RESUMO
Lispro (LP) and regular human (HR) insulins were compared in Type 1 diabetic (T1DM) patients on either a Mediterranean diet or normal diet. Twelve T1DM patients were recruited and randomized into two groups of 6, groups A and B. They were treated in different sequences (in 3-month intervals for 1 year). Group A: LP insulin and normal diet, LP insulin and Mediterranean diet, regular insulin and Mediterranean diet, regular insulin and normal diet. Group B: regular insulin and normal diet, regular insulin and Mediterranean diet, LP insulin and Mediterranean diet, LP insulin and normal diet. Each patient was treated with rapid acting insulin, either LP insulin or HR insulin, before each main meal and a dose of slow acting insulin at bedtime. Every 15 days the glycemic control, the incidence and frequency of hypoglycemic episodes, and any adverse events were evaluated. Every 3 months, hematology and a chemistry panel, pre- and post-prandial glycemic and insulinemic profiles were evaluated in all patients. HbA1c levels significantly decreased in LP patients on normal diet, post-prandial glycemic levels were significantly lower in LP than in HR patients from 30 min onwards, 15-min post-prandial insulin levels higher in LP- than in HR-treated patients, and hypoglycemic episodes were significantly less in LP- than in HR-treated patients. LP insulin, irrespective of the type of diet, results in more effective glycemic control, significantly reduces hypoglycemic episodes as opposed to traditional insulin therapy and seems to be more effective with a normal diet than with a Mediterranean diet.
Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Dieta , Hipoglicemiantes/uso terapêutico , Insulina/análogos & derivados , Insulina/uso terapêutico , Adolescente , Adulto , Área Sob a Curva , Glicemia/análise , Estudos Cross-Over , Diabetes Mellitus Tipo 1/dietoterapia , Feminino , Hemoglobinas Anormais/análise , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemia/prevenção & controle , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/efeitos adversos , Insulina/administração & dosagem , Insulina/efeitos adversos , Insulina Lispro , MasculinoRESUMO
Wall shear stress contributes to the endothelial production of vasoactive mediators, like nitric oxide (NO). Brachial artery vasodilation that follows increased blood flow is regulated by NO release. Aim of the present study was to investigate whether resting wall shear stress of the brachial artery is related to flow-mediated vasodilation (FMD) induced by forearm ischemia. Wall shear stress was calculated according to the following formula: Wall shear stress=Blood viscosity x Blood velocity/Internal diameter. FMD was calculated as percentage change of brachial artery diameter following forearm ischemia. Twenty-seven healthy male subjects were investigated. Peak wall shear stress and FMD were 37.3+/-12.8 dynes/cm(2) and 110.7+/-5.6%, respectively (mean+/-S.D.). In simple regression analyses, age was inversely associated with wall shear stress (r=48, P<0.01) and, marginally, with FMD (r=0.33, P=0.08). Wall shear stress and FMD were directly related (r=0.60, P<0.001). In multiple regression analysis, including wall shear stress, age, blood pressure, lipids, glucose and Body Mass Index as independent variables, wall shear stress was the only variable independently associated with FMD (standardized beta coefficient=0.690, P=0.005). To avoid the influence of brachial artery size on FMD, the regression analysis was restricted to subjects with similar diameter (n=12). In these subjects wall shear stress continued to be significantly associated with FMD (r=0.69, P=0.01). Our results demonstrate a strong association between resting wall shear stress and FMD in the brachial artery in healthy men in vivo. This association is independent of age and vessel diameter.
Assuntos
Artéria Braquial/fisiologia , Vasodilatação/fisiologia , Adulto , Idoso , Viscosidade Sanguínea/fisiologia , Artéria Braquial/fisiopatologia , Antebraço/irrigação sanguínea , Humanos , Isquemia/fisiopatologia , Masculino , Pessoa de Meia-Idade , Valores de Referência , Fluxo Sanguíneo Regional/fisiologia , Estresse MecânicoRESUMO
The association between angiotensin-converting enzyme (ACE) gene polymorphism and insulin resistance (IR) in hypertensive subjects remains controversial. Thus, we evaluated the possible association between IR and ACE gene polymorphism in a group of hypertensive, never-treated patients compared with that in a normotensive control group. We enrolled 200 (114 men and 86 women; age, 45.5 +/- 4.7 yr) hypertensive patients and 96 (54 men and 42 women; age, 44.0 +/- 4.7 yr) normotensive subjects. A double PCR assay was used to identify ACE genotypes. We determined fasting glucose and insulin by the glucose oxidase method and using a standard RIA technique. IR was estimated using the homeostasis model assessment (HOMA(IR)). Both fasting glucose (5.0 +/- 0.3 vs. 4.7 +/- 0.3 mmol/L; P < 0.0001), insulin levels (12.3 +/- 4.7 vs. 4.9 +/- 1.5 muU/mL; P < 0.0001), and HOMA(IR) (2.7 +/- 1.1 vs. 1.1 +/- 0.3; P < 0.0001) were significantly higher in hypertensive patients than in the normotensive control group. When we subdivided hypertensive patients according to ACE genotype, we observed that fasting insulin and HOMA(IR) were 16.3 +/- 3.3 and 3.6 +/- 0.8 in the DD genotype, 9.4 +/- 3.1 and 2.1 +/- 0.7 in the ID genotype, and 8.3 +/- 2.8 and 1.9 +/- 0.7 muU/mL in the II group (P < 0.0001, by ANOVA). No significant differences were observed in the normotensive control group. In conclusion, we extended previous data regarding the relationship of hypertension and IR by demonstrating a dependence of this relationship upon the ACE gene polymorphism.
