Human osteoblasts' proliferative responses to strain and 17beta-estradiol are mediated by the estrogen receptor and the receptor for insulin-like growth factor I.

The mechanism by which mechanical strain and estrogen stimulate bone cell proliferation was investigated using monolayer cultures of human osteoblastic TE85 cells and female human primary (first-passage) osteoblasts (fHOBs). Both cell types showed small but statistically significant dose-dependent increases in [3H]thymidine incorporation in response to 17beta-estradiol and to a single 10-minute period of uniaxial cyclic strain (1 Hz). In both cell types, the peak response to 17beta-estradiol occurred at 10(-8) - 10(-7) M and the peak response to strain occurred at 3500 microstrain ((mu)epsilon). Both strain-related and 17beta-estradiol-related increases in [3H]thymidine incorporation were abolished by the estrogen receptor (ER) modulator ICI 182,780 (10-8 M). Tamoxifen (10(-9) - 10(-8) M) increased [3H]thymidine incorporation in both cell types but had no effect on their response to strain. In TE85 cells, tamoxifen reduced the increase in [3H]thymidine incorporation associated with 17beta-estradiol to that of tamoxifen alone but had no such effect in fHOBs. In TE85 cells, strain increased medium concentrations of insulin-like growth factor (IGF) II but not IGF-I, whereas 17beta-estradiol increased medium concentrations of IGF-I but not IGF-II. Neutralizing monoclonal antibody (MNAb) to IGF-I (3 microg/ml) blocked the effects of 17beta-estradiol and exogenous truncated IGF-I (tIGF-I; 50 ng/ml) but not those of strain or tIGF-II (50 ng/ml). Neutralizing antibody to IGF-II (3 microg/ml) blocked the effects of strain and tIGF-II but not those of 17beta-estradiol or tIGF-I. MAb aIR-3 (100 ng/ml) to the IGF-I receptor blocked the effects on [3H]thymidine incorporation of strain, tIGF-II, 17beta-estradiol, and tIGF-I. HOBs and TE85 cells, act similarly to rat primary osteoblasts and ROS 17/2.8 cells in their dose-related proliferative responses to strain and 17beta-estradiol, both of which can be blocked by the ER modulator ICI 182,780. In TE85 cells (as in rat primaries and ROS 17/2.8 cells), the response to 17beta-estradiol is mediated by IGF-I, and the response to strain is mediated by IGF-II. Human cells differ from rat cells in that tamoxifen does not block their response to strain and reduces the response to 17beta-estradiol in TE85s but not primaries. In both human cell types (unlike rat cells) the effects of strain and IGF-II as well as estradiol and IGF-I can be blocked at the IGF-I receptor.     

Intravascular brachytherapy: a systematic review of its role in reducing restenosis after endovascular treatment in peripheral arterial disease.

INTRODUCTION: Intravascular brachytherapy (IVBT) utilises the percutaneous insertion of a radioactive source to inhibit myointimal hyperplasia in arteries treated by balloon angioplasty or stenting. A systematic review was performed of trials of IVBT in patients with Peripheral Arterial Disease (PAD). METHODS: Search strategy - the reviewers searched Medline, Embase, the Cochrane Peripheral Vascular Diseases Group trials register, DARE, CCT and NHS EED for clinical studies and trials of adjuvant IVBT in PAD. Two reviewers assessed trial quality independently. RESULTS: Fourteen clinical trials were identified by the search, representing five clinical studies (all allocated D for not randomised) and one randomised controlled trial (allocated A). The randomised trial showed a benefit for IVBT compared with placebo (OR 0.35, 95% CI 0.24-0.53). In the non-randomised studies, 12 month cumulative patency rates ranged from 60-87%. There were few technical complications. In the only report involving IVBT and routine concurrent stent insertion acute thrombosis occurred in 7 (21%) of patients. CONCLUSION: Early reports have confirmed the safety and technical feasibility of IVBT. However, follow-up is too short at present to assess the durability and long-term complications of this new therapeutic option.     

Effects of Metal Exposures on Juvenile Clams,Mercenaria mercenaria

Bulletin of Environmental Contamination and Toxicology - Elevated metal concentrations occur throughout the coastal zone due to urbanization and various anthropogenic activities. The lethal...     

Intrapartum-related birth asphyxia in South Africa--lessons from the first national perinatal care survey.

BACKGROUND: The recent amalgamation of data by users of the Perinatal Problem Identification Programme (PPIP) throughout South Africa has culminated in the publication of the Saving Babies report. OBJECTIVES: To determine the absolute rate of death from intrapartum-related birth asphyxia, and the contribution of intrapartum-related asphyxia to total perinatal mortality in South African hospitals, and to identify the primary obstetric causes and avoidable factors for these deaths. METHODS: The amalgamated PPIP data for the year 2000 were obtained from 27 state hospitals (6 metropolitan, 12 town and 9 rural) in South Africa. In PPIP-based audit, all perinatal deaths are assigned primary obstetric causes and avoidable factors, and these elements were obtained for all deaths resulting from intrapartum-related birth asphyxia. RESULTS: There were 123,508 births in the hospitals surveyed, with 4,142 perinatal deaths among infants > or = 1,000 g, giving a perinatal mortality rate of 33.5/1,000 births. The perinatal mortality rate from intrapartum-related birth asphyxia was 4.8/1,000 births. The most frequent avoidable factors were delay by mothers in seeking attention during labour (36.6%), signs of fetal distress interpreted incorrectly (24.9%), inadequate fetal monitoring (18.0%) and no response to poor progress in labour (7.0%). The perinatal mortality rates for metropolitan, town, and rural areas were 30.0, 39.4 and 30.9/1,000 births respectively. The contribution of intrapartum-related birth asphyxia to perinatal mortality in these areas was 10.8%, 16.7% and 26.4% respectively. CONCLUSION: The high rates of perinatal death from intrapartum-related birth asphyxia in South Africa are typical of those in underdeveloped countries, with the most serious deficiencies in rural areas. Most of these deaths are avoidable and the reduction of these rates presents an important challenge to providers of perinatal care in this country. Areas worthy of research and action include provision of mothers' waiting facilities in rural regions, improvements in fetal monitoring, partogram-based labour management, and the establishment of midwifery staffing norms for South African labour units.     

Increased ratio of saturated to unsaturated C18 fatty acids in colonic adenocarcinoma: Implications for cryotherapy and lipid raft function

Mammalian fatty acid synthase (FASE) overexpression has been shown in a number of human malignancies including colonic adenocarcinoma. Since FASE synthesizes only saturated fatty acids, we hypothesized that cancer cells have a greater proportion of long-chain saturated fatty acids. We studied and found an unequivocal increase in saturated C18 fatty acid (stearic acid) in colonic adenocarcinoma compared to adjacent normal colonic mucosa. The increase is even more striking when measured as a ratio of stearic acid to the unsaturated C18 fatty acids (oleic acid and linoleic acid). This change in fatty acid composition of the cancer cells should significantly alter their physical and biological properties. The increase in relative proportion of saturated fatty acids should make the cancer cells more susceptible to cryodamage and measurement of fatty acid composition of cancer cells may help individualize the temperature for cryotherapy. Also, the lipid alterations may affect the structure and functions of lipid rafts, which may enable the cancer cells to affect signaling mechanisms such as those involved in cell growth and apoptosis. Dietary or therapeutic interventions targeting lipid rafts may thus be an option for cancer treatment.