Effectiveness of the CAGE questionnaire, gamma-glutamyltransferase and mean corpuscular volume of red blood cells as markers for alcohol-related problems in the workplace

Objective: To evaluate the usefulness of gamma-glutamyltransferase (GGT) and mean corpuscular volume (MCV), as well as that of the CAGE questionnaire, in workplace screening for alcohol abuse/dependence. Methods: A total of 183 male employees were submitted to structured interviews (Structured Clinical Interview for DSM-IV 2.0 and CAGE questionnaire). Blood samples were collected. Diagnostic accuracy and odds ratio were determined for the CAGE, GGT and MCV. Results: The CAGE questionnaire presented the best sensitivity for alcohol dependence (91%; specificity, 87.8%) and for alcohol abuse (87.5%, specificity, 80.9%), which increased when the questionnaire was used in combination with GGT (sensitivity, 100% and 87.5%, respectively; specificity, 68% and 61.5, respectively). CAGE positive results and/or alterations in GGT were less likely to occur among employees not presenting alcohol abuse/ dependence than among those presenting such abuse (OR for CAGE = 13, p < 0.05; OR for CAGE-GGT = 11, p < 0.05) or dependence (OR for CAGE = 76, p < 0.0 1; OR for GGT = 5, p < 0.0 1). Employees not presenting alcohol abuse/dependence were also several times more likely to present negative CAGE or GGT results. Conclusions: The use short, simple questionnaires, combined with that of low-cost biochemical markers, such as GGT, can serve as an initial screening for alcohol-related problems, especially for employees in hazardous occupations. The data provided can serve to corroborate clinical findings. (C) 2008 Elsevier Ltd. All rights reserved.

Influence of Lactic Acid on Endogenous and Viral RNA-Induced Immune Mediator Production by Vaginal Epithelial Cells

OBJECTIVE: To evaluate the influence of lactic acid on immune mediator release from vaginal epithelial cells. METHODS: The human vaginal epithelial cell line, VK2/E6E7, was cultured in the presence or absence of physiological concentrations of lactic acid, and in the presence or absence of the viral Toll-like receptor 3 agonist, poly (inosinic acid: cytidylic acid). Supernatants were assayed by enzyme-linked immunosorbent assay (ELISA) for interleukin (IL)-1 beta, IL-6, IL-8, IL-23, transforming growth factor (TGF)-beta and secretory leukocyte protease inhibitor. RESULTS: Vaginal epithelial cells spontaneously released IL-1 beta (25.9 pg/mL), IL-8 (1.0 ng/mL), TGF-beta (175 pg/mL), and secretory leukocyte protease inhibitor (33.8 ng/mL). Only TGF-beta production was marginally enhanced (49%) by addition of lactic acid alone. Poly (inosinic acid: cytidylic acid) by itself stimulated the release of IL-6 (305 pg/mL) and enhanced IL-8 production (2.8 ng/mL). The combination of poly (inosinic acid: cytidylic acid) and lactic acid markedly increased IL-8 production (5.0 ng/mL) and induced the release of IL-1 beta (96.2 pg/mL). The poly (inosinic acid: cytidylic acid)-mediated lactic acid effect on IL-1 beta and IL-8 release was abrogated when the lactic acid was neutralized or if acetic acid was substituted for lactic acid. CONCLUSION: Lactic acid enhances the release of selective mediators from vaginal epithelial cells and stimulates antiviral immune responses. (Obstet Gynecol 2011;118:840-6) DOI: 10.1097/AOG.0b013e31822da9e9

Bariatric Surgery Reverses Natural Killer (NK) Cell Activity and NK-Related Cytokine Synthesis Impairment Induced by Morbid Obesity

