Phosphodiesterase Type 5 Inhibitors, Sport and Doping

Phosphodiesterase type 5 inhibitors (PDE5i) (e.g., sildenafil, tadalafil, vardenafil, and avanafil) are drugs commonly used to treat erectile dysfunction, pulmonary arterial hypertension, and benign prostatic hyperplasia. PDE5i are not prohibited by the World Anti-Doping Agency (WADA) but are alleged to be frequently misused by healthy athletes to improve sporting performance. In vitro and in vivo studies have reported various effects of PDE5i on cardiovascular, muscular, metabolic, and neuroendocrine systems and the potential, therefore, to enhance performance of healthy athletes during training and competition. This suggests well-controlled research studies to examine the ergogenic effects of PDE5i on performance during activities that simulate real sporting situations are warranted to determine if PDE5i should be included on the prohibited WADA list. In the meantime, there is concern that some otherwise healthy athletes will continue to misuse PDE5i to gain an unfair competitive advantage over their competitors

Moringa oleifera leaf extract influences oxidative metabolism in C2C12 myotubes through SIRT1-PPARα pathway

Abstract Background Moringa oleifera is an important traditional multipurpose plant, due to the presence of many bioactive compounds. Moringa oleifera leaf extracts (MOLE) have been shown to have many beneficial properties in pathological conditions including diabete. However, the lack of information about its exact molecular mechanism of action might hinder other potential use in different areas such as skeletal muscle physiology. Hypothesis/purpose Skeletal muscle represents about 40-50% of the total mass of a lean individual and is an insulin-sensitive tissue with wide variations in energy requirements. We aimed to test the effects of MOLE on oxidative metabolism and the molecular mechanism involved on myotubes by using C2C12 cell line, a well known model for in vitro skeletal muscle studies. Study design C2C12 myotubes were treated with MOLE at different working solutions for 24 and 48 hours and then culture media and cellular extracts were collected. MOLE was screened for phytochemicals determination. Methods Glucose and free fatty acids consumption along with lactate release were assessed in the culture media. Citrate sinthase, 3-hydroxy acylCoA dehydrogenase, alanine transglutaminase and creatine kinase enzyme activities, as well as the metabolic regulatory SIRT1 and PPARα protein levels were evaluated in cellular extracts. Results MOLE administration induced a dose and time dependent increase in substrates consumption accompanied by an increase in intracellular oxidative metabolism enzymatic activity levels. The extracts were also able to modulate positively the protein expression of SIRT1 and PPARα. Conclusion Altogether, these data indicate that MOLE could represent a valid nutritional support for improving skeletal muscle metabolism: in fact MOLE treatment increased oxidative energy metabolism and possibly favours mitochondrial biogenesis through SIRT1/PPARα pathway. future studies will clarify wether Moringa oleifera leaf extracts consumption may be useful to improve physical performance and metabolic-related skeletal muscle diseases

Explosive type of moderate-resistance training induces functional, cardiovascular, and molecular adaptations in the elderly

Current recommendations aimed at reducing neuromuscular and functional loss in aged muscle have identified muscle power as a key target for intervention trials, although little is known about the biological and cardiovascular systemic response in the elderly. This study investigated the effects of 12 weeks of low-frequency, moderate-intensity, explosive-type resistance training (EMRT) on muscle strength and powerin oldcommunity-dwellingpeople(70–75years), monitoring functional performance linked to daily liv- ing activities (ADL) and cardiovascular response, as well as biomarkers of muscle damage, cardiovascular risk, and cellular stress response. The present study provides the first evidence that EMRT was highly effective in achieving a significant enhancement in muscular strength and power as well as in functional performance without causing any detrimental modification in cardiovascular, inflammatory, and damage parameters. Moreover, trained elderly subjects showed an adaptive response at both systemic and cellular levels by modulation of antioxidant and stress-induced markers such as myeloperoxidase (MPO), heat shock protein 70 (Hsp70) and 27 (Hsp27), and thioredoxin reductase 1 (TrxR1)

Human alpha rhythms during visual delayed choice reaction time tasks: A magnetoencephalography study, Human Brain Mapping 2005;24(3):184–192

The original article to which this Erratum refers was published in the March 2005 issue of Human Brain MappingHuman Brain Mapping (2005) 24(3) 184–192

Architectural Competition for Akama National Forest Park

MencióPostprint (published version

Tadalafil alters energy metabolism in C2C12 skeletal muscle cells

Phosphodiesterases (PDEs) are a family of enzymes that hydrolyze cyclic nucleotides, thereby modulating cell functions. Three highly selective PDE5 inhibitors (PDE5i), sildenafil, vardenafil and tadalafil, have been developed for treatment of erectile dysfunction (ED). Experimental evidence showed that chronic treatment with sildenafil PDE5i in a mouse model of diet-induced obesity and insulin resistance improved insulin action and decreased circulating fatty acid levels. It has recently been shown that healthy athletes use PDE5i as performance enhancers, hence in the present study we investigated whether the long-lasting PDE5i tadalafil influences energy metabolism in C2C12 skeletal muscle cells by evaluating lactate production, glucose consumption, and citrate synthase and 3-OH acyl CoA dehydrogenase activities. Our data demonstrate that tadalafil is able to modulate energy homeostasis in mouse skeletal muscle cells, depending on the treatment length and dose

