No abstract

The in-vitro effects of avocado and soybean unsaponifiable residues on neutral metalloproteinase activity, cytokines and prostaglandin E2 (PGE2) production by human articular chondrocytes were investigated. Avocado and soybean unsaponifiable residues were mixed in three ratios: 1:2 (A1S2), 2:1 (A2S1) or 1:1 (A2S2). Freshly isolated human chondrocytes were cultured for 72 h in the absence or presence of interleukin-1beta, (IL-1beta) (17 ng/ml), with or without unsaponifiable residue mixtures at a concentration of 10 microg/ml. A/S unsaponifiable residues were also tested separately at concentrations of 3.3, 6.6 and 10 microg/ml. All A/S unsaponifiable mixtures reduced the spontaneous production of stromelysin, interleukin-6 (IL-6), interleukin-8 (IL-8) and prostaglandin E2 (PGE2) by chrondrocytes. At concentrations of 3.3 and 6.6 microg/ml, A/S residues, tested separately, were potent inhibitors of the production of IL-8 and PGE2. Nevertheless, only avocado residue inhibited IL-6 production at these concentrations. A/S unsaponifiable mixtures had a more pronounced inhibitory effect on cytokine production than avocado or soybean residues added alone. As anticipated, IL-1beta induced a marked release of collagenase, stromelysin, IL-6, IL-8 and PGE2. A/S unsaponifiable mixtures partially reversed the IL-1 effects on chrondrocytes. These findings suggest a potential role for A/S unsaponifiable extracts in mitigating the deleterious effects of IL-1beta: on cartilage.

Based on previous studies showing that strontium ranelate (S12911) modulates bone loss in osteoporosis, it could be hypothesized that this drug also is effective on cartilage degradation in osteoarthritis (OA). This was investigated in vitro on normal and OA human chondrocytes treated or not treated with interleukin-1␤ (IL-1␤). This model mimics, in vitro, the imbalance between chondroformation and chondroresorption processes observed in vivo in OA cartilage. Chondrocytes were isolated from cartilage by enzymatic digestion and cultured for 24 -72 h with 10 ؊4 -10 ؊3 M strontium ranelate, 10 ؊3 M calcium ranelate, or 2 ⅐ 10 ؊3 M SrCl 2 with or without IL-1␤ or insulin-like growth factor I (IGF-I). Stromelysin activity and stromelysin quantitation were assayed by spectrofluorometry and enzyme amplified sensitivity immunoassay (EASIA), respectively. Proteoglycans (PG) were quantified using a radioimmunoassay. Newly synthesized glycosaminoglycans (GAGs) were quantified by labeled sulfate (Na 2 35 SO 4 ) incorporation. This method allowed the PG size after exclusion chromatography to be determined. Strontium ranelate, calcium ranelate, and SrCl 2 did not modify stromelysin synthesis even in the presence of IL-1␤. Calcium ranelate induced stromelysin activation whereas strontium compounds were ineffective. Strontium ranelate and SrCl 2 both strongly stimulated PG production suggesting an ionic effect of strontium independent of the organic moiety.

The present study was designed to visit elderly women living in nursing homes and to compare their femoral neck bone mineral density (BMD) and circulating levels of parathyroid hormone (PTH) and 25-OH vitamin D (25-OHD) with those of subjects living at home, in the immediate vicinity of the nursing homes. Of 1483 women, aged 70 years and older, who were selected, 993 agreed to participate in this trial. Their femoral neck BMD (n = 993) was measured by dual-energy X-ray absorptiometry, with a specific device installed in a mobile truck. The circulating levels of 25-OHD and PTH were assessed after an overnight fast (n = 748). After stratification for age, there were no significant differences in mean femoral neck BMD values, prevalence of femoral neck osteoporosis, mean serum 25-OHD and prevalence of absolute or relative 25-OHD deficiency between the two groups. Serum levels of PTH were significantly higher in women over 80 years old living in nursing homes, compared with the community-dwelling women. After adjustment for age, a significant relation was found between femoral neck BMD and PTH levels in the whole population (p = 0.004) and in community-dwelling subjects (p = 0.039). When stratifying our population by quartiles of serum PTH values, the odds ratios for femoral neck osteoporosis were significantly increased for the top two quartiles compared with the lowest one both before (p = 0.00146) and after (p = 0.0013) adjustment for age and type of housing. From this study we conclude that femoral osteoporosis is largely underestimated in European women. Living in a nursing home is not, per se, a risk factor for decreased femoral BMD, and circulating PTH levels are a key determinant of low femoral bone density and osteoporosis.

Endothelins (ET) are potent vasoconstrictors that are directly mitogenic for vascular smooth muscle cells and fibroblasts. It is possible that the vasoconstrictor and mitogenic effects of ET could play a significant role in the vascular remodeling process that occurs in chronic vascular rejection (CVR). We have previously shown that cardiac allografts in the indefinitely surviving major histocompatibility complex identical WF.1L (RT1(1)) to Lewis (LEW) (RT1(1)) inbred rat strain combination provide a highly reproducible model of progressive CVR. The objective of this investigation was to measure endothelin-1 ventricular content of WF.1L-LEW cardiac allografts and to determine the immunohistochemical patterns of ET cellular reactivity at well defined posttransplant time periods. Data were compared with those obtained in similar studies of LEW-LEW syngeneic: heart grafts as well as all recipients' own hearts. The ventricular ET-1 content of the WF.1L cardiac allografts was markedly higher (4.3-, 7.0-, and 4.8-fold at 20, 40, and 60 days, respectively) than in corresponding recipients' hearts. Also, the increase in ventricular ET-1 levels as compared with the recipients' hearts rose significantly only in the allograft group. No comparable differences were observed in the syngeneic heart graft controls. Allografts consistently showed ET staining of intimal myocytes at sites of occlusive and subocclusive intimal proliferation associated with CVR. Allografts also showed ET cellular staining in areas of reparative fibrosis associated with indolent interstitial rejection and ischemic myocardial damage. The results of this study strongly suggest that ET may play a significant role in the pathogenesis of CVR.