Sérgio Saldanha Menna-Barreto

Treatment with N-acetylcysteine plus deferoxamine protects rats against oxidative stress and improves survival in sepsis

ObjectiveOxidative stress plays an important role in the development of multiple organ failure and septic shock. Here we have evaluated the effects of a combination of antioxidants (N-acetylcysteine plus deferoxamine) in a murine model of polymicrobial sepsis induced by cecal ligation and puncture (CLP). DesignProspective, randomized, controlled experiment. SettingAnimal basic science laboratory. SubjectsMale Wistar rats, weighing 300–350 g. InterventionsRats subjected to CLP were treated with either N-acetylcysteine (20 mg/kg, 3 hrs, 6 hrs, 12 hrs, 18 hrs, and 24 hrs after CLP, subcutaneously) plus deferoxamine (20 mg/kg, 3 hrs and 24 hrs after CLP, subcutaneously) or vehicle with or without “basic support” (saline at 50 mL/kg immediately and 12 hrs after CLP plus ceftriaxone at 30 mg/kg and clindamycin 25 mg/kg every 6 hrs). Measurements and Main ResultsAfter 12 hrs, tissue myeloperoxidase (indicator of neutrophil infiltration), thiobarbituric acid reactive species (as a marker of oxidative stress), catalase and superoxide dismutase activities (antioxidant enzymes), and mitochondrial superoxide production (index of uncoupling of electron transfer chain) were measured in major organs involved in septic response. Rats treated with antioxidants had significantly lower myeloperoxidase activity and thiobarbituric acid reactive species formation in all organs studied. Mitochondrial superoxide production was significantly reduced by antioxidant treatment. Furthermore, antioxidants significantly improved the balance between catalase and superoxide dismutase activities. Survival in untreated septic rats was 10%. Survival increased to 40% with fluids and antibiotics. In rats treated only with N-acetylcysteine plus deferoxamine, survival was also significantly improved (47%) in a manner similar to basic support. Survival increased to 66% with basic support with N-acetylcysteine plus deferoxamine. ConclusionsOur data provide the first experimental demonstration that N-acetylcysteine plus deferoxamine reduces the consequences of septic shock induced by CLP in the rat, by decreasing oxidative stress and limiting neutrophil infiltration and mitochondrial dysfunction, thereby improving survival.

Obesity and Its Relationship with Asthma Prevalence and Severity in Adolescents from Southern Brazil

Obesity has been pointed out as a risk factor for higher prevalence of asthma and asthma-related symptoms in adolescents. The objective was to evaluate the relationship between the prevalence of asthma and obesity in adolescents living in Santa Maria and surroundings (state of Rio Grande do Sul, southern Brazil), applying the International Study of Asthma and Allergies in Childhood (ISAAC) protocol. A total of 4,010 of 6,123 schoolchildren, 13 to 14 years of age, enrolled in the ISAAC phase III protocol (asthma core questionnaire) and were nutritionally evaluated: height, weight, and triceps skinfold (TSF) measurements. Prevalence of asthma (wheeze in the last 12 months) and prevalence of severe asthma (two or more affirmative responses to: more than 4 acute attacks of asthma, speech disturbance, sleep disturbance, wheezing with exercise) were evaluated and compared according to their nutritional status: obese and non-obese. Obese adolescents were defined by body mass index (BMI, in kg/m2) ≥85th percentile and TSF ≥85th percentile. Obese and non-obese groups were compared for prevalence of asthma and asthma severity using the Chi-square test and odds ratio (OR) with 95% confidence interval. Analyzing all adolescents, we observed a significant positive relationship between the prevalence of obesity and affirmative responses to “wheeze ever” (OR = 1.28; 95% CI 1.08–1.52), “wheezing with exercise” (OR = 1.36; 95% CI 1.11–1.66), “asthma ever” (OR = 1.29; 95% CI 1.03–1.62), and severe asthma (OR = 1.55; 95% CI 1.12–2.14). Among the boys, there was a significant positive association between obesity and “wheeze ever” (OR = 1.49; 95% CI 1.13–1.86). In girls, there was a significant positive relationship with “asthma ever” (OR = 1.38; 95% CI 1.01–1.88) and “wheezing with exercise” (OR = 1.36; 95% CI 1.11–1.66). This cross-sectional study with adolescents living in the southern region of Brazil showed that there is a positive association between obesity and prevalence of asthma symptoms and asthma severity, a finding mainly confined to girls.

