The means by which muscle function modulates bone homeostasis is poorly understood. To begin to address this issue, we have developed a novel murine model of unilateral transient hindlimb muscle paralysis using botulinum toxin A (Botox). Female C57BL/6 mice (16 weeks) received IM injections of either saline or Botox (n = 10 each) in both the quadriceps and calf muscles of the right hindleg. Gait dysfunction was assessed by multi-observer inventory, muscle alterations were determined by wet mass, and bone alterations were assessed by micro-CT imaging at the distal femur, proximal tibia, and tibia mid-diaphysis. Profound degradation of both muscle and bone was observed within 21 days despite significant restoration of weight bearing function by 14 days. The muscle mass of the injected quadriceps and calf muscles was diminished −47.3% and −59.7%, respectively, vs. saline mice (both P < 0.001). The ratio of bone volume to tissue volume (BV/TV) within the distal femoral epiphysis and proximal tibial metaphysis of Botox injected limbs was reduced −43.2% and −54.3%, respectively, while tibia cortical bone volume was reduced −14.6% (all P < 0.001). Comparison of the contralateral non-injected limbs indicated the presence of moderate systemic effects in the model that were most probably associated with diminished activity following muscle paralysis. Taken as a whole, the micro-CT data implied that trabecular and cortical bone loss was primarily achieved by bone resorption. These data confirm the decisive role of neuromuscular function in mediating bone homeostasis and establish a model with unique potential to explore the mechanisms underlying this relation. Given the rapidly expanding use of neuromuscular inhibitors for indications such as pain reduction, these data also raise the critical need to monitor bone loss in these patients.

Moderate exercise is an ineffective strategy to build bone mass. The authors present data demonstrating that allowing bone to rest between each load cycle transforms low- and moderate-magnitude mechanical loading into a signal that potently induces bone accretion. They hypothesize that the osteogenic nature of rest-inserted loading arises by enabling osteocytes to communicate as a small world network.

The purpose of this study was to evaluate the coupled beta-adrenergic receptor (BAR) and adenylate cyclase (AC) system of the lung during the course of the bleomycin-(Bleo) induced pulmonary fibrosis in hamsters. The BAR population, dissociation constants (Kd), AC activity, and its sensitivity to various stimulators were studied at 2, 4, 7, 14, and 21 days after intratracheal administration of either 1 unit of Bleo or an equivalent volume of saline. The BAR population in the lungs of Bleo-treated animals did not differ from control at the early times, but it was significantly reduced to 5.9 X 10(3) fmol and 3.6 X 10(3) fmol from the control values of 1.1 X 10(4) fmol and 1.5 X 10(4) fmol per lung at 14 and 21 days after treatment, respectively. The Kd values for control hamster lung ranged from 2.5 X 10(-11) M to 3.7 X 10(-11) M, and for Bleo-treated hamster lung, from 2.7 X 10(-11) M to 4.8 X 10(-11) M. The Kd at the earliest time, 2 days after treatment, did not differ significantly from the Kd values at the subsequent times in control, while for Bleo-treated hamster lung, the Kd values at 7, 14, and 21 days were significantly higher than the Kd at 2 days after treatment. The Kd values for Bleo-treated hamster lung were also significantly higher than control at 14 and 21 days. The AC activity of the lung in Bleo-treated hamster was significantly reduced to 67%, 40%, 38%, and 50% of their respective controls in response to H2O (basal), GTP (10(-4) M), GTP + isoproterenol (10(-4) M each), and NaF (10 mM) at 21 days after treatment. The extent of AC stimulation in Bleo-treated hamster lung in response to various stimulators was generally less than that of saline control. Reductions in the BAR population and increased Kd values in Bleo-treated hamster lung were attributed to its fibrogenic ability and not to nutritional deficiency, which may partly be accountable for decreased AC activity of the lung in these animals. However, there were qualitative differences in the lung AC activity between Bleo-treated and nutritionally deprived hamsters, since the enzyme from the latter group was generally more responsive to stimulators than the enzyme from the former group. It was concluded from the findings of this study that an impairment in the coupled BAR and AC system of the lung may be partly responsible for the fibrogenic ability of bleomycin.

LESS than a dozen cases of solid tumour of the umbilical cord are recorded. Although this casc is not strictly an example of neoplasm of the cord, the diagnosis from new growth could not easily be made clinically. Theories of aetiology can be measured against the detailed findings and are of more general interest. For these reasons a detailed report is given.The maternal history was abnormal but probably unrelated to the foetal condition. The mother had had toxaemia in a previous pregnancy, and had also suffered from asthma since adolescence. Continuous asthma of a severe degree had been experienced for z days before admission and continued, despite the usual remedies, during the one day in hospital before delivery.Birth was assisted by the forceps when the head reached the perineum. The infant was cyanosed to about the same degree as the mother, hiit recovered rapidly after a few respirations.A pyriform turnour, zf inches in diameter, was found at the foetal end of the umbilical cord. The cord itself was oedematous, and the veins were dilated for 6 inches distal to the tuniour. The surface of the mass was smooth and the contour regular. The consistence was firm, and fluctuation could not be elicited; on the other hand, the volumr decreased slightly during steady pressure and increased after release of control. The mass was opaque. The narrow end passed into the umbilical opening so that the upper limit could not be defined, but impulse was absent when the infant strained. The tumour did not pulsate. Abnormalities other than the above were not found in the infant.As the tumour breached the abdominal n d l and was covered only by Wharton's jelly and the amnion, early operation was necessary to prevent the development of peritonitis. One day was allotted to permit the child to recover from the stresses of parturition.246

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