controls. Endothelial function was measured by an organ bath technique. Blood plasma CD31+/annexin V+ endothelial microparticles as well as sca1/flk1+ endothelial progenitor cells in blood and bone marrow were analyzed by flow cytometry. The findings were that intermittent hypoxia impaired endothelial function (56.6±6.2% of maximal phenylephrine-induced vasoconstriction vs. 35.2±4.1% in control) and integrity (increased percentage of endothelial microparticles: 0.28±0.05% vs. 0.15±0.02% in control) in early preatherosclerosis. Peripheral repair capacity expressed as the number of endothelial progenitor cells in blood was attenuated under hypoxia (2.0±0.5% vs. 5.3±1.9% in control), despite the elevated number of these cells in the bone marrow (2.0±0.4% vs. 1.1±0.2% in control). In contrast, endothelial function, as well as microparticle and endothelial progenitor cell levels were similar under hypoxia vs. control in advanced preatherosclerosis. We conclude that hypoxia aggravates endothelial dysfunction and destruction in early preatherosclerosis.
Asunto(s)
Aorta Torácica/fisiopatología , Aterosclerosis/fisiopatología , Células Endoteliales/patología , Hipoxia/fisiopatología , Apnea Obstructiva del Sueño/fisiopatología , Células Madre/patología , Animales , Anexina A5/genética , Anexina A5/metabolismo , Antígenos Ly/genética , Antígenos Ly/metabolismo , Aorta Torácica/efectos de los fármacos , Aorta Torácica/metabolismo , Apolipoproteínas E/deficiencia , Apolipoproteínas E/genética , Aterosclerosis/complicaciones , Aterosclerosis/metabolismo , Micropartículas Derivadas de Células/química , Micropartículas Derivadas de Células/metabolismo , Colesterol/administración & dosificación , Dieta Alta en Grasa , Células Endoteliales/efectos de los fármacos , Células Endoteliales/metabolismo , Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/metabolismo , Endotelio Vascular/fisiopatología , Femenino , Expresión Génica , Hipoxia/complicaciones , Hipoxia/metabolismo , Masculino , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Ratones , Ratones Noqueados , Técnicas de Cultivo de Órganos , Fenilefrina/farmacología , Molécula-1 de Adhesión Celular Endotelial de Plaqueta/genética , Molécula-1 de Adhesión Celular Endotelial de Plaqueta/metabolismo , Apnea Obstructiva del Sueño/complicaciones , Apnea Obstructiva del Sueño/metabolismo , Células Madre/efectos de los fármacos , Células Madre/metabolismo , Factores de Tiempo , Receptor 2 de Factores de Crecimiento Endotelial Vascular/genética , Receptor 2 de Factores de Crecimiento Endotelial Vascular/metabolismo , Vasoconstricción/efectos de los fármacosRESUMEN
STUDY DESIGN: Although the knowledge described about risk factors and venous thromboembolism (VT) in the general population, the impact of these factors in the development of thromboembolic events in patients with spinal injury (SI) caused by spinal cord injury (SCI) is poorly understood. OBJECTIVE: Evaluate the impact of risk factors in the development of thromboembolic events in patients with SCI. SETTING: Brazil, São Paulo. METHODS: Observational, prospective and cross-study. Eligible patients (n=100) had SI by SCI, >18 years. The degree of motor and sensory lesion was evaluated based on American Spinal Injury Association (ASIA) Impairment Scale (AIS). Blood samples were collected for coagulation exams, hemogram, laboratory and biochemical analyses. Ultrasonography analyzes were performed from deep and superficial venous systems of lower limbs. Quantitative real-time PCR experiments were performed in order to investigate mutations in the prothrombin (G20210A) and Leiden factor V (G1691A) genes. RESULTS: The main finding of this study was the higher occurrence of deep venous thrombosis (DVT) in patients with Leiden factor V and hyperhomocysteinemia. There was no association between SI for DVT, VT and thrombophilia. Also, there was no relation between lupus anticoagulant and anti-cardiolipin. CONCLUSION: There is an important difference in the incidence of DVT in patients with SI by acute and chronic SCI. Therefore, the conduct of the investigation for thrombophilia should be based on clinical factors, risk factors for DVT and family history of thrombosis.
