DOI: 10.1556/2060.106.2019.35

Abstract: Chronic kidney diseases (CKDs) are the most common forms of kidney disease all around the world. The incidence of CKD is rising, which is mainly driven by population aging as well as by a global rise in hypertension, metabolic syndrome, and metabolic risk factors, particularly obesity and type-2 diabetes. The high mortality, morbidity of CKD, and the health care costs of the renal replacement therapy have led investigators to seek recent and potentially modifiable risk factors such as non-alcoholic fatty liver disease (NAFLD). NAFLD is the hepatic manifestation of metabolic syndrome and the most common cause of chronic liver disease. It incorporates a spectrum of liver diseases ranging from simple steatosis to steatohepatitis, liver cirrhosis, and hepatocellular carcinoma. On the basis of recent publications, the prevalence of CKD is significantly increased among patients with NAFLD, and the prevalence of NAFLD is also higher in CKD patients than in patients without NAFLD. These findings suggest that patients with NAFLD should be screened for CKD and patients with CKD and metabolic syndrome should be screened for NAFLD. Patients with NAFLD and CKD should be treated and followed up by a multidisciplinary team that involves specialists in hepatology, nephrology, diabetes, and cardiology.

Keywords: cardiovascular risk, chronic kidney diseases, epiGFR, metabolic syndrome, non-alcoholic fatty liver disease

DOI: 10.1556/2060.106.2019.29

Abstract: Introduction: Microgravity has been shown to impose various effects on breast cancer cells. We exposed human breast cancer cells to simulated microgravity and studied morphology and alterations in gene expression. Materials and methods: Human breast cancer cells were exposed to simulated microgravity in a random positioning machine (RPM) for 24 h. Morphology was observed under light microscopy, and gene alteration was studied by qPCR. Results: After 24 h, formation of three-dimensional structures (spheroids) occurred. BRCA1 expression was significantly increased (1.9×, p < 0.05) in the adherent cells under simulated microgravity compared to the control. Expression of KRAS was significantly decreased (0.6×, p < 0.05) in the adherent cells compared to the control. VCAM1 was significantly upregulated (6.6×, 2.0×, p < 0.05 each) in the adherent cells under simulated microgravity and in the spheroids. VIM expression was significantly downregulated (0.45×, 0.44×, p < 0.05 each) in the adherent cells under simulated microgravity and in the spheroids. There was no significant alteration in the expression of MAPK1, MMP13, PTEN, and TP53. Conclusions: Simulated microgravity induces spheroid formation in human breast cancer cells within 24 h and alters gene expression toward modified adhesion properties, enhanced cell repair, and phenotype preservation. Further insights into the underlying mechanisms could open up the way toward new therapies.

Keywords: breast cancer, microgravity, multicellular spheroids, cultured neoplastic cells, gene expression

DOI: 10.1556/2060.106.2019.26

Abstract: Betulin, a pentacyclic triterpene, possesses antioxidant, anti-inflammatory and hepatoprotective properties. The aim of this study was to evaluate the impact of liver mitochondria in hepatoprotection of betulin using a rat model of alcoholic steatohepatitis induced by ethanol administration (4 g/kg, intragastric) for 8 weeks. The treatment with betulin (50 and 100 mg/kg b.w., intragastric) during this period attenuated the histological signs of steatohepatitis and lowered the serum and liver triglyceride contents, as well as the serum activities of aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase. Betulin (100 mg/kg) decreased the liver/body weight ratio and inhibited the increase in the serum levels of TNFα, IL-1β, TGFβ, and hyaluronic acid, demonstrating hepatoprotective, anti-inflammatory, and antifibrotic potential. Betulin also inhibited the formation of superoxide anions in mitochondria and the end-products of lipid peroxidation in liver tissue, the amount of which was significantly increased in ethanol-treated rats. The disturbances in mitochondrial respiration, uncoupling of oxidative phosphorylation and decreasing of mitochondrial complex I, II, and IV activities in rats with steatohepatitis, were reverted by betulin administration. The increased susceptibility of mitochondria to Ca2+-induced permeability transition pore formation in the hepatitis group was improved in rats treated with betulin. In conclusion, betulin, having antioxidant properties, exerts a beneficial effect in the rat model of alcoholic steatohepatitis via prevention of liver mitochondria dysfunction, which may be attributed to the inhibition of mitochondrial permeability transition.