Background Obesity is related to a higher rate of infections and some types of cancer. Here we analyzed the impact of obesity and weight loss induced by Roux-en-Y gastric bypass (RYGB) on immunological parameters, i.e., cytokine productions and natural killer cell function. Methods We analyzed 28 morbidly obese patients before and 6 months after RYGB. Biochemical parameters were analyzed in plasma. The percent of natural killer (NK) cells, their cytotoxicity, and the production of cytokines by peripheral blood mononuclear cells were analyzed. The percent of NK cells was determined by flow cytometry and cytokine production determined by enzyme-linked immunosorbent assay. NK cytotoxicity was determined by the lactate dehydrogenase release assay. Results The weight loss 6 months following surgery was 35.3 +/- 4.5 kg. RYGB also improves biochemical parameters. No significant difference was found in the percent of NK cells after surgery. We found an increase in the production of interferon-gamma, interleukin (IL)-12 and IL-18, but not in IL-2, 6 months after RYGB. Cytotoxic activity of NK cells was significantly enhanced 6 months after RYGB [17.1 +/- 14.7% before RYGB vs 51.8 +/- 11.3% at 6 months after, at 40: 1 effector to target cell ratio; p<0.001]. We observed significant post-surgical improvement in the cytotoxic activity curve in 22 out of 28 patients (78.6%), irrespective of the target to effector cell ratio. Conclusions The weight loss induced by RYGB modifies the production of cytokines related with NK cell function and improves its activity.

Inflammatory Cytokines during Liver Transplantation: Prospective Randomized Trial Comparing Conventional and Piggyback Techniques

Background/Aims: Cytokines have a significant role in the response to injury following liver transplantation, but the origin and course of such molecules are not completely known. The aim of this study was to evaluate the production and liver metabolism of the inflammatory cytokines interleukin (IL)-1 beta, IL-6, IL-8, interferon (IFN)-Y and tumor necrosis factor (TNF)-alpha in orthotopic liver transplantation (OLT), comparing the conventional and the piggyback methods. Methodology: We performed a study of 30 patients who underwent elective OLT and were randomized for the conventional or piggyback techniques at the beginning of the operation. The amount of cytokines and their hepatic metabolism were calculated based on plasma concentrations and vascular blood flow at 2, 5, 10, 15, 30, 60, 90, and 120 minutes after revascularization. Results: The amount of IL-1 beta in portal blood was higher in patients who underwent surgery using the conventional technique (estimate interest = 63,783.9 +/- 16,586.1 pg/min, versus 11,979.6 +/- 16,585.7 pg/min in the piggyback group, p=0.035). There were no significant differences between the two operative`s methods for IL-6, IL-8, IFN-Y and TNF-alpha production. The hepatic metabolism of cytokines was not different between groups. Although all the curves showed higher amounts of cytokines with the conventional technique, these were not statistically significant. Conclusion: The study shows the similarity between the two techniques concerning the stimuli for the production of inflammatory molecules.

Measurements of adipocity and high blood pressure among children and adolescents living in Belo Horizonte

Objective: To verify an association, if it exists, between obesity and blood pressure raised beyond the 90th percentile in children and adolescents, and to determine the measure of adiposity that best correlates with blood pressure in these subjects. Design: Cross-sectional study. Setting: A school-based study in Belo Horizonte, Brazil. Participants: We selected randomly 1,403 students, aged from 6 to 18 years, from 545,046 students attending 521 public and private schools. Those selected completed the study. Main measures of outcome: We recorded the weight, height, skin fold in the triceps, subscapular, and suprailiac areas, waist and hip circumference, body-mass index, and resting systolic and diastolic blood pressures using a mercury sphygmomanometer. Results: In univariate analyses, body mass index greater or lesser than 85th percentile, measurements of skin thickness in the subscapular and suprailiac areas, and the sum of all measurements of skinfold thickness, were associated with both systolic and diastolic measurements of blood pressure. After multivariate analyses that adjusted for all measurements of adiposity except itself, and age, race, and socioeconomic state, we found that the increased body mass index was associated with a 3.6-fold increased frequency of elevated systolic measurements of blood pressure, with 9596 confidence intervals from 2.2 to 5.8, and a 2.7-fold increased frequency of elevated measurements of diastolic blood pressure, with 95% confidence intervals from 1.9 to 4.0. Conclusions: Body-mass index serves as a better predictor of elevated blood pressure among children than do local measurements of adiposity.