Protective effect of N-acetylcysteine and deferoxamine on carbon tetrachloride-induced acute hepatic failure in rats.

Objective:Carbon tetrachloride (CCl4) is a lipid-soluble potent hepatotoxic; thus, it widely is used as an animal model of severe hepatic failure. Treatment with antioxidants may modulate the toxic effects of CCl4 on liver, generally with drug administration before CCl4, which can restrict its use in the clinical setting. We here describe the effects of N-acetylcysteine, deferoxamine, or both in the treatment of CCl4-induced hepatic failure. Design:Prospective, randomized, controlled experiment. Setting:Animal basic science laboratory. Subjects:Male Wistar rats, weighing 200–250 g. Interventions:Rats exposed to CCl4 were treated with N-acetylcysteine and/or deferoxamine or vehicle. Measurements and Main Results:N-acetylcysteine plus deferoxamine treatment significantly attenuated hepatic and central nervous system oxidative damage after acute hepatic failure induced by CCl4. In addition, the serum levels of alanine aminotransferase, total bilirubin, and prothrombin time in the N-acetylcysteine plus deferoxamine group were significantly lower than those in the N-acetylcysteine or deferoxamine and saline groups. After N-acetylcysteine plus deferoxamine treatment, hepatocellular necrosis and inflammatory infiltration induced by carbon tetrachloride were greatly decreased. Survival in untreated rats was 5%. Survival increased to 25% and 35%, respectively, with N-acetylcysteine and deferoxamine treatment. In rats treated with N-acetylcysteine plus deferoxamine, survival was 80%. Conclusions:Our data provide the first experimental demonstration that N-acetylcysteine plus deferoxamine reduces mortality rate, decreases oxidative stress, and limits inflammatory infiltration and hepatocyte necrosis induced by CCl4 in the rat.

Effects of Expiratory Positive Airway Pressure on Dynamic Hyperinflation During Exercise in Patients With COPD

BACKGROUND: Expiratory positive airway pressure (EPAP) is a form of noninvasive positive-pressure ventilatory support that, in spite of not unloading respiratory muscles during inspiration, may reduce the inspiratory threshold load and attenuate expiratory dynamic airway compression, contributing to reduced expiratory air-flow limitation in patients with COPD. We sought to determine the effects of EPAP on operational lung volumes during exercise in COPD patients. METHODS: This was a nonrandomized, experimental comparison of 2 exercise conditions (with and without EPAP); subjects completed a treadmill exercise test and performed, before and immediately after exercise, lung volume measurements. Those who overtly developed dynamic hyperinflation (DH), as defined by at least a 15% reduction from pre-exercise inspiratory capacity (IC), were invited for an additional research visit to repeat the same exercise protocol while receiving EPAP through a spring loaded resistor face mask. The primary outcome was IC variance (pre-post exercise) comparison under the 2 exercise conditions. RESULTS: Forty-six subjects (32 males), a mean 65.0 ± 8.2 years of age, and with moderate to severe COPD (FEV1 = 38 ± 16% predicted) were initially enrolled. From this initial sample, 17 (37%) presented overt DH, as previously defined. No significant difference was found between these subjects and the rest of the initial sample. Comparing before and after exercise, there was significantly less reduction in IC observed when EPAP was used (−0.18 ± 0.35 L vs −0.57 ± 0.45 L, P = .02), allowing greater IC final values (1.45 ± 0.50 L vs 1.13 ± 0.52 L, P = .02). CONCLUSIONS: The application of EPAP reduced DH, as shown by lower operational lung volumes after submaximal exercise in COPD patients who previously manifested exercise DH.

Sleep abnormalities in untreated patients with mucopolysaccharidosis type VI.

