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Bezafibrate (BZF) is a drug that reduces cholesterol and triglyceride levels in the blood. Research indicates that BZF, through activation of PPAR receptors, regulates the expression of genes involved in lipid homeostasis, inflammation, cell differentiation, and proliferation. This study investigated the in vitro and in vivo effects of BZF on activated hepatic stellate cells (HSCs) and on carbon tetrachloride-induced liver fibrosis in mice. After 72 h of treatment in vitro, BZF decreased cell proliferation, reversed the phenotype, decreased cell contraction, and induced autophagy. In addition, BZF promoted a protective effect on tetrachloride-induced liver fibrosis in mice, through antifibrotic actions. These findings suggest that BZF may have a potential antifibrotic effect, which could emerge as a possible new therapy for the treatment of liver fibrosis., Competing Interests: Declaration of competing interest The authors affirm that there are no conflicts of interest. They have all reviewed and approved the manuscript for submission., (Copyright © 2025 Elsevier Ltd. All rights reserved.)

Background: Cystic fibrosis (CF) patients experience pulmonary exacerbations and the three-minute step test (3-min step test) may be a simple and easy-to-perform functional test to help identify such episodes. The present study aimed to evaluate the association of the 3-min step test with the occurrence of pulmonary exacerbations in children with CF., Methods: Cross-sectional study of CF patients aged 6 years and older. Pulmonary exacerbations were assessed using both the Fuchs criteria and the Kanga Score. The 3-min step test was performed using a 15 cm-high step and heart rate (HR), oxygen saturation (SpO2), and dyspnea were measured before and after the test. Correlations between the test and the scores, as well as comparisons between patients experiencing or not an exacerbation, were performed., Results: Sixty-two patients (11.1±4.3 years) were included. Both the Fuchs criteria and the Kanga score correlated significantly with age, forced expiratory volume in the first second (FEV1), final SpO2, and 1-min recovery SpO2. A fall greater than 4% in the final SpO2 was significantly associated with the presence of a pulmonary exacerbation, considering both Fuchs and Kanga criteria. Age, resting HR, and HR after 1-min recovery were significantly higher, while FEV1, SpO2 at rest, final SpO2, and SpO2 after 1-min recovery were significantly lower in patients classified as exacerbated., Conclusions: Physiological responses to the 3-min step test are associated with the occurrence of pulmonary exacerbation in children with CF. Desaturation at the end of the test or during 1-min recovery may be the best variable to monitor.

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are syndromes of acute hypoxemic respiratory failure resulting from a variety of direct and indirect injuries to the gas exchange parenchyma of the lungs. During the ALI, we have an increase release of proinflammatory cytokines and high reactive oxygen species (ROS) formation. These factors are responsible for the release and activation of neutrophil-derived proteases and the formation of neutrophil extracellular traps (NETs). The excessive increase in the release of NETs cause damage to lung tissue. Recent studies have studies involving the administration of mesenchymal stem cells (MSCs) for the treatment of experimental ALI has shown promising results. In this way, the objective of our study is to evaluate the ability of MSCs, in a lipopolysaccharide (LPS)-induced ALI model, to reduce inflammation, oxidative damage, and consequently decrease the release of NETs. Mice were submitted lung injury induced by intratracheal instillation of LPS and subsequently treated or not with MSCs. Treatment with MSCs was able to modulate pulmonary inflammation, decrease oxidative damage, and reduce the release of NETs. These benefits from treatment are evident when we observe a significant increase in the survival curve in the treated animals. Our results demonstrate that MSCs treatment is effective for the treatment of ALI. For the first time, it is described that MSCs can reduce the formation of NETs and an experimental model of ALI. This finding is directly related to these cells modulate the inflammatory response and oxidative damage in the course of the pathology., (© 2017 Wiley Periodicals, Inc.)

Hepatic fibrosis is an extracellular matrix deposition by hepatic stellate cells (HSC). Fibrosis can be caused by iron, which will lead to hydroxyl radical production and cell damage. Fructose-1,6-bisphosphate (FBP) has been shown to deliver therapeutic effects in many pathological situations. In this work, we aimed to test the effects of FBP in HSC cell line, GRX, exposed to an excess of iron (Fe). The Fe-treatment increased cell proliferation and FBP reversed this effect, which was not due to increased necrosis, apoptosis or changes in cell cycle. Oil Red-O staining showed that FBP successfully increased lipid content and lead GRX cells to present characteristics of quiescent HSC. Fe-treatment decreased PPAR-γ expression and increased Col-1 expression. Both effects were reversed by FBP which also decreased TGF-β1 levels in comparison to both control and Fe groups. FBP, also, did not present scavenger activity in the DPPH assay. The treatment with FBP resulted in decreased proliferation rate, Col-1 expression and TGF-β1 release by HSC cells. Furthermore, activated PPAR-γ and increased lipid droplets induce cells to become quiescent, which is a key event to reversion of hepatic fibrosis. FBP also chelates iron showing potential to improve Cell redox state.

Hepatocellular carcinoma (HCC) is the most prevalent primary liver tumor that affects the world population. Liver cancer inevitably causes great harms and its treatment is extremely difficult. Its development is related to the existence of chronic liver injury, such as in cirrhosis. Cancer is a disease related to the process of inflammation so, research with anti-inflammatory agents has been performed for the development of anti-tumor drugs. Fructose-1,6-bisphosphate (FBP), a metabolite of the glycolytic route, has shown anti-inflammatory actions. The purpose of this study is to investigate the effect of FBP on HepG2 cells growth and inflammatory parameters. Results showed that FBP decreased the proliferation of HepG2 cells through trypan blue assay, without causing necrosis, shown by the intracellular release of LDH. By flow cytometry, we observed a significant IL-8 decrease which is closely related to the tumoral progression and chemotherapeutic resistance, especially in HCC. Then, we found, by RT-PCR, a high expression level of pro-apoptotic protein, such as Bax and p53, and decreased the expression levels of anti-apoptotic proteins, like Bcl-2 suggesting apoptosis. Finally, our results showed that FBP can be a potential therapeutic agent to slow the progress of HCC., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Exposure to early life stress has been associated with memory impairments related to changes in brain-derived neurotrophic factor (BDNF) signaling. However, the potential impact of physical exercise to reverse these effects of maternal separation has been under investigated. Mice were subjected to maternal separation during the first 2 weeks of life and then exposed to a 3-week running protocol during adolescence. The spontaneous object recognition task was performed during adolescence followed by analysis of hippocampal expression of exons I, IV, and IX of the BDNF gene. As expected, maternal separation impaired recognition memory and this effect was reversed by exercise. In addition, running increased BDNF exon I expression, but decreased expression of BDNF exon IV in all groups, while exon IX expression increased only in MS animals exposed to exercise. Our data suggest that memory deficits can be attenuated by exercise and specific transcripts of the BDNF gene are dynamically regulated following both MS and exercise., (© 2016 Wiley Periodicals, Inc.)