Dietary salt restriction increases plasma lipoprotein and inflammatory marker concentrations in hypertensive patients

Background: Dietary salt restriction has been reported to adversely modify the plasma lipoprotein profile in hypertensive and in normotensive subjects. We investigated the effects of the low sodium intake (LSI) on the plasma lipoprotein profile and on inflammation and thrombosis biomarkers during the fasting and postprandial periods. Methods: Non-obese, non-treated hypertensive adults (n=41) were fed strictly controlled diets. An initial week on a control diet (CID, Na=160 mmol/day) was followed by 3 weeks on LSI (Na=60mmol/day). At admission and on the last day of each period, the 24-h ambulatory blood pressure was monitored and blood was drawn after an overnight fasting period and after a fat-rich test meal. Results: The dietary adherence was confirmed by 24-h urinary sodium excretion. Fasting triglyceride (TG), chylomicron-cholesterol, hsC-reactive protein (CRP), tumor necrosis factor-a (TNF-alpha). interleukin-6 (IL-6) concentrations, renin activity, aldosterone, insulin, and homeostasis model assessment insulin resistance (HOMA-IR) Values were higher, but non-esterified fatty acids (NEFA) were lower on LSI than on CD. For LSI, areas under the curve (AUC) of TG, chylomicron-cholesterol, apoB and the cholesterol/apoB ratio were increased, whereas AUC-NEFA was lowered. LSI did not modify body weight, hematocrit, fasting plasma cholesterol, glucose, adiponectin, leptin, fibrinogen and factor VII (FVII), and AUC of lipoprotein lipase and of lipoprotein remnants. Conclusion: LSI induced alterations in the plasma lipoproteins and in inflammatory markers that are common features of the metabolic syndrome. (C) 2008 Elsevier Ireland Ltd. All rights reserved.

Human immunodeficiency virus test-seeking blood donors in a large blood bank in Sao Paulo, Brazil

BACKGROUND: Persons with human immunodeficiency virus (HIV) risk behaviors are excluded from donation to reduce the risk of transfusion-transmitted infection. Persons donating to be tested for HIV may therefore deny risk behaviors. STUDY DESIGN AND METHODS: A random sample of donors completed a survey on motivations, knowledge, and attitudes on the screening process. Donors were considered test seekers if they agreed with two statements ""I think that blood donation is a good, fast, and anonymous way to get my blood tested"" and ""I donate to get my test results."" This study was conducted from June to November 2006 at the largest blood bank in Sao Paulo, Brazil. RESULTS: Of 3061 participants, 208 (7%) were test seekers. They tended to be male and had a lower educational level. They were more likely to have incorrect knowledge about blood safety (e.g., not knowing that a unit can test antibody negative and still transmit infection, 60% vs. 42%, p = 0.02), express dissatisfaction with screening questions (e.g., feeling that important questions were not asked, 14% vs. 5%, p < 0.01), and concur that donors do not answer questions truthfully (e.g., donors have more sexual partners than they admit, 29% vs. 18%, p < 0.01). Test seekers were more likely to believe that it is acceptable to donate blood to get tested for HIV (41% vs. 10%, p < 0.01). CONCLUSIONS: Test-seeking motivation, coupled with low knowledge of window period risk, is counter to improving blood safety and to donor prevention needs. Donor education needs to be improved along with availability of appropriate HIV counseling and testing.