Assuntos
Hipertensão/fisiopatologia , Resistência à Insulina , Peptidil Dipeptidase A/genética , Polimorfismo Genético , Adulto , Alelos , Glicemia/análise , Feminino , Frequência do Gene , Genótipo , Homeostase , Humanos , Hipertensão/genética , Insulina/sangue , Masculino , Pessoa de Meia-Idade , Valores de ReferênciaRESUMO
Endothelial dysfunction has been reported in obese subjects, but its mechanism has not been elucidated. We have therefore investigated 1) the possible relationship among BMI, waist-to-hip ratio (WHR), and endothelium-dependent vasodilation and 2) whether oxidative stress participates in endothelial dysfunction. We recruited 76 healthy subjects (50 men and 26 women aged 21-45 years) and measured their BMI (kg/m2), WHR, and insulin resistance (IR) estimated by the homeostasis model assessment (HOMA). Endothelium-dependent and -independent vasodilation were assessed by increasing doses of acetylcholine (ACh) (7.5, 15, and 30 pg x ml(-1) x min(-1)) and sodium nitroprusside (SNP) (0.8, 1.6, and 3.2 microg x ml(-1) x min(-1)) during saline and vitamin C coinfusion (24 mg/min). The effects of cyclooxygenase activity were evaluated by a dose-response curve to intrabrachial coinfusion of ACh and indomethacin (500 microg/min). Three different groups have been identified according to their BMI: group A (BMI <25), consisting of 10 men and 5 women; group B (BMI between 25 and 29), consisting of 16 men and 8 women; and group C (BMI > or =30), consisting of 24 men and 13 women. Obese subjects had significantly lower forearm blood flow (FBF) during ACh infusions (means +/- SD): 19.8 +/- 2.8, 10.8 +/- 2.7, and 6.5 +/- 1.8 ml x 100 ml(-1) tissue x min(-1) (P < 0.0001) for groups A, B, and C, respectively. SNP caused comparable increments in FBF in all groups. Regression analysis revealed a significant negative correlation between BMI (r = -0.676, P < 0.0001), WHR (r = -0.631, P < 0.0001), fasting insulin (r = -0.695, P < 0.0001), HOMA-IR (r = -0.633, P < 0.0001), and percent peak increase in FBF during ACh infusion. In obese subjects, both vitamin C and indomethacin increased the impaired vasodilating response to ACh, whereas the SNP effect was unchanged. In conclusion, in obese subjects, ACh-stimulated vasodilation is blunted, and the increase in FBF is inversely related to BMI, WHR, fasting insulin, and HOMA-IR. The effects of both vitamin C and indomethacin on impaired ACh-stimulated vasodilation support the hypothesis that oxidative stress contributes to endothelial dysfunction in human obesity.
Assuntos
Tecido Adiposo/patologia , Antioxidantes/farmacologia , Ácido Ascórbico/farmacologia , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/fisiopatologia , Obesidade/fisiopatologia , Estresse Oxidativo , Acetilcolina/farmacologia , Adulto , Combinação de Medicamentos , Feminino , Humanos , Indometacina/farmacologia , Injeções Intra-Arteriais , Masculino , Nitroprussiato/farmacologia , Vasodilatação , Vasodilatadores/farmacologiaRESUMO
We tested the effects of vitamin C and atorvastatin treatment on endothelium-dependent and endothelium-independent vasodilation in 18 hypercholesterolemic patients (ten men and eight women, aged 20-46 years) in comparison with 12 normal volunteers (seven men and five women, aged 20-45 years). The responses of the forearm blood flow (FBF) to acetylcholine (ACh) (7.5, 15 and 30 microg/min), sodium nitroprusside (SNP) (0.8, 1.6, 3.2 microg/min) and L-NMMA (2, 4, 8 micromol/min) were evaluated at baseline and after 1 month of atorvastatin (10 mg/day) treatment. Drugs were infused into the brachial artery and FBF was measured by strain-gauge plethysmography. At baseline, the response to ACh was significantly attenuated in hypercholesterolemics versus controls: at the highest dose (30 microg/min), FBF was 27.0+/-3.4 versus 11.5+/-1.9 ml.100 ml tissue(-1).min(-1) respectively (P<0.0001). No significant differences were found between groups during SNP infusion. The atorvastatin treatment significantly improved ACh-stimulated FBF: at highest dose the FBF increased to 14.9+/-1.5 ml.100 ml tissue(-1). min(-1) (P<0.0001). Similarly, the L-NMMA endothelial effects were significantly enhanced by lipid-lowering treatment, supporting the improvement of basal nitric oxide. Vitamin C increased ACh-vasodilation in the same way before and after atorvastatin treatment. In conclusion, the endothelial dysfunction in hypercholesterolemics is due to an oxidative stress and atorvastatin rapidly improves both basal and stimulated endothelium-dependent vasodilation.
