Gynostemma Pentaphyllum Increases Exercise Performance and Alters Mitochondrial Respiration and AMPK in Healthy Males.

This research aimed to determine the effects of Gynostemma pentaphyllum (G. pentaphyllum) on exercise performance, AMP-activated protein kinase (AMPK), and mitochondrial signaling in human muscle. This randomized double-blind placebo control crossover study provided placebo or 450 mg of G. pentaphyllum dried leaf extract equivalent to 2.25 g of dry leaf per day for four weeks to 16 healthy untrained young males, separated by four weeks wash-out. Following 4-week supplementation with G. pentaphyllum, participants had significantly lower leptin and blood glucose levels and improved time trial performance over 20 km, which corresponded with a higher muscle oxygen flux compared to placebo. Muscle AMPK Thr172 phosphorylation significantly increased after 60 min exercise following G. pentaphyllum supplementation. AMPK Thr172 phosphorylation levels relative to total AMPK increased earlier following exercise with G. pentaphyllum compared to placebo. Total ACC-α was lower following G. pentaphyllum supplementation compared to placebo. While further research is warranted, G. pentaphyllum supplementation improved exercise performance in healthy untrained males, which corresponded with improved mitochondrial respiration, altered AMPK and ACC, and decreased plasma leptin and glucose levels.

Effect of inorganic nitrate on exercise capacity, mitochondria respiration, and vascular function in heart failure with reduced ejection fraction.

Chronic underperfusion of the skeletal muscle tissues is a contributor to a decrease in exercise capacity in patients with heart failure with reduced ejection fraction (HFrEF). This underperfusion is due, at least in part, to impaired nitric oxide (NO) bioavailability. Oral inorganic nitrate supplementation increases NO bioavailability and may be used to improve exercise capacity, vascular function, and mitochondrial respiration. Sixteen patients with HFrEF (fifteen men, 63 ± 4 yr, body mass index: 31.8 ± 2.1 kg/m2) participated in a randomized, double-blind, crossover design study. Following consumption of either nitrate-rich beetroot juice (16 mmol nitrate/day) or a nitrate-depleted placebo for 5 days, participants completed separate visits for assessment of exercise capacity, endothelial function, and muscle mitochondrial respiration. Participants then had a 2-wk washout before completion of the same protocol with the other intervention. Statistical significance was set a priori at P < 0.05, and between-treatment differences were analyzed via paired t test analysis. Following nitrate supplementation, both plasma nitrate and nitrite increased (933%, P < 0.001 and 94%, P < 0.05, respectively). No differences were observed for peak oxygen consumption (nitrate: 18.5 ± 1.4 mL·kg-1·min-1, placebo: 19.3 ± 1.4 mL·kg-1·min-1; P = 0.13) or time to exhaustion (nitrate: 1,165 ± 92 s, placebo: 1,207 ± 96 s; P = 0.16) following supplementation. There were no differences between interventions for measures of vascular function, mitochondrial respiratory function, or protein expression (all P > 0.05). Inorganic nitrate supplementation did not improve exercise capacity and skeletal muscle mitochondrial respiratory function in HFrEF. Future studies should explore alternative interventions to improve peripheral muscle tissue function in HFrEF.NEW & NOTEWORTHY This is the largest study to date to examine the effects of inorganic nitrate supplementation in patients with heart failure with reduced ejection fraction (HFrEF) and the first to include measures of vascular function and mitochondrial respiration. Although daily supplementation increased plasma nitrite, our data indicate that supplementation with inorganic nitrate as a standalone treatment is ineffective at improving exercise capacity, vascular function, or mitochondrial respiration in patients with HFrEF.

Influence of Perioperative Serum Magnesium for Cardiac and Noncardiac Morbidity and Mortality Following Emergency Peripheral Vascular Surgery.

