Utilizing PET and MALDI Imaging for Discovery of a Targeted Probe for Brain Endocannabinoid α/ß-Hydrolase Domain 6 (ABHD6).

Multimodal imaging provides rich biological information, which can be exploited to study drug activity, disease associated phenotypes, and pharmacological responses. Here we show discovery and validation of a new probe targeting the endocannabinoid α/ß-hydrolase domain 6 (ABHD6) enzyme by utilizing positron emission tomography (PET) and matrix-assisted laser desorption/ionization (MALDI) imaging. [18F]JZP-MA-11 as the first PET ligand for in vivo imaging of the ABHD6 is reported and specific uptake in ABHD6-rich peripheral tissues and major brain regions was demonstrated using PET. A proof-of-concept study in nonhuman primate confirmed brain uptake. In vivo pharmacological response upon ABHD6 inhibition was observed by MALDI imaging. These synergistic imaging efforts used to identify biological information cannot be obtained by a single imaging modality and hold promise for improving the understanding of ABHD6-mediated endocannabinoid metabolism in peripheral and central nervous system disorders.

HIIT produces increases in muscle power and free testosterone in male masters athletes.

High-intensity interval training (HIIT) improves peak power output (PPO) in sedentary aging men but has not been examined in masters endurance athletes. Therefore, we investigated whether a six-week program of low-volume HIIT would (i) improve PPO in masters athletes and (ii) whether any change in PPO would be associated with steroid hormone perturbations. Seventeen male masters athletes (60 ± 5 years) completed the intervention, which comprised nine HIIT sessions over six weeks. HIIT sessions involved six 30-s sprints at 40% PPO, interspersed with 3 min active recovery. Absolute PPO (799 ± 205 W and 865 ± 211 W) and relative PPO (10.2 ± 2.0 W/kg and 11.0 ± 2.2 W/kg) increased from pre- to post-HIIT respectively (P < 0.001, Cohen's d = 0.32-0.38). No significant change was observed for total testosterone (15.2 ± 4.2 nmol/L to 16.4 ± 3.3 nmol/L (P = 0.061, Cohen's d = 0.32)), while a small increase in free testosterone occurred following HIIT (7.0 ± 1.2 ng/dL to 7.5 ± 1.1 ng/dL pre- to post-HIIT (P = 0.050, Cohen's d = 0.40)). Six weeks' HIIT improves PPO in masters athletes and increases free testosterone. Taken together, these data indicate there is a place for carefully timed HIIT epochs in regimes of masters athletes.

Utility of the hypertriglyceridemic waist phenotype in the cardiometabolic risk assessment of youth stratified by body mass index.

BACKGROUND: It is unclear whether the hypertriglyceridemic waist phenotype (HTWP) can be used to identify those at most risk of cardiometabolic disorders. OBJECTIVES: The utility of the HTWP as a useful predictor of cardiometabolic risk in youth stratified by body mass index was assessed. METHODS: Three hundred and eighty-seven children (12-17.5 years) were used within this cross-sectional study. Participants were classified as normal weight or overweight/obese according to the International Obesity Task Force criteria. The HTWP phenotype was defined as having a waist circumference ≥90th percentile for age and gender with concomitant triglyceride concentrations ≥1.24 mmol L(-1) . Cardiometabolic risk profiles were compared using MANCOVA. RESULTS: Normal weight participants with the HTWP had significantly higher levels of C-reactive protein 2.6 ± 0.4 vs. 1.6 ± 0.3 mg L(-1) (P < 0.05) and cardiometabolic risk scores (1.3 ± 0.3 vs. -0.7 ± 0.2 and 2.1 ± 0.4 vs. -0.5 ± 0.2; both P < 0.05) compared with those of a normal weight without the HTWP. Overweight/obese participants with the HTWP had significantly higher C-reactive protein levels (3.5 ± 0.6 vs. 2.6 ± 0.5; P < 0.05) as well as both cardiometabolic risk scores (1.6 ± 0.6 vs. 0.9 ± 0.2 and 2.2 ± 0.6 vs. 0.8 ± 0.2; both P < 0.001) when compared with overweight/obese participants without the HTWP. CONCLUSIONS: The HTWP may serve as a simple and clinically useful approach to identify youth at increased cardiometabolic risk.

Sprint interval training (SIT) is an effective method to maintain cardiorespiratory fitness (CRF) and glucose homeostasis in Scottish adolescents.

