A Microfluidic Multisize Spheroid Array for Multiparametric Screening of Anticancer Drugs and Blood-Brain Barrier Transport Properties.

Physiological-relevant in vitro tissue models with their promise of better predictability have the potential to improve drug screening outcomes in preclinical studies. Despite the advances of spheroid models in pharmaceutical screening applications, variations in spheroid size and consequential altered cell responses often lead to nonreproducible and unpredictable results. Here, a microfluidic multisize spheroid array is established and characterized using liver, lung, colon, and skin cells as well as a triple-culture model of the blood-brain barrier (BBB) to assess the effects of spheroid size on (a) anticancer drug toxicity and (b) compound penetration across an advanced BBB model. The reproducible on-chip generation of 360 spheroids of five dimensions on a well-plate format using an integrated microlens technology is demonstrated. While spheroid size-related IC50 values vary up to 160% using the anticancer drugs cisplatin (CIS) or doxorubicin (DOX), reduced CIS:DOX drug dose combinations eliminate all lung microtumors independent of their sizes. A further application includes optimizing cell seeding ratios and size-dependent compound uptake studies in a perfused BBB model. Generally, smaller BBB-spheroids reveal an 80% higher compound penetration than larger spheroids while verifying the BBB opening effect of mannitol and a spheroid size-related modulation on paracellular transport properties.

Improved Walking Claudication Distance with Transcutaneous Electrical Nerve Stimulation: An Old Treatment with a New Indication in Patients with Peripheral Artery Disease.

OBJECTIVE: The aim of this study was to determine whether 45 mins of transcutaneous electrical nerve stimulation before exercise could delay pain onset and increase walking distance in peripheral artery disease patients. DESIGN: After a baseline assessment of the walking velocity that led to pain after 300 m, 15 peripheral artery disease patients underwent four exercise sessions in a random order. The patients had a 45-min transcutaneous electrical nerve stimulation session with different experimental conditions: 80 Hz, 10 Hz, sham (presence of electrodes without stimulation), or control with no electrodes, immediately followed by five walking bouts on a treadmill until pain occurred. The patients were allowed to rest for 10 mins between each bout and had no feedback concerning the walking distance achieved. RESULTS: Total walking distance was significantly different between T10, T80, sham, and control (P < 0.0003). No difference was observed between T10 and T80, but T10 was different from sham and control. Sham, T10, and T80 were all different from control (P < 0.001). There was no difference between each condition for heart rate and blood pressure. CONCLUSIONS: Transcutaneous electrical nerve stimulation immediately before walking can delay pain onset and increase walking distance in patients with class II peripheral artery disease, with transcutaneous electrical nerve stimulation of 10 Hz being the most effective.

Effect of lactate supplementation and sodium bicarbonate on 40-km cycling time trial performance.

The use of nutritional supplements to improve sporting performance and increase training adaptations is commonplace among athletes and is an expanding market in terms of product choice and availability. The purpose of this study was to examine the effects of 2 ergogenic aids with extracellular blood buffering potential, namely sodium bicarbonate (NaHCO3) and a lactate supplement, during a 40-km cycling time trial. Seven recreationally active men (age, 22.3 ± 3.3 years; height, 182.5 ± 6.5 cm; body mass, 79.2 ± 6.3 kg) completed five 40-km cycling time trials, including a familiarization trial in a randomized, blind, double placebo-controlled design. Subjects ingested (a) 300 mg·kg-1 body mass NaHCO3 (BICARB), (b) 45 mg·kg-1 body mass sodium chloride (PL-BICARB) as the placebo for the NaHCO3 trial, (c) 1115 mg lactate (LACTATE), or (d) plain flour as the placebo for the lactate trial (PL-LACTATE) 60 minutes before exercise. There was no significant difference in performance between the 4 conditions (p > 0.05). Although NaHCO3 ingestion induced significant changes in all the acid-base variables (all p < 0.05), no significant change was seen following lactate ingestion (p > 0.05). Subjects in the LACTATE condition did have a significantly higher heart rate (p < 0.05) without experiencing any greater perceived exertion (p > 0.05) than the other 3 conditions. Neither NaHCO3 nor lactate supplementation seem to improve 40-km cycling time trial performance. However, the potential benefits following LACTATE regarding perceived exertion require further research.