Air Pollution and Mortality in Latin America The Role of Education

Background: People with less education in Europe, Asia, and the United States are at higher risk of mortality associated with daily and longer-term air pollution exposure. We examined whether educational level modified associations between mortality and ambient particulate pollution (PM(10)) in Latin America, using several timescales. Methods: The study population included people who died during 1998-2002 in Mexico City, Mexico; Santiago, Chile; and Sao Paulo, Brazil. We fit city-specific robust Poisson regressions to daily deaths for nonexternal-cause mortality, and then stratified by age, sex, and educational attainment among adults older than age 21 years (none, some primary, some secondary, and high school degree or more). Predictor variables included a natural spline for temporal trend, linear PM(10) and apparent temperature at matching lags, and day-of-week indicators. We evaluated PM(10) for lags 0 and I day, and fit an unconstrained distributed lag model for cumulative 6-day effects. Results: The effects of a 10-mu g/m(3) increment in lag 1 PM(10) on all nonextemal-cause adult mortality were for Mexico City 0.39% (95% confidence interval = 0.131/-0.65%); Sao Paulo 1.04% (0.71%-1.38%); and for Santiago 0.61% (0.40%-0.83%. We found cumulative 6-day effects for adult mortality in Santiago (0.86% [0.48%-1.23%]) and Sao Paulo (1.38% [0.85%-1.91%]), but no consistent gradients by educational status. Conclusions: PM(10) had important short- and intermediate-term effects on mortality in these Latin American cities, but associations did not differ consistently by educational level.

Acquisition of Serum Antibodies Reactive With Enterohemorrhagic Escherichia coli Virulence-Associated Factors by Healthy Brazilian Children and Adults

Background: Patients with hemorrhagic colitis or hemolytic uremic syndrome due to enterohemorrhagic Escherichia coli (EHEC) develop serum IgM and IgG response to lipopolysaccharide (LPS) and to virulence factors such as intimin. The small numbers of cases of diarrhea associated with EHEC strains in Brazil suggests a pre-existing immunity probably due to previous contact with diarrheagenic E. coli. Our aim was to evaluate the development of the serum antibody repertoire to EHEC virulence factors in Brazilian children and adults. Methods: Serum IgM and IgG antibodies were determined by enzyme-linked immunosorbent assay with LPS O111, LPS O26, and LPS O157 in 101 children between 2 months and 10 years of age and in 100 adult sera, by immunoblotting with protein membrane extracts and purified beta intimin; the ability of adult sera to neutralize Shiga toxin2 was also investigated. Results: Children older than 24 months had IgM concentrations reactive with the 3 LPS equivalent to those seen in the adult group, and significantly higher than the group of younger children (P < 0.05). Anti-O26 and anti-O157 LPS IgG concentrations were equivalent between the 2 groups of children and were significantly different from the adult group (P < 0.05). The anti-O111 LPS IgG levels in older children were intermediate between the younger group, and adults (P < 0.05). Immunoblotting revealed strong protein reactivity, including the conserved and variable regions of beta intimin and more than 50% of the adult samples neutralized Shiga toxin 2. Conclusions: Our results demonstrate an increasing anti-LPS and antiprotein antibody response with age, which could provide protection against EHEC infections.

Cross-cultural Adaptation, Reliability and Validity of the DAFS-R in a Sample of Brazilian Older Adults

The Direct Assessment of Functional Status-Revised (DAFS-R) is an instrument developed to objectively measure functional capacities required for independent living. The objective of this study was to translate and culturally adapt the DAFS-R for Brazilian Portuguese (DAFS-BR) and to evaluate its reliability and validity. The DAFS-BR was administered to 89 older patients classified previously as normal controls, mild cognitive impairment (MCI) and Alzheimer`s disease (AD). The results indicated good internal consistency (Cronbach`s alpha = 0.78) in the total sample. The DAFS-BR showed high interobserver reliability (0.996; p < .001) as well as test-retest stability over 1-week interval (0.995; p < .001). Correlation between the DAFS-BR total score and the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) was moderate and significant (r = -.65, p < .001) in the total sample, whereas it did not reach statistical significance within each diagnostic group. Receiver operating characteristic curve analyses suggested that DAFS-BR has good sensitivity and specificity to identify MCI and AD. Results suggest that DAFS-BR can document degrees of severity of functional impairment among Brazilian older adults.

