Identification and characterization of drought/wet events homogeneous environments based on regional climate simulations

The objective of this study was to identify and characterize homogeneous environments based on the probability of drought/wet occurrence in the central-northern Brazil, considering Rondonia, Mato Grosso, Goias and Tocantins States. The drought index denominated the moisture anomaly Z-index (Z-index) was used. The input climate data for the drought index was generated by the regional climate model RegCM3 for the period from 1975 to 1989. As result of cluster analysis, it was identified 13 homogeneous environments. These environments were characterized based on the probability of drought/wet, relative density of drought/wet occurrence, annual rainfall variability and probability of drought occurrence during the rainy season (October to March). The Mato Grosso State had the highest number of homogeneous environments and the environment 11, located at southwest of this State had the highest probability of drought occurrence, 9%. The environment 10, located at the extreme east of Goias State, showed the lowest median for the total annual rainfall. The climatic event with the highest probability of occurrence in the study area is close to normal or normality moisture.

The I405V and Taq1B polymorphisms of the CETP gene differentially affect sub-clinical carotid atherosclerosis

Background: Cholesteryl ester transfer protein (CETP) plays a major role in lipid metabolism, but studies on the association of CETP polymorphisms with risks of cardiovascular disease are inconsistent. This study investigated whether the CETP gene I405V and Taq1B polymorphisms modified subclinical atherosclerosis in an asymptomatic Brazilian population sample. Methods: The polymorphisms were analyzed using polymerase chain reaction in 207 adult volunteers. Serum lipid profiles, oxLDL Ab titers, C-reactive protein and tumor necrosis factor-a concentrations and CETP and phospholipid transfer protein (PLTP) activities were determined, and common carotid artery intima-media thickness (cIMT) was measured using ultrasonography. Results: No differences in cIMT were observed between the presence or absence of the minor B2 and V alleles in either polymorphism. However, inverse correlations between mean cIMT and CETP activity in the presence of these polymorphisms were observed, and positive correlations of these polymorphisms with PLTP activity and oxLDL Ab titers were identified. Moreover, logistic multivariate analysis revealed that the presence of the B2 allele was associated with a 5.1-fold (CI 95%, OR: 1.26 - 21.06) increased risk for cIMT, which was equal and above the 66th percentile and positively interacted with age. However, no associations with the V allele or CETP and PLTP activities were observed. Conclusions: None of the studied parameters, including CETP activity, explained the different relationships between these polymorphisms and cIMT, suggesting that other non-determined factors were affected by the genotypes and related to carotid atherosclerotic disease.

Coronary to Bronchial Artery Fistula: Are We Treating it Right?

Fistulas between coronary artery and bronchial artery may be present from birth, with few hemodynamic consequences, and may remain closed due to similarity of the filling pressures at these 2 sites.(1) They can also be secondary to pulmonary artery occlusive disease or chronic pulmonary inflammation.(2,3) These pulmonary changes may cause a dilation of the fistula and make it functional, causing angina pectoris by coronary steal syndrome, which is the most common symptom. The presentation may also be composed of episodes of hemoptysis, heart failure, and infective endocarditis. However, most patients remain asymptomatic. The ones that need treatment may not have a good response to the medical management, requiring an intervention. This can be done using embolization coils, stents grafts, and performing surgical ligation of the fistulas.(2-4) J INVASIVE CARDIOL 2012;24(11):E303-E304

RegCM3 nested in HadAM3 scenarios A2 and B2: projected changes in extratropical cyclogenesis, temperature and precipitation over the South Atlantic Ocean