Asunto(s)
Traumatismos de la Médula Espinal/complicaciones , Tromboembolia Venosa/etiología , Enfermedad Aguda , Adulto , Anciano , Brasil , Enfermedad Crónica , Factor V/genética , Femenino , Humanos , Incidencia , Extremidad Inferior/irrigación sanguínea , Extremidad Inferior/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Protrombina/genética , Factores de Riesgo , Índice de Severidad de la Enfermedad , Traumatismos de la Médula Espinal/sangre , Traumatismos de la Médula Espinal/diagnóstico por imagen , Traumatismos de la Médula Espinal/genética , Trombofilia/sangre , Trombofilia/diagnóstico por imagen , Trombofilia/etiología , Trombofilia/genética , Ultrasonografía , Tromboembolia Venosa/sangre , Tromboembolia Venosa/diagnóstico por imagen , Tromboembolia Venosa/genética , Trombosis de la Vena/sangre , Trombosis de la Vena/diagnóstico por imagen , Trombosis de la Vena/etiología , Trombosis de la Vena/genética , Adulto JovenRESUMEN
The aim of the study was to evaluate the diagnostic accuracy of thromboelastometry for assessing rivaroxaban concentrations. The accuracy of thromboelastometry was compared with the high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) method, which is the gold standard for drug plasma monitoring (the reference standard). Forty-six clinically stable patients were treated with 10, 15, or 20 mg of rivaroxaban once daily (OD group) or 15 mg twice a day (BID group) (no particular indication for treatment). Patient samples were collected 2 h after the use of the medication (peak) and 2 h before the next dose (trough). The rivaroxaban plasma concentrations were determined via HPLC-MS/MS, and thromboelastometry was performed using a ROTEM® delta analyzer. There were significant prolongations in clotting time (CT) for the 10, 15, and 20 mg of rivaroxaban treatments in the OD groups. In the 15 mg BID group, the responses at the peak and trough times were similar. At the peak times, there was a positive correlation between the plasma concentration of rivaroxaban and CT (Spearman correlation rho=0.788, P<0.001) and clot formation time (rho=0.784, P<0.001), and a negative correlation for alpha angle (rho=-0.771, P<0.001), amplitude after 5 min (rho=-0.763, P<0.001), and amplitude after 10 min (rho=-0.680, P<0.001). The CT presented higher specificity and sensitivity using the cut-off determined by the receiver characteristics curve. ROTEM has potential as screening tool to measure possible bleeding risk associated with rivaroxaban plasma levels.
Asunto(s)
Monitoreo de Drogas/métodos , Inhibidores del Factor Xa/sangre , Hemorragia/prevención & control , Rivaroxabán/sangre , Adulto , Anciano , Anciano de 80 o más Años , Pruebas de Coagulación Sanguínea , Cromatografía Líquida de Alta Presión , Exactitud de los Datos , Inhibidores del Factor Xa/administración & dosificación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Rivaroxabán/administración & dosificación , Espectrometría de Masas en Tándem , TromboelastografíaRESUMEN
The stability of samples is crucial for getting reliable concentrations of many analytes, including lipid profile. Thus, the goal of this study was to analyze lipid profile under different storage and temperature conditions. This was a prospective study with 809 patients of both genders. Total cholesterol, triglycerides, high-density lipoprotein cholesterol, low density lipoprotein cholesterol and non-high-density lipoprotein were measured within 1 h from collection at room temperature, after 2-3 h of refrigeration (8°C) and after 4-5 h at room temperature. The processing time and storage conditions did not affect the analytes measured. These findings are important for multicenter studies, because of the difficulties related to centrifugation and freezing of samples immediately after collection.