Assuntos
Anticolesterolemiantes/uso terapêutico , Antioxidantes/farmacologia , Ácido Ascórbico/farmacologia , Endotélio Vascular/fisiopatologia , Ácidos Heptanoicos/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipercolesterolemia/fisiopatologia , Pirróis/uso terapêutico , Acetilcolina/farmacologia , Adulto , Antioxidantes/administração & dosagem , Ácido Ascórbico/administração & dosagem , Atorvastatina , Velocidade do Fluxo Sanguíneo , Estudos Cross-Over , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Antebraço/irrigação sanguínea , Humanos , Hipercolesterolemia/tratamento farmacológico , Infusões Intra-Arteriais , Masculino , Pessoa de Meia-Idade , Nitroprussiato/farmacologia , Pletismografia , Vasodilatação/efeitos dos fármacos , Vasodilatadores/farmacologia , ômega-N-Metilarginina/farmacologiaRESUMO
A common variant in the promoter of the human stromelysin gene, causing reduced enzyme expression, has been associated with the progression of coronary atherosclerosis. On the other hand, increased stromelysin activity may promote plaque rupture. The present study was undertaken to investigate the relationship between the genetic variation in the human stromelysin gene promoter and common carotid geometry. Forty-two healthy male subjects without major coronary heart disease risk factors were investigated. The polymorphism in the stromelysin gene promoter was studied through polymerase chain reaction amplification with the use of mutagenic primers. Age, blood pressure, lipids, glucose, viscosity, and body mass index were similar in homozygotes for the 5A allele (5A/5A), heterozygotes (5A/6A), and homozygotes for the 6A allele (6A/6A). Serum matrix metalloproteinase-3 levels did not differ significantly among genotypes. Common carotid diameters and intima-media thickness, measured by noninvasive ultrasonography, were significantly larger in 6A/6A subjects (for respective 6A/6A, 5A/6A, and 5A/5A subjects, diameter at the R wave was 0.63+/-0.09, 0.55+/-0.06, and 0.53+/-0.04 cm [mean+/-SD], P<0.005 by ANOVA; intima-media thickness was 765+/-116, 670+/-116, and 630+/-92 microm [mean+/-SD], P<0.05 by ANOVA). Wall shear stress, calculated as blood velocityxblood viscosity/internal diameter, was significantly lower in 6A/6A subjects (for respective 6A/6A, 5A/6A, and 5A/5A subjects, mean wall shear stress was 10.4+/-2.9, 13.5+/-3.5, and 12.6+/-1.9 dyne/cm(2) [mean+/-SD], P<0.05 by ANOVA). The results demonstrate that the gene polymorphism in the promoter region of stromelysin is associated with structural and functional characteristics of the common carotid artery in healthy male subjects without major risk factors for atherosclerosis. Individuals with the 6A/6A genotype (associated with lower enzyme activity) show a triad of events, namely, increased wall thickness, enlarged arterial lumen, and local reduction of wall shear stress, which might predispose them to atherosclerotic plaque localization.
Assuntos
Artéria Carótida Primitiva/diagnóstico por imagem , Variação Genética , Metaloproteinase 3 da Matriz/genética , Regiões Promotoras Genéticas , Adulto , Alelos , Arteriosclerose/genética , Velocidade do Fluxo Sanguíneo , Glicemia/análise , Pressão Sanguínea , Hemorreologia , Heterozigoto , Homozigoto , Humanos , Lipídeos/sangue , Masculino , Metaloproteinase 3 da Matriz/sangue , Pessoa de Meia-Idade , Polimorfismo Genético , Fatores de Risco , UltrassonografiaRESUMO
OBJECTIVE: To evaluate the relationship between ACE-gene polymorphism and left ventricular geometry in never treated hypertensives. METHODS: We enrolled 200 hypertensive outpatients that underwent clinical and ambulatory blood pressure measurements, echocardiographic evaluation and analysis for insertion (I)/deletion (D) polymorphism by PCR. Patients with normal or increased (> 125 g/m2 in males and > 110 g/m2 in females) left ventricular mass were considered to have concentric remodeling or concentric left ventricular hypertrophy if their relative wall thickness was > or = 0.45. RESULTS: The left ventricular mass index values (g/m2) were 136 +/- 30 in DD genotype, 124 +/- 26 in ID genotype, and 116 +/- 20 in II genotype (DD vs. ID P < 0.005; DD vs. II P < 0.05), and were unrelated to blood pressure. Ninety-six patients presented left ventricular hypertrophy (48.0%): 51 with concentric and 45 with eccentric hypertrophy. The eccentric left ventricular hypertrophy was detected in 32 (36.8%) DD patients, in ten (10.5%) ID patients (P < 0.05), and in three (16.6%) II patients. The relative septal thickness was 0.43 +/- 0.09 in DD genotype, 0.45 +/- 0.08 in ID genotype, and 0.43 +/- 0.10 in II genotype. In DD and ID genotypes, the relative posterior wall thickness (0.37 +/- 0.07 vs. 0.41 +/- 0.07; P < 0.0001) and the end-diastolic left ventricular internal dimension (52.8 +/- 3.3 mm vs. 48.3 +/- 2.8 mm; P < 0.0001) were statistically different. CONCLUSIONS: The DD genotype of the ACE-gene is associated with an increased left ventricular mass and with a significantly higher prevalence of eccentric left ventricular hypertrophy, when compared to ID genotype.
