Thiamine increases resident endoglin positive cardiac progenitor cells and atrial contractile force in humans: A randomised controlled trial.

BACKGROUND: The heart has an intrinsic ability to regenerate, orchestrated by progenitor or stem cells. However, the relative complexity of non-resident cardiac progenitor cell (CPC) therapy makes modulation of resident CPCs a more attractive treatment target. Thiamine analogues improve resident CPC function in pre-clinical models. In this double blinded randomised controlled trial (identifier: ACTRN12614000755639), we examined whether thiamine would improve CPC function in humans. METHODS AND RESULTS: High dose oral thiamine (one gram twice daily) or matching placebo was administered 3-5 days prior to coronary artery bypass surgery (CABG). Right atrial appendages were collected at the time of CABG, and CPCs isolated. There was no difference in the primary outcome (proliferation ability of CPCs) between treatment groups. Older age was not associated with decreased proliferation ability. In exploratory analyses, isolated CPCs in the thiamine group showed an increase in the proportion of CD34-/CD105+ (endoglin) cells, but no difference in CD34-/CD90+ or CD34+ cells. Thiamine increased maximum force developed by isolated trabeculae, with no difference in relaxation time or beta-adrenergic responsiveness. CONCLUSION: Thiamine does not improve proliferation ability of CPC in patients undergoing CABG, but increases the proportion of CD34-/CD105+ cells. Having not met its primary endpoint, this study provides the impetus to re-examine CPC biology prior to any clinical outcome-based trial examining potential beneficial cardiovascular effects of thiamine.

Rating of Perceived Exertion for Quantification of Training and Combat Loads During Combat Sport-Specific Activities: A Short Review.

The aim of this short review was to summarize data pertaining to the rating of perceived exertion (RPE) methods (RPE value and session-RPE) during combat sport-specific activities (i.e., competition and training) based on many factors, including contest type (i.e., official vs. simulated vs. training), combat rounds, age of participants and muscle groups, and their correlation with physiological variables (i.e., blood lactate concentration [La] and heart rate [HR]). The current review shows higher RPE in a match of mixed martial arts (MMAs) than Brazilian jiu-jitsu and kickboxing matches and during the competitive period compared with the precompetitive period. This could be explained by the longer duration of bouts, the higher percentage contribution of aerobic metabolism in MMA than other combat sports and contest type differences (simulated vs. official matches). Thus, this review found significant correlations between RPE or session-RPE, [La] and HR. Particularly, there was a stronger correlation between RPE and [La] during official striking (r = 0.81) than grappling combat sports matches (r = 0.53). In addition, a variation of correlation (moderate to large) between session-RPE and HR-based methods has been reported (i.e., Edwards' training load [r ranged between 0.58 and 0.95] and Banister training impulse [r ranged between 0.52 and 0.86]). Specifically, stronger correlation was apparent in combat sport competition that required a much higher percentage contribution of aerobic metabolism (e.g., karate) and in adult athletes than anaerobic-based combat sports (e.g., taekwondo) and young athletes, respectively. Indeed, the current review highlights that the correlations between session-RPE and HR-based methods were higher during official competition than training sessions. Session-RPE was affected by participants' competitive level, the intensity of session (high vs. low), the training modalities (tactical-technical vs. technical-development vs. simulated competition), and the training volume in combat sports athletes. Rating of perceived exertion is a valid tool for quantifying internal training and combat loads during short- and long-term training and simulated and official competitions in novice and elite combat sport athletes. Furthermore, both RPE methods may be a more reliable measure of intensity or effort when both anaerobic and aerobic systems are appreciably activated. Coaches, sports scientists, and athletes can use session-RPE method to quantify short-term training and combat loads in adult athletes during precompetitive period much more than long-term training and in young athletes during the competitive period. They can also use RPE to monitor combat and short- and long-term training loads to better plan and assist training programs and competitions.

Endogenous hypothalamic somatostatins differentially regulate growth hormone secretion from goldfish pituitary somatotropes in vitro.

Using Southern blot analysis of RT-PCR products, mRNA for three different somatostatin (SS) precursors (PSS-I, -II, and -III), which encode for SS(14), goldfish brain (gb)SS(28), and [Pro(2)]SS(14), respectively, were detected in goldfish hypothalamus. PSS-I and -II mRNA, but not PSS-III mRNA, were also detected in cultured pituitary cells. We subsequently examined the effects of the mature peptides, SS(14), gbSS(28), and [Pro(2)]SS(14), on somatotrope signaling and GH secretion. The gbSS(28) was more potent than either SS(14) or [Pro(2)]SS(14) in reducing basal GH release but was the least effective in reducing basal cellular cAMP. The ability of SS(14), [Pro(2)]SS(14), and gbSS(28) to attenuate GH responses to GnRH were comparable. However, gbSS(28) was less effective than SS(14) and [Pro(2)]SS(14) in diminishing dopamine- and pituitary adenylate cyclase-activating polypeptide-stimulated GH release, as well as GH release resulting from the activation of their underlying signaling cascades. In contrast, the actions of a different 28-amino-acid SS, mammalian SS(28), were more similar to those of SS(14) and [Pro(2)]SS(14). We conclude that, in goldfish, SSs differentially couple to the intracellular cascades regulating GH secretion from pituitary somatotropes. This raises the possibility that such differences may allow for the selective regulation of various aspects of somatotrope function by different SS peptides.