OBJECTIVES: To examine the influence of serum magnesium on 30-day mortality and cardiac and noncardiac morbidity. DESIGN: Retrospective cross-sectional observational study of routinely collected prospective data. SETTING: Single-center tertiary vascular center in the United Kingdom. PARTICIPANTS: All patients undergoing arterial peripheral vascular surgery during an unplanned admission. INTERVENTIONS: Observational, no interventions implemented. MEASUREMENTS AND MAIN RESULTS: In the study, n = 197. One hundred thirty-eight were male (70.1%). Median age at procedure was 70.0 years (interquartile range 20.0). Of those with a documented history, 37.9% had diabetes, 81.7% had a smoking history, 63.7% had hypertension, and 26.5% had known ischemic heart disease or heart failure. There was a significant perioperative change in magnesium (p < 0.001), calcium (p < 0.001), and creatinine (p = 0.004), with no significant alteration in potassium (p = 0.096). Thirty-day mortality was 4.6%. Thirty-day cardiac morbidity was 4.1%. Thirty-day noncardiac morbidity was 32.3%. Postoperative magnesium was independently predictive for 30-day mortality (p = 0.02, odds ratio [OR] 0.96, 95% confidence interval [CI] 0.94-0.99) and cardiac morbidity (p = 0.03, OR 0.97, 95% CI 0.95-1.00). Only a previous smoking history was independently predictive of noncardiac morbidity (p = 0.03, OR 9.67, 95% CI 1.20-78.15). CONCLUSION: Perioperative changes in serum magnesium may have an influence on short-term mortality and cardiac complications. This should be considered in the management of patients undergoing unplanned peripheral vascular surgery; however, further research is needed to examine the benefit of supplementation perioperatively and to explore the exact mechanisms.

A case of Paget-Schroetter syndrome (PSS) in a young judo tutor: a case report.

BACKGROUND: We present a case of unsuspected Paget-Schroetter syndrome (also called effort thrombosis), one of the rare causes of upper extremity deep vein thrombosis. To the best of our knowledge, this was the first such case in our hospital. Our patient may have been discharged with an incomplete diagnosis and inappropriate management but for one of the few physicians who knew about effort thrombosis, made the diagnosis, and referred the patient promptly to the appropriate team. CASE PRESENTATION: A 37-year-old Caucasian man who was an active judo tutor presented to the acute medical unit in our hospital. He had initially presented to his primary care physician complaining of redness and swelling of his right arm and elbow of 1 week's duration. He had been prescribed some antibiotics by his general practitioner, but his symptoms worsened. At that point, he was referred to our hospital for further review of his arm swelling. CONCLUSIONS: When considering a diagnosis of deep vein thrombosis, the age, hobbies, and occupation, among other things, of individual patients should be put into context at all times to avoid missing rare causes such as Paget-Schroetter syndrome. This report is intended to raise awareness of this rare condition. Knowledge of this condition and its management is essential for all medical practitioners, especially medical doctors who are involved in unselected medical admissions in accident and emergency or medical admission units, where the majority of such patients are seen.

No effect of acute beetroot juice ingestion on oxygen consumption, glucose kinetics, or skeletal muscle metabolism during submaximal exercise in males.

Beetroot juice, which is rich in nitrate (NO3 (-)), has been shown in some studies to decrease oxygen consumption (V̇o2) for a given exercise workload, i.e., increasing efficiency and exercise tolerance. Few studies have examined the effect of beetroot juice or nitrate supplementation on exercise metabolism. Eight healthy recreationally active males participated in three trials involving ingestion of either beetroot juice (Beet; ∼8 mmol NO3 (-)), Placebo (nitrate-depleted Beet), or Beet + mouthwash (Beet+MW), all of which were performed in a randomized single-blind crossover design. Two-and-a-half hours later, participants cycled for 60 min on an ergometer at 65% of V̇o2 peak. [6,6-(2)H]glucose was infused to determine glucose kinetics, blood samples obtained throughout exercise, and skeletal muscle biopsies that were obtained pre- and postexercise. Plasma nitrite [NO2 (-)] increased significantly (∼130%) with Beet, and this was attenuated in MW+Beet. Beet and Beet+MW had no significant effect on oxygen consumption, blood glucose, blood lactate, plasma nonesterified fatty acids, or plasma insulin during exercise. Beet and Beet+MW also had no significant effect on the increase in glucose disposal during exercise. In addition, Beet and Beet+MW had no significant effect on the decrease in muscle glycogen and phosphocreatine and the increase in muscle creatine, lactate, and phosphorylated acetyl CoA carboxylase during exercise. In conclusion, at the dose used, acute ingestion of beetroot juice had little effect on skeletal muscle metabolism during exercise.

