The bisphosphonate alendronate and conjugated equine estrogens are both widely used for the treatment of postmenopausal osteoporosis. Acting by different mechanisms, these two agents decrease bone ...resorption and thereby increase or preserve bone mineral density (BMD). The comparative and combined effects of these medications have not been rigorously studied. This prospective, double blind, placebo-controlled, randomized clinical trial examined the effects of oral alendronate and conjugated estrogen, in combination and separately, on BMD, biochemical markers of bone turnover, safety, and tolerability in 425 hysterectomized postmenopausal women with low bone mass. In addition, bone biopsy with histomorphometry was performed in a subset of subjects. Treatment included placebo, alendronate (10 mg daily), conjugated equine estrogen (CEE; 0.625 mg daily), or alendronate (10 mg daily) plus CEE (0.625 mg daily) for 2 yr. All of the women received a supplement of 500 mg calcium daily. At 2 yr, placebo-treated patients showed a mean 0.6% loss in lumbar spine BMD, compared with mean increases in women receiving alendronate, CEE, and alendronate plus CEE of 6.0% (P < 0.001 vs. placebo), 6.0% (P < 0.001 vs. placebo), and 8.3% (P < 0.001 vs. placebo and CEE; P = 0.022 vs. alendronate), respectively. The corresponding changes in total proximal femur bone mineral density were +4.0%, +3.4%, +4.7%, and +0.3% for the alendronate, estrogen, alendronate plus estrogen, and placebo groups, respectively. Both alendronate and CEE significantly decreased biochemical markers of bone turnover, specifically urinary N-telopeptide of type I collagen and serum bone-specific alkaline phosphatase. The alendronate plus CEE combination produced slightly greater decreases in these markers than either treatment alone, but the mean absolute values remained within the normal premenopausal range. Alendronate, alone or in combination with CEE, was well tolerated. In the subset of patients who underwent bone biopsies, histomorphometry showed normal bone histology with the expected decrease in bone turnover, which was somewhat more pronounced in the combination group. Thus, alendronate and estrogen produced favorable effects on BMD. Combined use of alendronate and estrogen produced somewhat larger increases in BMD than either agent alone and was well tolerated.
Marked elevation of transforming growth factor-beta 1 (TGF-beta 1) has been demonstrated clinically following injury and in sepsis. While alterations in the monocyte binding site (CD14) for the ...lipopolysaccharide (LPS)-lipopolysaccharide binding protein (LBP) complex have been noted with exposure to LPS, immune complexes, gamma-interferon, and IL-4, it is not known whether TGF-beta 1 can alter CD14 expression. To study the effect of TGF-beta 1 on monocyte CD14 expression, human leukocytes were isolated from healthy donors with discontinuous gradient centrifugation and incubated at 37 degrees C for 2 and 24 hr with increasing doses of purified human platelet TGF-beta 1. Monocytes were immunofluorescently stained with monoclonal antibodies recognizing CD14 and CD16. The cells were analyzed by flow cytometry. At 2 hr, 50 ng/ml TGF-beta 1 significantly lowered CD14 expression (51%, P = 0.043). At 24 hr, there was no significant difference between cells stimulated by TGF-beta 1 and control cells. To confirm that TGF-beta 1 was active at 24 hr, we examined levels of CD16. CD16 expression was increased by 10 ng/ml of TGF-beta 1. These observations suggest that high physiologic concentrations of TGF-beta 1 cause early monocyte suppression of CD14. Thus, CD14 may be marker for the transition of monocytes to macrophages and TGF-beta 1 may be responsible for the down-regulation of CD14 expression observed in monocytes obtained from septic patients.
Plasma and lipoprotein cholesterol and triglycerides, and plasma apolipoproteins AI, AII and B were compared in patients with chronic airflow limitation, and normal controls matched for body mass ...index. The controls were non-smokers, and free from respiratory disease.
High-density lipoprotein (HDL) cholesterol concentration was significantly elevated in the patients, due mainly to a raised HDL2 cholesterol level. HDL triglyceride was significantly lower in the patients. All other lipids were not different from normal. Apolipoprotein AI levels were significantly raised in the patients but other apolipoproteins were unchanged.
The changes found may account in part for the fact that patients with chronic airflow limitation have a lower incidence of atherosclerotic heart disease.
Marine invertebrates produce a large variety of mucussecretions which are rich in glycoproteins. As part of our studies of natural antifouling mechanisms, mucussecretions from the starfish ...Marthasterias glacialis and Porania pulvillus and the brittlestar Ophiocomina nigra have been used to characterise the structure and function of some of the glycoproteins present in these secretions. Mucus was collected from all three species and fractionated by size exclusion chromatography. A high molecular weight glycoprotein fraction was collected from each species. Monosaccharide analysis and FTIR demonstrated a composition consistent with a mucin-type glycoprotein. The mucin from M. glacialis and O. nigra inhibited in vitro bacterial adhesion in a dose-dependent manner. In contrast, the mucin from P. pulvillus promoted bacterial adhesion in a dose-dependent manner. All of the mucins inhibited the adhesion of human neutrophils to cultured human vascular endothelial cells (HUVECs) and had no anticoagulant activity. The mucins described here have adhesion-regulating functions that may have a role in the antifouling or feeding mechanisms of the organisms that produce them. These mucins may also be of therapeutic value through their ability to regulate human neutrophil adhesion or bacterial adhesion.
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