Visceral fat loss in response to four‐cycle ergometer training regimens with explicit differences in exercise intensity and modality was compared. Fifty‐nine obese young women (body fat percentage ≥ 30%) were randomized to a 12‐week intervention consisting of either all‐out sprint interval training (SITall‐out, n = 11); supramaximal SIT (SIT120, 120% O2peak, n = 12); high‐intensity interval training (HIIT90, 90% O2peak, n = 12), moderate‐intensity continuous training (MICT, 60% O2peak, n = 11), or no training (CON, n = 13). The total work done per training session in SIT120, HIIT90, and MICT was confined to 200 kJ, while it was deliberately lower in SITall‐out. The abdominal visceral fat area (AVFA) was measured through computed tomography scans. The whole‐body and regional fat mass were assessed through dual‐energy X‐ray absorptiometry. Pre‐, post‐, and 3‐hour post‐exercise serum growth hormone (GH), and epinephrine (EPI) were measured during selected training sessions. Following the intervention, similar reductions in whole‐body and regional fat mass were found in all intervention groups, while the reductions in AVFA resulting from SITall‐out, SIT120, and HIIT90 (>15 cm2) were greater in comparison with MICT (<3.5 cm2, P < .05). The AVFA reductions among the SITs and HIIT groups were similar, and it was concomitant with the similar exercise‐induced releases of serum GH and EPI. CON variables were unchanged. These findings suggest that visceral fat loss induced by interval training at or above 90% O2peak appeared unresponsive to the change in training intensity. Nonetheless, SITall‐out is still the most time‐efficient strategy among the four exercise‐training regimes for controlling visceral obesity. 相似文献
The ε4 allele of the APOE gene is thought to increase risk from amnestic mild cognitive impairment (aMCI) to Alzheimer’s disease. Cognitive decline in the condition is increasingly considered to worsen functional disconnections in brain network composed of gray matter and white matter. Nevertheless, Whether APOEε4 targets specific white matter functional connectivity in patients with aMCI remains mostly unexplored, mainly due to the challenges of detecting BOLD signals in white matter. Here, we applied a novel approach to investigate APOEε4-related specific bundles and cortical area alterations in aMCI subjects, in order to characterize white matter-gray matter functional connectivity differences throughout the brain. We analyzed 75 patients with aMCI and 76 demographically matched normal controls. The aMCI APOEε4 carriers showed decreased functional connectivity located at left corticospinal tract, bilateral posterior limb of internal capsule, and right temporopolaris, which was different from the regions of aMCI-related changes. We further found that recognition scores were positively associated with the right temporopolaris in aMCI APOEε4 carriers. Collectively, the data provide new evidence that APOEε4 genotype exerts a negative impact on neural activity in both gray and white matter in aMCI, which potentially contributes to functional disconnection and memory decline. A novel method provides full-scale measuring effect of disease conditions on functional architecture throughout the brain. Trial registration: https://www.ClinicalTrials.gov (Identifier: NCT02225964). Registered January 2014.
A roadmap for the selection of a pharmaceutical salt form for a development candidate is presented. The free base of the candidate did not have sufficient chemical stability for development. The initially selected salt form turned out to be undevelopable because it was unstable during scale-up synthesis and storage. The rationale for the new solid form screening and the criteria for selection are discussed. Before the final selection, the pH solubility profiles of the 2 new salts, a benzoate and a besylate, were compared. Atypical solubility behavior was observed for the benzoate salt in hydrochloric acid with and without normal saline. A scheme is proposed illustrating how the pKas of the counterion and active pharmaceutical ingredient, the medium composition, and final pH affect the solubility and solution equilibria of the 2 selected salt forms. This scheme also includes the equilibria between solution and solid phases in different pH ranges. The pharmaceutical importance of this research is that it sheds light on how the acidity of the counterion can affect the solubility of the selected salt form in the gastric environment. With a well-designed formulation strategy, this property potentially can be translated to optimal biopharmaceutical performance of the drug product. 相似文献
An accurate dosage determination is required in neonates when antibiotics are used. The adult data cannot be simply extrapolated to the pediatric population due to significant individual differences. We aimed to identify factors impacting ceftazidime exposure in neonates and to provide drug dosing guidance to clinicians. Forty-three neonates aged less than 60 days with proven or suspected infections were enrolled in this study. After intravenous administration, blood samples were collected, and plasma ceftazidime concentration was determined using a HPLC method. Pharmacokinetic data were fitted using a nonlinear mixed-effects model approach. One-compartmental model could nicely characterize the ceftazidime in vivo behavior. The covariate test found that the postmenstrual age (day) was strongly associated with systemic drug clearance (L/h), and the effect of body weight (kg) was identified as the covariate on distribution volume (L). Compared with the base model, the addition of covariates improved the goodness-of-fit of the final model. Model validation (bootstrap, visual predictive check, and prediction-corrected visual predictive check) suggested a robust and reliable pharmacokinetic model was developed. Personalized dosage regimens were provided based on model simulations. The intravenous dose should be adjusted according to postmenstrual age, body weight, and minimum inhibitory concentration. 相似文献