Objective: To evaluate the association of 6-minute walk test (6MWT) and other variables (anthropometry, chronic Pseudomonas aeroginosa colonization, pulmonary function, and respiratory muscle strength) with the risk of hospitalization for pulmonary exacerbation in children and adolescents with cystic fibrosis (CF)., Study Design: Cohort study that included patients with CF aged 6-18 years. All participants underwent spirometry, manovacuometry, and 6MWT during the 5-year follow-up. Anthropometric and clinical data were collected and the time to first hospitalization, total days of hospitalization, and antibiotic use during follow-up was recorded., Results: A total of 26 patients with CF, mean age 10.2 ± 2.8 years, were included. The group had mild impairment of lung function with a significant decline in forced expiratory volume in 1 second (P = .019) over the 5 years. Respiratory muscle strength and 6MWT proved to be preserved, although maximum inspiratory pressure increased (P < .001) and maximum expiratory pressure and 6-minute walk distance (6MWD) remained stable. There were inverse associations of 6MWD in meters (r = -0.813, P < .001) and z score (r = -0.417, P = .015) with total days of hospitalization. Moreover, there was a reduction in the risk of a first hospitalization (Cox HR 0.32; P = .037) in patients with a greater 6MWD., Conclusions: We found an association between the 6MWT and the risk of hospitalization in children and adolescents with CF. Furthermore, functional capacity apparently does not follow the expected decline in pulmonary function over time, whereas inspiratory muscle strength increases with disease progression., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Aims: To generate reference values for two inspiratory muscle endurance (IME) protocols in healthy children and adolescents., Materials and Methods: This is an observational, cross-sectional study, in healthy children and adolescents from 4 to 18 years of age. Weight, height, maximal inspiratory pressure (MIP) and IME were measured using two protocols. A fixed load of 30% of MIP with a 10% increment every 2 minutes was used in the incremental threshold loading protocol. As for the maximal loading protocol, a fixed load of 70% of MIP was used and the time limit (Tlim) achieved until fatigue was measured., Results: A total of 462 participants were included, 281 corresponding to the incremental loading protocol and 181 to maximal loading. There were moderate and positive correlations between IME and age, MIP, weight and height in the incremental threshold loading. However, the regression model demonstrated that MIP and age were the best variables to predict the IME. Otherwise, weak and positive correlations with age, weight and height were found in the maximal loading. Only age and height influenced endurance in the regression model. The predictive power (r2) of the incremental threshold loading protocol was 0.65, while the maximal loading was 0.15. The reproducibility measured by the intraclass correlation coefficient (ICC) was higher in the incremental loading (0.96) compared to the maximal loading test (0.69)., Conclusion: IME in healthy children and adolescents can be explained by age, height and MIP. The incremental threshold loading protocol showed more reliable results and should be the model of choice to evaluate IME in the pediatric age group., Competing Interests: The authors have declared that no competing interests exist.

Background: Acute viral bronchiolitis is an inflammatory disease of the lower respiratory tract. This study aimed to compare the immediate effects of retrograde rhinopharyngeal clearance with nasopharyngeal aspiration in children admitted with acute viral bronchiolitis., Methods: This was a randomized controlled clinical trial with children admitted for acute viral bronchiolitis up to 12 months old. Subjects were divided into a nasopharyngeal aspiration group and a clearance group, submitted to retrograde rhinopharyngeal clearance with physiological solution (0.9%) instillation. In both groups, there were 3 evaluations on the same day (data collections 1, 2, and 3), including cardiorespiratory parameters, clinical score of respiratory dysfunction, and adverse effects., Results: One hundred children were included, with no statistical differences between groups regarding the characteristics of the sample. There was a significant reduction (P < .05) in heart rate in data collections 1 and 2 after 10 and 30 min. The number of episodes of nasal bleeding (28 vs 1) and vomiting (11 vs 7) was higher in the aspiration group compared with the clearance group. Children classified as moderate showed a significant reduction of retractions (100% vs 84.6%) and nasal bleeding (44.8% vs 0%). An increase of 6.7 and 19.5% in wheezing and retractions, respectively, was shown for the aspiration group, whereas the clearance group showed only 4.6% for both parameters., Conclusions: The use of retrograde rhinopharyngeal clearance in the management of infants with acute viral bronchiolitis can be an alternative for the clearance of the upper airways, since it showed immediate positive effects on the occurrence of complications and signs of respiratory effort compared with nasopharyngeal aspiration. Children classified with a moderate clinical score appear to benefit the most. (ClinicalTrials.gov registration NCT02460614.)., (Copyright © 2016 by Daedalus Enterprises.)

Objective: To compare inspiratory muscle function (strength and endurance) between asthmatics and healthy controls, and the influence of age, nutritional status and physical activity on them., Methods: This is a cross-sectional study. Asthmatic and healthy subjects, aged 6 to 18 years old, recruited from two public schools in Southern Brazil were included in the study. Asthmatic subjects were selected using the criteria presented by the International Study on Asthma and Allergies in Children and control subjects based on the absence of respiratory symptoms. Anthropometric data was measured, body mass index calculated and subjects classified as normal weight, overweight or obese. Physical activity levels, maximum inspiratory pressure (MIP) and inspiratory muscle endurance (IME) were also evaluated., Results: A total of 314 participants were included, separated into control group (181) and asthmatics (133), with a total mean age of 11 years. When both groups were compared, there were no significant differences in both MIP and IME. However, when groups were analyzed subdivided in children and adolescents, IME was significantly reduced (p = 0.003) in asthmatic adolescents. Indeed, when groups were also stratified considering the nutritional status, IME showed a reduction in asthmatic adolescents with overweight (p = 0.042) and obesity (p = 0.041) when compared to healthy controls. No effects of physical activity levels between groups were found., Conclusions: Results demonstrate a reduction in the IME in asthmatic adolescents with overweight and obesity, indicating an association between asthma, nutritional status and respiratory muscle function.

Adversities faced during the prenatal period can be related to the onset of diseases in adulthood. However, little is known about the effects on the respiratory system. This study aimed to evaluate the effects of prenatal stress in two different time-points during pregnancy on pulmonary function and on the inflammatory profile of mice exposed to an asthma model. Male and female BALB/c mice were divided into 3 groups: control (CON), prenatal stress from the second week of pregnancy (PNS1) and prenatal stress on the last week of pregnancy (PNS2). Both PNS1 and PNS2 pregnant females were submitted to restraint stress. As adults, fear/anxiety behaviors were assessed, and animals were subjected to an asthma model induced by ovalbumin. Pulmonary function, inflammatory parameters in bronchoalveolar lavage (BAL) and histology were evaluated. There was a significant decrease in the number of entries and time spent in the central quadrant on the open field test for the PNS1 animals. Females (PNS1) showed improved pulmonary function (airway resistance, tissue damping and pulmonary elastance), significant increase in the percentage of neutrophils and lymphocytes and a decrease in eosinophils when compared to controls. There was a significant decrease in inflammatory cytokines in BAL of both males (IL-5 and IL-13) and females (IL-4, IL-5 and IL-13) from PNS1 and PNS2 when compared to the CON group. Prenatal stress starting from the beginning of pregnancy reduces the impact of asthma development in adult female mice, showing an improved pulmonary function and a lower inflammatory response in the lungs., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Interactive video games are recently being used as an exercise tool in cystic fibrosis (CF). This study aimed to assess the literature describing whether video games generate a physiological response similar to the exercise intensity needed for training in CF., Methods: An online search in PubMed, Embase, Cochrane, SciELO, LILACS and PEDro databases was conducted and original studies describing physiological responses of the use of video games as exercise in CF were included., Results: In four, out of five studies, the heart rate achieved during video games was within the standards recommended for training (60-80%). Two studies assessed VO 2 and showed higher levels compared to the six-minute walk test. No desaturation was reported. Most games were classified as moderate intensity. Only one study used a maximum exercise test as comparator., Conclusion: Interactive video games generate a heart rate response similar to the intensity required for training in CF patients., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

The aim of this study is to evaluate the response to an inflammatory stimulus in mice exposed to LPS-induced neonatal stress at different ages and sexes. Balb/c mice were submitted to intraperitoneal injections on postnatal days 3 and 10 with lipopolysaccharide (nLPS) or saline solution (nSal). At 21 or 60 days, either saline solution was injected or an inflammatory stimulus was induced by the injection of 1% carrageenan. Inflammatory cytokines, reactive oxygen species, and neutrophil extracellular traps (NETs) production were measured in peritoneal fluid. LPS-induced neonatal stress can reduce inflammatory cytokines in males and females. An increase in NETs production was observed when 60 day nLPS animals were compared to 21 day mice in both sexes. The ROS production was not affected by neonatal stress. The results shown here indicate that LPS-induced neonatal stress can alter cytokine production in response to inflammatory stimuli at different ages, in a sex-dependent effect. © 2016 Wiley Periodicals, Inc. Dev Psychobiol 58: 600-613, 2016., (© 2016 Wiley Periodicals, Inc.)

