Molecular and signaling mechanisms of atherosclerosis in insulin resistance.

Although the prevalence of cardiovascular complications is increased in insulin-resistant individuals, the underlying causes of this link have been elusive. Recent work suggests that several intracellular signal transduction pathways are inappropriately activated by hyperinsulinemia, hyperglycemia, increased free fatty acids, dyslipidemia, various inflammatory cytokines and adipokines--factors that are increased in insulin resistance. Once activated, substantial cross talk occurs between these pathways, especially a self-reinforcing cascade of vascular inflammation and cell dysfunction, greatly increasing the risk and severity of atherosclerosis in the insulin-resistant individual. We review several key cell-signalling pathways, describe how they are activated in they insulin-resistant state and the damage they induce, and discusses possible therapeutic approaches to limit vascular damage.     

Predictors of Partner Notification for C. trachomatis and N. gonorrhoeae: An Examination of Social Cognitive and Psychological Factors

Efforts to control chlamydial and gonococcal infections include notifying eligible sexual partners of possible infection, primarily by asking the diagnosed patient to notify their partners. This approach, known as patient referral, is widely used but poorly understood. The current study examined psychosocial and cognitive factors associated with patient referral among an urban, minority sample of 168 participants recently diagnosed with Chlamydia trachomatis or Neisseria gonorrhoeae. At a follow-up interview 1-month from diagnosis, participants were more likely to have notified all eligible partners if they had greater intention to notify at baseline (OR = 3.72; 95% CI = 1.34, 10.30) and if they had only one partner at baseline (OR = 4.08; 95% CI = 1.61, 10.31). There were also gender differences as well as differences based on type of partner (i.e., regular, casual, one-time). The implications of these findings for the design of programs to promote patient referral for sexually transmitted infections are discussed. Schwartz, Malka, Augenbraun, McCormack, and Wilson are with the State University of New York, Downstate Medical Center, Brooklyn, NY, USA; Rubin is with the New York City Department of Health, Bureau of STD Control, New York, NY, USA; Rubin, Hogben, and Liddon are with the Centers for Disease Control and Prevention, Atlanta, GA, USA; Schwartz is with the Department of Preventive Medicine and Community Health, SUNY Downstate Medical Center, Box 1240, 450 Clarkson Avenue, Brooklyn, NY 11203, USA.     

Pretreatment of bone with osteoclasts affects phenotypic expression of osteoblast-like cells.

Implant surface morphology regulates osteoblast phenotypic expression. Osteoblast sensitivity to non-biologic surfaces suggests that native bone surface features may also affect osteoblast response. To test this, MG63 osteoblast-like cells were grown for 7 days on bovine cortical bone wafers pretreated with rat bone marrow osteoclasts for 0, 10 or 20 days. Response to osteoclast-treated surfaces was compared to the response of MG63 cells to titanium surfaces with smooth and rough microtopographies. Cell number, differentiation (alkaline phosphatase activity and osteocalcin levels), and local factors (PGE(2) and TGF-beta1) were measured in confluent cultures. Compared to culture on plastic, cell number was reduced on all three types of bone wafers; this effect was dose-dependent with increasing resorption of the surface. Alkaline phosphatase specific activity was increased (P相似文献   

Functional and morphologic endothelial damage in rabbit external jugular veins stored in heparinized normal saline.

Previous studies have demonstrated that vein storage in normal saline leads to significant mechanical morphological, and biochemical aberrations. However, little information is available regarding the functional damage that occurs. The purpose of this study was to evaluate the effect of saline storage on venous smooth muscle and endothelial function. Segments of ten external jugular veins from male New Zealand White rabbits were placed nondistended in either modified Krebs solution at 37 degrees C (Krebs-stored, KS) or heparinized normal saline at room temperature (saline-stored, SS) for 1 h. Segments 4 mm in length were then simultaneously studied in vitro under isometric tension. There was no difference in maximum tension or sensitivity to either bradykinin or histamine. Acetylcholine-induced relaxation in KS segments was not significantly different from relaxation in a historical cohort of nonstored segments (nonstored 87.4 +/- 1.0% vs. KS 84.5 +/- 2.0%; p = NS). However, there were significant attenuations in SS segment endothelium-dependent relaxation in response to both acetylcholine (KS 84.5 +/- 2.0% vs. SS 76.4 +/- 2.7%, p less than 0.02) and adenosine diphosphate (KS 47.9 +/- 2.9% vs. SS 40.6 +/- 3.7%, p less than 0.002). Relaxant responses to sodium nitroprusside (endothelium-independent) were not significantly different in the two groups (KS 94.6 +/- 1.6% vs. SS 95.7 +/- 2.2%; p = NS). Electron microscopic evaluation of SS segments revealed endothelial cell disruption with cellular edema and loss of intact junctions.(ABSTRACT TRUNCATED AT 250 WORDS)     