Assuntos
Hipertensão/patologia , Peptidil Dipeptidase A/genética , Polimorfismo Genético , Remodelação Ventricular , Fatores Etários , Análise de Variância , Estudos de Avaliação como Assunto , Feminino , Genótipo , Humanos , Hipertensão/genética , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Fatores SexuaisRESUMO
The localization of atherosclerotic lesions is influenced by hemodynamic factors, namely, shear stress and tensive forces. The present study investigated the relationships between shear stress and circumferential wall tension and between these hemodynamic factors and the intima-media thickness (IMT) of the common carotid artery in healthy men. Fifty-eight subjects were studied. Shear stress was calculated as blood viscosityxblood velocity/internal diameter. Circumferential wall tension was calculated as blood pressurexinternal radius. Blood velocity, internal diameter, and IMT were measured by high-resolution echo-Doppler. Mean shear stress was 12.6+/-3.3 dynes/cm(2) (mean+/-SD; range, 4.8 to 20.4) and was inversely related with age, blood pressure, and body mass index (BMI). Mean circumferential wall tension was 3.4+/-0.6x10(4) dynes/cm (range 2.4 to 5.6) and was directly associated with age and BMI. IMT was inversely associated with shear stress (r=0.55, P<0. 0001) and directly associated with circumferential wall tension (r=0. 43, P<0.0001). Shear stress and circumferential wall tension were inversely correlated (r=0.66, P<0.0001). In multiple regression analysis, shear stress and (marginally) cholesterol were independently associated with IMT, whereas circumferential wall tension, age, and BMI were not. These findings confirm that common carotid shear stress varies among healthy individuals and decreases as age, blood pressure, and BMI increase. Our findings also demonstrate that circumferential wall tension is directly associated with wall thickness, age, and BMI and that shear stress is associated with common carotid IMT independent of other hemodynamic, clinical, or biochemical factors.
Assuntos
Artéria Carótida Primitiva/patologia , Artéria Carótida Primitiva/fisiologia , Hemodinâmica , Adulto , Fatores Etários , Velocidade do Fluxo Sanguíneo , Pressão Sanguínea/fisiologia , Viscosidade Sanguínea , Índice de Massa Corporal , Artéria Carótida Primitiva/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Cardiovasculares , Análise de Regressão , Estresse Mecânico , Túnica Íntima/patologia , Túnica Média/patologia , Ultrassonografia DopplerRESUMO
OBJECTIVE: To examine whether middle (two months) and long-term (six months) isradipine sustained-release treatment improves endothelium-dependent vasodilation in never treated hypertensive patients. METHODS: The responses of the forearm vasculature to acetylcholine (7.5, 15 and 30 micrograms/min) and sodium nitroprusside (0.8, 1.6, 3.2 micrograms/min) were evaluated in 12 normotensive controls (seven men and five women, aged 25 to 49 years), and in 12 hypertensives (eight men and four women, aged 20 to 47 years) at baseline and after two and six months of isradipine sustained-release treatment. Drugs were infused into the brachial artery, and forearm blood flow was measured by strain-gauge plethysmography. RESULTS: At baseline, the response to acetylcholine was significantly lower in hypertensives vs controls: at the highest dose (30 micrograms/min), forearm blood flow was 28.6 +/- 2.4 ml/100 ml of tissue per min in the controls vs 8.9 +/- 1.0 ml/100 ml of tissue per min in hypertensive (p < 0.0001). Similarly, vascular resistance was significantly (p < 0.0001) higher in hypertensives: 4.8 +/- 0.5 units (controls) vs 15.1 +/- 1.7 units (hypertensives). After isradipine treatment, the forearm blood flow in hypertensive patients changed from 8.9 +/- 1.0 ml/100 ml of tissue per min to 16.0 +/- 1.2 ml/100 ml of tissue per min (two months; p < 0.0001) and 15.2 +/- 1.4 ml/100 ml of tissue per min (six months; p < 0.0001). Isradipine treatment did not modify the vasodilating effect of sodium nitroprusside. CONCLUSIONS: Our data demonstrate for the first time that the calcium antagonist isradipine improves acetylcholine-induced vasodilation in hypertensives.