Keywords: liver, mitochondria, alcoholic steatohepatitis, betulin, mitochondrial permeability transition

DOI: 10.1556/2060.106.2019.31

Abstract: Aim: This study investigated whether kisspeptin-10 (KP-10) prevents diabetic rhesus monkeys from insulin-induced hypoglycemic shock. Materials and methods: Thirty-six adult male rhesus monkeys were used, six in each group. Diabetes was induced with streptozotocin (45 mg/kg b.w.; single dose i.v.). Groups were as: saline control, insulin alone, pre-insulin (treated with KP-10, 30 min before insulin), post-insulin (treated with KP-10, 30 min after insulin), treated with premix dose of KP-10 (50 μg) and insulin, and the group treated with the kisspeptin antagonist P234 (50 μg). Following an overnight fast, each animal was subjected to respective treatment, and blood glucose concentrations were recorded every 30-min interval for 3 h. Results: Intergroup comparisons demonstrated that treatment with KP-10 prior to insulin administration and kisspeptin–insulin premix treatment allowed blood glucose levels to rise to significantly higher levels (p < 0.001) by 180 min in diabetic and healthy animals compared to treatment with insulin alone. However, intragroup comparisons revealed a significant decrease in blood glucose level in diabetic animals only. Treatment with P234 antagonist followed by insulin administration abolished the preventive action of kisspeptin, whereby blood glucose decreased significantly (p < 0.001) in both diabetic and healthy animals. KP-10 post-insulin treatment, however, remained ineffective and led, instead, to significantly decreased glucose concentrations by 180 min in both diabetic and healthy animals when compared to animals treated with insulin alone. Conclusions: KP-10 bears therapeutic potential to prevent hypoglycemic shock that may sometimes occur during intensive insulin therapy. Several pharmacological aspects of its interaction with insulin and other drugs, however, remain to be investigated.

Keywords: hypoglycemic shock, diabetes, kisspeptin, insulin-induced hypoglycemia, rhesus monkeys

DOI: 10.1556/2060.106.2019.33

Abstract: Purpose: Proprioception plays an essential role in motor control and in psychological functioning: it is the basis of body schema and the feeling of body ownership. There are individual differences in the processing accuracy of proprioceptive stimuli. Although proprioceptive acuity plays an important role in physical competence, there are contradictory findings concerning the role it plays in healthy psychological functioning. This study aims to shed more light on this association. Material and methods: Sixty-eight young adults participated in this study. We estimated proprioceptive acuity by the reposition accuracy of elbow joint positions. We tested both dominant and non-dominant hands with two different versions of Joint Position Reproduction Test. Perceived physical competence, body awareness, and affectivity were assessed using questionnaires (Physical Competence scale of Body Consciousness Questionnaire, Somatic Absorption Scale, and Positive and Negative Affectivity Schedule, respectively). Results: No significant association between proprioceptive acuity and body awareness, perceived body competence, and positive and negative affect was found. Conclusion: Proprioceptive acuity, measured in the elbow joint, does not play a substantial role in body awareness, perceived body competence, and affect.

Keywords: proprioception, proprioceptive accuracy, physical competence, body awareness, affect

DOI: 10.1556/2060.106.2019.32

Abstract: This study aimed to investigate the effects of a gradually decreasing intensity training from that corresponding to maximal anaerobic power (MAnP) to that of near maximal oxygen uptake (V˙O2max) (decrescent intensity training) on MAnP, maximal accumulated oxygen deficit (MAOD), and V˙O2max in untrained young men. Seventeen untrained young men were randomly divided into either a training (TR; n = 9) group or a control (CON; n = 8) group. The TR group performed the decrescent intensity training, whereas the CON group did not perform any exercises. The mean training time per session throughout the training period was 275 ± 135 s. There was a Group × Time interaction for both absolute and relative (p < 0.01) values of V˙O2max, MAOD, and MAnP. The TR group had significantly increased values for all variables after the 8-week training program, and the relative values of all variables were significantly higher in the TR group than in the CON group. Muscle thicknesses in the anterior and posterior aspects of the thigh and maximal isokinetic knee extension and flexion strengths improved only in the TR group (p < 0.05). A single-exercise training with gradually decreasing intensity from that corresponding to the MAnP to that of approximately 100% V˙O2max improves MAnP, MAOD, and V˙O2max concurrently, despite the short training time per session.