Bony allografts and prosthetic replacement of the acetabular aspect of the hip

Summary 51 cases of repeat hip replacement have been reviewed, using allografts for acetabular bone loss, stages 2 and 3 (27 lyophilised and 24 deep-frozen). Mean follow-up was 4 years. Loosening was the reason for intervention; 14% of cases were septic. Massive grafts were used in 75% of cases and smaller grafts in 25% of cases. In addition a reinforcement ring was necessary in 75% of cases. Merle d'Aubigné's rating scale was used to assess results. The radiologic assessment score was that of Gross and De Lee.There was no difference between lyophilised and deep-frozen grafts. Clinical scores found 55% of excellent results; 11% were poor, the rest were good or fair. Stability was more troublesome than pain. Radiologic screening showed union between graft and host in 53% of cases but in 41% there was incomplete fusion. In the non-weight-bearing area bone lysis appeared in 14 cases out of 20. Five cases were complete failures; four of these were infected and were reoperated, the bone-graft acting as a foreign body.To date, we have no better bone replacement material than allografts. Fixation of the graft must be secure. An infected hip is not a good indication for this type of operation. Clinical results are satisfactory in more than 80% of cases, although 40% of grafts seem to be incompletely integrated.     

Familias Unidas: The Efficacy of an Intervention to Promote Parental Investment in Hispanic Immigrant Families

This paper reports a test of the efficacy of Familias Unidas, a Hispanic-specific, ecologically focused, parent-centered preventive intervention, in promoting protection against and reducing risk for adolescent behavior problems. Specifically, the intervention was designed to foster parental investment, reduce adolescent behavior problems, and promote adolescent school bonding/academic achievement, all protective factors against drug abuse and delinquency. One-hundred sixty seven Hispanic families of 6th and 7th grade students from three South Florida public schools were stratified by grade within school and randomly assigned to intervention and no-intervention control conditions. Results indicated that Familias Unidas was efficacious in increasing parental investment and decreasing adolescent behavior problems, but that it did not significantly impact adolescent school bonding/academic achievement. Summer-vacation rates of adolescent behavior problems were six times higher in the control condition than in the intervention condition. Furthermore, change in parental investment during the intervention was predictive of subsequent levels of adolescent behavior problems. The findings suggest that Familias Unidas is efficacious in promoting protection and reducing risk for adolescent problem behaviors in poor immigrant Hispanic families.     

Recombinant bone morphogenetic protein (BMP)-2 regulates costochondral growth plate chondrocytes and induces expression of BMP-2 and BMP-4 in a cell maturation-dependent manner

This study examined the effect of recombinant human bone morphogenetic protein-2 on several parameters of growth, differentiation, and matrix synthesis and on the endogenous production of mRNA of bone morphogenetic proteins 2 and 4 by growth plate chondrocytes in culture. Chondrocytes from resting and growth zones were obtained from rat costochondral cartilage and cultured for 24 or 48 hours in medium containing 0.05-100 ng/ml recombinant human bone morphogenetic protein-2 and 10% fetal bovine serum. Incorporation of [³H]thymidine, cell number, alkaline phosphatase specific activity, incorporation of [³H]proline into collagenase-digestible protein and noncollagenase-digestible protein, and incorporation of [³⁵S]sulfate were assayed as indicators of cell proliferation, differentiation, and extracellular matrix synthesis. mRNA levels T for bone morphogenetic proteins 2 andv4 were determined by Northern blot analysis. Recombinant human bone morphogenetic protein-2 increased the incorporation of [³H]thymidine by quiescent resting-zone and growth-zone cells in a similar manner, whereas it had a differential effect on nonquiescent cultures. At 24 and 48 hours, 12.5-100 ng/ml recombinant human bone morphogenetic protein-2 caused a dose-dependent increase in cell number and DNA synthesis in resting-zone chondrocytes. No effect was seen in growth-zone cell Recombinant human bone morphogenetic protein-2 stimulated alkaline phosphatase specific activity in resting-zone chondrocytes in a bimodal manner, causing significant increases between 0.2 and 0.8 ng/ml and again between 25 and 100 ng/ml. In contrast, alkaline phosphatase specific activity in growth-zone chondrocytes was significantly increased only between 12.5 and 100 ng/ml. Recombinant human bone morphogenetic protein-2 increased the production of both collagenase-digestible protein and noncollagenase-digestible protein by resting-zone and growth-zone cells, but incorporation of [³⁵S]sulfate was unaffected. Administration of recombinant human bone morphogenetic protein-2 also increased incorporation of [³H]uridine in both resting-zone and growth-zone chondrocytes; these cells produced mRNA for bone morphogenetic proteins 2 and 4. Bone morphogenetic protein-2 mRNA levels in both resting-zone and growth-zone chondrocytes increased in the presence of recombinant human bone morphogenetic protein-2; however, bone morphogenetic protein-4 mRNA levels in growth-zone cells decreased under its influence, and those in resting-zone cells were upregulated only with a dose of 10 ng/ml. This indicates that recombinant human bone morphogenetic protein-2 regulates chondrocyte proliferation, differentiation, and matrix production, and the effects are dependent on the stage of cell maturation. Resting-zone chondrocytes were more sensitive, suggesting that they are targeted by bone morphogenetic protein-2 and that this growth factor may have autocrine effects on these cells.