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)

Recruitment maneuver in pulmonary and extrapulmonary experimental acute lung injury

Objective. The aim of this study is to test the hypothesis that recruitment maneuvers (RMs) might act differently in models of pulmonary (p) and extrapulmonary (exp) acute lung injury (ALI) with similar transpulmonary pressure changes. Design: Prospective, randomized, controlled experimental study. Setting. University research laboratory. Subjects: Wistar rats were randomly divided into four groups. In control groups, sterile saline solution was intratracheally (0.1 mL, Cp) or intraperitoneally (1 mL, Cexp) injected, whereas ALI animals received Escherichia coli lipopolysaccharide intratracheally (100 jig, ALIp) or intraperitoneally (1 mg, ALIexp). After 24 hrs, animals were mechanically ventilated (tidal volume, 6 mL/kg; positive end-expiratory pressure, 5 cm H2O) and three RMs (pressure inflations to 40 cm H2O for 40 secs, 1 min apart) applied. Measurements and Main Results. Pao(2), lung resistive and viscoelastic pressures, static elastance, lung histology (light and electron microscopy), and type III procollagen messenger RNA expression in pulmonary tissue were measured before RMs and at the end of 1 hr of mechanical ventilation. Mechanical variables, gas exchange, and the fraction of area of alveolar collapse were similar in both ALI groups. After RMs, lung resistive and viscoelastic pressures and static elastance decreased more in ALIexp (255%,180%, and 118%, respectively) than in ALIp (103%, 59%, and 89%, respectively). The amount of atelectasis decreased more in ALIexp than in ALIp (from 58% to 19% and from 59% to 33%, respectively). RMs augmented type III procollagen messenger RNA expression only in the ALIp group (19%), associated with worsening in alveolar epithelium injury but no capillary endothelium lesion, whereas the ALIexp group showed a minor detachment of the alveolar capillary membrane. Conclusions. Given the same transpulmonary pressures, RMs are more effective at opening collapsed alveoli in ALIexp than in ALIp, thus improving lung mechanics and oxygenation with limited damage to alveolar epithelium.

Recruitment maneuver in experimental acute lung injury: The role of alveolar collapse and edema

Objective: In acute lung injury, recruitment maneuvers have been used to open collapsed lungs and set positive end-expiratory pressure, but their effectiveness may depend on the degree of lung injury. This study uses a single experimental model with different degrees of lung injury and tests the hypothesis that recruitment maneuvers may have beneficial or deleterious effects depending on the severity of acute lung injury. We speculated that recruitment maneuvers may worsen lung mechanical stress in the presence of alveolar edema. Design: Prospective, randomized, controlled experimental study. Setting: University research laboratory. Subjects: Thirty-six Wistar rats randomly divided into three groups (n = 12 per group). Interventions: In the control group, saline was intraperitoneally injected, whereas moderate and severe acute lung injury animals received paraquat intraperitoneally (20 mg/kg [moderate acute lung injury] and 25 mg/kg [severe acute lung injury]). After 24 hrs, animals were further randomized into subgroups (n = 6/each) to be recruited (recruitment maneuvers: 40 cm H(2)O continuous positive airway pressure for 40 secs) or not, followed by 1 hr of protective mechanical ventilation (tidal volume, 6 mL/kg; positive end-expiratory pressure, 5 cm H(2)O). Measurements and Main Results: Only severe acute lung injury caused alveolar edema. The amounts of alveolar collapse were similar in the acute lung injury groups. Static lung elastance, viscoelastic pressure, hyperinflation, lung, liver, and kidney cell apoptosis, and type 3 procollagen and interleukin-6 mRNA expressions in lung tissue were more elevated in severe acute lung injury than in moderate acute lung injury. After recruitment maneuvers, static lung elastance, viscoelastic pressure, and alveolar collapse were lower in moderate acute lung injury than in severe acute lung injury. Recruitment maneuvers reduced interleukin-6 expression with a minor detachment of the alveolar capillary membrane in moderate acute lung injury. In severe acute lung injury, recruitment maneuvers were associated with hyperinflation, increased apoptosis of lung and kidney, expression of type 3 procollagen, and worsened alveolar capillary injury. Conclusions: In the presence of alveolar edema, regional mechanical heterogeneities, and hyperinflation, recruitment maneuvers promoted a modest but consistent increase in inflammatory and fibrogenic response, which may have worsened lung function and potentiated alveolar and renal epithelial injury. (Crit Care Med 2010; 38: 2207-2214)

