Fabricia J. Neves

Mortalidade por câncer de cólon e reto nas capitais brasileiras no período 1980-1997

BACKGROUND In Brazil, colorectal tumors are among the five more important sites of neoplasms, for both sexes, in terms of mortality. The etiology of colon and rectal cancer is complex and some of the factors involved in its genesis are related to diet. Brazilian geographic regions present heterogeneous alimentary profiles, that could be influencing the distribution of the mortality rates for these tumors. OBJECTIVE To describe the patterns of mortality from cancers of the colon and the rectum in Brazilian State capitals in the period 1980-1997. MATERIAL AND METHODS Mortality data for individuals of both sexes, residents in Brazilian State capitals (except Palmas, Tocantins) was obtained from the Ministry of Health Mortality System (SIM/MS). We considered as death from colon and rectum cancers those whose underlying cause of death was coded as 153.0 to 153.9, 154.0 and 154.1, according to ICD 9, in the period 1980-95; C18.0 to C18.9, C19 and C20,according to ICD 10, in the period 1996-97. The trends of the standardized mortality rates from colon and rectum cancer were analyzed through linear regression models. RESULTS The highest standardized mortality rates for colorectal cancer were observed in the South and Southeastern regions and varied between 8,0 and 10,7/100000 inhabitants. Porto Alegre (11,9), São Paulo (10,8) and Rio de Janeiro (9,6) presented the greatest rates among the State capitals in the study period. In the South region, rates of mortality for Porto Alegre and Florianópolis presented an increasing trend in the study period and the same behavior was observed for São Paulo and Vitória in the Southeastern region. Brasilia and the other capitals of the Midwest, with the exception of Goiânia, showed a tendency of increment of the mortality rates. Among the capitals of the North and Northeast regions, an increasing trend of mortality was observed in Rio Branco and Fortaleza. The separate analysis of the mortality rates for tumors of the colon and for tumors of the rectum showed a similar pattern, with higher values being observed for colon neoplasia. DISCUSSION Regional differences in the mortality rates for colon and rectum neoplasias have been discussed for different authors, who point to the contribution of cultural and alimentary habits, and differences of life style and socioeconomic status to this heterogeneity, besides other aspects related to access to health services and quality of hospital care and preventive services. These factors must be considered in the evaluation of the differences observed in Brazilian capitals. Although the State capitals situated in South and Southeastern regions presented higher rates than the others, mortality rates of Porto Alegre (9,8/100.000) and Rio de Janeiro (9,0/100.000), in period 1983- 85, were about three times lower than those observed in the United States, Canada and France, in 1985. The sex distribution pattern of the mortality rates in Brazilian capitals was not uniform, with higher rates in men. We observed a trend of increment of the mortality rates of colorectal cancer in all Brazilian regions, similar to that was observed in some countries of the world, although with different gradients. CONCLUSIONS The standardized mortality rates for colon and rectum neoplasias presented important regional differences among Brazilian State capitals. The highest rates were observed in the South and Southeastern regions. A trend of increment of the standardized mortality rates for cancers of the colon and the rectum was observed in all Brazilian regions in the period 1980-1997.

Impaired hemodynamic response to mental stress in subjects with prehypertension is improved after a single bout of maximal dynamic exercise

INTRODUCTION: High blood pressure during mental stress in subjects with prehypertension is associated with blunted vasodilation in skeletal muscles, which might be improved by an acute bout of exercise. OBJECTIVE: To investigate the hemodynamic responses to mental stress before and after a bout of exercise in subjects with prehypertension. METHOD: Eighteen subjects with prehypertension and 16 with normotension underwent a mental stress test before and after a maximal cardiopulmonary exercise test on a treadmill. Blood pressure was measured by auscultation, and forearm blood flow was measured by venous occlusion plethysmography; from these measurements, the vascular conductance was calculated. RESULTS: Subjects with prehypertension had a higher mean blood pressure during mental stress (prehypertension 112±2 vs. normotension 101±3 mm Hg, p<0.05), and their vascular conductance did not increase (baseline 0.025±0.004 vs. mental stress 0.022±0.003 a.u., p>0.05). After the exercise bout, the mean blood pressure during mental stress was lower in subjects with prehypertension (before exercise 112±2 vs. after exercise 107±2 mm Hg, p<0.05), and vascular conductance increased (baseline 0.011±0.001 vs. mental stress 0.024±0.004 a.u., p<0.05). CONCLUSION: Subjects with prehypertension had elevated blood pressure and a blunted vasodilator response during mental stress, but their blood pressure was attenuated and their vasodilator response was normalized after a single bout of maximal dynamic exercise.