Lack of Association Between a 3 ` UTR VNTR Polymorphism of Dopamine Transporter Gene (SLC6A3) and ADHD in a Brazilian Sample of Adult Patients

Objective: To investigate a possible association between a 3`UTR VNTR polymorphism of the dopamine transporter gene (SLC6A3) and ADHD in a Brazilian sample of adult patients. Method: Study Case-control with 102 ADHD adult outpatients (DSM-IV criteria) and 479 healthy controls. The primers` sequence used were: 3`UTR-Forward: 5`TGT GGT GAT GGG AAC GGC CTG AG 3` and 3`UTR-Reverse: 5`CTT CCT GGA GGT CAC GGC TCA AGG 3`. Alleles of the 3`UTR were coded according to their number of repeats: 6- repeat 320 bp (allele 6), 8- repeat 400 bp (allele 8), 9-repeat 480 bp (allele 9), 10- repeat 480 bp (allele 10), and 11- repeat 520 bp (allele 11). Results: There were no allelic (chi(2) = 2.67, 5df, p = .75) and genotypic (chi(2) = 7.20, 1df, p = .61) association between adult ADHD and VNTR 3`UTR polymorphism of SLC6A3. Conclusion: Our findings do not support SLC6A3 as marker genetic susceptibility factor in adult ADHD. More comprehensive polymorphism coverage within the SLC6A3 region should be conducted in larger samples, including comparisons in clinical subgroups, and in samples with different ethnic backgrounds. (J. of Att. Dis. 2011; 15(4) 305-309)

Collagen V and vascular injury promote lung architectural changes in systemic sclerosis

Background: Systemic sclerosis (SSc) is a multisystem disorder characterized by inflammation, fibrosis and vascular damage. The aim of this study was to evaluate the interactions between basement membrane disruption, endothelial injury and collagen V deposition on the vascular wall, as well as their association with pulmonary function tests in patients with SSc. Method: The endothelial apoptosis was assessed by TUNEL and electron microscopy, and quantified through the point-counting technique. To evaluate basement membrane integrity, laminin immunostaining and electron microscopy were used. Immunofluorescence and morphometric analysis were used to determine the amount of collagen V in the vascular walls in 23 open lung biopsies of patients with SSc without pulmonary hypertension. Normal lung tissue was obtained from five individuals who had died of traumatic injuries. Results: The apoptosis index in SSc was higher in the endothelial cells (13.83 +/- 6.83) when compared with the control (2.51 +/- 2.06) group (P < 0.001) and confirmed by electron microscopy. We observed an important disruption of the basement membrane on the vascular wall shown by discontinuous laminin immunostaining and electron microscopy. An increase in collagen V on the vascular wall of the SSc group was observed (45.28 +/- 13.21), when compared with control group (22.90 +/- 4.13, P < 0.001), and this difference was statistically significant. An inverse correlation was found between vital capacity, forced vital capacity, forced expiratory volume in 1 s, vascular collagen V and endothelial apoptosis (P < 0.05). Conclusions: We conclude that the endothelial apoptosis and vascular collagen V interaction reinforce the vascular pathway in the SSc pathogenesis. Further studies are needed to determine whether this relationship is causal or consequential. Please cite this paper as: Parra ER, Aguiar AC Jr, Teodoro WR, de Souza R, Yoshinari NH and Capelozzi VL. Collagen V and vascular injury promote lung architectural changes in systemic sclerosis. The Clinical Respiratory Journal 2009; 3: 135-142.

Prone position prevents regional alveolar hyperinflation and mechanical stress and strain in mild experimental acute lung injury

Prone position may delay the development of ventilator-induced lung injury (VILI), but the mechanisms require better elucidation. In experimental mild acute lung injury (ALI), arterial oxygen partial pressure (Pa(O2)), lung mechanics and histology, inflammatory markers [interleukin (IL)-6 and IL-1 beta], and type III procollagen (PCIII) mRNA expressions were analysed in supine and prone position. Wistar rats were randomly divided into two groups. In controls, saline was intraperitoneally injected while ALI was induced by paraquat. After 24-h, the animals were mechanically ventilated for 1-h in supine or prone positions. In ALI, prone position led to a better blood flow/tissue ratio both in ventral and dorsal regions and was associated with a more homogeneous distribution of alveolar aeration/tissue ratio reducing lung static elastance and viscoelastic pressure, and increasing end-expiratory lung volume and Pa(O2). PCIII expression was higher in the ventral than dorsal region in supine position, with no regional changes in inflammatory markers. In conclusion, prone position may protect the lungs against VILI, thus reducing pulmonary stress and strain. (C) 2009 Elsevier B.V. All rights reserved.