Nitric oxide modulates lipopolysaccharide-induced endothelial platelet endothelial cell adhesion molecule expression via interleukin-10

We have shown previously that nitric oxide (NO) controls platelet endothelial cell adhesion molecule (PECAM-1) expression on both neutrophils and endothelial cells under physiological conditions. Here, the molecular mechanism by which NO regulates lipopolysaccharide (LPS)-induced endothelial PECAM-1 expression and the role of interleukin (IL)-10 on this control was investigated. For this purpose, N-(G)-nitro-L-arginine methyl ester (L-NAME; 20 mg/kg/day for 14 days dissolved in drinking water) was used to inhibit both constitutive (cNOS) and inducible nitric oxide (iNOS) synthase activities in LPS-stimulated Wistar rats (5 mg/kg, intraperitoneally). This treatment resulted in reduced levels of serum NO. Under this condition, circulating levels of IL-10 was enhanced, secreted mainly by circulating lymphocytes, dependent on transcriptional activation, and endothelial PECAM-1 expression was reduced independently on reduced gene synthesis. The connection between NO, IL-10 and PECAM-1 expression was examined by incubating LPS-stimulated (1 mu g/ml) cultured endothelial cells obtained from naive rats with supernatant of LPS-stimulated lymphocytes, which were obtained from blood of control or L-NAME-treated rats. Supernatant of LPS-stimulated lymphocytes obtained from L-NAME-treated rats, which contained higher levels of IL-10, reduced LPS-induced PECAM-1 expression by endothelial cells, and this reduction was reversed by adding the anti-IL-10 monoclonal antibody. Therefore, an association between NO, IL-10 and PECAM-1 was found and may represent a novel mechanism by which NO controls endothelial cell functions.

Peripheral blood chimerism following human liver transplantation

The aim of this study was to prospectively investigate the peak levels and kinetics of donor leucocyte chimerism in human recipients following liver transplantation, The peak levels of chimerism mere observed within the first 48 hours following transplantation and ranged from 0.15% to 20% of total peripheral blood mononuclear cells, In all but one patient, who developed graft versus host disease, there was an early peak level of chimerism that declined over time such that donor leukocytes mere only intermittently detectable after 3 to 4 weeks. In 8 patients who had no episodes of graft rejection, the peak level of donor leukocyte chimerism ranged from 1.3% to 20% (mean +/- SEM; 5.5% +/- 2.1%). In 3 patients who were treated for episodes of acute graft rejection during the first four postoperative weeks, the peak level of donor leukocyte chimerism ranged from 0.15% to 0.2% (0.18 +/- 0.02, P = .012), The results demonstrate a marked variation in the total number of donor leukocytes detectable in the peripheral blood early after liver transplantation and also, that lower levels of chimerism may be associated with lower rates of initial graft acceptance and a higher incidence of acute rejection.

Interleukin-1 receptor antagonist gene (IL1RN) polymorphism possibly associated to severity of rheumatic carditis in a Brazilian cohort

Aims: To evaluate the IL1RN polymorphism as a possible marker for Rheumatic Fever (RF) susceptibility or disease severity. Methods: The genotypes of 84 RF patients (Jones criteria) and 84 normal race-matched controls were determined through the analysis of the number of 86-bp tandem repeats in the second intron of IL1RN. The DNA was extracted from peripheral-blood leukocytes and amplified with specific primers. Clinical manifestations of RF were obtained through a standardized questionnaire and an extensive chart review. Carditis was defined as new onset cardiac murmur that was perceived by a trained physician with corresponding valvae regurgitation or stenosis on echocardiogram. Carditis was classified as severe in the presence of congestive heart failure or upon the indication for cardiac surgery. The statistical association among the genotypes, RF and its clinical variations was determined. Results: The presence of allele I and the genotype A1/A1 were found less frequently among patients with severe carditis when compared to patients without this manifestation (OR = 0.11, p = 0.031; OR = 0.092, p = 0.017). Neither allele I nor allele 2 were associated with the presence of RF (p = 0.188 and p = 0.106), overall carditis (p = 0.578 and p = 0.767), polyarthritis (p = 0.343 and p = 0.313) and chorea (p = 0.654 and p = 0.633). Conclusion: In the Brazilian population, the polymorphism of the IL-1ra gene is a relevant factor for rheumatic heart disease severity. (C) 2009 Elsevier Ltd. All rights reserved.