Asunto(s)
Recolección de Muestras de Sangre/métodos , Lípidos/sangre , Adulto , Anciano , Anciano de 80 o más Años , Análisis Químico de la Sangre , Conservación de la Sangre , Recolección de Muestras de Sangre/instrumentación , Recolección de Muestras de Sangre/normas , Colesterol/sangre , Femenino , Humanos , Laboratorios/normas , Lipoproteínas/sangre , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Temperatura , Factores de Tiempo , Triglicéridos/sangre , Adulto JovenRESUMEN
An alternative device for the immobilization of the hind limb of the rat was developed to study the effects of chronic disuse on the soleus and tibialis anterior muscles, maintained for 3 weeks in the shortening and the stretching positions, respectively. The proposed device is made of steel mesh and cotton materials, and has some advantages when compared to cast or plaster cast: it is cheaper, lighter (12 g or 4% of the body weight of the rat) and the same unit can be easily adjusted and used several times in the same animal or in animals of similar size. Immobilization is also useful to restrain the movements of the hip, knee, and ankle joints. Male rats (291 +/- 35 g and aged 14 +/- 2 weeks) were used to develop and test the model. The soleus muscle of 18 rats was maintained in a shortened position for 21 consecutive days and lost 19 +/- 7% of its length (P = 0.008) and 44 +/- 6% of its weight (P = 0.002) compared to the contralateral intact muscle. No difference (P = 0.67) was found in the stretched tibialis anterior of the same hind limb when compared to the contralateral muscle. No ulcer, sore or foot swelling was observed in the animals. Immobilization was effective in producing chronic muscle disuse in the hind limbs of rats and is an acceptable alternative to the traditional methods of immobilization such as cast or plaster cast.
Asunto(s)
Inmovilización , Modelos Animales , Músculo Esquelético/fisiología , Trastornos Musculares Atróficos/etiología , Adaptación Fisiológica , Animales , Fibra de Algodón , Pierna , Masculino , Contracción Muscular/fisiología , Tono Muscular , Ratas , Ratas WistarRESUMEN
We determined the effect of stretching applied once a week to the soleus muscle immobilized in the shortened position on muscle fiber morphology. Twenty-six male Wistar rats weighing 269 +/- 26 g were divided into three groups. Group I, the left soleus was immobilized in the shortened position for 3 weeks; group II, the soleus was immobilized in the shortened position and stretched once a week for 3 weeks; group III, the soleus was submitted only to stretching once a week for 3 weeks. The medial part of the soleus muscle was frozen for histology and muscle fiber area evaluation and the lateral part was used for the determination of number and length of serial sarcomeres. Soleus muscle submitted only to immobilization showed a reduction in weight (44 +/- 6%, P = 0.002), in serial sarcomere number (23 +/- 15%) and in cross-sectional area of the fibers (37 +/- 31%, P < 0.001) compared to the contralateral muscles. The muscle that was immobilized and stretched showed less muscle fiber atrophy than the muscles only immobilized (P < 0.05). Surprisingly, in the muscles submitted only to stretching, fiber area was decreased compared to the contralateral muscle (2548 +/- 659 vs 2961 +/- 806 microm(2), respectively, P < 0.05). In conclusion, stretching applied once a week for 40 min to the soleus muscle immobilized in the shortened position was not sufficient to prevent the reduction of muscle weight and of serial sarcomere number, but provided significant protection against muscle fiber atrophy. In contrast, stretching normal muscles once a week caused a reduction in muscle fiber area.