Endothelial nitric oxide synthase polymorphisms and adaptation of parasympathetic modulation to exercise training.

PURPOSE There is a large interindividual variation in the parasympathetic adaptation induced by aerobic exercise training, which may be partially attributed to genetic polymorphisms. Therefore, we investigated the association among three polymorphisms in the endothelial nitric oxide gene (-786T>C, 4b4a, and 894G>T), analyzed individually and as haplotypes, and the parasympathetic adaptation induced by exercise training. METHODS Eighty healthy males, age 20-35 yr, were genotyped by polymerase chain reaction-restriction fragment length polymorphism analysis, and haplotypes were inferred using the software PHASE 2.1. Autonomic modulation (i.e., HR variability and spontaneous baroreflex sensitivity) and peak oxygen consumption (VO(2peak)) were measured before and after training (running, moderate to severe intensity, three times per week, 60 min·day(-1), during 18 wk). RESULTS Training increased VO(2peak) (P < 0.05) and decreased mean arterial pressure (P < 0.05) in the whole sample. Subjects with the -786C polymorphic allele had a significant reduction in baroreflex sensitivity after training (change: wild type (-786TT) = 2% ± 89% vs polymorphic (-786TC/CC) = -28% ± 60%, median ± quartile range, P = 0.03), and parasympathetic modulation was marginally reduced in subjects with the 894T polymorphic allele (change: wild type (894GG) = 8% ± 67% vs polymorphic (894GT/TT) = -18% ± 59%, median ± quartile range, P = 0.06). Furthermore, parasympathetic modulation percent change was different between the haplotypes containing wild-type alleles (-786T/4b/894G) and polymorphic alleles at positions -786 and 894 (-786C/4b/894T) (-6% ± 56% vs -41% ± 50%, median ± quartile range, P = 0.04). CONCLUSIONS The polymorphic allele at position -786 and the haplotype containing polymorphic alleles at positions -786 and 894 in the endothelial nitric oxide gene were associated with decreased parasympathetic modulation after exercise training.

Effect of the 894G>T polymorphism of the endothelial nitric oxide synthase on vascular reactivity following maximal dynamic exercise.

Background Considering that the role of nitric oxide as a vasodilator is increased after an acute bout of exercise and that the 894G>T polymorphism of the endothelial nitric oxide synthase seems to reduce the nitric oxide release in response to shear stress, the present study investigated the 894G>T polymorphism in relation to vascular reactivity following maximal dynamic exercise. Method We studied 110 healthy volunteers (wild-type group 45.5% and polymorphic group 54.5%). The protocol included vascular reactivity assessment at baseline and during reactive hyperemia, before, 10, 60 and 120 min after a maximal cardiopulmonary exercise test. Genomic DNA was extracted from blood samples to determine the 894G>T polymorphism. Results There were no differences between the wild-type and polymorphic groups concerning anthropometric, metabolic and hemodynamic characteristics. Blood flow, before maximal exercise, was similar between the wild-type and the polymorphic groups. The polymorphic group presented lower vascular reactivity regardless of time (P = 0.019 for group main effect), and posthoc analysis revealed that polymorphic patients had lower values than wild-type only at the 120 min measurement (P = 0.002). Concerning within-group analysis, vascular reactivity increased at 10 min after exercise (P = 0.029) returning to baseline at 120 min (P = 0.005) in the polymorphic group. Conclusion Patients with the 894G>T polymorphism had lower vascular reactivity after a single bout of exercise.

