Practical advancement of multipollutant scientific and risk assessment approaches for ambient air pollution

Objectives: The U.S. Environmental Protection Agency is working toward gaining a better understanding of the human health impacts of exposure to complex air pollutant mixtures and the key features that drive the toxicity of these mixtures, which can then be used for future scientific and risk assessments.Data sources: A public workshop was held in Chapel Hill, North Carolina, 22-24 February 2011, to discuss scientific issues and data gaps related to adopting multipollutant science and risk assessment approaches, with a particular focus on the criteria air pollutants. Expert panelists in the fields of epidemiology, toxicology, and atmospheric and exposure sciences led open discussions to encourage workshop participants to think broadly about available and emerging scientific evidence related to multipollutant approaches to evaluating the health effects of air pollution.Synthesis: Although there is clearly a need for novel research and analytical approaches to better characterize the health effects of multipollutant exposures, much progress can be made by using existing scientific information and statistical methods to evaluate the effects of single pollutants in a multipollutant context. This work will have a direct impact on the development of a multipollutant science assessment and a conceptual framework for conducting multipollutant risk assessments.Conclusions: Transitioning to a multipollutant paradigm can be aided through the adoption of a framework for multipollutant science and risk assessment that encompasses well-studied and ubiquitous air pollutants. Successfully advancing methods for conducting these assessments will require collaborative and parallel efforts between the scientific and environmental regulatory and policy communities.     

Cardiac and skeletal muscle energy metabolism in heart failure: beneficial effects of voluntary activity

OBJECTIVE: Mitochondrial function and metabolic profile of slow and fast skeletal muscles and cardiac muscle are altered in chronic heart failure (CHF), suggesting a generalized metabolic myopathy in this disease. The aim of this study was to investigate the potential beneficial effects of voluntary activity on cardiac and skeletal muscle energetics in heart failure. METHODS: Heart failure was induced in rats by aortic stenosis. Four months after surgery, part of sham and CHF animals were randomly assigned to activity cages equipped with running wheels for 8 weeks or kept sedentary. Mitochondrial capacity and regulation were measured using saponin skinned fibers in left ventricle, slow and fast skeletal muscles, and metabolic and myosin profiles were established. RESULTS: Despite four times lower performances of CHF rats, alterations in metabolic and myosin parameters (oxidative capacity, mitochondrial enzymes, cytosolic and mitochondrial creatine kinase, myosin heavy chains) observed in all muscles of CHF animals were almost fully restored in soleus muscle though unchanged in heart and fast skeletal muscles. CONCLUSIONS: These results show the powerful beneficial effect of physical activity specifically on active slow oxidative skeletal muscle in CHF, without the worsening of cardiac muscle metabolism.     

Transgenic control of mitochondrial fission induces mitochondrial uncoupling and relieves diabetic oxidative stress

Mitochondria are the essential eukaryotic organelles that produce most cellular energy. The energy production and supply by mitochondria appear closely associated with the continuous shape change of mitochondria mediated by fission and fusion, as evidenced not only by the hereditary diseases caused by mutations in fission/fusion genes but also by aberrant mitochondrial morphologies associated with numerous pathologic insults. However, how morphological change of mitochondria is linked to their energy-producing activity is poorly understood. In this study, we found that perturbation of mitochondrial fission induces a unique mitochondrial uncoupling phenomenon through a large-scale fluctuation of a mitochondrial inner membrane potential. Furthermore, by genetically controlling mitochondrial fission and thereby inducing mild proton leak in mice, we were able to relieve these mice from oxidative stress in a hyperglycemic model. These findings provide mechanistic insight into how mitochondrial fission participates in regulating mitochondrial activity. In addition, these results suggest a potential application of mitochondrial fission to control mitochondrial reactive oxygen species production and oxidative stress in many human diseases.     

Diabetes management issues for patients with chronic kidney disease

Chronic kidney disease is in continuous increase and can be found in up to 23% of patients with diabetes. Glycemic control is difficult to assess and medication therapy for diabetes may require dose adjustments part of the alteration of drug's pharmacokinetics and the insulin resistance which is predicting cardiovascular events. The recommended hemoglobin A1c goal is also lower than 7.0% without hypoglycemia. In this article, we review the therapeutic management of diabetic patients in chronic renal failure stage which is difficult and the ways to control blood glucose. Multidisciplinary approach, which is including management of comorbid diseases, is necessary to provide the optimal care of these patients.     

Preparation and characterization of poly-epsilon-caprolactone nanoparticles containing griseofulvin

Griseofulvin is an antifungal agent with poor solubility and low bioavailability. The aim of this work was to prepare poly-epsilon-caprolactone nanospheres and nanocapsules of griseofulvin by nanoprecipitation and to characterize them. Nanoparticles of griseofulvin were obtained with high encapsulation efficiency. The particle size was about 250-326 nm for nanospheres and 390-400 nm for nanocapsules. The dissolution rate of griseofulvin nanoparticles was higher than that of micronized griseofulvin therefore recourse to nanoencapsulation of griseofulvin should enhance its bioavailability and possibly its efficiency for the treatment of dermatomycosis.     

Sarcoidosis following pegylated interferon therapy: two cases

One side effect of the immunomodulatory effect of interferon is the possible triggering or exacerbation of systemic or cutaneous sarcoidosis. We report two new cases and offer an exhaustive review of the literature. A 39-year-old man with type C chronic active hepatitis developed new respiratory symptoms and pulmonary infiltrates with hilar and mediastinal adenopathy after 7 months of treatment with pegylated interferon. The evolution was favourable after stopping treatment. The second patient developed cutaneous lesions after 6 months of treatment. Resolution occurred after the discontinuation of the treatment. In these two cases ribavirin was stopped before the first signs of sarcoidosis.