Exposure to fine particulate matter in the air alters placental structure and the renin-angiotensin system.

METHODS: Female Wistar rats were exposed to filtered air (F) or to concentrated fine particulate matter (P) for 15 days. After mating, the rats were divided into four groups and again exposed to F or P (FF, FP, PF, PP) beginning on day 6 of pregnancy. At embryonic day 19, the placenta was collected. The placental structure, the protein and gene expression of TGFß1, VEGF-A, and its receptor Flk-1 and RAS were evaluated by indirect ELISA and quantitative real-time PCR. RESULTS: Exposure to P decreased the placental mass, size, and surface area as well as the TGFß1, VEGF-A and Flk-1 content. In the maternal portion of the placenta, angiotensin II (AngII) and its receptors AT1 (AT1R) and AT2 (AT2R) were decreased in the PF and PP groups. In the fetal portion of the placenta, AngII in the FP, PF and PP groups and AT2R in the PF and PP groups were decreased, but AT1R was increased in the FP group. VEGF-A gene expression was lower in the PP group than in the FF group. CONCLUSIONS: Exposure to pollutants before and/or during pregnancy alters some characteristics of the placenta, indicating a possible impairment of trophoblast invasion and placental angiogenesis with possible consequences for the maternal-fetal interaction, such as a limitation of fetal nutrition and growth.

The effects of individually ventilated cages on the respiratory systems of male and female Wistar rats from birth until adulthood.

OBJECTIVE:: To evaluate the respiratory systems of male and female rats maintained in individually ventilated cages (IVCs) from birth until adulthood. METHODS:: Female Wistar rats were housed in individually ventilated cages or conventional cages (CCs) and mated with male Wistar rats. After birth and weaning, the male offspring were separated from the females and kept in cages of the same type until 12 weeks of age. RESULTS:: The level of food consumption was lower in male offspring (IVC=171.7±9; CC=193.1±20) than in female offspring (IVC=100.6±7; CC=123.4±0.4), whereas the water intake was higher in female offspring (IVC=149.8±11; CC=99.2±0) than in male offspring (IVC=302.5±25; CC=249.7±22) at 11 weeks of age when housed in IVCs. The cage temperature was higher in individually ventilated cages than in conventional cages for both male (IVCs=25.9±0.5; CCs=22.95±0.3) and female (IVCs=26.2±0.3; CCs=23.1±0.3) offspring. The respiratory resistance (IVC=68.8±2.8; CC=50.6±3.0) and elastance (IVC=42.0±3.9; CC=32.4±2.0) at 300 µm/kg were higher in the female offspring housed in ventilated cages. The ciliary beat values were lower in both the male (IVCs=13.4±0.2; CC=15±0.4) and female (IVC=13.5±0.4; CC=15.9±0.6) offspring housed in individually ventilated cages than in those housed in conventional cages. The total cell (IVC=117.5±9.7; CC=285.0±22.8), neutrophil (IVC=13.1±4.8; CC=75.6±4.1) and macrophage (IVC=95.2±11.8; CC=170.0±18.8) counts in the bronchoalveolar lavage fluid were lower in the female offspring housed in individually ventilated cages than in those housed in conventional cages. CONCLUSIONS:: The environmental conditions that exist in individually ventilated cages should be considered when interpreting the results of studies involving laboratory animals. In this study, we observed gender dimorphism in both the water consumption and respiratory mechanics of rats kept in ventilated cages.