Acute tadalafil administration increases plasma fatty acids without changes in the inflammatory response in healthy men

Purpose: Tadalafil, the phosphodiesterase type 5 inhibitor (PDE5I), has been shown to reduce visceral adipose tissue in rabbit and to improve lean mass content in non-obese men. In order to clarify this effect in humans, in the present study we determined the impact of an acute oral tadalafil administration on lipolysis by evaluating plasma free fatty acids (FFAs) and glycerol. FFAs are potential modulator of inflammation response that we evaluated through tumor necrosis factor alpha (TNFα), interleukin 6 (IL6), interleukin 8 (IL8) and interleukin 10 (IL10) plasma levels. Moreover, we determined whether the effects of tadalafil would be reflected in variation of plasma levels of cGMP and NO, two important molecules involved in PDE5Is signaling. Methods: Twelve healthy subjects were supplemented with 20 mg of tadalafil or a placebo, in a double-blind, randomized, cross-over design. Blood samples were collected immediately before, and at 2, 6, and 24 hours post ingestion, and assayed for biochemical analysis. Results: A condition effect was noted for FFAs and glycerol, with values higher for tadalafil when compared to the placebo group, at 2 and 6 hours post ingestion. No statistically significant effects were noted for glucose, cGMP, nitrate and nitrite. No inflammatory response was induced by tadalafil. Conclusion: Tadalafil, in human subjects, increases lipolysis as evidenced by a significant increase in circulating FFAs and glycerol, without affecting the plasma cGMP and NO levels; noticeably, the increase in FFAs did not develop an inflammatory response. Further well-controlled studies are warranted to assess the impact of tadalafil administration on weight/fat loss

The largest university in europe, the oldest university in rome

Sapienza carries out outstanding scientific research in most disciplines, achieving impressive results both on a national and international level. It is in every regard a research and teaching university. The Campus, situated in Rome not far from the city centre, is the largest in Europe - a real city within a city. Since its founding, over 700 years ago, Sapienza has contributed to the development of Italian and European science and culture in all fields of knowledge. In the field of Arts and Humanities, Sapienza taught some of the main masters of the twentieth century, such as the poet Giuseppe Ungaretti. The university is considered a true “school” in the field of archaeological excavations. In this regard, it has achieved results of worldwide importance in Syria (with the discovery of the ancient Ebla in 1964), in Turkey, in Libya and on the Palatine Hill in Rome. In 2006, the Nobel Prize winner Dario Fo was awarded the laurea honoris causa by Sapienza, with the famous intellectual visiting the University and lecturing the students on this occasion. In the field of physics, the legacy of the members of the “via Panisperna” group, among them the 1938 Nobel Prize winner Enrico Fermi, as well as Edoardo Amaldi and Emilio Segrè, has been developed to include quantum physics, physics of disordered systems and astrophysics. Medicine, psychology, biology and other sciences have also been substantially developed over the years, especially in terms of studies about the human brain and its functions, as well as seismology and robotics. Sapienza enhances research by offering opportunities to academia on a global scale. Thanks to a special programme for visiting professors, many foreign researchers and lecturers periodically visit our university, greatly contributing to the quality of our education and research programmes.Sapienza carries out outstanding scientific research in most disciplines, achieving impressive results both on a national and international level. It is in every regard a research and teaching university. The Campus, situated in Rome not far from the city centre, is the largest in Europe - a real city within a city. Since its founding, over 700 years ago, Sapienza has contributed to the development of Italian and European science and culture in all fields of knowledge. In the field of Arts and Humanities, Sapienza taught some of the main masters of the twentieth century, such as the poet Giuseppe Ungaretti. The university is considered a true “school” in the field of archaeological excavations. In this regard, it has achieved results of worldwide importance in Syria (with the discovery of the ancient Ebla in 1964), in Turkey, in Libya and on the Palatine Hill in Rome. In 2006, the Nobel Prize winner Dario Fo was awarded the laurea honoris causa by Sapienza, with the famous intellectual visiting the University and lecturing the students on this occasion. In the field of physics, the legacy of the members of the “via Panisperna” group, among them the 1938 Nobel Prize winner Enrico Fermi, as well as Edoardo Amaldi and Emilio Segrè, has been developed to include quantum physics, physics of disordered systems and astrophysics. Medicine, psychology, biology and other sciences have also been substantially developed over the years, especially in terms of studies about the human brain and its functions, as well as seismology and robotics. Sapienza enhances research by offering opportunities to academia on a global scale. Thanks to a special programme for visiting professors, many foreign researchers and lecturers periodically visit our university, greatly contributing to the quality of our education and research programmes