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Duchenne muscular dystrophy is a severe wasting disease, involving replacement of necrotic muscle tissue by fibrous material and fatty infiltrates. One primary animal model of this human disease is the X chromosome-linked mdx strain of mice. The goals of the present work were to validate and quantify the capability of both energy and entropy metrics of radio-frequency ultrasonic backscatter to differentiate among normal, dystrophic, and steroid-treated skeletal muscle in the mdx model. Thirteen 12-month-old mice were blocked into three groups: 4 treated mdx-dystrophic that received daily subcutaneous steroid (prednisolone) treatment for 14 days, 4 positive-control mdx-dystrophic that received saline injections for 14 days, and 5 negative-control animals. Biceps muscle of each animal was imaged in vivo using a 40-MHz center frequency transducer in conjunction with a Vevo-660 ultrasound system. Radio-frequency data were acquired (1 GHz, 8 bits) corresponding to a sequence of transverse images, advancing the transducer from "shoulder" to "elbow" in 100-micron steps. Data were processed to generate both "integrated backscatter" (log energy), and "entropy" (information theoretic receiver, Hf) representations. Analyses of the integrated-backscatter values delineated both treated- and untreated-mdx biceps from normal controls (p .( 0.01). Complementary analyses of the entropy images differentiated the steroid-treated and positive-control mdx groups (p < 0.01). To our knowledge, this study represents the first reported use of quantitative ultrasonic characterization of skeletal muscle in mdx mice. Successful differentiation among dystrophic, steroid-treated, and normal tissues suggests the potential for local noninvasive monitoring of disease severity and therapeutic effects. [ABSTRACT FROM AUTHOR]

Objective: To evaluate a widely used intervention to reduce college student alcohol use, we studied student drinking patterns at colleges that employed social norms marketing programs and those that did not. Method: We examined responses of students in the Harvard School of Public Health College Alcohol Study (CAS) 1997, 1999 and 2001 data sets at 37 colleges that employed social norms marketing programs and at 61 that did not. Information about the students' drinking behavior and their familiarity with social norms marketing messages at their schools was analyzed, as were college administrators' reports about the implementation of social norms marketing campaigns. Schools were grouped on the basis of student reports of exposure to programmatic materials. Trend analyses were conducted on seven standard measures of alcohol consumption, including annual and 30-day use, frequency, usual quantity and volume consumed, heavy episodic use, and drunkenness. Results: Almost half of the CAS colleges sampled adopted social norms programs. Those that did were more likely to have large enrollments, not to be religiously affiliated and to have high rates of alcohol use. No decreases were noted in any of the seven measures of alcohol use at schools with social norms programs, even when student exposure and length of program existence were considered. Increases in measures of monthly alcohol use and total volume consumed, however, were observed at schools employing social norms programs. Conclusions: This study does not provide evidence to support the effectiveness of social norms marketing programs, as currently utilized, in reducing alcohol use among college students. [ABSTRACT FROM AUTHOR]

The effect of a disrupted immune system on the neuromuscular system is poorly characterized. We compared the strength and fatigue of RAG2(-/-) mice, which lack T-cells and B-cells, with immune intact controls. RAG2(-/-) mice demonstrated fatigue with shorter inverted hang-times (HT) and voluntary wheel-running (VWR) distance and total run times; they increased body weight more slowly but had proportionally normal forelimb grip strength (FGS) and VWR speed. Medial rectus femoris histopathology showed no change in fiber type proportions, no variation in type 2b fiber diameter, and no change in the percentage of central nuclei. There was no change in serum creatine kinase (CK) levels. Thus, in RAG2(-/-) mice body weight and fatigue were directly affected by a hypoactive immune system. Whether these effects were centrally or peripherally mediated is unknown. This model may help to explain fatigue in human conditions in which the immune system is suppressed or absent.

Although corticosteroids alleviate weakness in mdx mice, no long-term treatment has determined whether this benefit is maintained. We studied mdx mice forelimb grip strength and fatigue from 3 through 84 weeks and followed survival through 104 weeks. The mdx mice were given twice weekly oral prednisolone (5 mg/kg) beginning at 3 or 4 weeks. Treated mdx mice survived longer than untreated mice. Between 3 and 10 weeks, treated and untreated mdx mice had similar strength. Between 10 and 24 weeks, strength and strength per gram body weight declined more slowly in treated than untreated mdx mice. Between 24 and 84 weeks, treated and untreated mdx mice declined in strength at the same rate, although treated mice remained stronger. Forelimb grip fatigue was present in untreated mdx mice at all time-points compared to wild-type and was not changed significantly by treatment. We have demonstrated long-term benefit of oral prednisolone in the mdx mouse model of Duchenne muscular dystrophy (DMD). As corticosteroids remain the most validated long-term treatment of DMD, this work may allow for better prediction of synergistic treatments likely to translate to effective improvement for boys with this progressive muscular dystrophy.

Complement deposition and macrophages are common in biopsies of children with muscular dystrophy. While the presumed roles of complement and macrophages have been those of scavenger to remove and clear necrotic fibers, there is some evidence that they play a primary role in the pathogenesis of these diseases. Here, we explore the role of complement in the pathogenesis of the most severe animal model of congenital dystrophy, the dy-/- mouse, which is laminin alpha2-deficient. We generated animals deficient in both C3 and laminin alpha2. C3 is the third component of the complement cascade and is required for activation of either the classical or alternative pathways. Thirty-three percent of the dy-/-:C3+ mice (n=59) died before 24 weeks while only 14% of the dy-/-:C3-/- (n=29) mice died (p=0.04). Absolute forepaw strength was 25-30% greater for the dy-/-:C3-/- mice up to 20 weeks of age (p<0.05 compared to complement-sufficient). Forepaw strength adjusted for weight also showed significant differences with C3-/- mice being stronger up to 20 weeks (p<0.05). However, by 24 weeks, the two groups did not differ for strength. Next, we treated 20 mice with twice weekly oral prednisolone. Survival at 24 weeks for the prednisolone treated dy-/- mice (C3-/- or C3+) was 90% (p=0.04). This work shows that complement insufficiency and weekly prednisone prolong survival and improve strength of the laminin alpha2-deficient mouse. This work suggests that the complement system may contribute directly to the pathogenesis of this form of dystrophy. Because complement activity may be modified pharmacologically, this work may have implications for treatment of children with congenital muscular dystrophy secondary to laminin alpha2 deficiency.