Asunto(s)
Inmovilización , Fibras Musculares Esqueléticas/patología , Músculo Esquelético/patología , Atrofia Muscular/patología , Animales , Peso Corporal , Masculino , Atrofia Muscular/prevención & control , Ratas , Ratas Wistar , Sarcómeros/patología , Factores de TiempoRESUMEN
The aim of the present study was to determine the effect of stretching applied every 3 days to the soleus muscle immobilized in the shortened position on muscle fiber morphology. Eighteen 16-week-old Wistar rats were used and divided into three groups of 6 animals each: a) the left soleus muscle was immobilized in the shortened position for 3 weeks; b) during immobilization, the soleus was stretched for 40 min every 3 days; c) the non-immobilized soleus was only stretched. Left and right soleus muscles were examined. One portion of the soleus was frozen for histology and muscle fiber area evaluation, while the other portion was used to identify the number and length of serial sarcomeres. Immobilized muscles (group A) showed a significant decrease in weight (44 +/- 6%), length (19 +/- 7%), serial sarcomere number (23 +/- 15%), and fiber area (37 +/- 31%) compared to the contralateral muscles (P < 0.05, paired Student t-test). The immobilized and stretched soleus (group B) showed a similar reduction but milder muscle fiber atrophy compared to the only immobilized group (22 +/- 40 vs 37 +/- 31%, respectively; P < 0.001, ANOVA test). Muscles submitted only to stretching (group C) significantly increased the length (5 +/- 2%), serial sarcomere number (4 +/- 4%), and fiber area (16 +/- 44%) compared to the contralateral muscles (P < 0.05, paired Student t-test). In conclusion, stretching applied every 3 days to immobilized muscles did not prevent the muscle shortening, but reduced muscle atrophy. Stretching sessions induced hypertrophic effects in the control muscles. These results support the use of muscle stretching in sports and rehabilitation.
Asunto(s)
Inmovilización , Fibras Musculares Esqueléticas/patología , Músculo Esquelético/patología , Atrofia Muscular/prevención & control , Animales , Peso Corporal , Masculino , Ratas , Ratas Wistar , Sarcómeros/patología , Factores de TiempoRESUMEN
It is not known whether the addition of ezetimibe to statins adds cardiovascular protection beyond the expected changes in lipid levels. Subjects with coronary heart disease were treated with four consecutive 1-week courses of therapy (T) and evaluations. The courses were: T1, 100 mg aspirin alone; T2, 100 mg aspirin and 40 mg simvastatin/10 mg ezetimibe; T3, 40 mg simvastatin/10 mg ezetimibe, and 75 mg clopidogrel (300 mg initial loading dose); T4, 75 mg clopidogrel alone. Platelet aggregation was examined in whole blood. Endothelial microparticles (CD51), platelet microparticles (CD42/CD31), and endothelial progenitor cells (CD34/CD133; CDKDR/CD133, or CD34/KDR) were quantified by flow cytometry. Endothelial function was examined by flow-mediated dilation. Comparisons between therapies revealed differences in lipids (T2 and T3Asunto(s)
Azetidinas/farmacología
, Micropartículas Derivadas de Células/efectos de los fármacos
, Enfermedad Coronaria/tratamiento farmacológico
, Células Progenitoras Endoteliales/efectos de los fármacos
, Agregación Plaquetaria/efectos de los fármacos
, Simvastatina/farmacología
, Anciano
, Anticolesterolemiantes/farmacología
, Aspirina/uso terapéutico
, LDL-Colesterol/sangre
, Clopidogrel
, Combinación de Medicamentos
, Ezetimiba
, Femenino
, Citometría de Flujo
, Humanos
, Masculino
, Persona de Mediana Edad
, Inhibidores de Agregación Plaquetaria/uso terapéutico
, Ticlopidina/análogos & derivados
, Ticlopidina/uso terapéutico
, Triglicéridos/sangre
RESUMEN
The aim of the study was to evaluate the diagnostic accuracy of thromboelastometry for assessing rivaroxaban concentrations. The accuracy of thromboelastometry was compared with the high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) method, which is the gold standard for drug plasma monitoring (the reference standard). Forty-six clinically stable patients were treated with 10, 15, or 20 mg of rivaroxaban once daily (OD group) or 15 mg twice a day (BID group) (no particular indication for treatment). Patient samples were collected 2 h after the use of the medication (peak) and 2 h before the next dose (trough). The rivaroxaban plasma concentrations were determined via HPLC-MS/MS, and thromboelastometry was performed using a ROTEM® delta analyzer. There were significant prolongations in clotting time (CT) for the 10, 15, and 20 mg of rivaroxaban treatments in the OD groups. In the 15 mg BID group, the responses at the peak and trough times were similar. At the peak times, there was a positive correlation between the plasma concentration of rivaroxaban and CT (Spearman correlation rho=0.788, P<0.001) and clot formation time (rho=0.784, P<0.001), and a negative correlation for alpha angle (rho=−0.771, P<0.001), amplitude after 5 min (rho=−0.763, P<0.001), and amplitude after 10 min (rho=−0.680, P<0.001). The CT presented higher specificity and sensitivity using the cut-off determined by the receiver characteristics curve. ROTEM has potential as screening tool to measure possible bleeding risk associated with rivaroxaban plasma levels.