Assuntos
Bloqueadores dos Canais de Cálcio/uso terapêutico , Hipertensão/tratamento farmacológico , Isradipino/uso terapêutico , Acetilcolina , Adulto , Análise de Variância , Estudos de Casos e Controles , Relação Dose-Resposta a Droga , Feminino , Antebraço/irrigação sanguínea , Humanos , Masculino , Pessoa de Meia-Idade , Nitroprussiato , Fluxo Sanguíneo Regional/efeitos dos fármacos , Fatores de Tempo , Resistência Vascular/efeitos dos fármacos , Vasodilatação/efeitos dos fármacos , VasodilatadoresRESUMO
BACKGROUND: Hypertensive patients are characterized by development of both left ventricular hypertrophy (LVH) and endothelial dysfunction METHODS AND RESULTS: We enrolled 65 never-treated hypertensive patients (36 men and 29 women aged 45.6+/-6.0 years) to assess the possible relationship between echocardiographic left ventricular mass (LVM) and endothelium-dependent vasodilation. Left ventricular measurements were performed at end diastole and end systole according to the recommendations of the American Society of Echocardiography and the Penn Convention. LVM was calculated with the Devereux formula and indexed by body surface area and height raised to the 2.7th power. The endothelial function was tested as responses of forearm vasculature to acetylcholine (ACh), an endothelium-dependent vasodilator (7.5, 15, and 30 microg. mL-1. min-1, each for 5 minutes), and sodium nitroprusside (SNP), an endothelium-independent vasodilator (0.8, 1.6, and 3.2 microg. mL-1. min-1, each for 5 minutes). Drugs were infused into the brachial artery, and forearm blood flow (FBF) was measured by strain-gauge plethysmography. A negative significant relationship between indexed LVM and peak of increase in FBF was found during ACh infusions (r=-0. 554; P<0.0001). In addition, hypertrophic patients had a significantly lower responsive to ACh than patients without LVH (the peak increase in FBF was 9.9+/-3.7 versus 16.1+/-8.1 mL per 100 mL of tissue per minute; P<0.0001). No significant correlation was observed between LVM and FBF during SNP infusion. CONCLUSIONS: Our data provide the first evidence that echocardiographic LVM in hypertensive patients is inversely related to FBF responses to the endothelium-dependent vasodilating agent ACh, but it is likely that both endothelium and LVM are damaged by hypertension.
Assuntos
Endotélio Vascular/fisiopatologia , Ventrículos do Coração/patologia , Hipertensão/complicações , Hipertrofia Ventricular Esquerda/etiologia , Vasodilatação/efeitos dos fármacos , Acetilcolina/farmacologia , Adaptação Fisiológica , Adulto , Doenças Cardiovasculares/epidemiologia , Diástole , Ecocardiografia , Feminino , Antebraço/irrigação sanguínea , Humanos , Hipertensão/fisiopatologia , Hipertrofia Ventricular Esquerda/patologia , Masculino , Pessoa de Meia-Idade , Óxido Nítrico/fisiologia , Nitroprussiato/farmacologia , Tamanho do Órgão , Pletismografia , Fatores de Risco , Sístole , Vasodilatadores/farmacologiaRESUMO
The mechanisms underlying macrovascular complications in NIDDM are partially understood. In addition to increased prevalence and severity of systemic cardiovascular risk factors, local alterations of arterial wall and hemodynamics may play a role. Atherosclerotic lesions usually lie in regions of low wall shear stress. We therefore investigated the wall shear stress--that is, the frictional force acting tangentially to the endothelial surface--in the common carotid artery of diabetic and control subjects. Enrolled were 18 male NIDDM subjects and 18 age-matched control subjects. None of the participants were hypertensive, hyperlipidemic, or a cigarette smoker. Common carotid wall shear stress was calculated according to the following equation: blood viscosity x blood velocity/internal diameter. Blood viscosity was measured by use of a cone/plate viscometer. Blood velocity and internal diameter were measured by high-resolution echo-Doppler. Wall shear stress was significantly lower in NIDDM subjects than in control subjects (mean wall shear stress: 9.7 +/- 2.4 vs. 11.7 +/- 2.6 dynes/cm2, P < or = 0.005). Six diabetic participants had a plaque in one carotid tree and no lesions in the contralateral carotid. Among these subjects, mean wall shear stress was significantly lower in the side with lesion (8.1 +/- 1.6 vs. 10.5 +/- 2.4 dynes/cm2, P < or = 0.02). These findings suggest that diabetes is associated with a more atherosclerosis-prone carotid hemodynamic profile, which might represent an additional factor contributing to the increased prevalence and severity of carotid atherosclerosis in diabetic patients compared with general population.