Cardiopulmonary Effects of Matching Positive End-Expiratory Pressure to Abdominal Pressure in Concomitant Abdominal Hypertension and Acute Lung Injury

Background: To evaluate the cardiopulmonary effects of positive end-expiratory pressure (PEEP) equalization to intra-abdominal pressure (IAP) in an experimental model of intra-abdominal hypertension (IAH) and acute lung injury (ALI). Methods: Eight anesthetized pigs were submitted to IAH of 20 mm Hg with a carbon dioxide insufflator for 30 minutes and then submitted to lung lavage with saline and Tween (2.5%). Pressure x volume curves of the respiratory system were performed by a low flow method during IAH and ALI, and PEEP was subsequently adjusted to 27 cm center dot H(2)O for 30 minutes. Results: IAH decreases pulmonary and respiratory system static compliances and increases airway resistance, alveolar-arterial oxygen gradient, and respiratory dead space. The presence of concomitant ALI exacerbates these findings. PEEP identical to AP moderately improved oxygenation and respiratory mechanics; however, an important decline in stroke index and right ventricle ejection fraction was observed. Conclusions: Simultaneous IAH and ALI produce important impairments in the respiratory physiology. PEEP equalization to AP may improve the respiratory performance, nevertheless with a secondary hemodynamic derangement.

Gender and schooling inequalities in risk and protective factors for chronic diseases among Brazilian adults, through telephone survey

OBJECTIVES: To assess risk and protective factors for chronic noncommunicable diseases (CNCD) and to identify social inequalities in their distribution among Brazilian adults. METHODS: The data used were collected in 2007 through VIGITEL, an ongoing population-based telephone survey. This surveillance system was implemented in all of the Brazilian State capitals, over 54,000 interviews were analyzed. Age-adjusted prevalence ratios for trends at different schooling levels were calculated using Poisson regression with linear models. RESULTS: These analyses have shown differences in the prevalence of risk and protective factors for CNCD by gender and schooling. Among men, the prevalence ratios of overweight, consumption of meat with visible fat, and dyslipidemia were higher among men with more schooling, while tobacco use, sedentary lifestyle, and high-blood pressure were lower. Among women, tobacco use, overweight, obesity, high-blood pressure and diabetes were lower among men with more schooling, and consumption of meat with visible fat and sedentary lifestyles were higher. As for protective factors, fruit and vegetables intake and physical activity were higher in both men and women with more schooling. CONCLUSION: Gender and schooling influence on risk and protective factors for CNCD, being the values less favorable for men. vigitel is a useful tool for monitoring these factors amongst the Brazilian population.

Protective effects of mate tea (Ilex paraguariensis) on H2O2-induced DNA damage and DNA repair in mice

Yerba mate (Ilex paraguariensis) is rich in several bioactive compounds that can act as free radical scavengers. Since oxidative DNA damage is involved in various pathological states such as cancer, the aim of this study was to evaluate the antioxidant activity of mate tea as well as the ability to influence DNA repair in male Swiss mice. Forty animals were randomly assigned to four groups. The animals received three different doses of mate tea aqueous extract, 0.5, 1.0 or 2.0 g/kg, for 60 days. After intervention, the liver, kidney and bladder cells were isolated and the DNA damage induced by H2O2 was investigated by the comet assay. The DNA repair process was also investigated for its potential to protect the cells from damage by the same methodology. The data presented here show that mate tea is not genotoxic in liver, kidney and bladder cells. The regular ingestion of mate tea increased the resistance of DNA to H2O2-induced DNA strand breaks and improved the DNA repair after H2O2 challenge in liver cells, irrespective of the dose ingested. These results suggest that mate tea could protect against DNA damage and enhance the DNA repair activity. Protection may be afforded by the antioxidant activity of the mate tea's bioactive compounds

