Testosterone and trenbolone enanthate increase mature myostatin protein expression despite increasing skeletal muscle hypertrophy and satellite cell number in rodent muscle.

The androgen-induced alterations in adult rodent skeletal muscle fibre cross-sectional area (fCSA), satellite cell content and myostatin (Mstn) were examined in 10-month-old Fisher 344 rats (n = 41) assigned to Sham surgery, orchiectomy (ORX), ORX + testosterone (TEST; 7.0 mg week-1 ) or ORX + trenbolone (TREN; 1.0 mg week-1 ). After 29 days, animals were euthanised and the levator ani/bulbocavernosus (LABC) muscle complex was harvested for analyses. LABC muscle fCSA was 102% and 94% higher in ORX + TEST and ORX + TREN compared to ORX (p < .001). ORX + TEST and ORX + TREN increased satellite cell numbers by 181% and 178% compared to ORX, respectively (p < .01), with no differences between conditions for myonuclear number per muscle fibre (p = .948). Mstn protein was increased 159% and 169% in the ORX + TEST and ORX + TREN compared to ORX (p < .01). pan-SMAD2/3 protein was ~30-50% greater in ORX compared to SHAM (p = .006), ORX + TEST (p = .037) and ORX + TREN (p = .043), although there were no between-treatment effects regarding phosphorylated SMAD2/3. Mstn, ActrIIb and Mighty mRNAs were lower in ORX, ORX + TEST and ORX + TREN compared to SHAM (p < .05). Testosterone and trenbolone administration increased muscle fCSA and satellite cell number without increasing myonuclei number, and increased Mstn protein levels. Several genes and signalling proteins related to myostatin signalling were differentially regulated by ORX or androgen therapy.

Effects of testosterone treatment on markers of skeletal muscle ribosome biogenesis.

The effects of testosterone (TEST) treatment on markers of skeletal muscle ribosome biogenesis in vitro and in vivo were examined. C2 C12 myotubes were treated with 100 nm TEST for short-term (24-h) and longer-term (96-h) treatments. Moreover, male 10-month-old Fischer 344 rats were housed for 4 weeks, and the following groups were included in this study: (i) Sham-operated (Sham) rats, (ii) orchiectomised rats (ORX) and (iii) ORX+TEST-treated rats (7.0 mg week-1 ). For in vitro data, TEST treatment increased c-Myc mRNA expression by 38% (P = 0.004) after 96 h, but did not affect total RNA, 47S pre-rRNA, Raptor mRNA, Nop56 mRNA, Bop1 mRNA, Ncl mRNA at 24 h or 96 h following the treatment. For in vivo data, ORX decreased levator ani/bulbocavernosus (LABC) myofibril protein versus Sham (P = 0.006), whereas ORX+TEST (P = 0.015) rescued this atrophic effect. ORX also decreased muscle ribosome content (total RNA) compared to Sham (P = 0.046), whereas ORX+TEST tended to rescue this effect (P = 0.057). However, other markers of ribosome biogenesis including c-Myc mRNA, Nop56 mRNA, Bop1 mRNA, Ncl mRNA decreased with ORX independently of TEST treatments (P < 0.05). Finally, lower phospho-(Ser235/236)-to-total rps6 protein and lower rpl5 protein levels existed in ORX+TEST rats versus other treatments, suggesting that chronic TEST treatment may lower translational capacity.

Exercise training improves endothelial function in resistance arteries of young prehypertensives.

