Particulate hexavalent chromium exposure induces DNA double-strand breaks and inhibits homologous recombination repair in rat and human lung tissues.

Lung cancer is an important human health concern because of its high mortality rate, with many cases caused by environmental chemicals other than tobacco. Particulate hexavalent chromium [Cr(VI)] is a well-established human lung carcinogen, but how Cr(VI) induces lung cancer is poorly understood. Chromosome instability, a hallmark of lung cancer, is considered a major driving factor in Cr(VI)-induced lung cancer.

Acute particulate hexavalent chromium exposure induces DNA double-strand breaks and activates homologous recombination repair in rat lung tissue.

Hexavalent chromium [Cr(VI)] is an established human lung carcinogen, but the carcinogenesis mechanism is poorly understood. Chromosome instability, a hallmark of lung cancer, is considered a major driver of Cr(VI)-induced lung cancer. Unrepaired DNA double-strand breaks are the underlying cause, and homologous recombination repair is the primary mechanism preventing Cr(VI)-induced DNA breaks from causing chromosome instability.

Chromium distribution in an oropharyngeal aspiration model for hexavalent chromium in rats.

Hexavalent chromium [Cr(VI)] is a well-known and widespread environmental contaminant associated with a variety of adverse health effects, in particular lung cancer. The primary route of exposure in humans is through inhalation. Particulate forms of Cr(VI) are the most potent but in vivo studies are difficult.

Pulmonary Function Testing in Animals.

Nanoparticles possess a number of useful properties that make them useful for a variety of industrial and commercial applications. The small size of nanoparticles means that they are respirable and can penetrate deep into the lung when inhaled. Because of this, there is interest in assessing possible toxic effects of nanoparticles on the respiratory system.

Inhibition of chlorine-induced airway fibrosis by budesonide.

Chlorine is a chemical threat agent that can be harmful to humans. Acute inhalation of high levels of chlorine results in the death of airway epithelial cells and can lead to persistent adverse effects on respiratory health, including airway remodeling and hyperreactivity. We previously developed a mouse chlorine exposure model in which animals developed inflammation and fibrosis in large airways.

Acute lung injury and persistent small airway disease in a rabbit model of chlorine inhalation.

Chlorine is a pulmonary toxicant to which humans can be exposed through accidents or intentional releases. Acute effects of chlorine inhalation in humans and animal models have been well characterized, but less is known about persistent effects of acute, high-level chlorine exposures. In particular, animal models that reproduce the long-term effects suggested to occur in humans are lacking.

Diabetic Microvascular Disease and Pulmonary Fibrosis: The Contribution of Platelets and Systemic Inflammation.

Diabetes is strongly associated with systemic inflammation and oxidative stress, but its effect on pulmonary vascular disease and lung function has often been disregarded. Several studies identified restrictive lung disease and fibrotic changes in diabetic patients and in animal models of diabetes. While microvascular dysfunction is a well-known complication of diabetes, the mechanisms leading to diabetes-induced lung injury have largely been disregarded.

Role of TRPA1 in acute cardiopulmonary toxicity of inhaled acrolein.

Acrolein is a highly toxic, volatile, unsaturated aldehyde generated during incomplete combustion as in tobacco smoke and indoor fires. Because the transient receptor potential ankyrin 1 (TRPA1) channel mediates tobacco smoke-induced lung injury, we assessed its role in high-level acrolein-induced toxicity in mice. Acrolein (100-275ppm, 10-30min) caused upper airway epithelial sloughing, bradypnea and oral gasping, hypothermia, cardiac depression and mortality.

Persistent effects of chlorine inhalation on respiratory health.

Chlorine gas is a toxic respiratory irritant that is considered a chemical threat agent because of the potential for release in industrial accidents or terrorist attacks. Chlorine inhalation damages the respiratory tract, including the airways and distal lung, and can result in acute lung injury. Some individuals exposed to chlorine experience a full recovery from acute injury, whereas others develop persistent adverse effects, such as respiratory symptoms, inflammation, and lung-function decrements.

Development and assessment of countermeasure formulations for treatment of lung injury induced by chlorine inhalation.

Chlorine is a commonly used, reactive compound to which humans can be exposed via accidental or intentional release resulting in acute lung injury. Formulations of rolipram (a phosphodiesterase inhibitor), triptolide (a natural plant product with anti-inflammatory properties), and budesonide (a corticosteroid), either neat or in conjunction with poly(lactic:glycolic acid) (PLGA), were developed for treatment of chlorine-induced acute lung injury by intramuscular injection. Formulations were produced by spray-drying, which generated generally spherical microparticles that were suitable for intramuscular injection.

Seed germination strategies: an evolutionary trajectory independent of vegetative functional traits.

Seed germination strategies vary dramatically among species but relatively little is known about how germination traits correlate with other elements of plant strategy systems. Understanding drivers of germination strategy is critical to our understanding of the evolutionary biology of plant reproduction.We present a novel assessment of seed germination strategies focussing on Australian alpine species as a case study.

Crystalline silica-induced leukotriene B4-dependent inflammation promotes lung tumour growth.