Neutrophil extracellular traps (NETs) are a combination of DNA fibers and granular proteins, such as neutrophil elastase (NE). NETs are released in the extracellular space in response to different stimuli. Carrageenan is a sulfated polysaccharide extracted from Chondrus crispus, a marine algae, used for decades in research for its potential to induce inflammation in different animal models. In this study, we show for the first time that carrageenan injection can induce NET release in a mouse model of acute peritonitis. Carrageenan induced NET release by viable neutrophils with NE and myeloperoxidase (MPO) expressed on DNA fibers. Furthermore, although this polysaccharide was able to stimulate reactive oxygen species (ROS) generation by peritoneal neutrophils, NADPH oxidase derived ROS were dispensable for NET formation by carrageenan. In conclusion, our results show that carrageenan-induced inflammation in the peritoneum of mice can induce NET formation in an ROS-independent manner. These results may add important information to the field of inflammation and potentially lead to novel anti-inflammatory agents targeting the production of NETs., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: Pulmonary changes that occur in cystic fibrosis may influence inspiratory muscle strength and endurance. We evaluated inspiratory muscle strength and endurance in children and adolescents with cystic fibrosis in comparison with healthy subjects., Methods: This is a cross-sectional observational study with subjects with cystic fibrosis and paired healthy individuals, age 6-18 y. Spirometry, impulse oscillometry, plethysmography, manovacuometry, and a protocol of inspiratory muscle endurance were performed., Results: Subjects with cystic fibrosis (n = 34) had higher maximum percent-of-predicted inspiratory pressure (PImax) than healthy (n = 68) subjects (118.5 ± 25.8% vs 105.8 ± 18.0%) and no significant difference in endurance (60.9 ± 13.3% vs 65.3 ± 12.3%). When restricting the analysis to subjects without Pseudomonas aeruginosa colonization and with FEV1 > 80%, PImax values were significantly higher, and inspiratory muscle endurance was lower, in comparison with the control group. PImax correlated significantly with FVC (r = 0.44, P = .02) and FEV1 (r = 0.41, P = .02), whereas endurance correlated better with total airway resistance (r = 0.35, P = .045) and with central airway resistance (r = 0.48, P = .004)., Conclusions: Children and adolescents with cystic fibrosis with no colonization by P. aeruginosa and normal lung function present increased inspiratory muscle strength and decreased endurance compared with healthy individuals, indicating that changes in the respiratory muscle function seem to be distinctly associated with pulmonary involvement. Strength was related to pulmonary function parameters, whereas endurance was associated with airway resistance., (Copyright © 2016 by Daedalus Enterprises.)

Background: Sepsis is a major health care problem, with a significant mortality rate in intensive care units. We evaluated biochemical and inflammatory markers in patients with severe sepsis and septic shock and its association of with mortality rates., Methods: Critically ill patients with diagnoses of sepsis - severe sepsis group (n=23) and septic shock group (n=25), and a control group (n=17) were recruited within 24h of entry into the ICU. Serum levels of inflammatory mediators were measured (IL-1β, IL-6, IL-8, IL-10, TNF-α, IL-18 and nitric oxide). We have also collected clinical parameters and laboratorial tests to estimate severity and organ dysfunction (APACHE II, SOFA, lactate). These results were compared between survivors and no survivors., Results: IL-18 was directly related to mortality independently of other inflammatory mediators, especially IL-1β, although the inflammatory pathway is closely linked to inflammasome activation and both have simultaneous release in the infectious process. Mortality was directly proportional to IL-18 plasma levels, which did not occur with other inflammatory mediators., Conclusions: IL-18 is an important predictor of mortality in humans with both severe sepsis and septic shock, independent of IL-1β., (Copyright © 2015 Elsevier B.V. All rights reserved.)

The present study aimed to evaluate the long-term effects of neonatal inflammation on the inflammatory and oxidative profile during experimental sepsis in adult life. Neonatal Balb/c mice received different treatments on day 10: LPS i.p. injection (100g/kg) (nLPS) or saline i.p. injection (nSal). As adults, fear/anxiety behavior was evaluated in the elevated plus maze. The following week, saline solution or LPS was administered and, after 12h, serum (inflammatory cytokines), liver (mitochondrial complexes and oxidative stress) and adrenal gland samples (angiotensin II type 1 and 2 receptors) were collected. There was an increase in the fear/anxiety behavior in the nLPS group. Neonatal administration of LPS increased the mRNA expression of the AT1 receptor and decreased the mRNA expression of the AT2 receptor in the adrenal glands of males. The complexes II and II-III increased in the nLPS saline male group when compared to control. The LPS administration in adult females, regardless of the neonatal treatment, induced a decrease of the glutathione enzyme activity. There were no differences in the inflammatory cytokines. The results showed that neonatal inflammation influenced mitochondrial respiratory chain metabolism and angiotensin II receptors in a sex-dependent manner. Balb/c mice fear and anxiety behaviors in adulthood were programmed by early life inflammatory stress., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: To determine whether the variation in lung function over one year is associated with worse clinical outcomes, as well as with a decline in lung function in the following years, in patients with cystic fibrosis (CF)., Methods: This was a retrospective study involving CF patients (4-19 years of age), evaluated over a three-year period. We evaluated demographic characteristics, chronic Pseudomonas aeruginosa infection, antibiotic use, hospitalization, six-minute walk distance (6MWD), and lung function. The inclusion criterion was having undergone pulmonary function testing at least three times in the first year and at least once in each of the next two years., Results: We evaluated 35 CF patients. The variation in FEV1 in the first year (ΔFEV1) was greater among those who, in the third year, showed reduced FEV1, had a below-average 6MWD, or were hospitalized than among those with normal FEV1, normal 6MWD, or no hospital admissions, in that same year (p < 0.05), although no such difference was found for antibiotic use in the third year. Subjects showing a ΔFEV1 ≥ 10% also showed a greater decline in FEV1 over the two subsequent years (p = 0.04). The ΔFEV1 also showed an inverse correlation with absolute FEV1 in the third year (r = -0.340, p = 0.04) and with the rate of FEV1 decline (r = -0.52, p = 0.001). Linear regression identified ΔFEV1 as a predictor of FEV1 decline (coefficient of determination, 0.27)., Conclusions: Significant variation in lung function over one year seems to be associated with a higher subsequent rate of FEV1 decline and worse clinical outcomes in CF patients. Short-term ΔFEV1 might prove useful as a predictor of CF progression in clinical practice.