Effects of continuous vs. interval exercise training on blood pressure and arterial stiffness in treated hypertension

Exercise is an effective intervention for treating hypertension and arterial stiffness, but little is known about which exercise modality is the most effective in reducing arterial stiffness and blood pressure in hypertensive subjects. Our purpose was to evaluate the effect of continuous vs. interval exercise training on arterial stiffness and blood pressure in hypertensive patients. Sixty-five patients with hypertension were randomized to 16 weeks of continuous exercise training (n=26), interval training (n=26) or a sedentary routine (n=13). The training was conducted in two 40-min sessions a week. Assessment of arterial stiffness by carotid-femoral pulse wave velocity (PWV) measurement and 24-h ambulatory blood pressure monitoring (ABPM) were performed before and after the 16 weeks of training. At the end of the study, ABPM blood pressure had declined significantly only in the subjects with higher basal values and was independent of training modality. PWV had declined significantly only after interval training from 9.44 +/- 0.91 to 8.90 +/- 0.96 m s(-1), P=0.009 (continuous from 10.15 +/- 1.66 to 9.98 +/- 1.81 m s(-1), P-ns; control from 10.23 +/- 1.82 to 10.53 +/- 1.97 m s(-1), P-ns). Continuous and interval exercise training were beneficial for blood pressure control, but only interval training reduced arterial stiffness in treated hypertensive subjects. Hypertension Research (2010) 33, 627-632; doi:10.1038/hr.2010.42; published online 9 April 2010

Regional Blood Flow Distribution and Oxygen Metabolism During Mesenteric Ischemia and Congestion

Background. Acute mesenteric ischemia is a potentially fatal vascular emergency with mortality rates ranging between 60% and 80%. Several studies have extensively examined the hemodynamic and metabolic effects of superior mesenteric artery occlusion. On the other hand, the cardiocirculatory derangement and the tissue damage induced by intestinal outflow obstruction have not been investigated systematically. For these reasons we decided to assess the initial impact of venous mesenteric occlusion on intestinal blood flow distribution, and correlate these findings with other systemic and regional perfusion markers. Methods. Fourteen mongrel dogs were subjected to 45 min of superior mesenteric artery (SMAO) or vein occlusion (SMVO), and observed for 120 min after reperfusion. Systemic hemodynamics were evaluated using Swan-Ganz and arterial catheters. Regional blood flow (ultrasonic flow probes), intestinal O(2)-derived variables, and mesenteric-arterial and tonometric-arterial pCO(2) gradients (D(mv-a)pCO(2) and D(t-a)pCO(2)) were also calculated. Results. SMVO was associated with hypotension and low cardiac output. A significant increase in the regional pCO(2) gradients was also observed in both groups during the ischemic period. After reperfusion, a progressive reduction in D(mv-a)pCO(2) occurred in the SMVO group; however, no improvement in D(t-p)CO(2) was observed. The histopathologic injury scores were 2.7 +/- 0.5 and 4.8 +/- 0.2 for SMAO and SMVO, respectively. Conclusions. SMV occlusion promoted early and significant hemodynamic and metabolic derangement at systemic and regional levels. Additionally, systemic pCO(2) gradient is not a reliable parameter to evaluate the local intestinal oxygenation. Finally, the D(t-a)pCO(2) correlates with histologic changes during intestinal congestion or ischemia. However, minor histologic changes cannot be detected using this methodology. (C) 2010 Elsevier Inc. All rights reserved.

