Acute cardiovascular effects of inhaled ambient particulate matter: Chemical composition-related oxidative stress, endothelin-1, blood pressure, and ST-segment changes in Wistar rats.

Short-term increases in particulate matter (PM) are associated with heightened morbidity and mortality from cardiovascular causes. Inhalation of PM is known to increase endothelin (ET)-1 levels. Yet, less is known about particle composition-related changes at the molecular level including the endothelinergic system and relationship with cardiovascular function changes.

The deubiquitinating enzyme USP25 binds tankyrase and regulates trafficking of the facilitative glucose transporter GLUT4 in adipocytes.

Key to whole body glucose homeostasis is the ability of fat and muscle cells to sequester the facilitative glucose transporter GLUT4 in an intracellular compartment from where it can be mobilized in response to insulin. We have previously demonstrated that this process requires ubiquitination of GLUT4 while numerous other studies have identified several molecules that are also required, including the insulin-responsive aminopeptidase IRAP and its binding partner, the scaffolding protein tankyrase. In addition to binding IRAP, Tankyrase has also been shown to bind the deubiquinating enzyme USP25.

Endosomal sorting of GLUT4 and Gap1 is conserved between yeast and insulin-sensitive cells.

The insulin-regulated trafficking of the facilitative glucose transporter GLUT4 in human fat and muscle cells and the nitrogen-regulated trafficking of the general amino acid permease Gap1 in the yeast Saccharomyces cerevisiae share several common features: Both Gap1 and GLUT4 are nutrient transporters that are mobilised to the cell surface from an intracellular store in response to an environmental cue; both are polytopic membrane proteins harbouring amino acid targeting motifs in their C-terminal tails that are required for their regulated trafficking; ubiquitylation of both Gap1 and GLUT4 plays an important role in their regulated trafficking, as do the ubiquitin-binding GGA (Golgi-localised, γ-ear-containing, ARF-binding) adaptor proteins. Here, we find that when expressed heterologously in yeast, human GLUT4 is subject to nitrogen-regulated trafficking in an ubiquitin-dependent manner similar to Gap1. In addition, by expressing a GLUT4/Gap1 chimeric protein in adipocytes we show that the carboxy-tail of Gap1 directs intracellular sequestration and insulin-regulated trafficking in adipocytes.

Inability of legumes to reverse diabetic-induced nephropathy in rats despite improvement in blood glucose and antioxidant status.

Diabetes mellitus has assumed epidemic proportions in most parts of the world, including developing countries, with vascular and renal complications being the major causes of death. Evidence is emerging that legumes play a beneficial role in diabetes and its associated complications. In connection with the above, four groups of alloxan-induced diabetic rats were fed on four different legume-based (Vigna unguiculata ssp.

Reversal of ionoregulatory disruptions in occupational lead exposure by vitamin C.

In order to investigate the toxic effects of lead during occupational exposure to this metal and the antidotal efficacy of ascorbic acid directed against these toxic effects, various artisans in Abeokuta, Nigeria, who have been shown to be occupationally exposed to lead were supplemented daily with 500mg ascorbic acid for 2 weeks. Ca(2+)-Mg(2+)-ATPase activity in erythrocyte membrane, as well as calcium and magnesium concentrations in plasma, erythrocytes, erythrocyte membrane and urine of the artisans were determined before and after ascorbic acid supplementation. The 2-week ascorbic acid administration resulted in the reversal of lead-induced accumulation of calcium and magnesium in the erythrocyte membranes of the artisans.

90-day repeated inhalation exposure of surfactant Protein-C/tumor necrosis factor-alpha, (SP-C/TNF-alpha) transgenic mice to air pollutants.

Tumor necrosis factor (TNF)-alpha, a cytokine present in inflammed lungs, is known to mediate some of the adverse effects of ozone and inhaled particles. The authors evaluated transgenic mice with constitutive pulmonary expression of TNF-alpha under transcriptional regulation of the surfactant protein-C promoter as an animal model of biological susceptibility to air pollutants. To simulate a repeated, episodic exposure to air pollutants, wild-type and TNF mice inhaled air or a mixture of ozone (0.

Soluble and insoluble air particle fractions induce differential production of tumor necrosis factor alpha in rat lung.

Altered cytokine production in the lung follows the deposition of urban air particles. The present study was designed to measure changes in tumor necrosis factoralpha (TNFalpha) and endothelin-1 (ET-1) levels in rat lung after instilling various fractions of the dust EHC-93, while in vitro, alveolar macrophages (AMs) and type 2 epithelial cells were studied to determine relative production of these molecules in response to the same particles. Whole dust and its soluble and leached components were instilled into rat lung and the animals were killed at intervals to 2 weeks; they received tritiated thymidine by intraperitoneal injection 1 hour before death.