The effects of individually ventilated cages on the respiratory systems of male and female Wistar rats from birth until adulthood

OBJECTIVE: To evaluate the respiratory systems of male and female rats maintained in individually ventilated cages (IVCs) from birth until adulthood. METHODS: Female Wistar rats were housed in individually ventilated cages or conventional cages (CCs) and mated with male Wistar rats. After birth and weaning, the male offspring were separated from the females and kept in cages of the same type until 12 weeks of age. RESULTS: The level of food consumption was lower in male offspring (IVC=171.7±9; CC=193.1±20) than in female offspring (IVC=100.6±7; CC=123.4±0.4), whereas the water intake was higher in female offspring (IVC=149.8±11; CC=99.2±0) than in male offspring (IVC=302.5±25; CC=249.7±22) at 11 weeks of age when housed in IVCs. The cage temperature was higher in individually ventilated cages than in conventional cages for both male (IVCs=25.9±0.5; CCs=22.95±0.3) and female (IVCs=26.2±0.3; CCs=23.1±0.3) offspring. The respiratory resistance (IVC=68.8±2.8; CC=50.6±3.0) and elastance (IVC=42.0±3.9; CC=32.4±2.0) at 300 µm/kg were higher in the female offspring housed in ventilated cages. The ciliary beat values were lower in both the male (IVCs=13.4±0.2; CC=15±0.4) and female (IVC=13.5±0.4; CC=15.9±0.6) offspring housed in individually ventilated cages than in those housed in conventional cages. The total cell (IVC=117.5±9.7; CC=285.0±22.8), neutrophil (IVC=13.1±4.8; CC=75.6±4.1) and macrophage (IVC=95.2±11.8; CC=170.0±18.8) counts in the bronchoalveolar lavage fluid were lower in the female offspring housed in individually ventilated cages than in those housed in conventional cages. CONCLUSIONS: The environmental conditions that exist in individually ventilated cages should be considered when interpreting the results of studies involving laboratory animals. In this study, we observed gender dimorphism in both the water consumption and respiratory mechanics of rats kept in ventilated cages.

Alterações placentárias em resposta à exposição de ratas Wistar à poluição atmosférica / Placental alterations in response to exposure of Wistar rats to air pollution

Introdução: A exposição à poluição atmosférica durante a gestação provoca alterações nas características da placenta e pode resultar em restrição de crescimento intrauterino. Sabe-se que o transforming growth factor beta 1 (TGFbeta1), o sistema renina-angiotensina uteroplacentário (SRA) e os fatores angiogênicos, tais como vascular endothelial growth factor A (VEGF-A) participam do processo de placentação e regulação do fluxo sanguíneo uteroplacentário. Assim, o objetivo do presente estudo foi investigar o efeito da exposição à poluição do ar sobre a morfologia, função e SRA placentários. Métodos: Ratas Wistar fêmeas foram expostas ao ar filtrado (F) ou ao material particulado 2.5um (P) durante 15 dias. Depois o cruzamento, as ratas foram divididas em 4 grupos e novamente expostas a F ou P (FF, FP, PF, PP). No 19º dia de gestação, as porções maternas e fetais das placentas foram coletadas. Estrutura da placenta, TGFbeta1, VEGF-A e seus receptores e os componentes do SRA foram avaliados. Resultados: A exposição ao material particulado diminuiu massa, tamanho e área de superfície placentária, um indicativo da interação materno-fetal. As concentrações placentárias de TGF beta1, VEGF-A e Flk-1 e os componentes do SRA foram alterados e isso pode indicar um prejuízo na invasão do trofoblasto, angiogênese placentária e troca de nutrientes e gases entre mãe e fetos. Discussão: Os resultados indicam que a exposição a partículas compromete a interação materno-fetal e pode refletir sobre a nutrição e crescimento fetal.

