Physical activity capacity in children with myelomeningocele

Thirty-three children (10 to 15 years of age) with myelomeningocele were studied to determine isometric muscle strength of hip and knee extension, range of hip and knee extension, usual and maximal ambulatory velocities, maximal aerobic capacity, and the energy cost (oxygen uptake) of ambulation versus wheelchair usage in subjects who both walked and wheeled. Subjects were placed into one of four groups depending on their level of motor function (those with motor levels at L2 and above, L3-4, L5 to sacral, and without motor deficit). Maximal ambulatory velocity correlated with strength of the hip extensor (r = 0.85) and knee extensor (r = 0.81) muscles. All variables were found highly dependent upon the level of motor function. Subjects with the greatest deficits had the most significant impairments and vice versa. It was found, however, that subjects without motor deficit had impairments in the usual speed of ambulation (9%), maximal running velocity (20%), and VO2 max (13%). These deficits were due to the measured strength deficits in these subjects as compared to normal values. This finding underscores the importance of quantitative assessment of muscle strength as significant deficits in strength can be missed with manual muscle testing. In those subjects who walked and wheeled, wheeling was found much more energy efficient. Wheeling at 4.8 km/hr was 11% more efficient than walking at 33% that velocity.     

Serum insulin-like growth factor-I (IGF-I) does not correlate positively with isometric strength, fatigue, and quality of life in post-polio syndrome

OBJECTIVES AND BACKGROUND: To determine if serum insulin-like growth factor-I (IGF-I) levels are associated with strength, body mass index (BMI), fatigue, or quality of life in post-poliomyelitis syndrome (PPS). PPS is likely due to a distal disintegration of enlarged post-polio motor units as a result of terminal axonal sprouting. Age-related decline in growth hormone and IGF-I (which support terminal axonal sprouts) is proposed as a contributing factor. METHODS: As part of the North American Post-Poliomyelitis Pyridostigmine Study (NAPPS), baseline data on maximum voluntary isometric contraction (MVIC), BMI, subjective fatigue (fatigue severity scale, Hare fatigue symptom scale), health-related quality of life (short form health survey-36; SF-36), and serum IGF-I levels were gathered on 112 PPS patients. Pearson correlation coefficients were calculated to evaluate the association between serum IGF-I and MVIC in 12 muscles, BMI, two fatigue scales, and SF-36 scale scores. RESULTS: There is a significant inverse correlation of IGF-I levels with MVIC in left ankle dorsiflexors (r=-0.30, P<0.01), and left and right knee extensors (r=-0.22, -0.25, P=<0.01, 0.01), but no significant correlations in other muscles. When men and women were evaluated separately, inverse correlations of IGF-I levels with MVIC were found only in men. IGF-I correlated inversely with BMI (r=-0.32, P=0006) and age (r=-0.32, P=0.0005). IGF-I did not correlate with the fatigue or SF-36 scales. CONCLUSIONS: In this exploratory study, we found that contrary to our expectations, IGF-I did not correlate positively with strength. IGF-I correlated negatively with strength in several lower extremity muscles, BMI, and age. IGF-I is likely not an important factor in the pathogenesis of fatigue and in determining quality of life in PPS, but its role on strength should be studied further.     

Altered ubiquitination and stability of aquaporin-1 in hypertonic stress

Aquaporin-1 (AQP1) water channel protein expression is increased by hypertonic stress. The contribution of changes in protein stability to hypertonic induction of AQP1 have not been described. Incubation of BALB/c fibroblasts spontaneously expressing AQP1 with proteasome inhibitors increased AQP1 expression, suggesting basal proteasome-dependent degradation of the protein. Degradation by the proteasome is thought to be triggered by polyubiquitination of a target protein. To determine whether AQP1 is ubiquitinated, immunoprecipitation with anti-AQP1 antibodies was performed, and the resultant samples were probed by protein immunoblot for the presence of ubiquitin. Immunoblots demonstrated ubiquitination of AQP1 under control conditions that increased after treatment with proteasome inhibitors (MG132, lactacystin). Exposure of cells to hypertonic medium for as little as 4 h decreased ubiquitination of AQP1, an effect that persisted through 24 h in hypertonic medium. Using metabolic labeling with [(35)S]methionine, the half-life of AQP1 protein under isotonic conditions was found to be <4 h. AQP1 protein half-life was markedly increased by exposure of cells to hypertonic medium. These observations provide evidence that aquaporins are a target for ubiquitination and proteasome-dependent degradation. Additionally, these studies demonstrate that reduced protein ubiquitination and increased protein stability lead to increased levels of AQP1 expression during hypertonic stress.     

Musculoskeletal profile of male collegiate soccer players

Twenty-five collegiate soccer players were evaluated for lower extremity flexibility and muscle strength at the end of preseason training and before the onset of the collegiate soccer season on two successive seasons. The purpose of the evaluation was to determine whether symmetry was present in their legs and whether deficits in flexibility or strength would affect the susceptibility to hamstring or groin muscle strain injuries. The mean (+/- SE) flexibility of the dominant leg for hip abduction was 41 degrees +/- 1.2 degree; for hip flexion, 76 degrees +/- 1.9 degree; for hip extension, 174 degrees +/- 0.7 degree; and for ankle dorsiflexion, 33 degrees +/- 1.3 degree. The mean (+/- SE) isokinetic torque of the dominant leg (tested at 30 degrees per second) for knee extension was 214 +/- 8 newton meters and for flexion was 128 +/- 4 newton meters, while isometric strength for hip flexion was 315 +/- 8 newtons and for ankle plantar flexion was 1721 +/- 58 newtons. No significant differences were found between the dominant and nondominant legs in flexibility or strength. During this study no hamstring or groin strain injuries occurred. The lack of leg muscle strain injuries appeared to be directly related to the initiation of a controlled warmup and stretching program and underlines the importance of this in injury prevention. Interestingly, more than 50% (13 of 25) of the players were found to have significant deficits in one or more specific muscle groups. Two athletes sustained low back strain injuries and one athlete had a knee sprain injury.(ABSTRACT TRUNCATED AT 250 WORDS)     

Synthesis and mycobacterial evaluation of 5‐substituted‐6‐acetyl‐2‐amino‐7‐methyl‐5,8‐dihydropyrido‐[2,3‐d]pyrimidin‐4(3H)‐one derivatives

5‐Substituted‐6‐acetyl‐2‐amino‐7‐methyl‐5,8‐dihydropyrido[2,3‐d]pyrimidin‐4(3H)‐one derivatives were synthesized and evaluated against Mycobacterium tuberculosis H37Rv, Mycobacterium aurum, Escherichia coli, and Staphylococcus aureus as well as a human monocyte‐derived macrophage (THP‐1), and murine macrophage (RAW 264.7) cell lines to assess their antibacterial and cytotoxic potential, respectively. The compounds showed activity in the range of 1.95–125 µg/ml against M. tuberculosis but showed no activity against M. aurum, E. coli, and S. aureus, indicating selectivity towards slow‐growing mycobacterial pathogens. The compounds exhibited very low to no cytotoxicity up to 500 µg/ml concentration against eukaryotic cell lines. The most potent molecule, 2l , showed a minimum inhibitory concentration of 1.95 µg/ml against M. tuberculosis H37Rv and a selectivity index of >250 against both the eukaryotic cell lines. Furthermore, 2l showed moderate inhibition of whole‐cell mycobacterial drug‐efflux pumps when compared to verapamil, a known potent inhibitor of efflux pumps. Thus, derivative 2l was identified as an antituberculosis hit molecule, which could be used to yield more potent lead molecules.