Differential production of metalloproteinases after instilling various urban air particle samples to rat lung.

Lung injury and inflammation are associated with exposure to various types of particulate air pollutants. The present study was used to determine whether metalloproteinases (MMPs) are secreted after instilling dust samples into the lung, and to relate levels of specific MMPs to different fractions of the ambient air particle sample EHC-93. Rats received an intratracheal injection of 5 mg dust samples in 0.

Comparative pulmonary toxicity of various soluble metals found in urban particulate dusts.

The potential toxicity of an atmospheric dust sample EHC-93 has been attributed to the soluble fraction and, more specifically, to the zinc component. The concentration of Zn is the highest among the metals present in the soluble EHC-93 fraction. We now determine whether other metal components of this dust could cause similar lung injury if present at the same concentration as Zn (4.

Inhalation toxicology of urban ambient particulate matter: acute cardiovascular effects in rats.

Wistar rats were exposed for 4 hours by nose-only inhalation to clean air, resuspended Ottawa ambient particles (EHC-93*, 48 mg/m3), the water-leached particles (EHC-93L, 49 mg/m3), diesel soot (5 mg/m3), or carbon black (5 mg/m3). Continuous data for physiologic endpoints (heart rate, blood pressure, body temperature, animal's activity) were captured by telemetry before and after exposure. Blood was sampled from jugular cannulas 1 to 3 days before exposure and at 2 and 24 hours after exposure, and by heart puncture on termination at 32 hours (histology group) or 48 hours (telemetry group) after exposure.

KGF and HGF are growth factors for mesothelial cells in pleural lavage fluid after intratracheal asbestos.

Mesothelial cells proliferate soon after asbestos deposition in the lung. The present study investigates whether the known mesothelial cell mitogens keratinocyte growth factor (KGF) and hepatocyte growth factor (HGF) are present in the lung and specifically in the pleural cavity during the phase of mesothelial cell growth. Rats received 1 mg crocidolite asbestos in 0.

Three-year assessment of methicillin-resistant Staphylococcus aureus clones in Latin America from 1996 to 1998.

Four hundred ninety-nine methicillin-resistant Staphylococcus aureus (MRSA) isolates recovered from 1996 to 1998 from 22 hospitals in five countries of Latin America-Argentina, Brazil, Chile, Uruguay and Mexico-were examined for antimicrobial susceptibility and clonal type in order to define the endemic clones in those hospitals. The hybridization of ClaI restriction digests with the mecA- and Tn554-specific DNA probes combined with pulsed-field gel electrophoresis of chromosomal SmaI digests (ClaI-mecA::ClaI-Tn554::PFGE clonal types) documented not only the predominance and persistence of the Brazilian clone (XI::B::B) in Brazil (97%) and Argentina (86%) but also its massive dissemination to Uruguay (100%). Moreover, a close relative of the Brazilian clone (XI::kappa::B) was highly represented in Chile (53%) together with a novel clone (47%) (II::E'::F) resistant to pencillin, oxacillin, ciprofloxacin, chloramphenicol, clindamycin, erythromycin, and gentamicin.

Proliferation of rat pleural mesothelial cells in response to hepatocyte and keratinocyte growth factors.

The proliferative response of cultured pulmonary mesothelial cells (MCs) to epithelial cell mitogens such as keratinocyte growth factor (KGF) and hepatocyte growth factor (HGF) is investigated. A cell line of rat pleural MCs and freshly prepared rat visceral and parietal MCs were studied. Both KGF and HGF stimulated thymidine uptake in the cell line when cultured for 2 d in serum-free conditions; the growth increase was magnified when tumor necrosis factor (TNF)-alpha was also added to the cultures.

Zinc is the toxic factor in the lung response to an atmospheric particulate sample.

The atmospheric dust sample EHC-93 is known to induce lung cell injury and inflammation in which the toxicity has been attributed to a soluble component, possibly metal ions. To determine whether any specific metal is responsible for the pulmonary reactivity, various metal salts, at the concentration of metal present in the soluble fraction of EHC dust, have now been instilled into mouse lung. After 3 days, only a solution containing all metals tested and that of a zinc salt alone induced an increase in inflammatory cells and protein in lung lavage fluid.

Relationship of keratinocyte growth factor and hepatocyte growth factor levels in rat lung lavage fluid to epithelial cell regeneration after bleomycin.

Keratinocyte growth factor (KGF) and hepatocyte growth factor (HGF) are known mitogens for normal alveolar Type 2 cells in vitro and in vivo. We wished to determine whether these two growth factors are involved in lung repair after epithelial cell necrosis by determining the levels of each factor in lung lavage fluid collected serially after bleomycin-induced injury, and how these values relate specifically to proliferation of bronchiolar and alveolar epithelial cells. Rats received an intratracheal injection of 1 unit bleomycin in 0.

