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The use of the herbicide paraquat (1,1'-dimethyl-4,4'-bipyridylium dichloride; PQ) has been fiercely challenged due to its severe acute toxicity, putative neurotoxicity after long-term exposure and lack of antidotes. Breakthrough research on PQ is therefore required for an effective risk control and to allow a safer use of PQ in the future. The silencing or inhibition of quinone oxidoreductase 2, a NAD(P)H-independent flavoenzyme, was shown to significantly attenuate PQ toxicity in vitro, in primary pneumocytes and astroglial U373 cells, and to strongly antagonize PQ-induced systemic toxicity and animal mortality. The novel results reported in this issue of BJP, added to recent findings using sodium salicylate and lysine acetylsalicylate, in which full survival of PQ-intoxicated rats was also achieved, open the door for new preventative and therapeutic strategies that may lead to safer use of this effective pesticide., (© 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.)

The muscle cells, or myofibers, are one of the three multinucleated cell types, along with osteoclasts and cytotrophoblasts. This aspect of skeletal muscle has led to the concept of myonuclear domain, which is defined as the theoretical amount of cytoplasm within a muscle fiber controlled by a single myonucleus. Considering the huge plasticity of skeletal muscle fibers, the myonuclear domain has become one aspect of major interest under situations leading to muscle atrophy (spinal cord isolation and transaction, microgravity, hindlimb suspension and chronic denervation) hypertrophy (synergist ablation and bouts of exercise) and day-to-day wear and tear (age, body size, muscle function and fiber type-related differences). This concept is supported by several studies reporting that changes in muscle fibers' cross-sectional area (CSA) are paralleled by an alteration in the number of myonuclei, maintaining constant the relationship between them. This implies a fairly strict regulation of the myonuclear number that is governed by two opposing mechanisms: the gain of myonuclei by the fusion of muscle stem cells into hypertrophying muscle fibers and the loss of myonuclei by apoptosis/necrosis in atrophying muscle fibers. The aim of this review is to scrutinize the changes in the myonuclear domain in skeletal muscle fibers considering the atrophic and hypertrophic processes, emphasizing the differences between the various methods utilized to achieve these morphological alterations, and the differences between muscle responses according to their phenotype (different function and fiber type composition) and animal age (relevance to sarcopenia). [ABSTRACT FROM AUTHOR]

The article discusses the role of apoptosis programmed cell death in exercise. The author inferred that apoptotis cell death dissents morphologically and biochemically from necrotic cell death although both appear to occur after exercise. It is averred that exercise-induced apoptosis is a normal regulatory process that serves to remove certain damaged cell without a pronounced inflammatory response, hence assuring optimal organism function.

Abstract: Alterations in muscle mitochondrial bioenergetics during cancer cachexia were previously suggested; however, the underlying mechanisms are not known. So, the goal of this study was to evaluate mitochondrial phospholipid remodeling in cancer-related muscle wasting and its repercussions to respiratory chain activity and fiber susceptibility to apoptosis. An animal model of urothelial carcinoma induced by exposition to N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN) and characterized by significant body weight loss due to skeletal muscle mass decrease was used. Morphological evidences of muscle atrophy were associated to decreased respiratory chain activity and increased expression of mitochondrial UCP3, which altogether highlight the lower ability of wasted muscle to produce ATP. Lipidomic analysis of isolated mitochondria revealed a significant decrease of phosphatidic acid, phosphatidylglycerol and cardiolipin in BBN mitochondria, counteracted by increased phosphatidylcholine levels. Besides the impact on membrane fluidity, this phospholipid remodeling seems to justify, at least in part, the lower oxidative phosphorylation activity observed in mitochondria from wasted muscle and their increased susceptibility to apoptosis. Curiously, no evidences of lipid peroxidation were observed but proteins from BBN mitochondria, particularly the metabolic ones, seem more prone to carbonylation with the consequent implications in mitochondria functionality. Overall, data suggest that bladder cancer negatively impacts skeletal muscle activity specifically by affecting mitochondrial phospholipid dynamics and its interaction with proteins, ultimately leading to the dysfunction of this organelle. The regulation of phospholipid biosynthetic pathways might be seen as potential therapeutic targets for the management of cancer-related muscle wasting. [Copyright &y& Elsevier]