The objective of this study was to examine the effects of cyclic compressive loading on chondrogenic differentiation of rabbit bone-marrow mesenchymal stem cells (BM-MSCs) in agarose cultures. Rabbit BM-MSCs were obtained from the tibias and femurs of New Zealand white rabbits. After the chondrogenic potential of BMMSCs was verified by pellet cultures, cell-agarose constructs were made by suspending BM-MSCs in 2% agarose (10 7 cells/ml) for a cyclic, unconfined compression test performed in a custom-made bioreactor. Specimens were divided into four groups: control; transforming growth factor (TGF-β β) (with TGF-β β1 treatment); loading (with stimulation of cyclic, unconfined compressive loading); and TGF-β β loading (with TGF-β β1 treatment and loading stimulation) groups. In the loading experiment, specimens were subjected to sinusoidal loading with a 10% strain magnitude at a frequency of 1 Hz for 4 hours a day. Experiments were conducted for 3, 7, and 14 consecutive days. While the experimental groups (TGF-β β, loading, and TGF-β β loading) exhibited significantly higher levels of expressions of chondrogenic markers (collagen II and aggrecan) at three time periods, there were no differences among the experimental groups after an extra 5-day culture. This suggests that compressive loading alone induces chondrogenic differentiation of rabbit BM-MSCs as effectively as TGF-β β or TGF-β β plus loading treatment. Moreover, both the compressive loading and the TGF-β β1 treatment were found to promote the TGF-β β1 gene expression of rabbit BMMSCs. These findings suggest that cyclic compressive loading can promote the chondrogenesis of rabbit BMMSCs by inducing the synthesis of TGF-β β1, which can stimulate the BM-MSCs to differentiate into chondrocytes.

Background Smoking marijuana has been reported to increase risk of myocardial infarction (MI) immediately after use, but less is known about the long-term impact of marijuana use among patients with established coronary disease. Methods The Determinants of MI Onset Study (MIOS) is a multicenter inception cohort study of MI patients enrolled in 1989–1996 and followed for mortality using the National Death Index. In an initial analysis of 1935 MI survivors followed for a median of 3.8 years, we found an increased mortality rate among marijuana users. The current paper includes 3886 MIOS patients followed for up to 18 years. We used Cox proportional hazards models to calculate the hazard ratio and 95% confidence interval for the association between marijuana use and mortality and a propensity score matched analysis to further control confounding. Results Over up to 18 years of follow-up, 519 patients died, including 22 of the 109 reporting marijuana use in the year prior to their MI. There was no statistically significant association between marijuana use and mortality. Compared to non-users, the mortality rate was 29% higher (95% confidence interval 0.81 to 2.05, p=0.28) among those reporting any marijuana use. Conclusions Habitual marijuana use among patients presenting with acute MI was associated with an apparent increased mortality rate over the following 18 years that did not reach nominal statistical significance. Larger studies with repeated measures of marijuana use are needed to definitively establish whether there are adverse cardiovascular consequences of smoking marijuana among patients with established coronary heart disease.

Although moderate alcohol drinkers have lower rates of incident coronary artery disease (CAD) than abstainers, much less is known about the health effects of different patterns of alcohol use in women with established CAD. In the Determinants of Myocardial Infarction Onset Study, 1,253 women hospitalized for acute myocardial infarction (AMI) in 64 centers nationwide from 1989–1996 were followed for mortality through 12/31/2007. Of the women, 761 (61%) reported abstention in the year prior to their MI, 280 (22%) reported consumption of <1 serving/week, 75 (6%) reported consumption of 1–3 servings/week, and 137 (11%) reported consumption of 3 or more servings/week. Using Cox proportional hazards models, we investigated the associations between total weekly volume of consumption, drinking days/week, drinks/drinking day, and beverage type with 10-year mortality adjusting for clinical and socioeconomic potential confounders. Compared with abstention, adjusted hazard ratios and 95% confidence intervals were 0.66 (0.50, 0.86) for <1 serving/wk, 0.65 (0.38, 1.11) for 1–3 servings/wk, and 0.65 (0.38, 1.11) for 3 or more servings/wk (p-trend 0.008). We found no differences by beverage type and generally inverse associations of both drinking frequency and quantity with mortality. In conclusion, in women who survive MI, moderate drinking is associated with a decreased risk of mortality, with no clear differences on the basis of pattern or beverage type. Our results suggest that women who survive MI need not abstain from alcohol, but any derived benefit would appear to occur well below currently recommended limits in alcohol consumption.