Assuntos
Artéria Carótida Primitiva/fisiopatologia , Diabetes Mellitus Tipo 2/fisiopatologia , Arteriosclerose/etiologia , Velocidade do Fluxo Sanguíneo/fisiologia , Viscosidade Sanguínea/fisiologia , Artérias Carótidas/patologia , Artéria Carótida Primitiva/diagnóstico por imagem , Diabetes Mellitus Tipo 2/patologia , Angiopatias Diabéticas/patologia , Angiopatias Diabéticas/fisiopatologia , Hemodinâmica/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Valores de Referência , Estresse Mecânico , UltrassonografiaRESUMO
The impact of molecular genetics in the diagnosis and management of various forms of heritable cardiac or vascular disorders is continuously increasing thanks to the newly available laboratory tools. Familial hypertrophic cardiomyopathy (FHC), an autosomal dominant inherited disease characterized by unexplained left ventricular hypertrophy and a wide range of clinical symptoms, is the first cardiac disorder whose genetic bases have been elucidated. Linkage analysis studies have shown a statistically significant association between the disease status and at least seven genetic loci, all coding for sarcomeric proteins, in unrelated kindreds. A major challenge for physicians is to make an accurate and early diagnosis, not only on the basis of the traditional tools (i.e. physical examination and electro-echocardiography) but also to focus on the impact of genotype on clinical manifestations of FHC. In this review we present the more recent findings on the genetic basis of FHC and analyze the genotype-phenotype correlations of this disorder, whose expression may be modulated by additional factors (modifier genes, genetic background, environmental factors) other than mutations in any of the sarcometric proteins.
Assuntos
Cardiomiopatia Hipertrófica/genética , Animais , Galinhas/genética , Genótipo , Humanos , Cadeias Pesadas de Miosina/genética , Cadeias Leves de Miosina/genética , Fenótipo , Proteína C/genética , Troponina T/genéticaRESUMO
The response of the forearm vasculature to acetylcholine (7.5, 15, and 30 microg/min, each for 5 minutes) and sodium nitroprusside (0.8, 1.6, and 3.2 microg/min, each for 5 minutes) was evaluated in 32 never-treated hypertensive outpatients (17 men and 15 women, aged 43+/-7 years) and in 24 normotensive control subjects (14 men and 10 women, aged 42+/-6 years). Drugs were infused into the brachial artery, and forearm blood flow was measured by strain-gauge plethysmography. In both hypertensive and normotensive groups, a deletion (D)/insertion (I) polymorphism in intron 16 of the angiotensin-converting enzyme (ACE) gene was determined by polymerase chain reaction. The response to acetylcholine was significantly reduced in hypertensive patients versus control subjects: at the highest dose (30 microg/min), forearm blood flow was 13.9+/-6.3 mL x 100 mL tissue(-1) x min(-1) in hypertensives versus 27.1+/-9.7 mL x 100 mL tissue(-1) x min(-1) in the controls (P<.001); similarly, vascular resistance was 10.6+/-5.6 U in hypertensive patients and 4.9+/-1.9 U in normotensive subjects. In the hypertensive group, the patients with DD genotype showed significantly less endothelium-dependent vasodilation compared with ID+II genotypes (at the highest dose of acetylcholine, forearm blood flow was 12.1+/-4.2 versus 17.0+/-4.1 mL x 100 mL tissue(-1) x min(-1)) (P<.005). The vasodilator effect of sodium nitroprusside infusions was not statistically different in DD and ID+II hypertensive patients. In conclusion, our data suggest that ACE polymorphism affects endothelium-dependent vasodilation in hypertensive patients and confirm that hypertensive patients had a blunted response to the endothelium-dependent agent acetylcholine.
Assuntos
Endotélio Vascular/fisiologia , Hipertensão/genética , Peptidil Dipeptidase A/genética , Vasodilatação/fisiologia , Adulto , Análise de Variância , Pressão Sanguínea , Feminino , Genótipo , Humanos , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Polimorfismo GenéticoRESUMO
The purpose of the present study was to assess the degree of awareness, treatment and control of hyperlipidaemia compared with hypertension and diabetes mellitus in a selected population of southern Italy. All participants to a cardiovascular disease prevention campaign examined between April 1994 and July 1995 were screened for hyperlipidaemia, hypertension and diabetes mellitus. Subjects received also ECG, echo-Doppler of carotid arteries and filled in a questionnaire concerning personal and familial cardiovascular diseases, smoking habit and drug consumption. Of the 742 participants, 327 were found to have hypertension, 73 to have diabetes mellitus, 287 to have mild hyperlipidaemia and 322 to have moderate-severe hyperlipidaemia. Among hypertensive subjects, 60.2% were aware of their condition, 53.5% were treated and 15.6% had their blood pressure controlled at the recommended level (< 140/90 mmHg). Among diabetic subjects, 76.7% were aware, 64.4% treated and 19.2% reached fasting blood glucose level of less than 7.77 mmol/l (140 mg/dl). Only 24.0% of subjects with mild hyperlipidaemia were aware of their condition. Of the subjects found to have moderate-severe hyperlipidaemia, 64.9% were aware, 32.3% were treated and 9.0% had plasma cholesterol and triglycerides concentration of less than 6.45 and 5.65 mmol/l (250 and 500 mg/dl), respectively (cutoffs chosen to separate mild from moderate-severe hyperlipidaemia). These results show that mild hyperlipidaemia is almost neglected whereas awareness of moderave-severe hyperlipidaemia is quite widespread and comparable to that of hypertension and diabetes mellitus. Prevalence of treatment and control of moderate-severe hyperlipidaemia is, however, much lower than that of hypertension and diabetes.