Effects of frequency and inspiratory plateau pressure during recruitment manoeuvres on lung and distal organs in acute lung injury

To evaluate the effects of frequency and inspiratory plateau pressure (Pplat) during recruitment manoeuvres (RMs) on lung and distal organs in acute lung injury (ALI). We studied paraquat-induced ALI rats. At 24 h, rats were anesthetized and RMs were applied using continuous positive airway pressure (CPAP, 40 cmH(2)O/40 s) or three-different sigh strategies: (a) 180 sighs/h and Pplat = 40 cmH(2)O (S180/40), (b) 10 sighs/h and Pplat = 40 cmH(2)O (S10/40), and (c) 10 sighs/h and Pplat = 20 cmH(2)O (S10/20). S180/40 yielded alveolar hyperinflation and increased lung and kidney epithelial cell apoptosis as well as type III procollagen (PCIII) mRNA expression. S10/40 resulted in a reduction in epithelial cell apoptosis and PCIII expression. Static elastance and alveolar collapse were higher in S10/20 than S10/40. The reduction in sigh frequency led to a protective effect on lung and distal organs, while the combination with reduced Pplat worsened lung mechanics and histology.

Pulmonary lesion induced by low and high positive end-expiratory pressure levels during protective ventilation in experimental acute lung injury

Objective: To investigate the effects of low and high levels of positive end-expiratory pressure (PEEP), without recruitment maneuvers, during lung protective ventilation in an experimental model of acute lung injury (ALI). Design: Prospective, randomized, and controlled experimental study. Setting: University research laboratory. Subjects: Wistar rats were randomly assigned to control (C) [saline (0.1 ml), intraperitoneally] and ALI [paraquat (15 mg/kg), intra peritoneally] groups. Measurements and Main Results: After 24 hours, each group was further randomized into four groups (six rats each) at different PEEP levels = 1.5, 3, 4.5, or 6 cm H(2)O and ventilated with a constant tidal volume (6 mL/kg) and open thorax. Lung mechanics [static elastance (Est, L) and viscoelastic pressure (Delta P2, L)] and arterial blood gases were measured before (Pre) and at the end of 1-hour mechanical ventilation (Post). Pulmonary histology (light and electron microscopy) and type III procollagen (PCIII) messenger RNA (mRNA) expression were measured after 1 hour of mechanical ventilation. In ALI group, low and high PEEP levels induced a greater percentage of increase in Est, L (44% and 50%) and Delta P2, L (56% and 36%) in Post values related to Pre. Low PEEP yielded alveolar collapse whereas high PEEP caused overdistension and atelectasis, with both levels worsening oxygenation and increasing PCIII mRNA expression. Conclusions: In the present nonrecruited ALI model, protective mechanical ventilation with lower and higher PEEP levels than required for better oxygenation increased Est, L and Delta P2, L, the amount of atelectasis, and PCIII mRNA expression. PEEP selection titrated for a minimum elastance and maximum oxygenation may prevent lung injury while deviation from these settings may be harmful. (Crit Care Med 2009; 37:1011-1017)

Early short-term versus prolonged low-dose methylprednisolone therapy in acute lung injury

The present study compared the effects of early short-term with prolonged low-dose corticosteroid therapy in acute lung injury (ALI). In total, 120 BALB/c mice were randomly divided into five groups. In the control group, saline was intratracheally (i.t.) instilled. In the ALI group, mice received Escherichia coli lipopolysaccharide (10 mu g i.t.). ALI animals were further randomised into four subgroups to receive saline (0.1 mL i.v.) or methylprednisolone (2 mg center dot kg(-1) i.v.) at 6 h, 24 h or daily (for 7 days, beginning at day 1). At 1, 3 and 8 weeks, in vivo and in vitro lung mechanics and histology (light and electron microscopy), collagen and elastic fibre content, cytokines in bronchoalveolar lavage fluid and the expression of matrix metalloproteinase (MMP)-9 and -2 were measured. In vivo (static elastance and viscoelastic pressure) and in vitro (tissue elastance and resistance) lung mechanics, alveolar collapse, cell infiltration, collagen and elastic fibre content and the expression of MMP-9 and MMP-2 were increased in ALI at 1 week. Methylprednisolone led to a complete resolution of lung mechanics, avoided fibroelastogenesis and the increase in the expression of MMP-9 and MMP-2 independent of steroid treatment design. Thus, early short-term, low-dose methylprednisolone is as effective as prolonged therapy in acute lung injury.