Mortalidade por câncer de cólon e reto e consumo alimentar em capitais brasileiras selecionadas

As taxas de mortalidade por câncer de colon e reto mostram uma variacao regional no Brasil e a heterogeneidade do padrao alimentar nas suas regioes geograficas poderia possivelmente explicar, pelo menos em parte, essas diferencas. Um estudo ecologico foi realizado com o objetivo de identificar possiveis associacoes entre padroes de consumo alimentar e taxas de mortalidade padronizadas por idade em capitais brasileiras selecionadas. O padrao de consumo alimentar em cada capital foi caracterizado com base no consumo de grupos de alimentos associados a essa neoplasia na literatura. Os dados de consumo de alimentos foram obtidos no ENDEF (Estudo Nacional de Despesas Familiares). A regressao linear multipla foi utilizada para analisar as correlacoes entre as taxas de mortalidade e as variaveis alimentares. Essas taxas mostraram uma correlacao positiva com o consumo de calorias, cereais, carnes, ovos/leite e legumes/frutas. Quando ajustado por consumo calorico total, carne e legumes/frutas foram as unicas variaveis que mantiveram uma correlacao positiva. O modelo multivariado final com essas variaveis foi capaz de explicar 92% da variacao das taxas de mortalidade nas capitais selecionadas. Esses resultados sugerem que diferencas no consumo calorico total e no consumo de carne e legumes/frutas poderiam explicar, parcialmente, os diferentes padroes de distribuicao da mortalidade por câncer de colon e reto no Brasil.

Hemodynamic mechanisms of the attenuated blood pressure response to mental stress after a single bout of maximal dynamic exercise in healthy subjects

To determine the hemodynamic mechanisms responsible for the attenuated blood pressure response to mental stress after exercise, 26 healthy sedentary individuals (age 29 ± 8 years) underwent the Stroop color-word test before and 60 min after a bout of maximal dynamic exercise on a treadmill. A subgroup (N = 11) underwent a time-control experiment without exercise. Blood pressure was continuously and noninvasively recorded by infrared finger photoplethysmography. Stroke volume was derived from pressure signals, and cardiac output and peripheral vascular resistance were calculated. Perceived mental stress scores were comparable between mental stress tests both in the exercise (P = 0.96) and control (P = 0.24) experiments. After exercise, the systolic blood pressure response to mental stress was attenuated (pre: 10 ± 13 vs post: 6 ± 7 mmHg; P < 0.01) along with lower values of systolic blood pressure (pre: 129 ± 3 vs post: 125 ± 3 mmHg; P < 0.05), stroke volume (pre: 89.4 ± 3.5 vs post: 76.8 ± 3.8 mL; P < 0.05), and cardiac output (pre: 7.00 ± 0.30 vs post: 6.51 ± 0.36 L/min; P < 0.05). Except for heart rate, the hemodynamic responses and the mean values during the two mental stress tests in the control experiment were similar (P > 0.05). In conclusion, a single bout of maximal dynamic exercise attenuates the blood pressure response to mental stress in healthy subjects, along with lower stroke volume and cardiac output, denoting an acute modulatory action of exercise on the central hemodynamic response to mental stress.

Endothelial nitric oxide gene haplotype reduces the effect of a single bout of exercise on the vascular reactivity in healthy subjects

