Adaptation and dysadaptation of abuse-independent physiological responses to amphetamine

[[abstract]]Although amphetamine (AMPH) is an addictive drug of abuse which exhibits toxicity to dopaminergic neurons in long-term abusers, AMPH shows some abuse-independent effects. AMPH increases dopamine (DA) release from striatum by enhancing cytosolic DA ＂via＂ the redistribution of neurotransmitters from synaptic vesicles to neuronal cytoplasm and the reverse transport of DA from cytoplasm to synapse ＂via＂ the dopamine transporter (DAT). AMPH competitively binds DAT by facilitating the exchange of cytosolic DA, and inhibits the monoamine oxidase to decreasing the metabolism of postsynaptic DA. AMPH locally applied in ventral tegmental area (VTA) enhances DA release in nucleus accumbens and medial prefrontal cortex by activating noradrenergic neurotransmission in VTA. DA levels in striatum can be enhanced by estradiol ＂via＂ an increase of DAT expression following the administration of AMPH. In male rat tests, AMPH inhibits the basal and human chorionic gonadotropin (hCG)-stimulated secretion of testosterone by increasing cyclic AMP production and decreasing the activities of calcium channel and steroidogenic enzymes. AMPH also inhibits gastric emptying and intestinal transit ＂via＂ a mechanism associated with the hypersecretion of endogenous cholecystokinin (CCK). The offspring of pregnant rats administrated with AMPH shows ventricular hypertrophy, systolic dysfunction, and apoptosis in cardiac muscles. The above findings indicate that AMPH demonstrates multiple effects on cardiac, endocrine and gastrointestinal systems. Both adaptation and dysadaptation of abuse-independent physiological responses to AMPH are highly suggested

Cardiac Fas-Dependent and Mitochondria-Dependent Apoptosis after Chronic Cocaine Abuse

To evaluate whether chronic cocaine abuse will increase cardiac Fas-dependent and mitochondria-dependent apoptotic pathways, thirty-two male Wistar rats at 3–4 months of age were randomly divided into a vehicle-treated group (phosphate-buffered saline, PBS, 0.5 mL, SQ per day) and a cocaine-treated group (Cocaine, 10 mg/kg, SQ per day). After 3 months of treatment, the excised left ventricles were measured by H&E staining, Western blotting, DAPI staining and TUNEL assays. More cardiac TUNEL-positive apoptotic cells were observed in the Cocaine group than the PBS group. Protein levels of TNF-alpha, Fas ligand, Fas death receptor, FADD, activated caspase-8, and activated caspase-3 (Fas-dependent apoptosis) extracted from excised hearts in the Cocaine group were significantly increased, compared to the PBS group. Protein levels of cardiac Bax, cytosolic cytochrome c, t-Bid-to-Bid, Bak-to-Bcl-xL, Bax-to-Bcl-2 ratio, activated caspase-9, and activated caspase-3 (mitochondria-dependent apoptosis) were significantly increased in the Cocaine group, compared to the PBS group. Chronic cocaine exposure appeared to activate the cardiac Fas-dependent and mitochondria-dependent apoptosis, which may indicate a possible mechanism for the development of cardiac abnormalities in humans with chronic cocaine abuse

Cardiac Fas-Dependent and Mitochondria-Dependent Apoptosis after Chronic Cocaine Abuse

To evaluate whether chronic cocaine abuse will increase cardiac Fas-dependent and mitochondria-dependent apoptotic pathways, thirty-two male Wistar rats at 3–4 months of age were randomly divided into a vehicle-treated group (phosphate-buffered saline, PBS, 0.5 mL, SQ per day) and a cocaine-treated group (Cocaine, 10 mg/kg, SQ per day). After 3 months of treatment, the excised left ventricles were measured by H&E staining, Western blotting, DAPI staining and TUNEL assays. More cardiac TUNEL-positive apoptotic cells were observed in the Cocaine group than the PBS group. Protein levels of TNF-alpha, Fas ligand, Fas death receptor, FADD, activated caspase-8, and activated caspase-3 (Fas-dependent apoptosis) extracted from excised hearts in the Cocaine group were significantly increased, compared to the PBS group. Protein levels of cardiac Bax, cytosolic cytochrome c, t-Bid-to-Bid, Bak-to-Bcl-xL, Bax-to-Bcl-2 ratio, activated caspase-9, and activated caspase-3 (mitochondria-dependent apoptosis) were significantly increased in the Cocaine group, compared to the PBS group. Chronic cocaine exposure appeared to activate the cardiac Fas-dependent and mitochondria-dependent apoptosis, which may indicate a possible mechanism for the development of cardiac abnormalities in humans with chronic cocaine abuse

Exploring the Potential Benefits of Interventions When Addressing Simulated Altitude Hypoxia during Male Cyclist Sports: A Systematic Review