Background and Objectives: As the population ages, osteometabolic diseases and osteoporotic fractures emerge, resulting in substantial healthcare resource utilization and impaired quality of life. Many types of mechanical stimulation have the potential of being recognized by bone cells after a mechanical sign is transformed into a biological one (a process called mechanotransduction). The therapeutic ultrasound (TU) is one of several resources capable of promoting bone cell mechanical stimulation. Therefore, the main purpose of present study was to evaluate the effect of TU on the proliferation of pre-osteoblasts using in vitro bioassays., Study Design/materials and Methods: We used MC3T3-E1 pre-osteoblast lineage cells kept in Alpha medium. Cells were treated using pulsed mode therapeutic ultrasound, with frequency of 1 MHz, intensity of 0.2 W/cm(2) (SATA), duty cycle of 20%, for 30 minutes. Nifedipine and rapamycin were used to further investigate the role of L-type Ca(2+) channels and mTOR pathway. Intracellular calcium, TGF-β1, magnesium, and the mRNA levels of osteopontin, osteonectin, NF-κB1, p38α were evaluated., Results: The results show that TU stimulates the growth of MC3T3-E1 cells and decreases the supernatant calcium and magnesium content. Also, it increases intracellular calcium, activates NF-κB1 and mTOR complex via p38α. Moreover, TU promoted a decrease in the TGF-β1 synthesis, which is a cell growth inhibitor., Conclusions: Therapeutic ultrasound, with frequency of 1 MHz, intensity of 0.2 W/cm(2) (SATA) and pulsed mode, for 30 minutes, was able to increase the proliferation of preosteoblast-like bone cells. This effect was mediated by a calcium influx, with a consequent activation of the mTOR pathway, through increased NF-κB1 and p38α., (© 2015 Wiley Periodicals, Inc.)

Several studies have investigated the antinociceptive, immunomodulatory and anti-inflammatory properties of compounds found in the lavender essential oil (LEO), however to date, there is still lack of substantial data. The objective of this study was to assess the antioxidant, anti-inflammatory and antinociceptive effects of lavender essential oil. The 1,1-diphenyl-2-picrylhydrazyl radical decolorization assay was used for antioxidant activity evaluation. The anti-inflammatory activity was tested using two models of acute inflammation: carrageenan-induced pleurisy and croton oil-induced ear edema. The antinociceptive activity was tested using the pain model induced by formalin. LEO has antioxidant activity, which is dose-dependent response. The inflammatory response evoked by carrageenan and by croton oil was reduced through the pre-treatment of animals with LEO. In the pleurisy model, the drug used as positive control, dexamethasone, was more efficacious. However, in the ear swelling, the antiedematogenic effect of the oil was similar to that observed for dexamethasone. In the formalin test, LEO consistently inhibited spontaneous nociception and presented a similar effect to that of tramadol. The results of this study reveal (in vivo) the analgesic and anti-inflammatory activities of LEO and demonstrates its important therapeutic potential.

Objective: To determine the success rate of the manovacuometry test in children between 4 and 12 years of age., Methods: Cross-sectional study involving children and adolescents from 4 to 12 years of age, enrolled in three basic education schools. All subjects had the anthropometric and respiratory muscle strength (maximum inspiratory pressure and maximum expiratory pressure) data measured. Students whose parents did not authorize participation or who did not want to undergo the test were excluded. The test was considered successful when the subject reached acceptability (no air leaks) and reproducibility (variation <10% between the two major maneuvers) criteria established by guidelines. Failure was defined when subjects did not meet the above criteria. Data were expressed as mean and standard deviation and in absolute and relative frequency. The comparison between proportions was performed using the chi-square test., Results: We included 196 children and adolescents, mean age of 8.4±2.5 years, 53.1% female. The success rate of the manovacuometry test in children and adolescents evaluated was 92.3%. When comparing the differences between the success rates of preschool children with those children and adolescents of school age, there was a significantly lower success rate in the pre-school (85.1%) group compared to the school group (94.6%) (p=0.032). However, no significant differences (p=0.575) were found when gender comparisons were performed., Conclusions: The manovacuometry test showed a high success rate in both preschool and school population assessed. Furthermore, the rate of success appears to be related to aging., (Copyright © 2015 Sociedade de Pediatria de São Paulo. Publicado por Elsevier Editora Ltda. All rights reserved.)

Objective: To evaluate postural changes and the distribution of plantar pressures in patients with cystic fibrosis (CF). We also sought to evaluate the effects of an educational guideline for physical activity on body posture in children and adolescents with CF., Study Design: This was a 2-phase study of individuals between age 7 and 20 years. Phase I was a cross-sectional study in which healthy subjects were selected for postural evaluation and baropodometry, aiming to perform a later comparison with patients with CF. In phase II, we performed a randomized controlled clinical trial to assess the influence of the exercise guideline on the postural changes. Patients were assigned to 2 groups: control and intervention. The intervention consisted of a handbook with instructions for aerobic exercise and stretching. Main outcomes were postural abnormalities, plantar pressure distribution, and lung function., Results: In phase I, 34 patients with CF and 34 healthy matched individuals were included. No significant baseline differences were identified. Children with CF presented more postural deviations compared with healthy subjects (P < .05), as to alignment of the head, shoulder girdle, and pelvis, increased cervical lordosis, and lateral chest distance. In phase II (n = 34), there were no baseline differences between groups. The intervention caused (P < .05) a decrease in cervical lordosis, thoracic kyphosis, lumbar lordosis, lateral chest distance, and abdominal protrusion, as well as in the baropodometric mean pressure and contact area., Conclusions: Children and adolescents with CF present postural changes when compared with healthy individuals. The educational guideline for exercise practice helped to improve posture, preventing the progression of some postural disorders., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Maternal social stress during late pregnancy programs hypothalamo-pituitary-adrenal (HPA) axis hyper-responsiveness to stressors, such that adult prenatally stressed (PNS) offspring display exaggerated HPA axis responses to a physical stressor (systemic interleukin-1β; IL-1β) in adulthood, compared with controls. IL-1β acts via a noradrenergic relay from the nucleus tractus solitarii (NTS) to corticotropin releasing hormone neurons in the paraventricular nucleus (PVN). Neurosteroids can reduce HPA axis responses, so allopregnanolone and 3β-androstanediol (3β-diol; 5α-reduced metabolites of progesterone and testosterone, respectively) were given subacutely (over 24 h) to PNS rats to seek reversal of the "programmed" hyper-responsive HPA phenotype. Allopregnanolone attenuated ACTH responses to IL-1β (500 ng/kg, i.v.) in PNS females, but not in PNS males. However, 3β-diol normalized HPA axis responses to IL-1β in PNS males. Impaired testosterone and progesterone metabolism or increased secretion in PNS rats was indicated by greater plasma testosterone and progesterone concentrations in male and female PNS rats, respectively. Deficits in central neurosteroid production were indicated by reduced 5α-reductase mRNA levels in both male and female PNS offspring in the NTS, and in the PVN in males. In PNS females, adenovirus-mediated gene transfer was used to upregulate expression of 5α-reductase and 3α-hydroxysteroid dehydrogenase mRNAs in the NTS, and this normalized hyperactive HPA axis responses to IL-1β. Thus, downregulation of neurosteroid production in the brain may underlie HPA axis hyper-responsiveness in prenatally programmed offspring, and administration of 5α-reduced steroids acutely to PNS rats overrides programming of hyperactive HPA axis responses to immune challenge in a sex-dependent manner., (Copyright © 2015 Brunton et al.)