Polymorphisms in the endothelial nitric oxide synthase (eNOS) gene reduce shear stress-induced nitric oxide production. Thus, we investigated the individual and combined impact of 3 variants in the eNOS gene (-786T>C, intron 4b4a, and 894G>T) on vascular reactivity before and after exercise. Sedentary, healthy subjects were studied (105 women/26 men, age 32 ± 1 years [mean ± standard error of the mean]). Genotypes were determined by polymerase chain reaction restriction fragment length polymorphism, and haplotypes were determined by a Bayesian-based algorithm. Vascular reactivity was evaluated by the percentage of change in forearm vascular conductance provoked by 5 minutes of circulatory occlusion before (baseline) and 10, 60, and 120 minutes after a maximal cardiopulmonary exercise test. Vascular reactivity increased 10 minutes after exercise in the entire sample (baseline: 218 ± 11% vs 10 minutes: 284 ± 15%, P < 0.001), remained increased at 60 minutes (239 ± 12%, P = 0.02 vs baseline), and returned to baseline at 120 minutes (210 ± 10%, P = 0.83 vs baseline). Genotype analysis showed that subjects with the 894G>T polymorphism had lower vascular reactivity than wild counterparts (group effect, P = 0.05). Furthermore, subjects with haplotype 2 (H2), containing the -786T>C and 894G>T polymorphisms, had lower vascular reactivity than wild counterparts (haplotype 1 [H1]) (group effect, P = 0.05), whereas subjects with haplotype 4 (H4), containing only the 894G>T polymorphism, had vascular reactivity similar to that of wild counterparts (H1) (group effect, P = 0.35). Altogether, these results indicate that the 894G>T polymorphism reduced exercise-mediated increase in vascular reactivity, particularly when it occurred concomitantly with the -786T>C polymorphism.

eNOS gene haplotype is indirectly associated with the recovery of cardiovascular autonomic modulation from exercise

Polymorphisms in the endothelial nitric oxide synthase (eNOS) gene decrease expression and activation of eNOS in vitro, which is associated with lower post-exercise increase in vasodilator reactivity in vivo. However, it is unknown whether such polymorphisms are associated with other eNOS-related phenotypes during recovery from exercise. Therefore, we investigated the impact of an eNOS haplotype containing polymorphic alleles at loci -786 and 894 on the recovery of cardiovascular autonomic function from exercise. Sedentary, non-obese, healthy subjects were enrolled [n = 107, age 32 ± 1 years (mean ± SEM)]. Resting autonomic modulation (heart rate variability, systolic blood pressure variability, and spontaneous baroreflex sensitivity) and vascular reactivity (forearm hyperemic response post-ischemia) were assessed at baseline, 10, 60, and 120 min after a maximal cardiopulmonary exercise test. Besides, autonomic function was assessed by heart rate recovery (HRR) immediately after peak exercise. Haplotype analysis showed that vagal modulation (i.e., HF n.u.) was significantly higher, combined sympathetic and vagal modulation (i.e., LF/HF) was significantly lower and total blood pressure variability was significantly lower post-exercise in a haplotype containing polymorphic alleles (H2) compared to a haplotype with wild type alleles (H1). HRR was similar between groups. Corroborating previous evidence, H2 had significantly lower post-exercise increase in vasodilator reactivity than H1. In conclusion, a haplotype containing polymorphic alleles at loci -786 and 894 had enhanced recovery of autonomic modulation from exercise, along with unchanged HRR, and attenuated vasodilator reactivity. Then, these results suggest an autonomic compensatory response of a direct deleterious effect of eNOS polymorphisms on the vascular function.

Impaired Vascular Reactivity in Healthy First-Degree Relatives of Subjects With Type 2 Diabetes Is Related to Metabolic Factors

Several studies have suggested that vascular changes precede the development of metabolic disorders in first-degree relatives of subjects with type 2 diabetes, indicating that being a first-degree relative of a subject with type 2 diabetes is a risk per se for vascular dysfunction (1–3). However, these studies have failed to control for relevant metabolic and inflammatory variables that are usually altered in first-degree relatives of subjects with type 2 diabetes and are known to impair vascular reactivity (4). To investigate the hypothesis that vascular reactivity in first-degree relatives of subjects with type 2 diabetes without metabolic disorders is similar to that in a control group without history of type 2 diabetes, 42 first-degree relatives of subjects with type 2 diabetes (79% women; mean ± SD age 33 ± 9 years) and 45 age- and sex-matched control subjects (78% women; age 34 ± 9 years) were recruited. Vascular reactivity was …