Asunto(s)
Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Monitoreo de Drogas/métodos , Inhibidores del Factor Xa/sangre , Rivaroxabán/sangre , Hemorragia/prevención & control , Tromboelastografía , Pruebas de Coagulación Sanguínea , Cromatografía Líquida de Alta Presión , Espectrometría de Masas en Tándem , Inhibidores del Factor Xa/administración & dosificación , Rivaroxabán/administración & dosificación , Exactitud de los DatosRESUMEN
Effective statin therapy is associated with a marked reduction of cardiovascular events. However, the explanation for full benefits obtained for LDL cholesterol targets by combined lipid-lowering therapy is controversial. Our study compared the effects of two equally effective lipid-lowering strategies on markers of cholesterol synthesis and absorption. A prospective, open label, randomized, parallel design study, with blinded endpoints, included 116 subjects. We compared the effects of a 12-week treatment with 40 mg rosuvastatin or the combination of 40 mg simvastatin/10 mg ezetimibe on markers of cholesterol absorption (campesterol and ß-sitosterol), synthesis (desmosterol), and their ratios to cholesterol. Both therapies similarly decreased total and LDL cholesterol, triglycerides and apolipoprotein B, and increased apolipoprotein A1 (P < 0.05 vs baseline for all). Simvastatin/ezetimibe increased plasma desmosterol (P = 0.012 vs baseline), and decreased campesterol and ß-sitosterol (P < 0.0001 vs baseline for both), with higher desmosterol (P = 0.007) and lower campesterol and ß-sitosterol compared to rosuvastatin, (P < 0.0001, for both). In addition, rosuvastatin increased the ratios of these markers to cholesterol (P < 0.002 vs baseline for all), whereas simvastatin/ezetimibe significantly decreased the campesterol/cholesterol ratio (P = 0.008 vs baseline) and tripled the desmosterol/cholesterol ratio (P < 0.0001 vs baseline). The campesterol/cholesterol and ß-sitosterol/cholesterol ratios were lower, whereas the desmosterol/cholesterol ratio was higher in patients receiving simvastatin/ezetimibe (P < 0.0001 vs rosuvastatin, for all). Pronounced differences in markers of cholesterol absorption and synthesis were observed between two equally effective lipid-lowering strategies.