Pulmonary toxicity of an atmospheric particulate sample is due to the soluble fraction.

Adverse health effects have been associated with the inhalation of a variety of atmospheric particles. The potential toxicity of a recently collected urban air particulate sample (EHC-93, mean diameter < 1 microm) was assessed after instilling 1 mg to mouse lung. A soluble fraction (15% of total) and an insoluble fraction of the original dust were also instilled at 1 and 0.

Cell injury and interstitial inflammation in rat lung after inhalation of ozone and urban particulates.

Coexposure of the lung to urban dust along with ozone appears to potentiate ozone-induced injury. This conclusion was derived from whole-lung studies involving tissue and lavaged cells, but we now speculate that the injury and inflammatory response at the main site of reactivity, the bronchoalveolar duct region, is underestimated by such whole-lung studies. We exposed rats to ozone at 0.

Acute effects of inhaled urban particles and ozone: lung morphology, macrophage activity, and plasma endothelin-1.

We studied acute responses of rat lungs to inhalation of urban particulate matter and ozone. Exposure to particles (40 mg/m3 for 4 hours; mass median aerodynamic diameter, 4 to 5 microm; Ottawa urban dust, EHC-93), followed by 20 hours in clean air, did not result in acute lung injury. Nevertheless, inhalation of particles resulted in decreased production of nitric oxide (nitrite) and elevated secretion of macrophage inflammatory protein-2 from lung lavage cells.

Collagenase and gelatinase activities in bronchoalveolar lavage fluids during bleomycin-induced lung injury.

Basement membrane degradation can be indicative of tissue injury, but the process may also release matrix-bound cytokines to stimulate cell regeneration. To investigate this process, acute lung injury was induced in rats by intratracheal bleomycin and animals were killed from 3 days to 8 weeks later. The lungs were lavaged with saline to collect bronchoalveolar lavage (BAL) fluid and cell proliferation was assessed by pulse incorporation of tritiated thymidine.

Silica deposition in the lung during epithelial injury potentiates fibrosis and increases particle translocation to lymph nodes.

Increased respiratory disease and daily mortality rates are associated with higher levels of fine particulate air pollutants. We examined the possibility that deposition of particles to previously injured lungs might accentuate pulmonary damage, by investigating how the lung handled silica deposited during a phase of epithelial injury. A low dose of intratracheal (i.

Surfactant versus saline as a vehicle for corticosteroid delivery to the lungs of ventilated rabbits.

Local administration of steroids to the lungs in ventilated newborn infants can minimize the harmful side effects that occur with systemic administration. An efficient system of drug delivery that provides uniform distribution within the lungs is essential for the treatment of bronchopulmonary dysplasia. In this study we compare surfactant with 0.

Acute pulmonary toxicity of urban particulate matter and ozone.

We have investigated the acute lung toxicity of urban particulate matter in interaction with ozone. Rats were exposed for 4 hours to clean air, ozone (0.8 ppm), the urban dust EHC-93 (5 mg/m3 or 50 mg/m3), or ozone in combination with urban dust.

Early mesothelial cell proliferation after asbestos exposure: in vivo and in vitro studies.

There is some evidence that proliferation of pleural mesothelial cells (MC) occurs soon after deposition of asbestos fibers. To study this effect, we instilled a single dose of 0.1 mg crocidolite into the lungs of mice for 1 and 6 weeks and counted labeled nuclei after 3H-thymidine (3HT) injection.

Lung mesothelial cell and fibroblast responses to pleural and alveolar macrophage supernatants and to lavage fluids from crocidolite-exposed rats.

An early phase of proliferation by mesothelial cells and fibroblasts occurs in the lung after asbestos deposition, but the source and identity of the cytokine(s) involved is not clear. In the present study, rats received crocidolite asbestos intratracheally and were killed at 1 and 6 wk later, animals received tritiated thymidine 1 h before death. An increase in inflammatory cells was found in bronchoalveolar and pleural lavage fluids at both times, and after 6 wk the lungs showed fibrosis which was confirmed biochemically.

Enhanced alveolar type II cell growth on a pulmonary extracellular matrix over fibroblasts.

The growth of alveolar type II cells was studied when these cells were maintained for 2 days on a pulmonary endothelium-derived extracellular matrix (ECM) on a filter with or without lung fibroblasts in the lower chambers of culture wells. Type II cell proliferation was enhanced by the ECM compared with other substrates but was significantly higher with fibroblasts beneath. This was determined by thymidine uptake and cell numbers.