The RegCM3 (Regional Climate Model-version 3) was nested in HadAM3 model to simulate present (1975-1989, referred hereafter as RegHad) and two future climate scenarios (A2 and B2 from 2071 to 2085, referred as RegA2 and RegB2) over the South America (SA) and South Atlantic Ocean (SAO). Projected changes in the air temperature, precipitation, low level circulation and cyclogenesis climatology were investigated. The cyclogenesis were identified using an automatic scheme for tracking based on the minimum of relative vorticity (zeta) from 10-m height wind. During summer, a general decrease (increase) in the precipitation is projected by RegA2 and RegB2 over the northeastern SA (center-west and south Brazil, north Argentina and Uruguay). For winter, an anomalous low level anticyclonic circulation is associated with the reduction in the rainfall over the central part of southern Brazil in RegA2 and RegB2 scenarios. Similar to HadAM3, RegCM3 projects larger warming in A2 scenario. For the present climate, when compared to HadAM3, RegHad defines better both the location of the main cyclogenetic areas and its annual cycle near southwestern SAO. The projections indicate a reduction in the total number of cyclones of -7.2% and -4.7% for RegA2 and RegB2, respectively, while HadAM3 reduction is -4.5% for both scenarios. The decrease is larger for initially intense cyclones (zeta <=-<= 2.5 x 10(-5) s-(1)): -20.9% (RegA2) and -11.3% (RegB2). For the lifetime, distance traveled and mean velocity of the cyclones, the A2 and B2 scenarios present mean values close to the present climate ( 3 days, 1900 km, and 9 m s(-1), respectively). Regarding the initial mean vorticity of the systems, RegB2 simulates values similar to the present climate, but they are initially weaker in RegA2. In general, RegA2 and RegB2 show a large decrease in the number of cyclones over the southern SAO due to an anticyclonic anomaly covering SAO between 30-55A degrees S. The reduction is larger in the scenario with higher concentrations of greenhouse gases (RegA2).

CYP3A5 and NAT2 gene polymorphisms: role in childhood acute lymphoblastic leukemia risk and treatment outcome

Susceptibility to acute lymphoblastic leukemia can be highly influenced by genetic polymorphisms in metabolizing enzyme genes of environmental carcinogens. This study aimed to evaluate the impact of the CYP3A5 and NAT2 metabolizing enzyme polymorphisms on the risk of childhood acute lymphoblastic leukemia. The analysis was conducted on 204 ALL patients and in 364 controls from a Brazilian population, using PCR-RFLP. The CYP3A5*3 polymorphic homozygous genotype was more frequent among ALL patients and the *3 allele variant was significantly associated with increased risk of childhood ALL (OR = 0.29; 95% CI, 0.14-0.60). The homozygous polymorphic genotype for the *6 allele variant was extremely rare and found in only two individuals. The heterozygous frequencies were similar for the ALL group and the control group. No significant differences were observed between the groups analyzed regarding NAT2 variant polymorphisms. None of the polymorphisms analyzed was related to treatment outcome. The results suggest that CYP3A5*3 polymorphism may play an important role in the risk of childhood ALL.

Effects of the administration of pentoxifylline and prednisolone on the evolution of portal fibrogenesis secondary to biliary obstruction in growing animals: immunohistochemical analysis of the expression of TGF-BETA; and VEGF