Training in hypoxic environments enhances endurance, but the various influences of training protocols and supplementation for efficient performance are not yet clear. This systematic review explored the effects of different supplementations and interventions used to optimize the aerobic and anaerobic performance of cyclists. Data were collected from the following sources: PubMed, Google Scholar, EMBASE, WOS, Cochrane Central Register of Controlled Trials, and randomized controlled trials (RCTs). Studies that explored the effects of supplementation or intervention during cycling were selected for analysis. Five studies (67 male cyclists; mean age, 23.74–33.56 years) reported different outcomes from supplementation or intervention during the acute hypoxia of cyclists. Three studies (42 male cyclists; mean age, 25.88–36.22 years) listed the benefits of beetroot juice in preserving SpO2 (pulse oxygen saturation) and enhancing high-intensity endurance performance, effectively preventing the reduction in power output. This systematic review provided evidence that the different effects of ischemic preconditioning (IPC), sildenafil, and beetroot (BR) supplementation and intervention did not present a statistically greater benefit than for normoxia groups, but BR supplementation promoted the benefits of SpO2. Future research should evaluate the duration and higher FiO2 (simulated altitude, hypoxia) levels of hypoxia in training protocols for cyclists. This is important when determining the effectiveness of supplements or interventions in hypoxic conditions and their impact on sports performance, particularly in terms of power output

Effects of periodic carbohydrate ingestion on endurance and cognitive performances during a 40-km cycling time-trial under normobaric hypoxia in well-trained triathletes

[[abstract]]The purpose of this study was to examine CHO ingestion on a cognitive task using a field-simulated time-trial (TT) under hypoxia in well-trained triathletes. Ten male triathletes (age: 22.1 ± 1.1 years; VO2max: 59.4 ± 1.4 ml/kg/min) participated in this double-blind/crossover/counter-balanced design study. Participants completed 3 TT trials: 1) normoxic placebo (NPLA; FiO2 = 20.9%), 2) hypoxic placebo (HPLA; FiO2 = 16.3%), and 3) hypoxic CHO (HCHO; 6% CHO provided as 2 ml/kg/15 min; FiO2 = 16.3%). During the TT, physiological responses (SpO2, HR, RPE, and blood glucose/lactate), cognitive performance, and cerebral haemodynamics were measured. Hypoxia reduced TT performance by ~3.5–4% (p < 0.05), but CHO did not affect TT performance under hypoxia. For the cognitive task, CHO slightly preserved exercise-induced cognitive reaction speed but did not affect response accuracy during hypoxic exercise. However, CHO did not preserve the decreased Hb-Diff (cerebral blood flow, CBF) and increased HHb in the prefrontal lobe (p < 0.05) during hypoxic exercise, and CHO failed to preserve hypoxia-suppressed prefrontal CBF and tissue oxygen saturation. In conclusion, the present study demonstrates that CHO is effective in sustaining reaction speed for a cognitive task but not promoting TT performance during hypoxic exercise, which would be important for strategy-/decision-making when athletes compete at moderate high-altitude

www.mdpi.com/journal/ijms Cardiac Fas-Dependent and Mitochondria-Dependent Apoptosis after Chronic Cocaine Abuse

These authors contributed equally to this work

An Amino Acids Mixture Attenuates Glycemic Impairment but Not Affects Adiposity Development in Rats Fed With AGEs-containing Diet

[[abstract]]Background: Unhealthy western dietary patterns lead to over-consumption of fat and advanced glycation end-products (AGEs), and these account for the developments of obesity, diabetes, and related metabolic disorders. Certain amino acids (AAs) have been recently demonstrated to improve glycemia and reduce adiposity. Therefore, our primary aims were to examine whether feeding an isoleucine-enriched AA mixture (4.5% AAs; Ile: 3.0%, Leu: 1.0%, Val: 0.2%, Arg: 0.3% in the drinking water) would affect adiposity development and prevent the impairments of glycemic control in rats fed with the fat/AGE-containing diet (FAD). Methods: Twenty-four male Sprague-Dawley rats were assigned into 1) control diet (CD, N = 8), 2) FAD diet (FAD, N = 8), and 3) FAD diet plus AA (FAD/AA, N = 8). After 9-weeks intervention, the glycemic control capacity (glucose level, ITT, and HbA1c levels), body composition, and spontaneous locomotor activity (SLA) were evaluated, and the fasting blood samples were collected for analyzing metabolic related hormones (insulin, leptin, adiponectin, and corticosterone). The adipose tissues were also surgically collected and weighed. Results: FAD rats showed significant increases in weight gain, body fat %, blood glucose, HbA1c, leptin, and area under the curve of glucose during insulin tolerance test (ITT-glucose-AUC) in compared with the CD rats. However, the fasting levels of blood glucose, HbA1c, leptin, and ITT-glucose-AUC did not differ between CD and FAD/AA rats. FAD/AA rats also showed a greater increase in serum testosterone. Conclusion: The amino acid mixture consisting of Ile, Leu, Val, and Arg showed clear protective benefits on preventing the FAD-induced obesity and impaired glycemic control