Keywords: maximal oxygen uptake, anaerobic capacity, anaerobic power, training, adaptation

DOI: 10.1556/2060.106.2019.34

Abstract: Background: Early repolarization in the anterior ECG leads (ERV2–4) is considered to be a sign of right ventricular (RV) remodeling, but its etiology and importance are unclear. Methods: A total of 243 top-level endurance-trained athletes (ETA; 183 men and 60 women, weekly training hours: 15–20) and 120 leisure-time athletes (LTA; 71 men and 49 women, weekly training hours: 5–6) were investigated. The ERV2–4 sign was evaluated concerning type of sport, gender, transthoracic echocardiographic parameters, and ECG changes, which can indicate elevated RV systolic pressure [left atrium enlargement (LAE), right atrium enlargement (RAE), RV conduction defect (RVcd)]. Results: Stroke volume and left ventricular mass were higher in ETAs vs. LTAs in both genders (p < 0.01). Prevalence of the ERV2–4 sign was significantly higher in men than in women [p = 0.000, odds ratio (OR) =36.4] and in ETAs than in LTAs (p = 0.000). The highest ERV2–4 prevalence appeared in themost highly trained triathlonists and canoe and kayak paddlers (OR = 13.8 and 5.2, respectively). Within the ETA group, the post-exercise LAE, RAE, and RVcd changes developed more frequently in cases with than without ERV2–4 (LAE: men: p < 0.05, females: p < 0.005; RAE: men: p < 0.05, females: p < 0.005; RVcd: N.S.). These post-exercise appearing LAE, RAE, and RVcd are associated with the ERV2–4 sign (OR = 4.0, 3.7, and 3.8, respectively). Conclusions: According to these results, ERV2–4 develops mainly in male ETAs due to long-lasting and repeated endurance training. The ERV2–4 sign indicates RV’s adaptation to maintain higher compensatory pulmonary pressure and flow during exercise but its danger regarding malignant arrhythmias is unclear.

Keywords: pulmonary artery pressure, early repolarization, exercise ECG, endurance athletes, right ventricular adaptation

DOI: 10.1556/2060.106.2019.30

Abstract: Purpose: Our intent was to (a) characterize weekly changes in resting testosterone (T), cortisol (C), and the T:C ratio in males during an intensive endurance training program, and (b) determine if clinical androgen deficiency (AD) based upon T-level criteria developed. Methods: An 18-week training program in which individual training volume (km/week) increased at 25% increments over baseline (BL) levels observed prior to the study beginning at 4-week intervals throughout the first 12 weeks. After 12 weeks, the volume was reduced to that of the first 4 weeks until the study end (week 18). Competitive performance running tests were assessed at BL and every 4 weeks, while blood T and C were assessed weekly. Results: Performance improved from BL at weeks 4–16 (p < 0.01). T was reduced (p < 0.01) from BL at weeks 3, and 5–18. The greatest reduction from BL was at week 13, subsequently T returned toward BL at week 18. C was highly variable, and no significant changes from BL were noted. The T:C ratio at weeks 5, 6, and 8–16 was significantly less than at BL (p < 0.01), the greatest reduction at week 13. The T:C ratio values also returned toward BL by week 18. Finally, ∼50% of the subjects reached T levels to be classified as AD. Conclusions: Sports scientists should recognize decreases in T or T:C ratio is not always indicative of compromised competitive performance potential. Clinicians should be aware increased training loads can lead to AD in men.

Keywords: overtraining, hormones, stress, hypogonadism, catabolic, adaptation, males