Mucopolysaccharidosis type VI (MPS VI) is a lysosomal storage disease that affects an enzyme responsible for the degradation of glycosaminoglycans (GAGs). Partially degraded GAGs accumulate in several tissues, such as the upper airways (UA), which leads to the development of obstructive sleep apnea (OSA). Our objective was to determine the prevalence of OSA in a group of untreated patients with MPS VI and the association of OSA with clinical and echocardiographic findings. Patients aged 4 years or older with a biochemical diagnosis of MPS VI were included. Data about clinical history, physical examination, Doppler echocardiogram, and overnight polysomnography (PSG) were collected. Our results showed that of the 28 participants, 14 were boys; mean age was 98.5 months, and mean age at MPS VI diagnosis was 48.4 months. Snoring, witnessed apnea, pectus carinatum, and macroglossia were the main clinical findings. PSG results showed that 23:27 patients (85.1%) had OSA which was mild in 4, moderate in 5, and severe in 14 patients. Echocardiograms showed evidence of pulmonary hypertension (PH) in 14 patients. Lower (P = 0.037) and nadir SpO2 (P = 0.007) were positively associated with PH. Clinical signs suggestive of respiratory abnormalities during sleep were not significantly correlated with the results of PSG. We conclude that the prevalence of OSA in patients with MPS VI was high, and the level of desaturation was positively correlated with PH. Symptoms during sleep were not associated with PSG findings, which suggests that this population should undergo routine PSG as earlier as possible. This study provides baseline data to estimate the potential impact of specific treatments in the sleep abnormalities presented by patients with MPS VI.

Prevalência de asma em adolescentes urbanos de Santa Maria (RS): Projeto ISAAC - International Study of Asthma and Allergies in Childhood

BACKGROUND: Asthma is the most common chronic disease among adolescents. OBJECTIVE: To determine the prevalence of asthma and asthma-related symptoms using the International Study of Asthma and Allergies in Childhood (ISAAC) protocol to evaluate adolescents in the city of Santa Maria, located in the state of Rio Grande do Sul, Brazil. METHOD: A cross-sectional study evaluating 3066 schoolchildren from 13 to 14 years of age, selected by random sampling, as indicated in the ISAAC protocol. Data were collected from March to June of 2003 using the standardized ISAAC questionnaire, which was completed by the adolescents in the classroom and under the supervision of the researchers. RESULTS: A total of 3066 valid questionnaires (95.5%) were collected. Among the asthma-related symptoms evaluated, the following prevalences were determined: history of wheezing: 42.1%; wheezing within the last 12 months: 16.7%; four or more wheezing attacks within the last 12 months: 1.9%; sleep disturbance on one or more nights a week within the last 12 months: 3.8%; impaired speech within the last 12 months: 3.8%; history of asthma: 14.9%; wheezing after exercise within the last 12 months: 19%; dry cough at night within the last 12 months: 32.4%. Values were significantly higher among females. CONCLUSION: The prevalence of asthma-related symptoms among adolescents living in the city of Santa Maria was high, predominantly among the females. However, the rate was comparable to the international average and was lower than those observed in larger metropolitan areas in Brazil. These findings underscore the need for regional studies in order to better understand the prevalence of asthma in Brazil.

Activity level predicts 6-minute walk distance in healthy older females: an observational study

BACKGROUND The 6-minute walk test (6MWT) is widely used in clinical practice and research. Few studies have investigated activity level as a predictor of 6-minute walk distance (6MWD), and existing predictive models do not allow for activity level. OBJECTIVES To evaluate if knowledge of the level of physical activity enhanced the ability to predict 6MWD, and if the inclusion of activity level added to the predictive accuracy of existing models for the 6MWT in healthy older women; and to validate existent predictive models for 6MWD in a new sample. DESIGN Cross-sectional, observational study. SETTING Four elderly communities. PARTICIPANTS A convenience sample of healthy active and sedentary older non-smoking females with no musculoskeletal or lung disorders. MAIN OUTCOME MEASURES Age, height, weight, spirometric values and 6MWD. RESULTS Seventy-seven out of 154 females met the inclusion criteria [mean age 66 (standard deviation 6.5) years]: 46 were active and composed the active group and 31 were sedentary and composed the sedentary group. The active group had significantly greater 6MWD than the sedentary group (mean 44m; 95% confidence interval 14 to 73m; P<0.01). Previous published models that did not allow for activity level either over or underestimated the 6MWD in this sample. The activity level was shown to be an important independent predictor of 6MWD. CONCLUSION This study demonstrates the importance of considering the level of physical activity when predicting 6MWD in older women.