Ventilation behavior in trained and untrained men during incremental test: evidence of one metabolic transition point

This study aimed to describe and compare the ventilation behavior during an incremental test utilizing three mathematical models and to compare the feature of ventilation curve fitted by the best mathematical model between aerobically trained (TR) and untrained ( UT) men. Thirty five subjects underwent a treadmill test with 1 km.h(-1) increases every minute until exhaustion. Ventilation averages of 20 seconds were plotted against time and fitted by: bi-segmental regression model (2SRM); three-segmental regression model (3SRM); and growth exponential model (GEM). Residual sum of squares (RSS) and mean square error (MSE) were calculated for each model. The correlations between peak VO2 (VO2PEAK), peak speed (Speed(PEAK)), ventilatory threshold identified by the best model (VT2SRM) and the first derivative calculated for workloads below (moderate intensity) and above (heavy intensity) VT2SRM were calculated. The RSS and MSE for GEM were significantly higher (p < 0.01) than for 2SRM and 3SRM in pooled data and in UT, but no significant difference was observed among the mathematical models in TR. In the pooled data, the first derivative of moderate intensities showed significant negative correlations with VT2SRM (r = -0.58; p < 0.01) and Speed(PEAK) (r = -0.46; p < 0.05) while the first derivative of heavy intensities showed significant negative correlation with VT2SRM (r = -0.43; p < 0.05). In UT group the first derivative of moderate intensities showed significant negative correlations with VT2SRM (r = -0.65; p < 0.05) and Speed(PEAK) (r = -0.61; p < 0.05), while the first derivative of heavy intensities showed significant negative correlation with VT2SRM (r= -0.73; p < 0.01), Speed(PEAK) (r = -0.73; p < 0.01) and VO2PEAK (r = -0.61; p < 0.05) in TR group. The ventilation behavior during incremental treadmill test tends to show only one threshold. UT subjects showed a slower ventilation increase during moderate intensities while TR subjects showed a slower ventilation increase during heavy intensities.

Adaptive Immunity against Leishmania Nucleoside Hydrolase Maps Its C-Terminal Domain as the Target of the CD4+ T Cell-Driven Protective Response

Nucleoside hydrolases (NHs) show homology among parasite protozoa, fungi and bacteria. They are vital protagonists in the establishment of early infection and, therefore, are excellent candidates for the pathogen recognition by adaptive immune responses. Immune protection against NHs would prevent disease at the early infection of several pathogens. We have identified the domain of the NH of L. donovani (NH36) responsible for its immunogenicity and protective efficacy against murine visceral leishmaniasis (VL). Using recombinant generated peptides covering the whole NH36 sequence and saponin we demonstrate that protection against L. chagasi is related to its C-terminal domain (amino-acids 199-314) and is mediated mainly by a CD4+ T cell driven response with a lower contribution of CD8+ T cells. Immunization with this peptide exceeds in 36.73 +/- 12.33% the protective response induced by the cognate NH36 protein. Increases in IgM, IgG2a, IgG1 and IgG2b antibodies, CD4+ T cell proportions, IFN-gamma secretion, ratios of IFN-gamma/IL-10 producing CD4+ and CD8+ T cells and percents of antibody binding inhibition by synthetic predicted epitopes were detected in F3 vaccinated mice. The increases in DTH and in ratios of TNF alpha/IL-10 CD4+ producing cells were however the strong correlates of protection which was confirmed by in vivo depletion with monoclonal antibodies, algorithm predicted CD4 and CD8 epitopes and a pronounced decrease in parasite load (90.5-88.23%; p = 0.011) that was long-lasting. No decrease in parasite load was detected after vaccination with the N-domain of NH36, in spite of the induction of IFN-gamma/IL-10 expression by CD4+ T cells after challenge. Both peptides reduced the size of footpad lesions, but only the C-domain reduced the parasite load of mice challenged with L. amazonensis. The identification of the target of the immune response to NH36 represents a basis for the rationale development of a bivalent vaccine against leishmaniasis and for multivalent vaccines against NHs-dependent pathogens.