Background: Regular aerobic exercise in patients with cystic fibrosis (CF) improves aerobic conditioning and delays disease progression, resulting in better quality of life. The purpose of this study was to evaluate the effect of an aerobic exercise program based on verbal and written guidelines on maximum exercise capacity using a cardiopulmonary exercise test, quality of life, and the self-reported aerobic exercise practice of children and adolescents with CF., Methods: This randomized controlled trial followed guidelines for physical exercise in a CF center. Subjects were assigned to 2 groups: intervention (group 1), with 17 subjects; and control (group 2), also with 17 subjects. Data were collected from October 2010 to October 2011, and the study population comprised 7-20-y-old children and adolescents with CF. The intervention consisted of handing out a manual with guidelines for aerobic physical exercises and reinforcing recommendations in telephone calls every 2 weeks., Results: Thirty-four subjects were included in the study, 20 of whom were boys (58.5%). The groups were similar at baseline. In group 1, 6 subjects (35.2%) reported practicing physical exercises regularly. The mean age was 13.4 ± 2.8 y, the mean percent-of-predicted FEV1 was 95.5 ± 17.9%, and the mean peak oxygen uptake (V̇O2 ) relative to body mass was 34.9 ± 9.0 mL/kg/min. In group 2, 4 subjects (23.5%) reported practicing physical exercises regularly. The mean age was 12.7 ± 3.3 y, the mean percent-of-predicted FEV1 was 100.1 ± 21.2%, and the mean peak V̇O2 was 33.2 ± 8.2 mL/kg/min. In group 1, there was a significant increase in physical exercise practice as reported by subjects after 3 months of intervention compared with group 2 (P = .01). No statistically significant differences were found for the other variables., Conclusions: Verbal and written guidelines for aerobic exercise, together with supervision over the telephone, had a positive impact on the self-reported regular physical exercise practice of children and adolescents. However, no improvement was found in lung function and maximum exercise capacity or domains of the quality of life questionnaire., (Copyright © 2015 by Daedalus Enterprises.)

Background: Septic shock presents as a continuum of infectious events, generating tissue hypoxia and hypovolemia, and increased oxidative stress. Chest physiotherapy helps reduce secretion, improving dynamic and static compliance, as well as improving secretion clearance and preventing pulmonary complications. The purpose of this study was to evaluate the immediate effect of chest physiotherapy on hemodynamic, metabolic, inflammatory, and oxidative stress parameters in subjects in septic shock., Methods: We conducted a quasi-experimental study in 30 subjects in septic shock, who underwent chest physiotherapy, without associated heart diseases and with vasopressors < 0.5 μg/kg/min. Venous and arterial blood gases, clinical and hemodynamic data, inflammatory data, lactate, and oxidative stress were evaluated before and 15 min after physiotherapy., Results: Thirty subjects with a mean age of 61.8 ± 15.9 y and Sequential Organ Failure Assessment of 8 (range 6-10) were included. Chest physiotherapy caused a normalization of pH (P = .046) and P(aCO2) (P = .008); reduction of lactate (P = .001); and an increase in P(aO2) (P = .03), arterial oxygen saturation (P = .02), and P(aO2)/F(IO2) (P = .034), 15 min after it was applied., Conclusions: The results indicate that chest physiotherapy has immediate effects, improving oxygenation and reducing lactate and oxidative damage in subjects in septic shock. However, it does not cause alterations in the inflammatory and hemodynamic parameters., (Copyright © 2014 by Daedalus Enterprises.)

Aim: To determine normative values for the Timed Up and Go (TUG) test in typically developing children and adolescents and to validate its use in individuals with Down syndrome., Method: Participants in this cross-sectional study were South Brazilian schoolchildren aged 3 to 18 years. In phase 1, 459 typically developing individuals (227 males, 232 females; mean age 10 y 8 mo (SD 4 y 4 mo) were included; and in phase 2, 40 individuals with Down syndrome (16 males, 24 females; mean age 10 y 6 mo (SD 4 y 4 mo). Anthropometric measurements, real leg length, TUG test scores, and Gross Motor Function Measure (GMFM) scores were evaluated. The association between the TUG test and possible predictive variables was analyzed., Results: In phase 1, the mean time to perform the TUG test was 5.61 seconds (SD 1.06). Values were stratified in age groups that served as normative data for both sexes. A multiple linear regression analysis was conducted and the best variables to predict TUG scores were age and weight. The best model obtained presented an R(2) of 0.25 and a standard error of the estimate of 0.92. Excellent intrasession reliability in the three tests performed (intraclass correlation coefficient [ICC] of 0.93, 0.94, and 0.95) and between the sessions (both with an ICC of 0.95) was demonstrated. In phase 2, the test also showed excellent reproducibility (ICC=0.82 between the two tests performed). The performance time was significantly longer (p<0.001) in individuals with Down syndrome compared with sex- age-, and weight-matched typically developing children with a mean difference of -3.53 (95% confidence interval -4.05 to -3.00). Dimension E of the GMFM (Walking, Running and Jumping) showed the highest correlation (r=-0.55, p<0.001) with the test., Interpretation: This study provides normative values for the TUG test and shows that TUG scores can be predicted as a function of age and weight in typically developing individuals. The test can also be used for assessment of functional mobility in individuals with Down syndrome., (© 2013 Mac Keith Press.)

OBJECTIVE To evaluate, by a literature review, the Timed "Up & Go" (TUG) test use and its main methodological aspects in children and adolescents. DATA SOURCES The searches were performed in the following databases: PubMed, CINAHL, Web of Science, SciELO and Cochrane Library, from April to July 2012. Studies published from 1990 to 2012 using the terms in Portuguese and English "Timed "Up & Go", "test", "balance", "child", and "adolescent" were selected. The results were divided into categories: general characteristics of the studies, population, test implementation METHODS, interpretation of results and associations with other measurements. DATA SYNTHESIS 27 studies were analyzed in this review and most of them used the TUG test along with other outcome measures to assess functional mobility or balance. Three studies evaluated the TUG test in significant samples of children and adolescents with typical development, and the most studied specific diagnoses were cerebral palsy and traumatic brain injury. The absence of methodological standardization was noted, but one study proposed adaptations to the pediatric population. In children and adolescents with specific clinical diagnoses, the coefficient of within-session reliability was found to be high in most studies, as well as the intra and inter-examiner reliability, which characterizes the good reproducibility of the test. CONCLUSIONS The TUG test was shown to be a good tool to assess functional mobility in the pediatric population, presenting a good reproducibility and correlation with other assessment tools.

Objective: To assess bone mineral density in patients with cystic fibrosis (CF), and to correlate it with possible intervening variables., Methods: Children and adolescents diagnosed with CF, aged 6 to 18 years, followed at the outpatient clinic were included in the study. First, demographic data were collected and, subsequently, patients underwent a spirometric test. All patients answered the Cystic Fibrosis Quality of Life Questionnaire (CFQ) and underwent the six-minute walk test (6MWT) and bone densitometry (DXA)., Results: A total of 25 CF patients were included, of which 56% were males. The mean age was 12.3±3.4 years; mean height was 149.2±14.4 cm; and mean weight was 44.4±13.9 kg. Most results on pulmonary function and bone mineral density (BMD) were within normal limits. The mean forced expiratory volume in one second (FEV) was 92.5±23.6 (% of predicted), mean forced vital capacity (FVC) was 104.4±21.3 (% of predicted), and1 mean BMD z-score was 0.1±1.0. BMD was moderately correlated with FEV (r = 0.43, p = 0.03) and FVC (r = 0.57, p = 0.003). Regarding chronological age and age at diagnosis, a moderate and inverse correlation was also found (r = -0.55, p = 0.004; r = -0.57, p = 0.003, respectively). However, no significant correlations were found with the data from CFQ, 6MWT, and body mass index., Conclusion: Most patients had BMD within normal limits and presented a positive correlation with pulmonary function, as well as a negative correlation with chronological age and age at diagnosis., (Copyright © 2013 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.)