Asunto(s)
Anticolesterolemiantes/administración & dosificación , Azetidinas/administración & dosificación , LDL-Colesterol/efectos de los fármacos , Fluorobencenos/administración & dosificación , Inhibidores de Hidroximetilglutaril-CoA Reductasas/administración & dosificación , Hipercolesterolemia/tratamiento farmacológico , Pirimidinas/administración & dosificación , Simvastatina/administración & dosificación , Sulfonamidas/administración & dosificación , Adulto , Anciano , Biomarcadores/sangre , LDL-Colesterol/sangre , Quimioterapia Combinada , Ezetimiba , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Rosuvastatina CálcicaAsunto(s)
Aterosclerosis/tratamiento farmacológico , Azetidinas/administración & dosificación , Biomarcadores/sangre , Endotelio Vascular/metabolismo , Inhibidores de Hidroximetilglutaril-CoA Reductasas/administración & dosificación , Adulto , Anciano , Anciano de 80 o más Años , Anticolesterolemiantes/administración & dosificación , Aterosclerosis/sangre , Relación Dosis-Respuesta a Droga , Quimioterapia Combinada , Ezetimiba , Femenino , Humanos , Masculino , Persona de Mediana Edad , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
It is not known whether the addition of ezetimibe to statins adds cardiovascular protection beyond the expected changes in lipid levels. Subjects with coronary heart disease were treated with four consecutive 1-week courses of therapy (T) and evaluations. The courses were: T1, 100 mg aspirin alone; T2, 100 mg aspirin and 40 mg simvastatin/10 mg ezetimibe; T3, 40 mg simvastatin/10 mg ezetimibe, and 75 mg clopidogrel (300 mg initial loading dose); T4, 75 mg clopidogrel alone. Platelet aggregation was examined in whole blood. Endothelial microparticles (CD51), platelet microparticles (CD42/CD31), and endothelial progenitor cells (CD34/CD133; CDKDR/CD133, or CD34/KDR) were quantified by flow cytometry. Endothelial function was examined by flow-mediated dilation. Comparisons between therapies revealed differences in lipids (T2 and T3<T1 and T4 for total cholesterol, LDL-C, and triglycerides; P<0.002 for all), as well as for endothelial function (T2>T1 and T4, P=0.001). Decreased platelet aggregation was observed after aspirin (arachidonic acid, T1<T3 and T4, P=0.034) and clopidogrel (adenosine, T3 and T4<T1 and T2, P<0.0001) therapy. Simvastatin/ezetimibe diphosphate did not change platelet aggregation, the amount of circulating endothelial and platelet microparticles, or endothelial progenitor cells. Cardiovascular protection following therapy with simvastatin/ezetimibe seems restricted to lipid changes and improvement of endothelial function not affecting the release of microparticles, mobilization of endothelial progenitor cells or decreased platelet aggregation.
Asunto(s)
Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Azetidinas/farmacología , Micropartículas Derivadas de Células/efectos de los fármacos , Enfermedad Coronaria/tratamiento farmacológico , Células Progenitoras Endoteliales/efectos de los fármacos , Agregación Plaquetaria/efectos de los fármacos , Simvastatina/farmacología , Anticolesterolemiantes/farmacología , Aspirina/uso terapéutico , LDL-Colesterol/sangre , Combinación de Medicamentos , Citometría de Flujo , Inhibidores de Agregación Plaquetaria/uso terapéutico , Ticlopidina/análogos & derivados , Ticlopidina/uso terapéutico , Triglicéridos/sangreRESUMEN
Effective statin therapy is associated with a marked reduction of cardiovascular events. However, the explanation for full benefits obtained for LDL cholesterol targets by combined lipid-lowering therapy is controversial. Our study compared the effects of two equally effective lipid-lowering strategies on markers of cholesterol synthesis and absorption. A prospective, open label, randomized, parallel design study, with blinded endpoints, included 116 subjects. We compared the effects of a 12-week treatment with 40 mg rosuvastatin or the combination of 40 mg simvastatin/10 mg ezetimibe on markers of cholesterol absorption (campesterol and β-sitosterol), synthesis (desmosterol), and their ratios to cholesterol. Both therapies similarly decreased total and LDL cholesterol, triglycerides and apolipoprotein B, and increased apolipoprotein A1 (P < 0.05 vs baseline for all). Simvastatin/ezetimibe increased plasma desmosterol (P = 0.012 vs baseline), and decreased campesterol and β-sitosterol (P < 0.0001 vs baseline for both), with higher desmosterol (P = 0.007) and lower campesterol and β-sitosterol compared to rosuvastatin, (P < 0.0001, for both). In addition, rosuvastatin increased the ratios of these markers to cholesterol (P < 0.002 vs baseline for all), whereas simvastatin/ezetimibe significantly decreased the campesterol/cholesterol ratio (P = 0.008 vs baseline) and tripled the desmosterol/cholesterol ratio (P < 0.0001 vs baseline). The campesterol/cholesterol and β-sitosterol/cholesterol ratios were lower, whereas the desmosterol/cholesterol ratio was higher in patients receiving simvastatin/ezetimibe (P < 0.0001 vs rosuvastatin, for all). Pronounced differences in markers of cholesterol absorption and synthesis were observed between two equally effective lipid-lowering strategies.