OBJECTIVE: During the neonatal and infancy periods, some chronic liver diseases may lead to progressive hepatic fibrosis, which is a condition that can ultimately result in the loss of organ function and severe portal hypertension necessitating hepatic transplantation. In a previous report, pharmacological interventions were demonstrated to modulate hepatic fibrosis induced by bile duct ligation in young rats. The administration of pentoxifylline or prednisolone, or the combination of both, resulted in reduced fibrogenesis in portal spaces. The objectives of the present study were to evaluate the expression of transforming growth factor beta and vascular endothelial growth factor after bile duct ligation in young rats and to assess the effect of those same drugs on cytokine expression. METHODS: In this experimental study, 80 young rats (21 or 22 days old) were submitted either to laparotomy and common bile duct ligation or to sham surgery. The animals were allocated into four groups according to surgical procedure, and the following treatments were administered: (1) common bile duct ligation + distilled water, (2) sham surgery + distilled water, (3) common bile duct ligation + pentoxifylline, or (4) common bile duct ligation + prednisolone. After 30 days, a hepatic fragment was collected from each animal for immunohistochemical analysis using monoclonal antibodies against transforming growth factor beta and vascular endothelial growth factor. Digital morphometric and statistical analyses were performed. RESULTS: The administration of pentoxifylline reduced the transforming growth factor beta-marked area and the amount of transforming growth factor beta expressed in liver tissue. This effect was not observed after the administration of prednisolone. There was a significant reduction in vascular endothelial growth factor expression after the administration of either drug compared with the non-treatment group. CONCLUSIONS: The administration of pentoxifylline to cholestatic young rats resulted in the diminished expression of transforming growth factor beta and vascular endothelial growth factor in liver tissue. The administration of steroids resulted in the diminished expression of vascular endothelial growth factor only. These pathways may be involved in hepatic fibrogenesis in young rats submitted to bile duct ligation and exposed to pentoxifylline or prednisolone.

Influence of brain death and associated trauma on solid organ histological characteristics

PURPOSE: To evaluate histopathological alterations triggered by brain death and associated trauma on different solid organs in rats. METHODS: Male Wistar rats (n=37) were anesthetized with isoflurane, intubated and mechanically ventilated. A trepanation was performed and a balloon catheter inserted into intracraninal cavity and rapidly inflated with saline to induce brain death. After induction, rats were monitored for 30, 180, and 360 min for hemodynamic parameters and exsanguinated from abdominal aorta. Heart, lung, liver, and kidney were removed and fixed in paraffin to evaluation of histological alterations (H&E). Sham-operated rats were trepanned only and used as control group. RESULTS: Brain dead rats showed a hemodynamic instability with hypertensive episode in the first minute after the induction followed by hypotension for approximately 1 h. Histological analyses showed that brain death induces vascular congestion in heart (p<0.05), and lung (p<0.05); lung alveolar edema (p=0.001), kidney tubular edema (p<0.05); and leukocyte infiltration in liver (p<0.05). CONCLUSIONS: Brain death induces hemodynamic instability associated with vascular changes in solid organs and compromises most severely the lungs. However, brain death associated trauma triggers important pathophysiological alterations in these organs.

Cytokine inhibition and time-related influence of inflammatory stimuli on the hyperalgesia induced by the nucleus pulposus

The symptoms of lumbar disc herniation, such as low back pain and sciatica, have been associated with local release of cytokines following the inflammatory process induced by the contact of the nucleus pulposus (NP) with the spinal nerve. Using an animal experimental model of intervertebral disc herniation and behavioral tests to evaluate mechanical (electronic von Frey test) and thermal (Hargreaves Plantar test) hyperalgesia in the hind paw of rats submitted to the surgical model, this study aimed to detect in normal intervertebral disc the cytokines known to be involved in the mechanisms of inflammatory hyperalgesia, to observe if previous exposure of the intervertebral disc tissue to specific antibodies could affect the pain behavior (mechanical and thermal hyperalgesia) induced by the NP, and to observe the influence of the time of contact of the NP with the fifth lumbar dorsal root ganglion (L5-DRG) in the mechanical and thermal hyperalgesia. The cytokines present at highest concentrations in the rat NP were TNF-alpha, IL-1 beta and CINC-1. Rats submitted to the disc herniation experimental model, in which a NP from the sacrococcygeal region is deposited over the right L5-DRG, showed increased mechanical and thermal hyperalgesia that lasted at least 7 weeks. When the autologous NP was treated with antibodies against the three cytokines found at highest concentrations in the NP (TNF-alpha, IL-1 beta and CINC-1), there was decrease in both mechanical and thermal hyperalgesia in different time points, suggesting that each cytokine may be important for the hyperalgesia in different steps of the inflammatory process. The surgical remotion of the NP from herniated rats 1 week after the implantation reduced the hyperalgesia to the level similar to the control group. This reduction in the hyperalgesia was also observed in the group that had the NP removed 3 weeks after the implantation, although the intensity of the hyperalgesia did not decreased totally. The removal of the NP after 5 weeks did not changed the hyperalgesia observed in the hind paw, which suggests that the longer the contact of the NP with the DRG, the greater is the possibility of development of chronic pain. Together our results indicate that specific cytokines released during the inflammatory process induced by the herniated intervertebral disc play fundamental role in the development of the two modalities of hyperalgesia (mechanical and thermal) and that the maintenance of this inflammation may be the most important point for the chronification of the pain.

Stress amplifies lung tissue mechanics, inflammation and oxidative stress induced by chronic inflammation

Background: Mechanisms linking behavioral stress and inflammation are poorly understood, mainly in distal lung tissue. Objective: We have investigated whether the forced swim stress (FS) could modulate lung tissue mechanics, iNOS, cytokines, oxidative stress activation, eosinophilic recruitment, and remodeling in guinea pigs (GP) with chronic pulmonary inflammation. Methods: The GP were exposed to ovalbumin or saline aerosols (2x/wk/4wks, OVA, and SAL). Twenty-four hours after the 4th inhalation, the GP were submitted to the FS protocol (5x/wk/2wks, SAL-S, and OVA-S). Seventy-two hours after the 7th inhalation, lung strips were cut and tissue resistance (Rt) and elastance (Et) were obtained (at baseline and after OVA and Ach challenge). Strips were submitted to histopathological evaluation. Results: The adrenals' weight, the serum cortisol, and the catecholamines were measured. There was an increase in IL-2, IL-5, IL-13, IFN-gamma, iNOS, 8-iso-PGF2 alpha, and in %Rt and %Et after Ach challenge in the SAL-S group compared to the SAL one. The OVA-S group has had an increase in %Rt and %Et after the OVA challenge, in %Et after the Ach and in IL-4, 8-iso-PGF2 alpha, and actin compared to the OVA. Adrenal weight and cortisol serum were increased in stressed animals compared to nonstressed ones, and the catecholamines were unaltered. Conclusion & clinical relevance: Repeated stress has increased distal lung constriction, which was associated with an increase of actin, IL-4, and 8-iso-PGF2 alpha levels. Stress has also induced an activation of iNOS, cytokines, and oxidative stress pathways.

Decreased RNA expression of interleukin 17A in skin of leprosy

Interleukin-17A (IL-17A) is a proinflamatory cytokine that plays an important role in fighting pathogens at mucosal interfaces, by summoning neutrophils and upregulating cytoplasmatic antimicrobial peptides. So far, the presence of IL-17A in leprosy has not been demonstrated. The expression of IL-17A and related cytokines (IL-6 and IL-23p19) was addressed through RNA extraction and cDNA quantitative amplification in macerated biopsies of active lesions of 48 leprosy patients and 20 fragments of normal skin of individuals. Blood levels of IL-17A, IL-23p19 and IL-6 were determined by ELISA. We found an abrogated mRNA IL-17A response in all biopsies of leprosy patients, as compared with controls. Circulating IL-17A and IL-23p19 were undetectable in both patients and controls, but IL-6 was higher in lepromatous patients. Although at low levels, IL-17A mRNA in lepromatous patients had an inverse linear correlation with bacillary burden. Low expression of IL-17A in patients may be a constitutive genetic feature of leprosy patients or a circumstantial event induced by the local presence of the pathogen, as an escape mechanism.