An AC-5 cathepsin B-like protease purified from Haemonchus contortus excretory secretory products shows protective antigen potential for lambs

The immunogenic properties of cysteine proteases obtained from excretory/secretory products (ES) of Haemonchus contortus were investigated with a fraction purified with a recombinant H. contortus cystatin affinity column. The enrichment of H. contortus ES for cysteine protease was confirmed with substrate SDS-PAGE gels since the cystatin-binding fraction activity was three times higher than total ES, despite representing only 3% of total ES. This activity was inhibited by a specific cysteine protease inhibitor (E64) and by recombinant cystatin. The one-dimensional profile of the cystatin-binding fraction displayed a single band with a molecular mass of 43 kDa. Mass spectrometry showed this to be AC-5, a cathepsin B-like cysteine protease which had not been identified in ES products of H. contortus before. The cystatin binding fraction was tested as an immunogen in lambs which were vaccinated three times (week 0, 2.5 and 5), challenged with 10 000 L3 H. contortus (week 6) before necropsy and compared to unvaccinated challenge controls and another group given total ES (n = 10 per group). The group vaccinated with cystatin-binding proteins showed 36% and 32% mean worm burden and eggs per gram of faeces (EPG) reductions, respectively, compared to the controls but total ES was almost without effect. After challenge the cystatin-binding proteins induced significantly higher local and systemic ES specific IgA and IgG responses.

Accelerating aging chemotherapy on aged animals: Protective effect from nutraceutical modulation

The aim of this study was to test a novel phytocompound in an experimental model of antitumor-induced immunosuppression. Five groups of mice were considered: young (Y) and aged (A) that were given intraperitoneally 10 doses of cyclophosphamide (CPX, 25mg/kg/bw) or CPX plus (150 mg/kg/bw) of the nutraceutical DTS (Denshichi-Tochiu-Sen), and control. After sacrifice, macrophage chemotaxis and serum levels of IFN-gamma, IL-2, and GM-CSF were determined. Liver and urinary bladder were examined histologically, as were the liver and kidney for redox enzymes. CPX significantly decreased macrophage chemotaxis and all cytokines (p < 0.05, A >> Y). DTS restored macrophage function and cytokine concentration (p < 0.001) and partly improved the necro-inflammatory score and substance P receptor expression in the bladder and the redox status in liver and kidney (p < 0.05). Such data suggest that DTS effectively prevents CPX-induced immune suppression and oxidative-inflammatory damage, which are particularly enhanced in aged organisms.

Evaluation of Protective Effect of a Water-In-Oil Microemulsion Incorporating Quercetin Against UVB-Induced Damage in Hairless Mice Skin

