Exercise training in heart failure

Chronic heart failure (CHF) is a common condition with a poor prognosis. It is associated with poor exercise tolerance and debilitating symptoms. These symptoms appear to be associated with pathophysiological changes that occur systemically in the patient with CHF. Exercise training in carefully selected patients has been shown to be safe and to improve exercise capacity. Many of the pathophysiological abnormalities of CHF are improved by training. Some studies have suggested a possible improvement in morbidity and mortality with training. This review analyzes the controlled clinical trials of exercise training in CHF published to date.     

Spatial and temporal expression of histone demethylase,Kdm2a,during murine molar development

The histone demethylase, lysine (K)-specific demethylase 2A (Kdm2a), is highly conserved and expressed ubiquitously. Kdm2a can regulate cell proliferation and osteo/dentinogenic, adipogenic and chondrogenic differentiation of mesenchymal stem cells (MSCs) derived from dental tissue. We used quantitative real-time RT-PCR analysis and immunohistochemistry to detect Kdm2a expression during development of the murine molar at embryonic days E12, E14, E16 and E17 and postnatal days P3 and P14. Immunohistochemistry results showed no positive staining of Kdm2a at E12. At E14, Kdm2a was expressed weakly in the inner enamel epithelium, stellate reticulum cells and dental sac. At E16, Kdm2a was expressed mainly in the inner and outer enamel epithelium, stratum intermedium and dental sac, but weaker staining was found in cervical loop and dental papilla cells adjacent to the basement membrane. At E17, the strongest Kdm2a staining was detected in the ameloblasts and stronger Kdm2a staining also was detected in the stratum intermedium, outer enamel epithelium and dental papilla cells compared to the expression at E16. Postnatally, we found that Kdm2a was localized in secretory and mature ameloblasts and odontoblasts, and dentin was unstained. Real-time RT-PCR showed that Kdm2a mRNA levels in murine germ cells increased from E12 to E14 and from E14 to E16; no significant change occurred at E16, E17 or P3, then the levels decreased at P14 compared to P3. Kdm2a expression may be closely related to cell proliferation, to ameloblast and odontoblast differentiation and to the secretion of extracellular enamel and dentin during murine tooth development.     

Role of nitric oxide and mitochondria in control of firefly flash

In light-producing cells (photocytes) of the firefly light organ,mitochondria are clustered in the cell periphery, positionedbetween the tracheolar air supply and the oxygen-requiring bioluminescentreactants which are sequestered in more centrally-localizedperoxisomes. This relative positioning suggests that mitochondriacould control oxygen availability for the light reaction. Wehypothesized that active cellular respiration would make theinterior regions of the photocytes relatively hypoxic, and thatthe "on" signal for production of bioluminescence might dependon inhibition of mitochondrial oxygen consumption, which wouldallow delivered oxygen to pass through the peripheral mitochondrialzone to reach peroxisomes deep in the cell interior. We publishedrecently that exogenous NO induces bioluminescence in the intactfirefly; that NO mediates octopamine-induced bioluminescencein the dissected lantern, and that nitric oxide synthase isabundant in cells of the tracheolar system of the light organ.Additional experiments showed that nitric oxide gas (NO) inhibitsrespiration in isolated lantern mitochondria. Inhibition isreversed by bright light, and this inhibition is relieved whenthe light is turned off. Altogether, the results support theidea that NO triggers light production by reversible inhibitionof mitochondrial respiration in lantern cells, and probablyin tracheolar cells as well. The data also suggest that thelight of bioluminescence itself relieves NO inhibition thuscontributing to rapid on/off switching. While other mechanismsmay be in play, NO production that is directly related to neuralinput appears to have a key role in the oxygen gating that controlsflash communication signals.     

Mitochondria as targets for detection and treatment of cancer

Mitochondria are dynamic intracellular organelles that play a central role in oxidative metabolism and apoptosis. The recent resurgence of interest in the study of mitochondria has been fuelled in large part by the recognition that genetic and/or metabolic alterations in this organelle are causative or contributing factors in a variety of human diseases including cancer. Several distinct differences between the mitochondria of normal cells and cancer cells have already been observed at the genetic, molecular and biochemical levels. As reviewed in this article, certain of these alterations in mitochondrial structure and function might prove clinically useful either as markers for the early detection of cancer or as unique molecular sites against which novel and selective chemotherapeutic agents might be targeted.