Recomendações para o manejo da tromboembolia pulmonar, 2010

Pulmonary thromboembolism and deep vein thrombosis together constitute a condition designated venous thromboembolism. Despite the advances, the morbidity and the mortality attributed to this condition are still high, because the patients present with more complex diseases, are submitted to a greater number of invasive procedures and survive longer. Although there are various international guidelines available, we decided to write these recommendations for their application in medical practice in Brazil. These recommendations are based on the best evidence in the literature and the opinion of the advisory committee. This document is only a tool for use in the management of patients. Although the recommendations it contains can be applied to most situations, physicians should adapt its content depending on their local context and on a case-by-case basis. Pulmonary thromboembolism is diagnosed by evaluating pre-test clinical probability (scores) together with the results of imaging studies, the current method of choice being CT angiography. Stratification of the risk for an unfavorable outcome is fundamental. Hemodynamic instability is the most important predictor. Low-risk patients should be treated with heparin, commonly low-molecular-weight heparins. High-risk patients require intensive monitoring and, in some cases, thrombolytic therapy. In the long term, patients should receive anticoagulants for at least three months. The decision to prolong this treatment is made based on the presence of risk factors for the recurrence of the condition and the probability of bleeding. Prophylaxis is highly effective and should be widely used in clinical and surgical patients alike, according to their risk group. Finally, we include recommendations regarding the prevention, diagnosis and treatment of pulmonary thromboembolism.

Padrões ventilatórios na espirometria em pacientes adolescentes e adultos com fibrose cística

OBJECTIVE To evaluate spirometric patterns of respiratory disorders and their relationship with functional severity and maximal expiratory flows at low lung volumes in patients with cystic fibrosis (CF). METHODS A retrospective cross-sectional study including adolescents and adults with CF. All of the patients were submitted to spirometry. Patients were classified as having preserved respiratory function, obstructive lung disease (OLD), OLD with reduced FVC, presumptive restrictive lung disease (RLD) or mixed obstructive and restrictive lung disease (MORLD). Maximal expiratory flows at low lung volumes were assessed using FEF(25-75%), FEF(75%) and FEF(75%)/FVC. We included 65 normal subjects, also submitted to spirometry, as a control group. RESULTS The study group included 65 patients: 8 (12.3%) with preserved lung function; 18 (27.7%) with OLD; 24 (36.9%) with OLD and reduced FVC; 5 (7.7%) with presumptive RLD; and 10 (15.4%) with MORLD. The FEV1 was significantly lower in the OLD with reduced FVC group and the MORLD group than in the other groups (p < 0.001). In the patients with preserved respiratory function, FEF(25-75%) and FEF(75%) were significantly reduced in 1 patient, as was FEF(75%)/FVC in 2 patients. CONCLUSIONS The respiratory pattern was impaired in 88% of the patients with CF. The most common pattern was OLD with reduced FVC. The degree of functional impairment was greater in the OLD with reduced FVC group and in the MORLD group than in the other groups. Maximal expiratory flows at low lung volumes were impaired in a low percentage of patients with preserved respiratory function.

Associação entre o estado nutricional e a ingestão dietética em pacientes com fibrose cística

OBJECTIVE To determine the relationship between nutritional status and dietary intake in patients with cystic fibrosis. METHODS Cross-sectional study involving 85 cystic fibrosis patients between 6 and 18 years of age. Dietary intake was evaluated by the 3-day diet record (weighing the food consumed). The outcome measures were the following nutritional status indicators: weight/height (W/H%) percentage, body mass index (BMI) percentiles, Z score for weight/age (W/A), Z score for height/age (H/A) and percentage of dietary intake compared with the Recommended Dietary Allowance (RDA). RESULTS The prevalence of well-nourished patients was 77.7%, using BMI above the 25th percentile as the cut-off value, and the W/H% was above 90% in 83.5%. The mean dietary intake, evaluated in 82 patients, was 124.5% of the RDA. In the univariate logistic regression analyses, we found a significant association between the independent variable calorie intake and the Z score for W/A. The multivariate analysis, based on the Z score for H/A and adjusted for FEV1, methicillin-resistant Staphylococcus aureus colonization and number of hospitalizations, demonstrated that a 1% increase in the calorie intake decreases the chance of having short stature by 2% (OR: 0.98; 95% CI: 0.96-1.00). Maternal level of education showed a borderline association (p = 0.054). CONCLUSIONS The prevalence of malnutrition was low in this sample of patients. The study model demonstrated an association between dietary intake and nutritional status. Dietary intake was a predictive factor of statural growth in patients with cystic fibrosis.