Purpose. Histological aspects were considered in order to evaluate the in vivo photoprotective effect of a w/o microemulsion containing quercetin against UVB irradiation-induced dermal damages. The toxicity in cell culture and the potential skin irritation resulting from topical application of this formulation were investigated. Methods. Mouse dorsal surfaces were treated topically with 300 mg of the unloaded and quercetin-loaded (0.3%, w/w) microemulsions before and after exposure to UVB (2.87 J/cm(2)) irradiation. The untreated control groups irradiated and non-irradiated were also evaluated. UVB-induced histopathological changes as well as the photoprotective effect of this formulation were evaluated considering the parameters of infiltration of inflammatory cells, epidermis thickening (basale and spinosum layers) and collagen and elastic fiber contents. The cytotoxicity of the reported formulation was evaluated in L929 mice fibroblasts by MTT assay and the skin irritation was investigated after topical application of both unloaded and quercetin-loaded microemulsions once a day for 15 days. Results. The results demonstrated that the w/o microemulsion containing quercetin reduced the incidence of histological skin alterations, mainly the connective-tissue damage, induced by exposure to UVB irradiation. This suggests that protective effects of this formulation against UV-induced responses are not secondary to the interference of UV transmission (i.e., blocking the UVB radiation from being absorbed by the skin), as is usually implied with UVB absorbers and sunscreens, but is instead due to different biological effects of this flavonoid. Furthermore, by evaluating the cytotoxic effect on L929 cells and histological aspects such as infiltration of inflammatory cells and epidermis thickness of hairless mice, the present study also demonstrated the lack of toxicity of the proposed system. Conclusion. Based on these mice models, a detailed characterization of the w/o microemulsion incorporating quercetin effects as a photochemoprotective agent on human skin is presented.

Chemical and in vitro study of the potential of 3-(aryl)-2-sulfanylpropenoic acids and their Zn(II) complexes as protective agents against cadmium toxicity

The free H(2)xspa ligands [xspa = pspa, Clpspa, tspa or fspa where p = 3-(phenyl), Clp = 3-(2-chlorophenyl), t = 3-(2-thienyl), f = 3-(2-furyl) and spa = 2-sulfanylpropenoato], their Zn(II) complexes of formula [HQ](2)[Zn(xspa)(2)] (HQ=diisopropylammonium) and the Cd(II) equivalents were prepared and characterized by elemental analysis and by IR, Raman and NMR ((1)H, (13)C) spectroscopy. X-Ray studies of the crystal structures of [HQ](2)[Zn(pspa)(2)], [HQ](2)[Zn(Clpspa)2], [HQ](2)[Zn(tspa)(2)] and [HQ](2)[Zn(fspa)(2)] show that the zinc atom is coordinated to two O atoms and two S atoms of the ligands in a distorted tetrahedral ZnO(2)S(2) environment. In the structures of [HQ](2)[Cd(pspa)(2)] and [HQ](2)[Cd(Clpspa)(2)] the cadmium atom is coordinated to three S atoms and two carboxylato O atoms of the ligands in a distorted trigonal bipyramidal environment. The interchange of ligands between Zn( II) and Cd( II) was studied by (113)Cd NMR spectroscopy. The in vitro protective effect of H(2)xspa and their Zn( II) complexes against Cd toxicity was investigated using the human hepatocarcinoma HepG2 cell line and the pig renal proximal tubule LLC-PK1 cell line. The incorporation of Zn( II) was found to be relevant in the case of H(2)pspa, with an increase observed in the cell viability of the LCC-PK1 cells with respect to the value for the free ligand.