Economic evaluation of pharmacological treatments for overactive bladder from the perspective of the UK National Health Service.

OBJECTIVE: To evaluate the costs and outcomes associated with different sequences of oral anti-muscarinic agents and the selective ß(3)-adrenoceptor agonist, mirabegron, for the treatment of overactive bladder (OAB). METHODS: A Markov model with monthly cycle length and time horizon up to 3 years was designed to compare two different sequences of up to three lines of oral therapy for OAB. Patients who discontinued one oral medication could switch to another oral medication or could discontinue treatment. Patients whose symptoms were not controlled were considered for botulinum toxin or sacral nerve stimulation. Outcomes were measured by (a) number of patients with controlled symptoms (no incontinence episodes and <8 micturitions per 24 h); (b) patients with no incontinence episodes per 24 hours; and (c) patients with <8 micturitions per 24 h. RESULTS: Including a third-line oral medication before considering other treatment options improved all patient outcomes, irrespective of the specific drugs used. A three-line sequence including two generic (oxybutynin first line and tolterodine extended-release second line) and one branded drug (solifenacin 5 mg third line) resulted in inferior patient outcomes at costs similar to a sequence of branded drugs (mirabegron first line, solifenacin 5 mg second line, solifenacin 10 mg third line): controlled patients (generic 29.6/1000 vs branded 38.7/1000); patients with no incontinence episodes (103.6/1000 vs 123.7/1000); patients with <8 micturitions (228.7/1000 vs 262.1/1000). Annual treatment costs per patient were similar (generic £1299 vs branded £1385). CONCLUSIONS: In the treatment of OAB, low-cost generic treatments are not necessarily more cost-effective than branded drugs, primarily because a better efficacy and tolerability balance improves both symptom control and persistence.

Skeletal muscle total creatine content and creatine transporter gene expression in vegetarians prior to and following creatine supplementation.

This study examined the effect of vegetarianism on skeletal muscle total creatine (TCr) content and creatine transporter (CreaT) gene expression, prior to and during 5 d of Cr supplementation (CrS). In a double-blind, crossover design, 7 vegetarians (VEG) and nonvegetarians (NVEG) were assigned Cr or placebo supplements for 5 d and after 5 wk, received the alternative treatment. Muscle sampling occurred before, and after 1 and 5 d of treatment ingestion. Basal muscle TCr content was lower (P < 0.05) in VEG compared with NVEG. Muscle TCr increased (P < 0.05) throughout the Cr trial in both groups but was greater (P < 0.05) in VEG compared with NVEG, at days 1 and 5. CreaT gene expression was not different between VEG and NVEG. The results indicate that VEG have a lower muscle TCr content and an increased capacity to load Cr into muscle following CrS. Muscle CreaT gene expression does not appear to be affected by vegetarianism.

Effect of creatine ingestion on glucose tolerance and insulin sensitivity in men.

PURPOSE: This study investigated whether acute (5 d) and/or short-term (28 d) creatine (Cr) ingestion altered glucose tolerance or insulin action in healthy, untrained men (aged 26.9 +/- 5.7 yr; SD). METHODS: Subjects were randomly allocated to either a Cr ( N= 8) or placebo group (N = 9) and were tested in the control condition (presupplementation), and after 5 and a further 28 d of supplementation. The Cr group ingested 20 g and 3 g.d (-1) of Cr for the first 5 and following 28 d, respectively. The placebo group ingested similar amounts of glucose over the same time period. During each testing period, subjects underwent an oral glucose tolerance test (OGTT) to determine insulin sensitivity, and six subjects from each group underwent a muscle biopsy before each OGTT. RESULTS: Cr supplementation resulted in an increased (P< 0.05) muscle TCr content after both the acute and short-term loading phase compared with placebo. Neither acute nor short-term Cr supplementation influenced skeletal muscle glycogen content, glucose tolerance, or measures of insulin sensitivity. CONCLUSIONS: These findings demonstrated that acute Cr supplementation (20 g.d(-1) for 5 d) followed by short-term Cr supplementation (3 g.d(-1) for 28 d) did not alter insulin action in healthy, active untrained men.