Distinct resistance mutation and polymorphism acquisition in HIV-1 protease of subtypes B and F1 from children and adult patients under virological failure

The goal of this work was to compare the differences between human immunodeficiency Virus type 1 (HIV-1) of B and F1 Subtypes in the acquisition of major and rninot- protease inhibitor (P1)-associated resistance mutations and of other polymorphisms at the protease (PR) gene, through a cross sectional Study. PR sequences from subtypes B and F1 isolates matched according to P1 exposure time from Brazilian patients were included in this study. Sequences were separated in four groups: 24 and 90 from children and 141 and 99 from adults infected with isolates of subtypes F1 and B, respectively. For comparison, 211 subype B and 79 subtype F1 PR sequences from drug-naive individuals Were included. Demographic and clinical data were similar among B- and F1-infected patients. In untreated patients, Mutations L1OV, K20R, and M361 were more frequent in subtype F1, while L63P, A7IT, and V771 were more prevalent in Subtype B. In treated patients, K20M, D30N, G73S, 184V, and L90M, were More prevalent in subtype B, and K20T and N88S Were more prevalent in Subtype F1. A higher proportion of subtype F1 than Of subtype B Strains Containing other polymorphisms was observed. V82L mutation was Present With increased frequency in isolates from children compared to isolates from adults infected with both subtypes. We could observe a faster resistance emergence in children than in adults, during treatment with protease inhibitors. This data provided evidence that, although rates of overall drug resistance do not differ between subtypes B and F1, the former accumulates resistance at higher proportion in specific amino acid positions of protease when compared to the latter. (c) 2008 Elsevier B.V. All rights reserved.

Intravenous glutamine decreases lung and distal organ injury in an experimental model of abdominal sepsis

Introduction The protective effect of glutamine, as a pharmacological agent against lung injury, has been reported in experimental sepsis; however, its efficacy at improving oxygenation and lung mechanics, attenuating diaphragm and distal organ injury has to be better elucidated. In the present study, we tested the hypothesis that a single early intravenous dose of glutamine was associated not only with the improvement of lung morpho-function, but also the reduction of the inflammatory process and epithelial cell apoptosis in kidney, liver, and intestine villi. Methods Seventy-two Wistar rats were randomly assigned into four groups. Sepsis was induced by cecal ligation and puncture surgery (CLP), while a sham operated group was used as control (C). One hour after surgery, C and CLP groups were further randomized into subgroups receiving intravenous saline (1 ml, SAL) or glutamine (0.75 g/kg, Gln). At 48 hours, animals were anesthetized, and the following parameters were measured: arterial oxygenation, pulmonary mechanics, and diaphragm, lung, kidney, liver, and small intestine villi histology. At 18 and 48 hours, Cytokine-Induced Neutrophil Chemoattractant (CINC)-1, interleukin (IL)-6 and 10 were quantified in bronchoalveolar and peritoneal lavage fluids (BALF and PLF, respectively). Results CLP induced: a) deterioration of lung mechanics and gas exchange; b) ultrastructural changes of lung parenchyma and diaphragm; and c) lung and distal organ epithelial cell apoptosis. Glutamine improved survival rate, oxygenation and lung mechanics, minimized pulmonary and diaphragmatic changes, attenuating lung and distal organ epithelial cell apoptosis. Glutamine increased IL-10 in peritoneal lavage fluid at 18 hours and bronchoalveolar lavage fluid at 48 hours, but decreased CINC-1 and IL-6 in BALF and PLF only at 18 hours. Conclusions In an experimental model of abdominal sepsis, a single intravenous dose of glutamine administered after sepsis induction may modulate the inflammatory process reducing not only the risk of lung injury, but also distal organ impairment. These results suggest that intravenous glutamine may be a potentially beneficial therapy for abdominal sepsis.

A rodent model of NASH with cirrhosis, oval cell proliferation and hepatocellular carcinoma

Background/Aims: Hepatocellular carcinoma (HCC) is a well recognized complication of advanced NASH (non-alcoholic steatohepatitis). We sought to produce a rat model of NASH, cirrhosis and HCC. Methods: Adult Sprague-Dawley rats, weighing 250-300 g, were fed a choline-deficient, high trans-fat diet and exposed to DEN in drinking water. After 16 weeks, the animals underwent liver ultrasound (US), sacrifice and assessment by microscopy, immunohistochemistry and transmission electron microscopy (TEM). Results: US revealed steatosis and focal lesions in 6 of 7. All had steatohepatitis defined as inflammation, advanced fibrosis and ballooning with Mallory-Denk bodies (MDB) with frank cirrhosis in 6. Areas of more severe injury were associated with anti-CK19 positive ductular reaction. HCC, present in all, were macro-trabecullar or solid with polyhedral cells with foci of steatosis and ballooned cells. CK19 was positive in single or solid nests of oval cells and in neoplastic hepatocytes. TEM showed ballooning with small droplet fat, dilated endoplasmic reticulum and MDB in non-neoplastic hepatocytes and small droplet steatosis in some cancer cells. Conclusions: This model replicated many features of NASH including steatohepatitis with ballooning, fibrosis, cirrhosis and hepatocellular carcinoma. Oval cell proliferation was evident and the presence anti-CK 19 positivity in the cancer suggests oval cell origin of the malignancy. (C) 2008 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.