Effects of Exercise Training on Myocardial Blood Flow Reserve in Patients With Heart Failure and Left Ventricular Systolic Dysfunction

Exercise training has been shown to be effective in improving exercise capacity and quality of life in patients with heart failure and left ventricular (LV) systolic dysfunction. Real-time myocardial contrast echocardiography (RTMCE) is a new technique that allows quantitative analysis of myocardial blood flow (MBF). The aim of this study was to determine the effects of exercise training on MBF in patients with LV dysfunction. We studied 23 patients with LV dysfunction who underwent RTMCE and cardiopulmonary exercise testing at baseline and 4 months after medical treatment (control group, n = 10) or medical treatment plus exercise training (trained group, n = 13). Replenishment velocity (0) and MBF reserves were derived from quantitative RTMCE. The 4-month exercise training consisted of 3 60-minute exercise sessions/week at an intensity corresponding to anaerobic threshold, 10% below the respiratory compensation point. Aerobic exercise training did not change LV diameters, volumes, or ejection fraction. At baseline, no difference was observed in MBF reserve between the control and trained groups (1.89, 1.67 to 1.98, vs 1.81, 1.28 to 2.38, p = 0.38). Four-month exercise training resulted in a significant increase in beta reserve from 1.72 (1.45 to 1.48) to 2.20 (1.69 to 2.77, p <0.001) and an MBF reserve from 1.81 (1.28 to 2.38) to 3.05 (2.07 to 3.93, p <0.001). In the control group, 13 reserve decreased from 1.51 (1.10 to 1.85) to 1.46 (1.14 to 2.33, p = 0.03) and MBF reserve from 1.89 (1.67 to 1.98) to 1.55 (1.11 to 2.27, p <0.001). Peak oxygen consumption increased by 13.8% after 4 months of exercise training and decreased by 1.9% in the control group. In conclusion, exercise training resulted in significant improvement of MBF reserve in patients with heart failure and LV dysfunction. (C) 2010 Elsevier Inc. All rights reserved. (Am J Cardiol 2010;105:243-248)

Age-dependent increase in blood pressure in two different Native American communities in Brazil

Objective Cardiovascular risk factors were surveyed in two Indian populations (Guarani, n=60; Tupinikin, n=496) and in a non-Indian group (n=114) living in the same reserve in southeast Brazilian coast. The relationship between an age-dependent blood pressure (BP) increase with salt consumption was also investigated. Methods Overnight (12 h) urine was collected to evaluate Na excretion. Fasting glucose and lipids, anthropometry, BP, ECG and carotid-femoral pulse wave velocity (PWV) were measured in a clinic visit. Participation (318 men/352 women, age 20-94 years; mean=37.6 +/- 14.9 years) comprised 80% of the eligible population. Results The prevalence of hypertension, diabetes and high cholesterol was similar in Tupinikins and in non-Indians and higher than in Guaranis. The prevalence of smoking and obesity was higher in the latter group. Hypertension and diabetes were detected in only one individual of the Guarani group. Mean BP adjusted to age and BMI was significantly lower (P<0.01) in Guaranis (82.8 +/- 1.6 mmHg) than in Tupinikins (92.3 +/- 0.5 mmHg) and non-Indians (91.6 +/- 1.1 mmHg). Urinary Na excretion (mEq/12h), however, was similar in the three groups (Guarani=94 +/- 40; Tupinikin=105 +/- 56; non-Indian=109 +/- 55; P>0.05). PWV (m/s) was lower (P<0.01) in Guarani (7.5 +/- 1.4) than in Tupinikins (8.8 +/- 2.2) and non-Indians (8.4 +/- 2.0). Multiple regression analysis showed that age and waist-to-hip ratio (WHR) were independent predictors of SBP and DBP (r(2)=0.44) in Tupinikins, whereas the WHR was the unique independent predictor of BP variability in Guaranis (r(2)=0.22). Conclusion Lower BP levels in Guaranis cannot be explained by low salt intake observed in other primitive populations. J Hypertens 27:1753-1760 (C) 2009 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.

Insertion/deletion polymorphism of the bradykinin type 2 receptor gene influence diastolic blood pressure

The contribution of kinins to the beneficial effects in cardiovascular risk reductions remains unclear. In this context, the present study examined whether the +9bp/-9 bp polymorphism in bradykinin type 2 receptor gene, predicts hypertension risk in a large urban Brazilian population. Our finding indicated that the -9 bp allele may contribute to hypertension because of increased diastolic pressure.