Asunto(s)
Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Anticolesterolemiantes/administración & dosificación , Azetidinas/administración & dosificación , LDL-Colesterol/efectos de los fármacos , Fluorobencenos/administración & dosificación , Inhibidores de Hidroximetilglutaril-CoA Reductasas/administración & dosificación , Hipercolesterolemia/tratamiento farmacológico , Pirimidinas/administración & dosificación , Simvastatina/administración & dosificación , Sulfonamidas/administración & dosificación , Biomarcadores/sangre , LDL-Colesterol/sangre , Quimioterapia Combinada , Estudios ProspectivosRESUMEN
An alternative device for the immobilization of the hind limb of the rat was developed to study the effects of chronic disuse on the soleus and tibialis anterior muscles, maintained for 3 weeks in the shortening and the stretching positions, respectively. The proposed device is made of steel mesh and cotton materials, and has some advantages when compared to cast or plaster cast: it is cheaper, lighter (12 g or 4 percent of the body weight of the rat) and the same unit can be easily adjusted and used several times in the same animal or in animals of similar size. Immobilization is also useful to restrain the movements of the hip, knee, and ankle joints. Male rats (291 ± 35 g and aged 14 ± 2 weeks) were used to develop and test the model. The soleus muscle of 18 rats was maintained in a shortened position for 21 consecutive days and lost 19 ± 7 percent of its length (P = 0.008) and 44 ± 6 percent of its weight (P = 0.002) compared to the contralateral intact muscle. No difference (P = 0.67) was found in the stretched tibialis anterior of the same hind limb when compared to the contralateral muscle. No ulcer, sore or foot swelling was observed in the animals. Immobilization was effective in producing chronic muscle disuse in the hind limbs of rats and is an acceptable alternative to the traditional methods of immobilization such as cast or plaster cast
Asunto(s)
Animales , Masculino , Ratas , Inmovilización , Músculo Esquelético , Fibra de Algodón , Pierna , Contracción Muscular , Tono Muscular , Ratas WistarRESUMEN
The aim of the present study was to determine the effect of stretching applied every 3 days to the soleus muscle immobilized in the shortened position on muscle fiber morphology. Eighteen 16-week-old Wistar rats were used and divided into three groups of 6 animals each: a) the left soleus muscle was immobilized in the shortened position for 3 weeks; b) during immobilization, the soleus was stretched for 40 min every 3 days; c) the non-immobilized soleus was only stretched. Left and right soleus muscles were examined. One portion of the soleus was frozen for histology and muscle fiber area evaluation, while the other portion was used to identify the number and length of serial sarcomeres. Immobilized muscles (group A) showed a significant decrease in weight (44 ± 6 percent), length (19 ± 7 percent), serial sarcomere number (23 ± 15 percent), and fiber area (37 ± 31 percent) compared to the contralateral muscles (P < 0.05, paired Student t-test). The immobilized and stretched soleus (group B) showed a similar reduction but milder muscle fiber atrophy compared to the only immobilized group (22 ± 40 vs 37 ± 31 percent, respectively; P < 0.001, ANOVA test). Muscles submitted only to stretching (group C) significantly increased the length (5 ± 2 percent), serial sarcomere number (4 ± 4 percent), and fiber area (16 ± 44 percent) compared to the contralateral muscles (P < 0.05, paired Student t-test). In conclusion, stretching applied every 3 days to immobilized muscles did not prevent the muscle shortening, but reduced muscle atrophy. Stretching sessions induced hypertrophic effects in the control muscles. These results support the use of muscle stretching in sports and rehabilitation.