Assuntos
Diabetes Mellitus/terapia , Conhecimentos, Atitudes e Prática em Saúde , Hiperlipidemias/terapia , Hipertensão/terapia , Adulto , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/prevenção & controle , Complicações do Diabetes , Feminino , Humanos , Hiperlipidemias/complicações , Hipertensão/complicações , Itália , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Fatores de Risco , Índice de Gravidade de Doença , Inquéritos e QuestionáriosRESUMO
BACKGROUND AND PURPOSE: It is known that atherosclerosis does not involve both carotid arteries to the same extent. Pathological investigations have demonstrated that lesions develop in regions of low wall shear stress. The aims of the present study were to verify the degree of carotid atherosclerosis asymmetry in a population-based study and to evaluate whether wall shear stress is lower in carotids with atherosclerotic lesions than in carotids without lesions. METHODS: Participants in a cardiovascular disease prevention campaign (n = 1166) were screened for carotid atherosclerosis by echo-Doppler examination. Of these, 23 subjects who presented plaque in the common carotid or bulb of one side and no plaque in the contralateral carotid tree were enrolled for common carotid wall shear stress measurement. Shear stress was calculated according to the following formula: Shear Stress = Blood Viscosity x Blood Velocity/Internal Diameter. RESULTS: Of the 1166 subjects screened, 400 (34%) had plaque and/or stenosis in the carotids. Ninety subjects had lesions exclusively in the right carotid, 111 had lesions exclusively in the left, 70 had lesions in both carotids but with different degrees of severity, and only 129 had similar lesions in both carotids. In the 23 subjects in whom wall shear stress was measured, peak shear stress was 18.7 +/- 4.1 and 15.3 +/- 4.0 dynes.cm-2 (mean +/- SD) (P < .0001) in the side without and the side with plaque, respectively. Mean shear stress yielded similar results. CONCLUSIONS: The present results demonstrate that the atherosclerotic involvement of carotid arteries is usually asymmetrical and that wall shear stress is lower in the carotid arteries where plaques are present than in plaque-free arteries. These findings provide in vivo evidence for a strong association between shear stress and atherosclerotic lesions.
Assuntos
Arteriosclerose/diagnóstico por imagem , Arteriosclerose/fisiopatologia , Doenças das Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/fisiopatologia , Velocidade do Fluxo Sanguíneo , Viscosidade Sanguínea , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Cardiovasculares , Estresse Mecânico , Túnica Íntima/diagnóstico por imagem , Túnica Média/diagnóstico por imagem , UltrassonografiaRESUMO
We report a clinical case of a patient affected by splenic non-Hodgkin lymphoma and virus C hepatitis. It seems that this kind of association is original because as far as we know the association between non-Hodgkin lymphoma and HCV did not include non-Hodgkin lymphoma involving the spleen. Indeed, in our patient, there was an increase of CD/57 lymphocytes. In our opinion this could be interesting in the disorders of the immune system associated with lymphoma.
Assuntos
Hepatite C/complicações , Linfoma Difuso de Grandes Células B/complicações , Neoplasias Esplênicas/complicações , Idoso , Humanos , MasculinoRESUMO
OBJECTIVES: This study sought to evaluate the possible association of polymorphism of the angiotensin-converting enzyme (ACE) gene with blood pressure and left ventricular mass index (LVMI). BACKGROUND: The renin-angiotensin system seems to be involved in the pathogenesis of essential hypertension. Moreover, recent epidemiologic observations demonstrate that many subjects with left ventricular hypertrophy have normal blood pressure levels, suggesting that factors other than hemodynamic overload may contribute to the hypertrophy. METHODS: The study included 140 untreated hypertensive outpatients who underwent ambulatory blood pressure monitoring, echocardiographic evaluation and analysis for insertion (I)/ deletion (D) polymorphism in intron 16 of the ACE gene by polymerase chain reaction. Blood pressure was measured at 24 h, and LVMI was calculated by the Devereux formula, in each patient. RESULTS: Left ventricular mass index values (mean +/- SD) were 137 +/- 28 g/m2 in patients with the DD genotype, 125 +/- 27 g/m2 in those with the ID genotype and 115 +/- 27 g/m2 in those with II genotype. The frequencies of the DD, ID and II genotypes were 45.71% (n = 64), 46.42% (n = 65) and 7.85% (n = 11), respectively, and were in Hardy-Weinberg equilibrium. The strongest association between left ventricular mass and DD genotype in our cohort appeared to be an independent cardiovascular risk factor (DD vs. ID: odds ratio [OR] 2.497, 95% confidence interval [CI] interval 1.158 to 5.412, p < 0.05; DD vs. II: OR 6.577, 95% CI 1.169 to 28.580, p < 0.02). CONCLUSIONS: Our data show that the LVMI was significantly enhanced in patients with the DD genotype.