Aim: To generate reference values for respiratory muscle strength in healthy children aged three to twelve years., Methods: Participants were recruited from three schools and selected after a respiratory disease questionnaire analysis and written informed consent by parents or guardians. All participants included in the study had normal spirometry, height and weight were measured on the same day. Respiratory muscle strength was evaluated by a single examiner following the guidelines for pulmonary function tests. The association between MIP and MEP values with the potential predictive variables was analyzed using a multiple linear regression model., Results: A total of 171 participants were selected and distributed evenly by age. The age, height, weight and forced vital capacity showed moderate to strong correlations with both respiratory pressures. However, the regression model showed that height and weight were the best variables to predict MIP in both sexes, and age and weight to predict MEP. The power of prediction (R²) ranged from 46 to 58%. The intraclass correlation coefficient was used in a subgroup and demonstrated excellent reproducibility between tests., Conclusion: The results of this study demonstrate that the behavior of respiratory muscle strength in healthy preschool and school children can be explained by age, height and weight., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

The aim of this study was to test the hypothesis that the renin-angiotensin system (RAS) components, as well as the oxidative stress system, would respond to early environmental changes. Thus, we have evaluated the effects of neonatal handling on both brain and kidney RAS and oxidative stress. Pups were divided into two groups: nonhandled and handled. The procedure consisted of handling them for 1 min/day in the first 10 days of life. On days 1, 5, and 10, animals were killed by decapitation. Blood samples were collected and the brain and kidneys were removed. Renin, AT(1), and AT(2) mRNA expression were evaluated through RT-PCR. Angiotensin II (ANG II) serum concentration was also measured. An increased ANG II concentration, brain and kidney AT(2) mRNA expression were demonstrated. The kidney mRNA AT(1) expression was decreased. There was also a kidney lipid peroxidation increase and a brain superoxide dismutase and catalase decrease. In conclusion, handling in the neonatal period induces the activation of the angiotensinergic system, as well as modulates its mRNA receptor expression. The oxidative stress balance system seems not to be involved., (Copyright © 2011 Wiley Periodicals, Inc.)

Unlabelled: The ventilatory mechanic changes that occur in cystic fibrosis (CF) patients may lead to alterations in the respiratory muscle strength levels. However, the findings regarding the strength profile in these patients are still contradictory., Objective: To evaluate, trough a literature review, the respiratory muscle strength behavior in CF patients. We have performed a search in Medline/Pubmed, Scielo, IBECS and LILACS databases selecting observational cross-sectional, prospective or retrospective studies, as well as randomized clinical trials, published between 1981 and 2011, using the following terms: cystic fibrosis, respiratory muscle strength, inspiratory maximal pressure and muscle training. The majority of the studies 71.24% have shown normal or above normal respiratory muscle strength, whilst 28.57% demonstrated reduced or near-normal values. Most of these findings were attributed to an increased work of breathing as a result of airway obstruction and chronic persistent cough. Taken together, the analyses of selected studies have showed conflicting findings regarding respiratory muscle strength behavior in these patients. However, most of the studies seem to indicate that CF patients presented maximum respiratory pressures normal or above predicted values.

Objective: To measure airway resistance with the interrupter resistance (Rint) technique in patients with cystic fibrosis (CF) and to determine whether Rint values correlate with spirometric parameters, as well as to evaluate the accuracy of the Rint technique in determining the airway response to a bronchodilator., Methods: This was a cross-sectional study involving 38 children and adolescents with CF followed at the Cystic Fibrosis Outpatient Clinic of the São Lucas Hospital, located in the city of Porto Alegre, Brazil. After Rint had been measured, the subjects underwent spirometry. To evaluate bronchodilator response, we repeated the measurements after the use of inhaled albuterol., Results: There was a strong correlation between inverse Rint and FEV1 (r = 0.8; p < 0.001), and there was a moderate correlation between inverse Rint and FEF25-75% (r = 0.74; p < 0.001), as well as between inverse Rint and body mass index (r = 0.62; p < 0.001). We used a ROC curve to compare the bronchodilator response, as determined by Rint, with spirometric values. For a Rint cut-off point of -28%, the area under the curve was 0.75, with a sensitivity of 66% and a specificity of 82%., Conclusions: Our findings suggest that Rint correlates well with spirometric parameters, although the Rint technique was not sufficiently accurate to replace spirometry in the evaluation of bronchodilator responses.

Sepsis is a syndrome caused by uncontrolled systemic inflammatory response of the individual, which represents a serious epidemiological problem worldwide. The aim of this study was to investigate the effect of N-acetylcysteine (NAC) and fructose-1,6-bisphosphate (FBP) in the treatment of experimental sepsis. We used rats that were divided into five experimental groups: normal control (not induced), septic control (induced using a capsule with non sterile fecal content and Escherichia coli), treated with FBP (500 mg/kg i.p.), treated with NAC (150 mg/kg i.p.), and treated with the combination of FBP with NAC. In the group treated with NAC, 16.68% of the mice survived, the FBP reduced the mortality of mice during the acute stage of the disease and increased the animals' survival time in 33.34%, and the combination of drugs had no effect. Our results show that NAC prevented the mortality of animals after septic induction. These data confirm the validity of the use of NAC in the treatment of sepsis. Our data also show that the synergistic action with FBP does not improve the picture.

We recently reported that male, but not female, offspring born to mothers exposed to social stress during late gestation show heightened anxiety-type behaviour in adulthood. The amygdala organises anxious behaviour, which involves actions of corticotropin-releasing hormone (CRH). CRH gene expression and/or its release are increased in the amygdala in prenatally stressed (PNS) rats. CRH type 1 receptor (CRH-R1) mediates actions of CRH and urocortin I to promote anxiety-like behaviour, whereas the CRH type 2 receptor (CRH-R2) may mediate anxiolytic actions, through actions of urocortins 2 and 3. Here, using quantitative in situ hybridisation, we investigated whether altered CRH receptor mRNA expression in the amygdaloid nuclei may explain the sex differences in anxiety behaviour in adult male and female PNS rats. CRH-R1 mRNA expression was significantly greater in the central amygdala and basolateral amygdala (BLA) in male PNS rats compared with controls, with no change in the basomedial amygdala (BMA) or medial amygdala (MeA). In PNS females, CRH-R1 mRNA expression was greater than controls only in the MeA. Conversely, CRH-R2 mRNA expression was significantly lower in the BMA of male PNS rats compared with controls, but greater in female PNS rats, with no change in the BLA or MeA in either sex. The ratio of CRH-R1:CRH-R2 mRNA in the amygdaloid nuclei was generally increased in PNS males, but not in the PNS females. In conclusion, sex differences in anxiety-type behaviour in PNS rats may be explained by differential mRNA expression for CRH-R1 (pro-anxiogenic) and CRH-R2 (pro-anxiolytic) in the amygdaloid complex.

RDV-8 [C(18)H(22)N(2)O(2)S (ethyl 1-butyl-6-methyl-2-phenyl-4-thioxo-1,4-dihydropyrimidine-5-carboxylate)] is derived from the 4-thioxopyrimidine, and presents important clinical effects. The present study explored the RDV-8 effects in the proliferation of human peripheral blood mononuclear cells (PBMCs), as well as in a pleurisy-induced rat model. PBMCs were directly plated in four different RDV-8 concentrations (0.0125, 0.025, 0.05 and 0.1 mg/mL). RDV-8 decreased cell proliferation and monocyte chemotactic protein 1 synthesis. The interleukin 1 levels and the cytotoxic effect were not significantly affected by RDV-8 treatment. In the carrageenan-induced pleurisy model, the RDV-8 (3 mg/kg) treatment induced a significant reduction in the exudate volume, in the polymorphonuclear leukocyte migration and in the pleural exudate NO levels. The results indicate that RDV-8 may have an immunomodulatory effect, as well as anti-inflammatory actions suggesting that it could represent a new strategy in the inflammatory response modulation.

Acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS) are common syndromes that affect both clinical and surgical patients. This study describes the effects of a potent and specific N-methyl-d-aspartate receptor antagonist (MK-801) against oxidative stress in acute lung injury induced by intratracheal lipopolysaccharide (LPS) injection. This study was performed using male Wistar rats weighing 200-250g. Rats were randomly divided into four groups: control with isotonic saline instillation (n=6); LPS (100μg/100g of body weight) treated with saline (n=6); LPS treated with MK-801 (0.3mg/kg, intraperitoneally; n=6); LPS treated with MK-801 (0.3mg/kg, intratracheally; n=6). Twelve hours after the LPS instillation, rats were anesthetized and a bronchoalveolar lavage (BAL) was performed in order to determine the alveolar-capillary membrane alterations and the inflammatory infiltrate level. Blood and lung samples were isolated and assayed for oxidative stress variables and histopathologic analysis. The use of MK-801 decreased bronchoalveolar lavage fluid protein, LDH activity and inflammatory cells. Indeed, the treatment with MK-801 significantly attenuated lung oxidative damage and histopathologic alterations after LPS instillation. Our data provide the first experimental demonstration that MK-801 decreases oxidative stress and limits inflammatory response and alveolar disarray in lipopolysaccharide-induced acute lung injury., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Cisplatin is one of the most active cytotoxic agents in the treatment of cancer, but its clinical use is frequently limited by nephrotoxicity. The study presented here attempted to evaluate the effect of fructose-1,6-bisphosphate in the cisplatin-induced nephrotoxicity in rats. The drugs were administered intraperitoneally as a single dose: sodium chloride 0.9%, cisplatin (6 mg/kg), fructose-1,6-bisphosphate (500 mg/kg), and cisplatin plus fructose-1,6-bisphosphate (6 and 500 mg/kg, respectively). The use of cisplatin resulted in significant elevation of serum creatinine and urea. The group that received cisplatin plus fructose-1,6-bisphosphate presented a significantly lower level of creatinine and urea compared to the cisplatin group. Acute tubular necrosis was demonstrated in the animals that received cisplatin and a less severe one in the cisplatin plus fructose-1,6-bisphosphate group. Fructose-1,6-bisphosphate has a protective effect over renal function and renal parenchyma in a rat experimental model of cisplatin-induced nephrotoxicity. The anti-inflammatory effect of fructose-1,6-bisphosphate confirms its protective effect in cases of cellular injury.

Objective: To evaluate the accuracy of the modified Borg scale to estimate lung impairment, measured via FEV(1) in children and adolescents with cystic fibrosis., Methods: This cross-sectional prospective study was conducted with cystic fibrosis patients, 6-18 y old. With the modified Borg scale we evaluated their subjective perceptions of dyspnea before and after submaximal exercises, and its correlation with lung function (spirometry), 6-min walk test (6MWT), and nutritional status according to body mass index., Results: Forty-one patients (mean +/- SD age range 11.1 +/- 4.1 y), were included in the study. The median (and interquartile range) modified Borg scale score after 6MWT was 2 (1-3). The mean percent-of-predicted FEV(1) (FEV(1)%) was 97 +/- 32%. The Z score of the 6MWT distance (6MWTZ) for 61% of the patients was < or = -2. The modified Borg scale correlated weakly with the other variables when all patients in the sample were analyzed. There was a significantly greater correlation of the Borg-scale score with FEV(1)% (r = -0.59, P = .003) and with 6MWTZ (r = 0.46, P = .03) when patients older than 9 years were evaluated separately. The receiver operating characteristic curve analysis revealed that a modified-Borg-scale cut-off point of 2.5 generated an area of 0.80, a sensitivity of 80%, a specificity of 77%, and an accuracy of 0.78 to predict FEV(1)% lower than 80% in the group of patients older than 9 years., Conclusions: The modified Borg scale is accurate to assess the subjective perception of dyspnea of children older than 9 years and adolescents with cystic fibrosis.

Objective: To establish reference values for the 6-min walk test in healthy children and adolescents aged 6-12 years., Methods: This cross-sectional, prospective study selected healthy children and adolescents aged 6-12 years, at three elementary schools in Porto Alegre. The anthropometric data of all the individuals were evaluated and two 6-min walk tests were performed. Based on this, a reference equation was generated, and the test reproducibility was evaluated., Results: One hundred eighty-eight children (92 boys) performed the test. Pearson correlation showed that age (r = 0.51), height (r = 0.49), difference in heart rate before and after the test (dif. HR) (r = 0.30), and weight (r = 0.29) were significantly correlated with the distance covered in 6 min. The best multiple regression model included these four variables resulting in the following equation: 145.343 + [11.78 x age (years)] + [292.22 x height (m)] + [0.611 x dif. HR (bpm)] - [2.684 x body weight (kg)]. The intraclass correlation coefficient confirmed the reproducibility among tests., Conclusion: The reference equation for the 6-min walk test was generated and the distance covered is influenced by age, height, difference in heart rate before and after the test, and body weight.

Background: Positive-expiratory-pressure (PEP) therapy uses positive airway pressure generated by a either a fixed-orifice resistor or a threshold resistor. We hypothesized that tubing diameter and length, and the diameter of the PEP bottle's air-escape orifice would impact the PEP pressure delivered to the airway and determine whether the PEP bottle acts as a threshold resistor or a fixed-orifice resistor., Methods: We designed a model composed of a bottle partially filled with water, a compressed air source, a pneumotachometer, and a manometer, to evaluate the effects of various tubing diameters (range 2-25 mm inner diameter) and lengths (range 20-80 cm long). In the first set of experiments, the PEP bottle had an open top, so there was no pressure other than the atmospheric pressure against the air escaping from the immersed tubing. The distal tip of the tube was 10 cm below the surface of the water (ie, a water-column pressure of 10 cm H(2)O), and we tested flows of 1, 5, 10, 15, 20, and 25 L/min. In the second set of experiments we tested a PEP bottle, the top of which was closed except for an air-escape orifice (4, 6, 8, 9, or 10 mm)., Results: With tubing of 2-6 mm inner diameter, the length of the tubing and the flow significantly affected the PEP pressure (ie, the system was not a threshold resistor). With tubing > or = 8 mm inner diameter there were no significant PEP-pressure differences with any of the tubing lengths or flows tested, which indicates a threshold-resistor system. The 4-mm and 6-mm air-escape orifices significantly increased the PEP pressure, whereas the 8 mm air-escape orifice did not increase the PEP pressure., Conclusions: To obtain a threshold-resistor PEP bottle system (ie, the PEP pressure is generated only by the water-column pressure), the tubing must be > or = 8 mm inner diameter, and the air-escape orifice must be > or = 8 mm.

Background/aims: To evaluate the effects of neonatal handling on hydroelectrolytic balance in adult rats., Methods: The litters were divided into two groups: nonhandled and handled. The procedure consisted of handling the pups for 1 min/day in the first 10 days postnatally. When adults, animals had their body weight verified and were housed in individual metabolic cages. After a 24-hour period, urine samples were collected and the urinary and water intake volumes measured. Blood samples to determine osmolality, aldosterone, corticosterone, angiotensin II, creatinine, urea, sodium and potassium levels were collected. The kidneys were removed for histological assessment. Urinary osmolality, sodium, urea and creatinine were also measured and the creatinine clearance (CC) calculated., Results: No difference between groups was found in the body weight. Handled animals showed a reduction in the total kidney wet weight, water intake, urinary volume, CC, plasma angiotensin II, corticosterone and aldosterone when compared to the nonhandled and an increase in the urinary osmolality and sodium excretion fraction. No differences in serum potassium and no evidence of structural changes were demonstrated by histological analysis., Conclusion: Neonatal handling induced long-lasting effects decreasing renal function without evidence of kidney structural changes., ((c) 2009 S. Karger AG, Basel.)