Ventilation behavior during upper-body incremental exercise

Pires, FO, Hammond, J, Lima-Silva, AE, Bertuzzi, RCM, and Kiss, MAPDM. Ventilation behavior during upper-body incremental exercise. J Strength Cond Res 25(1): 225-230, 2011-This study tested the ventilation (V(E)) behavior during upper-body incremental exercise by mathematical models that calculate 1 or 2 thresholds and compared the thresholds identified by mathematical models with V-slope, ventilatory equivalent for oxygen uptake (V(E)/(V) over dotO(2)), and ventilatory equivalent for carbon dioxide uptake (V(E)/(V) over dotCO(2)). Fourteen rock climbers underwent an upper-body incremental test on a cycle ergometer with increases of approximately 20 W.min(-1) until exhaustion at a cranking frequency of approximately 90 rpm. The V(E) data were smoothed to 10-second averages for V(E) time plotting. The bisegmental and the 3-segmental linear regression models were calculated from 1 or 2 intercepts that best shared the V(E) curve in 2 or 3 linear segments. The ventilatory threshold(s) was determined mathematically by the intercept(s) obtained by bisegmental and 3-segmental models, by V-slope model, or visually by V(E)/(V) over dotO(2) and V(E)/(V) over dotCO(2). There was no difference between bisegmental (mean square error [MSE] = 35.3 +/- 32.7 l.min(-1)) and 3-segmental (MSE = 44.9 +/- 47.8 l.min(-1)) models in fitted data. There was no difference between ventilatory threshold identified by the bisegmental (28.2 +/- 6.8 ml.kg(-1).min(-1)) and second ventilatory threshold identified by the 3-segmental (30.0 +/- 5.1 ml.kg(-1).min(-1)), V(E)/(V) over dotO(2) (28.8 +/- 5.5 ml.kg(-1).min(-1)), or V-slope (28.5 +/- 5.6 ml.kg(-1).min(-1)). However, the first ventilatory threshold identified by 3-segmental (23.1 +/- 4.9 ml.kg(-1).min(-1)) or by VE/(V) over dotO(2) (24.9 +/- 4.4 ml.kg(-1).min(-1)) was different from these 4. The V(E) behavior during upper-body exercise tends to show only 1 ventilatory threshold. These findings have practical implications because this point is frequently used for aerobic training prescription in healthy subjects, athletes, and in elderly or diseased populations. The ventilatory threshold identified by V(E) curve should be used for aerobic training prescription in healthy subjects and athletes.

Determination of particle concentration in the breathing zone for four different types of office ventilation systems

Many factors affect the airflow patterns, thermal comfort, contaminant removal efficiency and indoor air quality at individual workstations in office buildings. In this study, four ventilation systems were used in a test chamber designed to represent an area of a typical office building floor and reproduce the real characteristics of a modern office space. Measurements of particle concentration and thermal parameters (temperature and velocity) were carried out for each of the following types of ventilation systems: (a) conventional air distribution system with ceiling supply and return; (b) conventional air distribution system with ceiling supply and return near the floor; (c) underfloor air distribution system; and (d) split system. The measurements aimed to analyse the particle removal efficiency in the breathing zone and the impact of particle concentration on an individual at the workstation. The efficiency of the ventilation system was analysed by measuring particle size and concentration, ventilation effectiveness and the indoor/outdoor ratio. Each ventilation system showed different airflow patterns and the efficiency of each ventilation system in the removal of the particles in the breathing zone showed no correlation with particle size and the various methods of analyses used. (C) 2008 Elsevier Ltd. All rights reserved.

Protective effects of Mangifera indica L extract (Vimang), and its major component mangiferin, on iron-induced oxidative damage to rat serum and liver

In vivo preventive effects of a Mangifera indica L extract (Vimang) or its major component mangiferin on iron overload injury have been studied in rats given respectively, 50, 100, 250 mg kg(-1) body weight of Vimang, or 40 mg kg(-1) body weight of mangiferin, for 7 days prior to, and for 7 days following the administration of toxic amounts of iron-dextran. Both Vimang or mangiferin treatment prevented iron overload in serum as well as liver oxidative stress, decreased serum and liver lipid peroxidation, serum GPx activity, and increased serum and liver GSH, serum SOD and the animals overall antioxidant condition. Serum iron concentration was decreased although at higher doses, Vimang tended to increase it; percent tranferrin saturation, liver weight/body mass ratios, liver iron content was decreased. Treatment increased serum iron-binding capacity and decreased serum levels of aspartate-amine transferase (ASAT) and alanine-amine transferase (ALAT), as well as the number of abnormal Kupffer cells in iron-loaded livers. It is suggested that besides acting as antioxidants, Vimang extract or its mangiferin component decrease liver iron by increasing its excretion. Complementing earlier in vitro results from our group, it appears possible to support the hypothesis that Vimang and mangiferin present therapeutically useful effects in iron overload related diseases. (C) 2007 Elsevier Ltd. All rights reserved.