Assuntos
Deleção de Genes , Hipertensão/genética , Hipertrofia Ventricular Esquerda/genética , Peptidil Dipeptidase A/genética , Polimorfismo Genético , Adulto , Idoso , Ecocardiografia , Feminino , Genótipo , Humanos , Itália , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Atherosclerotic lesions lie in regions of low wall shear stress. No relationship between wall shear stress and intima-media thickness in vivo has been reported. Aims of the present study were to verify the reproducibility of wall shear stress measurement in vivo and to evaluate its association with intima-media thickness in the common carotid artery in healthy subjects. METHODS AND RESULTS: Wall shear stress was calculated according to the following formula: Shear Stress = Blood Viscosity x Blood Velocity/Internal Diameter. Blood viscosity was measured by use of a cone/plate viscometer. Blood velocity, internal diameter, and intima-media thickness were measured by high-resolution echo Doppler. Twenty-one healthy male subjects were investigated. Peak and mean shear stress values were 29.5 +/- 8.2 and 12.1 +/- 3.1 dynes/cm-2 (mean +/- SD), respectively. Peak shear stress was inversely related to intima-media thickness (r = .62), age (r = .77), systolic blood pressure (r = .61), and body mass index (r = .59) (P < .001 for all coefficients). Mean shear stress yielded similar results. The relationship between shear stress and intima-media thickness was independent of age, blood pressure, and body mass index. The reproducibility, calculated by Kendall's W test, was statistically significant. CONCLUSIONS: Our results demonstrate that common carotid artery wall shear stress measurement in vivo is reproducible. It inversely relates to intima-media thickness, age, systolic blood pressure, and body mass index. These findings confirm in vivo the role of shear stress in intima-media thickening.
Assuntos
Artéria Carótida Primitiva/anatomia & histologia , Artéria Carótida Primitiva/fisiologia , Túnica Íntima/anatomia & histologia , Túnica Íntima/fisiologia , Túnica Média/anatomia & histologia , Túnica Média/fisiologia , Adulto , Velocidade do Fluxo Sanguíneo , Glicemia/análise , Pressão Sanguínea , Viscosidade Sanguínea , Índice de Massa Corporal , Artéria Carótida Primitiva/diagnóstico por imagem , Colesterol/sangue , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Frequência Cardíaca , Humanos , Masculino , Valores de Referência , Reprodutibilidade dos Testes , Estresse Mecânico , Triglicerídeos/sangue , Túnica Íntima/diagnóstico por imagem , Túnica Média/diagnóstico por imagem , Ultrassonografia DopplerRESUMO
A previously undescribed de novo insertion-deletion mutation in the beta cardiac myosin heavy chain gene was found in a kindred with familial hypertrophic cardiomyopathy. In the mutated allele there is an inserted-deleted guanine at nucleotides 8823 and 8850 of the beta myosin heavy chain gene, resulting in a dramatic change of the amino acid sequence (AA 395-404). such a mutation, detected in the proband and in his son but not in the proband's parents, is likely to produce major impairment of myosin function.
Assuntos
Cardiomiopatia Hipertrófica/genética , Mutação , Cadeias Pesadas de Miosina/genética , Adulto , Humanos , Masculino , LinhagemRESUMO
Rendu-Osler-Weber disease is an hereditary disorder characterized by cutaneo-mucous telangiectasis and vascular abnormalities in several organs. Bleeding, especially epistaxis, represents the most important clinical feature. Pulmonary arteriovenous fistulae can cause hypoxaemia, haemoptysis, polycythaemia and clubbing. Diagnosis is based on family and personal history, teleangiectasis, laboratory (haemochrome, fibrinogen, PT, PTT) and instrumental findings (endoscopy and/or roentgen). Therapy depends on symptoms. Embolization of pulmonary arteriovenous fistulae and laser treatment of intestinal vascular abnormalities have been successful. Danazol treatment yielded controversial results. We report the case of a patient admitted for arterial hypertension and recurrent epistaxis. Rendu-Osler-Weber disease diagnosis was made based on positivity at family and personal history, clinical examination, laboratory and instrumental findings. In conclusion we underline the pivotal role of anamnesis and clinical examination in the differential diagnosis of hereditary bleeding disorders and emphasize the importance of early diagnosis for the correct therapeutic approach.