Physical or emotional stress can affect the female reproductive physiology and angiotensin II (Ang II) is a hormone that participates in the stress response and also in the control of reproductive hormones. The present study aimed at evaluating the effects of acute stress in the morning and afternoon of proestrus on sexual behavior and ovulation and the participation of Ang II in the stress-induced effects. Female rats with regular estrous cycles were used. Several different stress protocols were tested in the morning and in the afternoon of proestrus: restraint stress 10 min; restraint stress 1 h and ether stress, respectively. The participation of Ang II was evaluated by injecting Ang II receptor antagonists (losartan and PD123319) 15 min before stress. The lordosis quotient was recorded and the number of oocytes was counted. Plasma levels of luteinizing hormone, progesterone, prolactin and corticosterone were measured. All types of stress in the morning of proestrus induced a reduction in the number of oocytes. Restraint stress (1 h) in the afternoon of proestrus induced a significant reduction in the lordosis quotient. Peripheral and central losartan, but not PD123319, injections partly reverted the effects of stress on ovulation in the morning of proestrus. Acute stress in the morning of proestrus also reduced luteinizing hormone, progesterone and prolactin surges later on the same day. In conclusion, acute stress on the day of proestrus can affect female reproductive physiology. Moreover, the angiotensinergic system, through AT(1) receptors, participates in the effects of acute stress in the morning of proestrus.

Neonatal handling affects the hypothalamus-pituitary-gonadal axis in female rats. Indeed, postnatal handling induces anovulatory estrous cycles and decreases sexual receptiveness. On the other hand, Angiotensin II (Ang II) infused into the medial amygdala (MeA) reduces sexual behavior in male and female rats. Considering this, and that gonadal steroid secretion after copulatory behavior is important for reproductive success, the purpose of the present study was to investigate whether the reduction in sexual receptiveness in neonatally handled female rats is mediated by changes in Ang II receptor density in MeA. Moreover, gonadal steroid secretion after sexual behavior was analyzed. Two groups of female Wistar rats were studied: nonhandled (pups were left undisturbed) and handled (pups were handled for 1 min once a day during the first 10 days of life). Once they were 80-85 days old in the evening of the proestrus day, sexual receptiveness was recorded and after that the animals were killed by decapitation. Trunk blood samples were collected, and plasma estradiol and progesterone were measured by radioimmunoassay. The brains were removed for Ang II receptor autoradiography in MeA. The decreased lordosis quotient in the neonatally handled group was confirmed in the present study. Neonatal handling also reduced the progesterone concentration in the plasma, but did not change the estradiol and the density of Ang II receptors in MeA. The reduced progesterone could be due to the decreased lordosis frequency of handled females. However, this decreased sexual receptiveness is not mediated by changes in Ang II receptors in MeA.

The expression of angiotensin II (Ang II) receptors in the brain is modulated by estradiol and progesterone. Considering that Ang II plays a critical role in controlling prolactin secretion and that neurons in the arcuate nucleus (ARC) are the main regulator of this function, the present study aimed to evaluate ARC Ang II receptor binding in 2 experimental models with different estradiol and progesterone plasma levels. Animals were divided into 4 groups: ovariectomy (OVX) plus oil vehicle, OVX plus estradiol and progesterone replacement, lactating rats on day 7 postpartum, and lactating rats on day 20. Animals were killed by decapitation, and the brains were removed. Ang II receptors were quantified by autoradiography in ARC. Trunk blood samples were collected, and plasma estradiol and progesterone were measured by radioimmunoassay. Treatment of OVX rats with estradiol and progesterone increased Ang II receptor binding when compared to OVX vehicle-treated animals. Plasma estradiol (r = +0.77) and progesterone (r = +0.87) were highly correlated with Ang II receptors in ovariectomized animals. Lactating rats (day 20) showed a significant decrease in Ang II receptor binding and plasma progesterone when compared to lactating rats (day 7), however, no difference was seen in plasma estradiol. Plasma levels of progesterone (r = +0.81), but not estradiol (r = +0.32), were highly correlated with Ang II receptors in lactating rats. In conclusion, present results show that ARC Ang II receptors decreases on day 20 of lactation compared to day 7 and are highly correlated with plasma progesterone, indicating a pivotal role for progesterone in this regulation.

Neonatal handling alters the hypothalamic-pituitary-adrenal (HPA) axis and the hypothalamic-pituitary-gonads axis (HPG) in adult animals, and angiotensin II (Ang II) modulates the functions in these axes. We tested whether neonatal handling could change the density of Ang II receptors in some central areas in female rats. Results showed decreased density of the Ang II receptors in the medial preoptic area (MPOA) and hypothalamic paraventricular nucleus (PVN) of the neonatal handled group.

Angiotensin II (Ang II) receptors in specific brain areas and in the anterior pituitary are controlled by reproductive hormones. Since Ang II also plays a role in controlling reproductive functions, such as luteinizing hormone and prolactin secretion, the objective of the present study was to evaluate the regulation of Ang II receptors by estradiol (E(2)) and progesterone (P) in areas of the brain involved in homeostatic and reproductive functions, such as the locus coeruleus (LC), median preoptic nucleus (MnPO) and subfornical organ (SFO). Adult female rats were ovariectomized under anesthesia and divided into 2 groups after 2 weeks: OVX plus E(2)/P replacement (OVXE(2)P) and OVX plus oil vehicle (OVX). E(2) was injected for 3 consecutive days followed by an injection of P on the 4th day. Animals were killed by decapitation and the brains were removed and frozen. Consecutive coronal brain sections were cut in a cryostat and Ang II receptors were quantified by autoradiography in the MnPO, LC and SFO. Treatment of OVX rats with E(2) and P induced a significant increase in the Ang II receptor binding (fmol/mg protein) in the MnPO (OVX: 4.48 +/- 0.58 and OVXE(2)P: 9.89 +/- 1.65), LC (OVX: 2.72 +/- 0.37 and OVXE(2)P: 8.03 +/- 0.9) and SFO (OVX: 5.45 +/- 0.66 and OVXE(2)P: 10.73 +/- 1.79) compared to OVX animals treated with the vehicle, P < 0.05. In conclusion, these results show that Ang II receptors are upregulated by E(2) and P in the LC, MnPO and SFO of ovariectomized rats.

Angiotensin II (Ang II) is a peptide that exerts an inhibitory effect upon pituitary prolactin (PRL) release through the hypothalamic arcuate nucleus (ARC). Since both PRL and Ang II are known to be affected by stress, the experiments reported here were conducted to investigate the possible participation of Ang II in the stress-induced response of PRL in situations in which pre-stress PRL levels are high, as during the PRL surge induced by estradiol (E(2)) and progesterone (P) in ovariectomized rats (OVXE(2)P) and lactating females on day 7 post-partum. Adult female rats were stereotactically implanted with bilateral guide-cannulae in the ARC; 3 days later, they were microinjected with saline or losartan and, after a 15-min interval, they were submitted to stress by ether inhalation during 1 min. Five minutes after stress, trunk blood samples were collected. Plasma PRL was measured by radioimmunoassay (RIA). In OVXE(2)P and lactating rats, a significant reduction in PRL levels was detected after stress compared to non-stressed animals. The microinjection of losartan in the ARC before stress blocked the reduction of PRL in both OVXE(2)P and lactating females. In conclusion, the stress-induced reduction of plasma PRL in OVXE(2)P and lactating rats is mediated by Ang II through AT(1) receptors in the ARC.