Prehypertension is associated with reduced conduit artery endothelial function and perturbation of oxidant/antioxidant status. It is unknown whether endothelial dysfunction persists to resistance arteries and whether exercise training affects oxidant/antioxidant balance in young prehypertensives. We examined resistance artery function using venous occlusion plethysmography measurement of forearm (FBF) and calf blood flow (CBF) at rest and during reactive hyperaemia (RH), as well as lipid peroxidation (8-iso-PGF2α) and antioxidant capacity (Trolox-equivalent antioxidant capacity; TEAC) before and after exercise intervention or time control. Forty-three unmedicated prehypertensive and 15 matched normotensive time controls met screening requirements and participated in the study (age: 21.1±0.8 years). Prehypertensive subjects were randomly assigned to resistance exercise training (PHRT; n=15), endurance exercise training (PHET; n=13) or time-control groups (PHTC; n=15). Treatment groups exercised 3 days per week for 8 weeks. Peak and total FBF were lower in prehypertensives than normotensives (12.7±1.2 ml min(-1) per100 ml tissue and 89.1±7.7 ml min(-1) per 100 ml tissue vs 16.3±1.0 ml min(-1) per 100 ml tissue and 123.3±6.4 ml min(-1) per 100 ml tissue, respectively; P<0.05). Peak and total CBF were lower in prehypertensives than normotensives (15.3±1.2 ml min(-1) per 100 ml tissue and 74±8.3 ml min(-1) per 100 ml tissue vs 20.9±1.4 ml min(-1) per 100 ml tissue and 107±9.2 ml min(-1) per 100 ml tissue, respectively; P<0.05). PHRT and PHET improved humoral measures of TEAC (+24 and +30%) and 8-iso-PGF2α (-43 and -40%, respectively; P < or = 0.05). This study provides evidence that young prehypertensives exhibit reduced resistance artery endothelial function and that short-term (8 weeks) resistance or endurance training are effective in improving resistance artery endothelial function and oxidant/antioxidant balance in young prehypertensives.

Enhanced external counterpulsation improves peripheral artery function and glucose tolerance in subjects with abnormal glucose tolerance.

BACKGROUND: In coronary artery disease patients, enhanced external counterpulsation (EECP) improves peripheral arterial function and nitric oxide (NO) bioavailability, which have been implicated in the pathogenesis of abnormal glucose tolerance (AGT). We sought to evaluate the effects of EECP on outcomes of arterial function, glucose tolerance, and skeletal muscle morphology in subjects with AGT. METHODS AND RESULTS: 18 subjects with AGT were randomly (2:1 ratio) assigned to receive either 7 wk (35 1-h sessions) of EECP (n = 12) or 7 wk of standard care (control; n = 6). Peripheral vascular function, biochemical assays, glucose tolerance, and skeletal muscle morphology were evaluated before and after EECP or control. EECP increased normalized brachial artery (27%) and popliteal artery (52%) flow-mediated dilation. Plasma nitrite/nitrate (NOx) increased (30%) and 8-isoprostane-PGF-F(2α), a marker of lipid peroxidation in the plasma, decreased (-23%). Fasting plasma glucose declined (-16.9 ± 5.4 mg/dl), and the homeostasis model assessment of insulin resistance (HOMA-IR) decreased (31%) following EECP. Plasma glucose 120 min after initiation of oral glucose tolerance testing decreased (-28.3 ± 7.3 mg/dl), and the whole body composite insulin sensitivity index (C-ISI) increased (21%). VEGF concentrations increased (75%), and vastus lateralis skeletal muscle biopsies demonstrated improvements in capillary density following EECP. No change was observed in cellular signaling pathways, but there was a significant increase GLUT-4 protein expression (47%) following EECP. CONCLUSIONS: Our findings provide novel evidence that EECP has a beneficial effect on peripheral arterial function and glucose tolerance in subjects with AGT.

Planning for children whose parents are dying of HIV/AIDS. American Academy of Pediatrics. Committee on Pediatric AIDS, 1998-1999.

Although the character of acquired immunodeficiency syndrome is changing into a chronic illness, it is estimated that by the end of this century, 80 000 children and adolescents in the United States will be orphaned by parental death caused by human immunodeficiency virus infection. Plans for these children need to be made to ensure not only a stable, consistent environment that provides love and nurturing, but also the medical and social interventions necessary to cope with the tragic loss. Pediatricians should become aware of local laws and community resources and initiate discussion early in the course of parental illness to facilitate planning for the future care and custody of the children. States need to adopt laws and regulations that provide flexible approaches to guardianship and placement of children orphaned by acquired immunodeficiency syndrome.