Asunto(s)
Animales , Masculino , Ratas , Inmovilización , Fibras Musculares Esqueléticas , Músculo Esquelético/patología , Atrofia Muscular/prevención & control , Peso Corporal , Ratas Wistar , Sarcómeros/patología , Factores de TiempoRESUMEN
We determined the effect of stretching applied once a week to the soleus muscle immobilized in the shortened position on muscle fiber morphology. Twenty-six male Wistar rats weighing 269 ± 26 g were divided into three groups. Group I, the left soleus was immobilized in the shortened position for 3 weeks; group II, the soleus was immobilized in the shortened position and stretched once a week for 3 weeks; group III, the soleus was submitted only to stretching once a week for 3 weeks. The medial part of the soleus muscle was frozen for histology and muscle fiber area evaluation and the lateral part was used for the determination of number and length of serial sarcomeres. Soleus muscle submitted only to immobilization showed a reduction in weight (44 ± 6 percent, P = 0.002), in serial sarcomere number (23 ± 15 percent) and in cross-sectional area of the fibers (37 ± 31 percent, P < 0.001) compared to the contralateral muscles. The muscle that was immobilized and stretched showed less muscle fiber atrophy than the muscles only immobilized (P < 0.05). Surprisingly, in the muscles submitted only to stretching, fiber area was decreased compared to the contralateral muscle (2548 ± 659 vs 2961 ± 806 µm², respectively, P < 0.05). In conclusion, stretching applied once a week for 40 min to the soleus muscle immobilized in the shortened position was not sufficient to prevent the reduction of muscle weight and of serial sarcomere number, but provided significant protection against muscle fiber atrophy. In contrast, stretching normal muscles once a week caused a reduction in muscle fiber area.
Asunto(s)
Animales , Masculino , Ratas , Inmovilización , Fibras Musculares Esqueléticas , Músculo Esquelético , Atrofia Muscular , Peso Corporal , Ratas Wistar , Sarcómeros , Factores de TiempoRESUMEN
O uso da eletroestimulacao (EE) no tratamento das lesoes nervosas perifericas e controverso. Este estudo avaliou a alteracao da cronaxia, da reobase e da acomodacao no musculo tibial anterior (TA) desnervado de ratos submetidos a EE. Quatro grupos de ratos forma divididos: TA desnervado com eletrodiagnostico (ED) semanal (DSN+ED); TA desnervado com EE em dias alternados (DSN+EE+ED); TA direito desnervado (DSN); e TA inervado (INV). O eletrodiagnostico do grupo DSN+EE+ED forneceu os parametros EE (20 contracoes intensas com corrente monopolar, exponencial; periodo de pulso igual a 2x o valor da cronaxia; frequencia de 20Hz; amplitude em nivel motor; e tempo ON 3,0 s e OFF 6,0 s). Apos 4 semanas, nota-se, em todos os musculos desnervados, diminuicao na reobase, caracterizando hiperexcitabilidade muscular. A reobase foi mairo no musculo so desnervado (1+0 mA), se comparada ao DSN+ED (0,5+0mA, p=0,00006) e ao DSN+EE+ED (0,58+0,19mA, P=0,0001). A cronaxia do grupo DSN+EE+ED foi melhor (4,06+2,1ms) se comparada aos grupos DNS+ED (8,4+0,93MS,P=0006) e DSN (5,31+0,53ms, p=0,45). A acomodacao diminuiu nos grupos DSN+ED (0,75+0,42mA) e DSN+EE+ED (0,75+0,6mA), mantendo-se com valores proximos a pre-desnervacao no grupo somente desnervado (DSN 1,8+0,45mA). Concluiu-se que, embora a EE e o ED tenha atrasado a recuperacao da reobase e da acomodacao, sua utilizacao conjunta favoreceu a rcuperacao da cronaxia. Esse resultado indica o efeito benefico no tratamento do musculo desnervado