Extracellular matrix composition in COPD

Extracellular matrix (ECM) composition has an important role in determining airway structure. We postulated that ECM lung composition of chronic obstructive pulmonary disease (COPD) patients differs from that observed in smoking and nonsmoking subjects without airflow obstruction. We determined the fractional areas of elastic fibres, type-I, -III and -IV collagen, versican, decorin, biglycan, lumican, fibronectin and tenascin in different compartments of the large and small airways and lung parenchyma in 26 COPD patients, 26 smokers without COPD and 16 nonsmoking control subjects. The fractional area of elastic fibres was higher in non-obstructed smokers than in COPD and nonsmoking controls, in all lung compartments. Type-I collagen fractional area was lower in the large and small airways of COPD patients and in the small airways of non-obstructed smokers than in nonsmokers. Compared with nonsmokers, COPD patients had lower versican fractional area in the parenchyma, higher fibronectin fractional area in small airways and higher tenascin fractional area in large and small airways compartments. In COPD patients, significant correlations were found between elastic fibres and fibronectin and lung function parameters. Alterations of the major ECM components are widespread in all lung compartments of patients with COPD and may contribute to persistent airflow obstruction.

Effects of Hepatocyte Growth Factor Injection and Reinjection on Healing in the Rabbit Vocal Fold

Objectives/Hypothesis. Hepatocyte growth factor (HGF) is a multifunctional polypeptide that plays various roles in embryogenesis and tissue regeneration and exhibits marked antifibrotic activity. The present study sought to assess the effects of HGF injection and reinjection coinciding with its peak of activity on collagen density, vessel density, inflammatory reaction in the lamina propria, and mean epithelial thickness in the injured rabbit vocal fold. Study Design. Prospective, controlled, experimental animal study. Methods. Fourteen rabbits were subdivided into two groups and underwent injury of the vocal folds. Immediately after injury, animals in group 1 received HGF injections into the right vocal fold (RVF), whereas those in group 2 received bilateral HGF injections and a single reinjection into the RVF 10 days after the first, to coincide with the peak of HGF activity. The left vocal folds (LVFs) served as controls in both groups. Histological assessment of laryngeal specimens was performed at 30 and 40 days, respectively. Results. In both groups, collagen density was lower in the right (treated) vocal folds than in the left (control) folds (P = 0.018). Vessel density was higher in the RVFs in group 2 (P = 0.018). Differences were found in mean epithelial thickness and inflammatory reaction in the lamina propria but did not reach statistical significance. Conclusions. In the scarred rabbit vocal fold, HGF injection is associated with decreased collagen density in the lamina propria, whereas reinjection after 10 days produces decreased collagen density and higher vessel density.

Use of passive diffusion sampling method for defining NO2 concentrations gradient in São Paulo, Brazil

Abstract Background Air pollution in São Paulo is constantly being measured by the State of Sao Paulo Environmental Agency, however there is no information on the variation between places with different traffic densities. This study was intended to identify a gradient of exposure to traffic-related air pollution within different areas in São Paulo to provide information for future epidemiological studies. Methods We measured NO2 using Palmes' diffusion tubes in 36 sites on streets chosen to be representative of different road types and traffic densities in São Paulo in two one-week periods (July and August 2000). In each study period, two tubes were installed in each site, and two additional tubes were installed in 10 control sites. Results Average NO2 concentrations were related to traffic density, observed on the spot, to number of vehicles counted, and to traffic density strata defined by the city Traffic Engineering Company (CET). Average NO2concentrations were 63μg/m3 and 49μg/m3 in the first and second periods, respectively. Dividing the sites by the observed traffic density, we found: heavy traffic (n = 17): 64μg/m3 (95% CI: 59μg/m3 – 68μg/m3); local traffic (n = 16): 48μg/m3 (95% CI: 44μg/m3 – 52μg/m3) (p < 0.001). Conclusion The differences in NO2 levels between heavy and local traffic sites are large enough to suggest the use of a more refined classification of exposure in epidemiological studies in the city. Number of vehicles counted, traffic density observed on the spot and traffic density strata defined by the CET might be used as a proxy for traffic exposure in São Paulo when more accurate measurements are not available.