The present study examined the physiological impact of a school based sprint interval training (SIT) intervention in replacement of standard physical education (SPE) class on cardio-respiratory fitness (CRF) and glucose homeostasis during the semester following summer vacation. Participants (n=49) were randomly allocated to either intervention (SIT; n=26, aged 16.9 ± 0.3 yrs) or control group who underwent standard physical education (SPE; n=23, aged 16.8 ± 0.6 yrs). CRF (VO2max) and glucose homeostasis were obtained prior-to and following 7 weeks of SIT exercise. Significant group x time interaction was observed for CRF (P < 0.01) with non-significant trends for fasting insulin (P= 0.08), and HOMA-IR (P=0.06). CRF decreased (P < 0.01) in SPE such that POST intervention CRF was significantly lower (P< 0.05) in SPE. Fasting plasma glucose (P < 0.01), insulin (P< 0.01) and HOMA-IR (P< 0.01) increased significantly amongst SPE. The main finding of the present study is that 7-weeks of SIT exercise is an effective method of maintaining (but not improving) CRF and fasting insulin homeostasis amongst school-going adolescents. SIT exercise demonstrates potential as a time efficient physiological adjunct to standard PE class in order to maintain CRF during the school term.

Direct hits to the head during amateur boxing is associated with a rise in serum biomarkers for brain injury.

Boxing exposes participants to the physiological response to high intensity exercise and also to direct body and brain trauma. Amateur boxing is increasing and females have also been included in the Olympics. The aim of this study is to assess the stress response and possible brain injury incurred during a match by measuring serum biomarkers associated with stress and cellular brain injury before and after combat. Sixteen male amateur boxers were studied retrospectively. The study population was divided into two groups: (a) a group that received predominantly punches to the head (PTH) and (b) a group that received predominantly punches to the body (PTB). Blood samples were taken before and five minutes after each contest. They were analysed for S-100B, neuron-specific enolase (NSE), creatine kinase (CK) and cortisol. The PTH group received direct contacts to the head (not blocked, parried or avoided) and to the body (n=8, age: 17.6 ± 5.3, years; height: 1.68 ± 0.13, meters; mass: 65.4 ± 20.3, kg). The PTB group received punches to the body including blocked and parried punches, but received no direct punches to the head, (n=8, mean ± SD, age: 19.1 ± 3.2 years; height: 1.70 ± 0.75, meters; mass: 68.5 ± 15 kg). Significant increases (P<0.05) were observed between pre- and post-combat serum concentrations in serum concentrations in PTH of S-100B (0.35 ± 0.61 vs. 0.54 ± 0.73, µg.L-1) NSE (19.7 ± 14 vs.31.1 ± 26.6, ng.ml-1) and cortisol (373 ± 202 vs. 756 ± 93, nmol.L-1). Significant increases (P<0.05) of creatine kinase were recorded in both groups. This study demonstrates significant elevations in neurochemical biomarkers in boxers who received direct blows to the head. However, further work is required to quantify this volumetric brain damage and long term clinical sequelae.

Homocysteine induced cardiovascular events: a consequence of long term anabolic-androgenic steroid (AAS) abuse.

OBJECTIVES: The long term effects (>20 years) of anabolic-androgenic steroid (AAS) use on plasma concentrations of homocysteine (HCY), folate, testosterone, sex hormone binding globulin (SHBG), free androgen index, urea, creatinine, haematocrit (HCT), vitamin B12, and urinary testosterone/epitestosterone (T/E) ratio, were examined in a cohort of self-prescribing bodybuilders. METHODS: Subjects (n = 40) were divided into four distinct groups: (1) AAS users still using AAS (SU; n = 10); (2) AAS users abstinent from AAS administration for 3 months (SA; n = 10); (3) non-drug using bodybuilding controls (BC; n = 10); and (4) sedentary male controls (SC; n = 10). RESULTS: HCY levels were significantly higher in SU compared with BC and SC (p<0.01), and with SA (p<0.05). Fat free mass was significantly higher in both groups of AAS users (p<0.01). Daily energy intake (kJ) and daily protein intake (g/day) were significantly higher in SU and SA (p<0.05) compared with BC and SC, but were unlikely to be responsible for the observed HCY increases. HCT concentrations were significantly higher in the SU group (p<0.01). A significant linear inverse relationship was observed in the SU group between SHBG and HCY (r = -0.828, p<0.01), indicating a possible influence of the sex hormones in determining HCY levels. CONCLUSIONS: With mounting evidence linking AAS to adverse effects on some clotting factors, the significantly higher levels of HCY and HCT observed in the SU group suggest long term AAS users have increased risk of future thromboembolic events.

Raised concentrations of C reactive protein in anabolic steroid using bodybuilders.

OBJECTIVE: To examine levels of C reactive protein in users of anabolic androgenic steroids (AAS) compared with age matched control groups consisting of AAS using (but abstinent)/resistance trained and non-drug using/sedentary controls. METHOD: Subjects included AAS using bodybuilders (n = 10); bodybuilders who denied AAS use (n = 10); sedentary controls (n = 8). Venous blood was sampled, from which serum concentrations of C reactive protein, male sex hormones, and cardiac troponin T were determined. RESULTS: A significantly altered hormonal profile in the AAS using group provided indirect confirmation of AAS use. C reactive protein concentrations were significantly (p<0.05) higher in the AAS using bodybuilders. There was no relation between C reactive protein and cardiac troponin T. CONCLUSION: AAS using bodybuilders had significantly higher C reactive protein concentrations, indicating a greater propensity to develop peripheral arterial disease.