Motor function and respiratory capacity in patients with late‐onset pompe disease

Introduction: The relationship between skeletal muscle strength and respiratory dysfunction in Pompe disease has not been examined by quantitative methods. We investigated correlations among lower extremity proximal muscle strength, respiratory function, and motor performance. Methods: Concentric strength of the knee extensor and flexor muscles was measured with a dynamometer, and pulmonary function was evaluated using spirometry in 7 adult patients. The 6‐minute walk test and the 4‐step stair‐climb test were used for assessing aerobic endurance and anaerobic power, respectively. Results: Anaerobic motor performance correlated with strength of both thigh muscles. Respiratory function did not correlate with either muscle strength or motor function performance. Conclusions: Respiratory and lower extremity proximal muscles could be affected differentially by the disease in individual patients. Motor performance is influenced by thigh muscle strength and is less dependent of respiratory capacity in our cohort of ambulatory patients. Muscle Nerve 49:603–606, 2014     

Maximal strength,power, and aerobic endurance adaptations to concurrent strength and sprint interval training

Purpose

This study was designed to examine whether concurrent sprint interval and strength training (CT) would result in compromised strength development when compared to strength training (ST) alone. In addition, maximal oxygen consumption (VO₂max) and time to exhaustion (TTE) were measured to determine if sprint interval training (SIT) would augment aerobic performance.

Methods

Fourteen recreationally active men completed the study. ST (n = 7) was performed 2 days/week and CT (n = 7) was performed 4 days/week for 12 weeks. CT was separated by 24 h to reduce the influence of acute fatigue. Body composition was analyzed pre- and post-intervention. Anaerobic power, one-repetition maximum (1RM) lower- and upper-body strength, VO₂max and TTE were analyzed pre-, mid-, and post-training. Training intensity for ST was set at 85 % 1RM and SIT trained using a modified Wingate protocol, adjusted to 20 s.

Results

Upper- and lower-body strength improved significantly after training (p < 0.001) with no difference between the groups (p > 0.05). VO₂max increased 40.9 ± 8.4 to 42.3 ± 7.1 ml/kg/min (p < 0.05) for CT, whereas ST remained unchanged. A significant difference in VO₂max (p < 0.05) was observed between groups post-intervention (CT: 42.3 ± 7.1 vs. ST: 36.0 ± 3.0 ml/kg/min). A main effect for time and group was observed in TTE (p < 0.05). A significant main effect for time was observed in average power (p < 0.05).

Conclusion

Preliminary findings suggest that performing concurrent sprint interval and strength training does not attenuate the strength response when compared to ST alone, while also improves aerobic performance measures, such as VO₂max at the same time.     

Exercise Dependence in Amateur Competitors and Non-Competitor Recreational Exercisers

Research has demonstrated that exercising has health promoting effects. However, if habitual sporting activities become uncontrollable, detrimental health consequences can occur among a minority of individuals. Furthermore, such obligatory exercise can cause serious decline in school/work productivity, as well as financial problems, relationship problems, and poor psychological and physical wellbeing. The aim of the present study was to compare characteristics related to exercise dependence (ED) between recreational exercisers and amateur competitors. A total of 1439 participants (41.4 % male; mean age = 32 years) completed a battery of measures including the Exercise Dependence Scale (EDS), SCOFF, Well-Being Questionnaire, and Rosenberg’s Self-Esteem Scale. Results showed that 6.5 % of participants identified themselves as amateur competitive exercisers. Amateur competitors exercised significantly more (6.4 h) than non-competitor recreational exercisers (4.6 h). Amateur competitors also scored significantly higher on the EDS. Significant effects were found between competing and self-esteem concerning ED. Results showed that both features had a strong effect on ED. The study highlights the connection between ED symptoms and lower self-esteem and/or lower levels of subjective wellbeing. These influential factors are worth considering when planning preventive interventions addressing ED for both amateur competitors and non-competitive recreational athletes as well as when promoting sport as a healthy activity.     

Aging and exercise affect the level of protein acetylation and SIRT1 activity in cerebellum of male rats

Aging is associated with a gradual decline in cognitive and motor functions, the result of complex biochemical processes including pre- and posttranslational modifications of proteins. Sirtuins are NAD⁺ dependent protein deacetylases. These enzymes modulate the aging process by lysine deacetylation, which alters the activity and stability of proteins. Exercise can increase mean life-span and improve quality of life. Data from our laboratories revealed that 4 weeks of treadmill running improves performance in the Morris Maze test for young (4 months, old) but not old (30 months, old) male rats, and the exercise could not prevent the age-associated loss in muscle strength assessed by a gripping test. The positive correlation between protein acetylation and the gripping test suggests that the age-dependent decrease in relative activity of SIRT1 in the cerebellum impairs motor function. Similarly to the acetylation level of total proteins, the acetylation of ά -tubulin is also increased with aging, while the effect of exercise training was not found to be significant. Moreover, the protein content of nicotinamide phosphoribosyltransferase, one of the key enzymes of NAD biosynthesis, decreased in the young exercise group. These data suggest that aging results in decreased specific activity of SIRT1 in cerebellum, which could lead to increased acetylation of protein residues, including ά-tubulin, that interfere with motor function.     