Chronic exposure to crystalline silica (CS) causes silicosis, an irreversible lung inflammatory disease that may eventually lead to lung cancer. In this study, we demonstrate that in K-ras(LA1) mice, CS exposure markedly enhances the lung tumour burden and genetic deletion of leukotriene B4 receptor-1 (BLT1(-/-)) attenuates this increase. Pulmonary neutrophilic inflammation induced by CS is significantly reduced in BLT1(-/-)K-ras(LA1) mice.

Adaptive plasticity and epigenetic variation in response to warming in an Alpine plant.

Environmentally induced phenotypic plasticity may be a critical component of response to changing environments. We examined local differentiation and adaptive phenotypic plasticity in response to elevated temperature in half-sib lines collected across an elevation gradient for the alpine herb, Wahlenbergia ceracea. Using Amplified Fragment Length Polymorphism (AFLP), we found low but significant genetic differentiation between low- and high-elevation seedlings, and seedlings originating from low elevations grew faster and showed stronger temperature responses (more plasticity) than those from medium and high elevations.

Abnormal epithelial structure and chronic lung inflammation after repair of chlorine-induced airway injury.

Chlorine is a toxic gas used in a variety of industrial processes and is considered a chemical threat agent. High-level chlorine exposure causes acute lung injury, but the long-term effects of acute chlorine exposure are unclear. Here we characterized chronic pulmonary changes following acute chlorine exposure in mice.

Prognosis of hyponatremia in elderly patients with fragility fractures.

Background: Hyponatremia (serum sodium < 135 mmol/L) is the commonest electrolyte imbalance encountered in clinical practice. It is associated with multiple poor clinical outcomes including increased length of hospital stay, institutionalization and mortality. Prevalence of hyponatremia is higher in frail patient groups, and elderly patients with fragility fractures (EPFF) are particularly susceptible.

Bioelectrical impedance analysis is more accurate than clinical examination in determining the volaemic status of elderly patients with fragility fracture and hyponatraemia.

Objectives: Management of hyponatraemia depends crucially on accurate determination of volaemic (hydration) status but this is notoriously challenging to measure in older people. Bioelectrical impedance analysis (BIA) provides a validated means of determining total body water (TBW), but its clinical utility in determining volaemic status in hyponatraemia has never been tested. This study assessed the utility of BIA in the clinical management of hyponatraemia in elderly patients with fragility fractures (EPFF), a group at high risk of hyponatraemia.

Prevalence, incidence and etiology of hyponatremia in elderly patients with fragility fractures.

Introduction: Hyponatremia (serum sodium<135 mMol/L) is the commonest electrolyte imbalance encountered in clinical practice. It is associated with multiple poor clinical outcomes including increased mortality, longer hospital stay, falls and fractures. Prevalence is higher in frail patient groups, and elderly patients with fragility fractures (EPFF) are particularly susceptible.

Effects of reduced winter duration on seed dormancy and germination in six populations of the alpine herb Aciphyllya glacialis (Apiaceae).

The life stages of seed germination and seedling establishment play a vital role in maintaining plant populations and determining range dynamics of species. Thus, it is not surprising that specific germination requirements and dormancy mechanisms have evolved in all major angiosperm clades. In a rapidly changing climate, we face growing pressure to manage, conserve and restore native plant species and communities.

Inhibition of chlorine-induced pulmonary inflammation and edema by mometasone and budesonide.

Chlorine gas is a widely used industrial compound that is highly toxic by inhalation and is considered a chemical threat agent. Inhalation of high levels of chlorine results in acute lung injury characterized by pneumonitis, pulmonary edema, and decrements in lung function. Because inflammatory processes can promote damage in the injured lung, anti-inflammatory therapy may be of potential benefit for treating chemical-induced acute lung injury.

Soil warming increases plant species richness but decreases germination from the alpine soil seed bank.

Global warming is occurring more rapidly above the treeline than at lower elevations and alpine areas are predicted to experience above average warming in the future. Temperature is a primary factor in stimulating seed germination and regulating changes in seed dormancy status. Thus, plant regeneration from seed will be crucial to the persistence, migration and post disturbance recruitment of alpine plants in future climates.

Differential susceptibility of inbred mouse strains to chlorine-induced airway fibrosis.

Chlorine is a reactive gas that is considered a chemical threat agent. Humans who develop acute lung injury from chlorine inhalation typically recover normal lung function; however, a subset can experience chronic airway disease. To examine pathological changes following chlorine-induced lung injury, mice were exposed to a single high dose of chlorine, and repair of the lung was analyzed at multiple times after exposure.

Repair of tracheal epithelium by basal cells after chlorine-induced injury.

Background: Chlorine is a widely used toxic compound that is considered a chemical threat agent. Chlorine inhalation injures airway epithelial cells, leading to pulmonary abnormalities. Efficient repair of injured epithelium is necessary to restore normal lung structure and function.

Inhibition of chlorine-induced lung injury by the type 4 phosphodiesterase inhibitor rolipram.

Chlorine is a highly toxic respiratory irritant that when inhaled causes epithelial cell injury, alveolar-capillary barrier disruption, airway hyperreactivity, inflammation, and pulmonary edema. Chlorine is considered a chemical threat agent, and its release through accidental or intentional means has the potential to result in mass casualties from acute lung injury. The type 4 phosphodiesterase inhibitor rolipram was investigated as a rescue treatment for chlorine-induced lung injury.