Introduction: Exposure to air pollution during pregnancy causes alterations in placental characteristics and may result in intrauterine growth restriction. It was suggested that transforming growth factor beta 1 (TGFbeta1), the uteroplacental renin-angiotensin system (RAS) and angiogenic factors, such as vascular endothelial growth factor A (VEGF-A) participates of the placentation process and regulation of the uteroplacental blood flow. Thus, the aim of the present study was to investigate the effect of exposure to air pollution on the placental morphology, function and placental RAS. Methods: Female Wistar rats were exposed to filtrated air (F) or to concentrated particulate matter 2.5um (P) for 15 days. After mating, rats were divided in 4 groups and again exposed to F or P (FF, FP, PF, PP). At 19th day of pregnancy, maternal and fetal portions of placenta were collected. Placental structure, TGFbeta1, VEGF-A and its receptors and RAS components were evaluated. Results: Exposure to particulate matter decreased placental mass, size and surface area, an indicative of maternal-fetal interaction. Placental TGFbeta1, RAS components and VEGF-A and receptors Flk-1 concentrations were altered and this may indicate a prejudice in the trophoblast invasion, placental angiogenesis and maternal-fetal nutrients and gases exchange. Discussion: These findings indicate that exposure to particulate matter compromises the maternal-fetal interaction and may reflect on fetal nutrition and growth.

Effects of mycophenolate sodium on mucociliary clearance using a bronchial section and anastomosis rodent model.

OBJECTIVE: To study the effects of mycophenolate sodium on mucociliary clearance. INTRODUCTION: Mycophenolate is one of the most commonly used immunosuppressive drugs in lung transplantation. Although its pharmacokinetic properties are well defined, its side effects on mucociliary clearance have not yet been studied. METHODS: Sixty rats were subjected to left bronchial section and anastomosis. The right bronchus was used as a control. After surgery, the rats were assigned to two groups based on whether they received saline solution (n = 30) or mycophenolate sodium (n = 30). After 7, 15, or 30 days of treatment, 10 animals from each group were sacrificed, and in vitro mucus transportability, in situ mucociliary transport velocity and ciliary beat frequency were measured. RESULTS: The analysis of mucus transportability revealed that neither mycophenolate nor bronchial section altered any transportability related property for up to 30 days of treatment after surgery (p>0.05). With regard to ciliary beat frequency, the operated left bronchi from the mycophenolate group showed a significant decrease on post-surgical day 30 (p = 0.003). In addition, we found a significant reduction in the in situ mucociliary transport velocity in the mycophenolate-treated group (p = 0.0001). DISCUSSION: These data add important information regarding mucociliary clearance dysfunction following mycophenolate therapy and suggest that mycophenolate might contribute to the high incidence of respiratory tract infections in lung transplant patients. Further studies are needed to investigate the combined action of mycophenolate with other immunosuppressive drugs and to establish methods to protect and recover mucociliary clearance, an important airway defense mechanism.

Effects of mycophenolate sodium on mucociliary clearance using a bronchial section and anastomosis rodent model

OBJECTIVE: To study the effects of mycophenolate sodium on mucociliary clearance. INTRODUCTION: Mycophenolate is one of the most commonly used immunosuppressive drugs in lung transplantation. Although its pharmacokinetic properties are well defined, its side effects on mucociliary clearance have not yet been studied. METHODS: Sixty rats were subjected to left bronchial section and anastomosis. The right bronchus was used as a control. After surgery, the rats were assigned to two groups based on whether they received saline solution (n = 30) or mycophenolate sodium (n = 30). After 7, 15, or 30 days of treatment, 10 animals from each group were sacrificed, and in vitro mucus transportability, in situ mucociliary transport velocity and ciliary beat frequency were measured. RESULTS: The analysis of mucus transportability revealed that neither mycophenolate nor bronchial section altered any transportability related property for up to 30 days of treatment after surgery (p>0.05). With regard to ciliary beat frequency, the operated left bronchi from the mycophenolate group showed a significant decrease on post-surgical day 30 (p = 0.003). In addition, we found a significant reduction in the in situ mucociliary transport velocity in the mycophenolate-treated group (p = 0.0001). DISCUSSION: These data add important information regarding mucociliary clearance dysfunction following mycophenolate therapy and suggest that mycophenolate might contribute to the high incidence of respiratory tract infections in lung transplant patients. Further studies are needed to investigate the combined action of mycophenolate with other immunosuppressive drugs and to establish methods to protect and recover mucociliary clearance, an important airway defense mechanism.