Skeletal unloading induces resistance to insulin-like growth factor-I (IGF-I) by inhibiting activation of the IGF-I signaling pathways.

We showed that unloading markedly diminished the effects of IGF-I to activate its signaling pathways, and the disintegrin echistatin showed a similar block in osteoprogenitor cells. Furthermore, unloading decreased alphaVbeta3 integrin expression. These results show that skeletal unloading induces resistance to IGF-I by inhibiting activation of the IGF-I signaling pathways at least in part through downregulation of integrin signaling. INTRODUCTION: We have previously reported that skeletal unloading induces resistance to insulin-like growth factor-I (IGF-I) with respect to bone formation. However, the underlying mechanism remains unclear. The aim of this study was to clarify how skeletal unloading induces resistance to the effects of IGF-I administration in vivo and in vitro with respect to bone formation. MATERIALS AND METHODS: We first determined the response of bone to IGF-I administration in vivo during skeletal unloading. We then evaluated the response of osteoprogenitor cells isolated from unloaded bones to IGF-I treatment in vitro with respect to activation of the IGF-I signaling pathways. Finally we examined the potential role of integrins in mediating the responsiveness of osteoprogenitor cells to IGF-I. RESULTS: IGF-I administration in vivo significantly increased proliferation of osteoblasts. Unloading markedly decreased proliferation and blocked the ability of IGF-I to increase proliferation. On a cellular level, IGF-I treatment in vitro stimulated the activation of its receptor, Ras, ERK1/2 (p44/42 MAPK), and Akt in cultured osteoprogenitor cells from normally loaded bones, but these effects were markedly diminished in cells from unloaded bones. These results were not caused by altered phosphatase activity or changes in receptor binding to IGF-I. Inhibition of the Ras/MAPK pathway was more impacted by unloading than that of Akt. The disintegrin echistatin (an antagonist of the alphaVbeta3 integrin) blocked the ability of IGF-I to stimulate its receptor phosphorylation and osteoblast proliferation, similar to that seen in cells from unloaded bone. Furthermore, unloading significantly decreased the mRNA levels both of alphaV and beta3 integrin subunits in osteoprogenitor cells. CONCLUSION: These results indicate that skeletal unloading induces resistance to IGF-I by inhibiting the activation of IGF-I signaling pathways, at least in part, through downregulation of integrin signaling, resulting in decreased proliferation of osteoblasts and their precursors.     

Apoptosis: understanding the new molecular pathway.

Advances in science have increased the knowledge of how cells die in the body (apoptosis). A basic understanding of this process can improve nurses' ability to review new scientific literature and enable them to provide safer bedside care.     

An approach to fractures of the midface: An interactive tutorial

Purpose: To describe an educational computer aided instruction program dealing with diagnosis and classification of facial fractures. Methods: A program was created for use on Macintosh computers using a graphic presentation package. This program allows for the display of high resolution digitized radiographic images and illustrations, along with integrated voice and text information. Users can interact with the program to review complex concepts or study additional cases. Case material was obtained from selected high quality plain radiographs and computed tomography (CT) scans obtained in the trauma center of one institution, and was scanned on a high resolution digital scanner with image parameters optimized for viewing on the Macintosh high resolution color monitor. Results: The program has been installed in the computer aided instructional laboratories or trauma centers at The University of Texas Health Science Center, Houston; The University of Alabama, Birmingham; Emory University School of Medicine, Atlanta, Georgia; and The University of North Carolina, Chapel Hill. The program is available to radiology residents and medical students rotating on the trauma radiology services at these institutions. Completion of the program requires 30–45 minutes. Conclusion: Based on our initial experience, the program has been used by residents in the training programs of all institutions with favorable results.     

Perceived risk as a factor influencing attitudes toward physically disabled children

The effects of perceptions of risk on attitudes toward handicapped children were studied. Five hundred twenty two nonhandicapped children between the ages of 8 and 19 were assigned to one of four experimental conditions in a basic 2×2 (Risk×Interview) paradigm. Some subjects were assigned to a high risk condition whereby if they indicated they would like to be friends with a handicapped peer, they were told that they might actually have to befriend a handicapped youngster who was about to enter their class; other subjects were not told about any personal involvement with the handicapped child. In the Interview factor, about half the subjects were informed that their attitudes would be known to other group members, the other half of subjects were told their attitudes would remain private. The 2×2 paradigm was studied with children at three ages levels: 8–11; 12–15; 16–19. Results revealed three significant main effects, generally supporting the hypothesis regarding the effects of risk factors.     

GM1 ganglioside partially rescues cultured dopaminergic neurons from MPP-induced damage: dependence on initial damage and time of treatment

GM1 ganglioside is believed to be important in promoting the recovery of neurons from injury. The present study assesses the ability of GM1 to repair or prevent the damage of dopamine neurons caused by the neurotoxin 1-methyl-4-phenylpyridinium (MPP⁺). Treatment of mesencephalic cell cultures with 2.5 μM MPP⁺ resulted in the loss of 30% of tyrosine hydoxylase (TH) immunoreactive neurons. In contrast, cultures administered 100 μM GM1 ganglioside for 3 days after toxin treatment contained nearly control numbers of TH⁺ neurons (97%). This reparative effect of GM1 was reflected in parallel increases in TH enzyme activity, dopamine and dopac levels. Cultures sustaining greater insult from higher doses of MPP⁺ (5.0–10.0 μM) did not benefit from ganglioside treatment, suggesting that rescue by GM1 depended on the degree of initial damage to cells. Moreover, the timing of ganglioside treatment was critical; pretreatment with GM1 alone did not prevent or attenuate the damage caused by subsequent incubation in 2.5 μM MPP⁺.     

Modified crescentic osteotomy in children

A crescentic osteotomy of the first metatarsal is unstable during the preliminary healing stage. The authors present a modification in the direction of the cut of the osteotomy. This alteration increases stability at the first metatarsal base.     

Factors associated with work-related injury among hospital employees: a case-control study.

The Central Arkansas Veterans Healthcare System (CAVHS) spends $1 million annually on occupational illnesses and injuries. To address the problem of injuries among hospital employees, a retrospective case-control study was conducted to examine select risk factors for work-related injuries (WRI) among CAVHS employees. Study methods included a review of employee health charts and computer and manual databases from 1997 to 2002 (N = 2,050). The researchers found that WRI increased with age; WRI occurred more often in women than in men; WRI was greater among maintenance and custodial staff compared to direct caregivers, and less among clerical staff; WRI occurred less often in part-time than full-time staff; and WRI increased with increasing body mass index. Developing standards, guidelines, and policies for preplacement screening, preventive measures, training, and education may help to minimize WRI and associated costs.