Soymilk ingestion immediately after therapeutic exercise enhances rehabilitation outcomes in chronic stroke patients: A randomized controlled trial

[[abstract]]PURPOSE:This study investigates the effects of an 8-weeks rehabilitation exercise plus soymilk ingestion immediately after exercise on functional outcomes in chronic stroke patients. METHODS:Twenty-two stroke patients (age: 57–84 yrs; time since stroke onset: 2–19 yrs) participated and completed the study. A randomized, placebo-controlled and double-blind design was used. Participants were randomly allocated to either soymilk (SMS; n = 11) or placebo (PLA; n = 11) group and received identical 8-weeks rehabilitation intervention (3 sessions/week; 120 min/session) with corresponding treatment beverages. The physical and functional outcomes were evaluated before, during, and after the intervention. RESULTS:The 8-weeks rehabilitation program enhanced functional outcomes of participants. The immediate soymilk ingestion after exercise additionally improved hand grip strength (p = 0.021), 8-feet walking speed (p = 0.019), walking performance per unit lean mass (p = 0.024), and 6-minute walk performance (6MWT, p = 0.016) compared with PLA after the intervention. However, the improvements in the total score for short physical performance battery (SPPB) and lean mass did not differ between groups. CONCLUSION:Compared with rehabilitation alone, the 8-week rehabilitation program combined with immediate soymilk ingestion further improved walking speed, exercise endurance, grip strength, and muscle functionality in chronic stroke patients

Amphetamine-Decreased Progesterone and Estradiol Release in Rat Granulosa Cells: The Regulatory Role of cAMP- and Ca2+-Mediated Signaling Pathways

The purpose of this study is to evaluate the amphetamine effects on progesterone and estradiol production in rat granulosa cells and the underlying cellular regulatory mechanisms. Freshly dispersed rat granulosa cells were cultured with various test drugs in the presence of amphetamine, and the estradiol/progesterone production and the cytosolic cAMP level were measured. Additionally, the cytosolic-free Ca2+ concentrations ([Ca2+]i) were measured to examine the role of Ca2+ influx in the presence of amphetamine. Amphetamine in vitro inhibited both basal and porcine follicle-stimulating hormone-stimulated estradiol/progesterone release, and amphetamine significantly decreased steroidogenic enzyme activities. Adding 8-Bromo-cAMP did not recover the inhibitory effects of amphetamine on progesterone and estradiol release. H89 significantly decreased progesterone and estradiol basal release but failed to enhance a further amphetamine inhibitory effect. Amphetamine was capable of further suppressing the release of estradiol release under the presence of nifedipine. Pretreatment with the amphetamine for 2 h decreased the basal [Ca2+]i and prostaglandin F2α-stimulated increase of [Ca2+]i. Amphetamine inhibits progesterone and estradiol secretion in rat granulosa cells through a mechanism involving decreased PKA-downstream steroidogenic enzyme activity and L-type Ca2+ channels. Our current findings show that it is necessary to study the possibility of amphetamine perturbing reproduction in females

A Sports Nutrition Perspective on the Impacts of Hypoxic High-Intensity Interval Training (HIIT) on Appetite Regulatory Mechanisms: A Narrative Review of the Current Evidence

High-intensity interval training (HIIT) and low-oxygen exposure may inhibit the secretion of appetite-stimulating hormones, suppress appetite, and inhibit dietary intake. Physiological changes affecting appetite are frequent and include appetite hormone (ghrelin, leptin, PYY, and GLP-1) effects and the subjective loss of appetite, resulting in nutritional deficiencies. This paper is a narrative review of the literature to verify the HIIT effect on appetite regulation mechanisms and discusses the possible relationship between appetite effects and the need for high-intensity exercise training in a hypoxic environment. We searched MEDLINE/PubMed and the Web of Science databases, as well as English articles (gray literature by Google Scholar for English articles) through Google Scholar, and the searched studies primarily focused on the acute effects of exercise and hypoxic environmental factors on appetite, related hormones, and energy intake. In a general normoxic environment, regular exercise habits may have accustomed the athlete to intense training and, therefore, no changes occurred in their subjective appetite, but there is a significant effect on the appetite hormones. The higher the exercise intensity and the longer the duration, the more likely exercise is to cause exercise-induced appetite loss and changes in appetite hormones. It has not been clear whether performing HIIT in a hypoxic environment may interfere with the exerciser&rsquo;s diet or the nutritional supplement intake as it suppresses appetite, which, in turn, affects and interferes with the recovery efficiency after exercise. Although appetite-regulatory hormones, the subjective appetite, and energy intake may be affected by exercise, such as hypoxia or hypoxic exercise, we believe that energy intake should be the main observable indicator in future studies on environmental and exercise interventions