Low-Glucose Conditions of Tumor Microenvironment Enhance Cytotoxicity of Tetrathiomolybdate to Neuroblastoma Cells

Growth of tumor cells depends on sufficient supply of fermentable substrate, such as glucose. This provokes development of new anticancer therapies based on dietary restrictions. However, some tumor cells can lower their glucose dependency and activate processes of ATP formation/saving to retain viability even in limited glucose supply. In addition, tumor cells often lose sensitivity to many conventional anticancer drugs in the low-glucose conditions. Thus, development of the drugs effectively killing the tumor cells in nutrient-limited conditions is necessary. In this study, we show an enhanced cytotoxicity of tetrathiomolybdate, the drug exhibiting antiangiogenic and tumor-suppressing effects, to neuroblastoma SH-SY5Y and SK-N-BE(2) cells in the low-glucose conditions. This preference results from the tetrathiomolybdate-induced upregulation of cell dependency on glucose. The cells treated with tetrathiomolybdate increase the uptake of glucose, production of lactate, activate the Akt- and AMPK-signaling pathways and downregulate COX IV. In cells growing in the low-glucose conditions, these events result in significant decrease of the intracellular ATP supply and apoptosis. We propose tetrathiomolybdate as suitable agent to be used in combination with dietary restrictions in therapy of neuroblastoma.     

Peripheral blood natural killer cell count is associated with clinical outcome in patients with aaIPI 2-3 diffuse large B-cell lymphoma.

BACKGROUND: Lymphocytopenia is a prognostic factor in Hodgkin's disease. In diffuse large B-cell lymphoma (DLBCL), data are much less established, in spite of numerous reports on immune system-lymphoma interactions. This study addresses the prognostic value of blood lymphocyte subsets at diagnosis in DLBCL. PATIENTS AND METHODS: Absolute values of blood lymphocyte subsets and monocytes were prospectively determined by flow cytometry in 140 patients with 2 or 3 adverse age-adjusted International Prognostic Index (aaIPI) factors included in a Groupe d'Etude des Lymphomes de l'Adulte protocol (LNH98B3). Absolute cell counts at diagnosis and aaIPI were evaluated with regard to clinical outcome. RESULTS: Low median cell counts of 337, 211, and 104/mul were evidenced for the CD4+, CD8+ T, and natural killer (NK) cells, respectively. In univariate analysis, only NK cell count [odds ratio (OR) = 1.81 (1.27, 2.57), P = 0.001] and aaIPI [OR = 2.29 (0.95, 5.45), P = 0.06] were associated with induction treatment response. Low NK cell count [Hazard ratio (HR) = 1.27 (1.06, 1.52), P = 0.01] and aaIPI 3 [HR = 1.95 (1.20, 3.16), P = 0.01] were also associated with a shorter event free survival (EFS). In multivariate analysis, NK cell count was associated with response [OR = 1.77 (1.24, 2.54), P = 0.002] and EFS [HR = 1.25 (1.04, 1.50) P = 0.02] independently of aaIPI. CONCLUSIONS: This study shows an association between circulating NK cell number and clinical outcome in DLBCL, possibly important in the context of the broadening use of rituximab, a likely NK-dependent therapy.     

Expression of IL-2alpha and IL-2beta receptors on the membrane surface of human sperm

Cytokines are secreted proteins that act as local immunological mediators. Increased seminal cytokine concentrations are associated with fertility problems. The purpose of the present study was to investigate the presence of IL-2alpha, and IL-2beta receptors on fresh and isolated sperm by flow cytometry and transmission electron microscopy. Twenty sperm samples from oligospermic men were incubated with CD25, a mouse monoclonal antibody specific for IL-2alpha-chain receptor, and CD122, a mouse monoclonal antibody specific for IL-2beta-chain receptor. The strong initial fluorescence intensity and, subsequently, a labeling index yielded by CD25 and CD122 decreased in sperm centrifuged on a Percoll gradient (p < .05). The expression of CD25 and CD122 correlated negatively with fresh sperm concentration, but in sperm centrifuged on a Percoll gradient there was no correlation. Labeling with CD25 and CD122 antibody was evident on the head and the middle piece in fresh sperm, while in sperm centrifuged on a Percoll gradient a weak labeling was observed only on the principal piece. The authors have identified and localized cytokine receptors on human sperm for the first time. Cytokine receptors may be involved in the regulation of pathophysiological events in sperm cell functions and male infertility. The exact pathway involved in modulation of these receptors requires further investigation. These results contribute to the understanding of cytokine-sperm relationships.