Glutathione-S-transferases in lung and sputum specimens, effects of smoking and COPD severity

<p>Abstract</p> <p>Background</p> <p>Oxidative stress plays a potential role in the pathogenesis and progression of chronic obstructive pulmonary disease (COPD). Glutathione S-transferases (GSTs) detoxify toxic compounds in tobacco smoke via glutathione-dependent mechanisms. Little is known about the regulation and expression of GSTs in COPD lung and their presence in airway secretions.</p> <p>Methods</p> <p>GST alpha, pi and mu were investigated by immunohistochemistry in 72 lung tissue specimens and by Western analysis in total lung homogenates and induced sputum supernatants from non-smokers, smokers and patients with variable stages of COPD severity.</p> <p>Results</p> <p>GST alpha was expressed mainly in the airway epithelium. The percentage of GST alpha positive epithelial cells was lower in the central airways of patients with very severe (Stage IV) COPD compared to mild/moderate COPD (p = 0.02). GST alpha by Western analysis was higher in the total lung homogenates in mild/moderate COPD compared to cases of very severe disease (p < 0.001). GST pi was present in airway and alveolar epithelium as well as in alveolar macrophages. GST mu was expressed mainly in the epithelium. Both GST alpha and pi were detectable in sputum supernatants especially in patients with COPD.</p> <p>Conclusion</p> <p>This study indicates the presence of GST alpha and pi especially in the epithelium and sputum supernatants in mild/moderate COPD and low expression of GST alpha in the epithelium in cases of very severe COPD. The presence of GSTs in the airway secretions points to their potential protective role both as intracellular and extracellular mediators in human lung.</p

The 3-methylglutaconic acidurias: what’s new?

The heterogeneous group of 3-methylglutaconic aciduria (3-MGA-uria) syndromes includes several inborn errors of metabolism biochemically characterized by increased urinary excretion of 3-methylglutaconic acid. Five distinct types have been recognized: 3-methylglutaconic aciduria type I is an inborn error of leucine catabolism; the additional four types all affect mitochondrial function through different pathomechanisms. We provide an overview of the expanding clinical spectrum of the 3-MGA-uria types and provide the newest insights into the underlying pathomechanisms. A diagnostic approach to the patient with 3-MGA-uria is presented, and we search for the connection between urinary 3-MGA excretion and mitochondrial dysfunction

A review of zoonotic infection risks associated with the wild meat trade in Malaysia.

The overhunting of wildlife for food and commercial gain presents a major threat to biodiversity in tropical forests and poses health risks to humans from contact with wild animals. Using a recent survey of wildlife offered at wild meat markets in Malaysia as a basis, we review the literature to determine the potential zoonotic infection risks from hunting, butchering and consuming the species offered. We also determine which taxa potentially host the highest number of pathogens and discuss the significant disease risks from traded wildlife, considering how cultural practices influence zoonotic transmission. We identify 51 zoonotic pathogens (16 viruses, 19 bacteria and 16 parasites) potentially hosted by wildlife and describe the human health risks. The Suidae and the Cervidae families potentially host the highest number of pathogens. We conclude that there are substantial gaps in our knowledge of zoonotic pathogens and recommend performing microbial food safety risk assessments to assess the hazards of wild meat consumption. Overall, there may be considerable zoonotic risks to people involved in the hunting, butchering or consumption of wild meat in Southeast Asia, and these should be considered in public health strategies

Alperujo extract, hydroxytyrosol, and 3,4-dihydroxyphenylglycol are bioavailable and have antioxidant properties in vitamin E-deficient rats-a proteomics and network analysis approach

Scope: Olive products are rich in phenolic compounds, which are natural antioxidants in vitro. We tested the in vivo effects of alperujo, an olive production by-product, as well as hydroxytyrosol and 3,4-dihydroxyphenylglycol (DHPG) isolated from alperujo, on indices and pathways of oxidative and metabolic stress in a vitamin E-deficient rat model. Methods and results: Rats were fed a vitamin E-deficient diet for 10 weeks, followed by this diet supplemented with either 100 mg/kg diet dα-tocopherol, alperujo extract, hydroxytyrosol, or 10 mg/kg diet DHPG, for a further 2 weeks. We detected alperujo phenolics in tissues and blood, indicating they are bioavailable. Alperujo extract partially ameliorated elevated plasma levels of thiobarbituric acid reactive substances and also lowered plasma cholesterol levels, whereas hydroxytyrosol increased plasma triglyceride levels. Proteomics and subsequent network analysis revealed that hepatic mitochondrial aldehyde dehydrogenase (ALDH2), of which protein and activity levels were regulated by dα-tocopherol and olive phenolics, represents a novel central regulatory protein hub affected by the dietary interventions. Conclusion: The in vivo free radical scavenging properties of olive phenolics appear relatively modest in our model. But alternative mechanisms, including regulation of ALDH2, may represent relevant antioxidant mechanisms by which dietary olive phenolics could have beneficial impact on cardiovascular health. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim