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Biochim Biophys Acta. 2000 Nov 15;1502(3):351-62.
Antioxidant properties of colchicine in acute carbon tetrachloride induced rat liver injury and its role in the resolution of established cirrhosis.
Das D, Pemberton PW, Burrows PC, Gordon C, Smith A, McMahon RF, Warnes TW.
The Liver Unit, Manchester Road Infirmary, Manchester, UK.
Antioxidant and antifibrotic properties of colchicine were investigated in the carbon tetrachloride (CCl(4)) rat model. (1) The protective effect of colchicine pretreatment on CCl(4) induced oxidant stress was examined in rats subsequently receiving a single lethal dose of CCl(4). Urinary 8-isoprostane, kidney and liver malondialdehyde and kidney glutathione levels increased following CCl(4) treatment, but only the rise in kidney malondialdehyde was significantly inhibited by colchicine pretreatment. Serum total antioxidant levels were significantly higher in the colchicine pretreatment group. (2) The long term effects of colchicine treatment on CCl(4) induced liver damage were investigated using liver histology and biochemical markers (hydroxyproline and type III procollagen peptide). Co-administration of colchicine with sub-lethal doses of CCl(4) over 10 weeks did not prevent progression to cirrhosis. However, rats made cirrhotic with repeated CCl(4) challenge and subsequently treated with colchicine for 12 months, all showed histological regression of cirrhosis. (3) The antioxidant effect of colchicine in vitro was evident only at very high concentrations compared to other plasma antioxidants. In summary, colchicine has only weak antioxidant properties, but does afford some protection against oxidative stress; more importantly, long term treatment with this drug may be of value in producing regression of established cirrhosis.
online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11068178&dopt=Abstract
Osteoporos Int. 2000;11(7):583-91.
Polymorphisms of the VDR, ER and COLIA1 genes and osteoporotic hip fracture in elderly postmenopausal women.
Aerssens J, Dequeker J, Peeters J, Breemans S, Broos P, Boonen S.
Arthritis and Metabolic Bone Disease Research Unit, Division of Traumatology and Emergency Surgery, K.U. Leuven, Belgium.
In view of the reported associations between osteoporosis and polymorphisms of the vitamin D receptor (VDR), collagen Ialpha1 (COLIA1) and estrogen receptor (ER) genes, an association study was performed between VDR, COLLIA1, and ER genotypes and bone mineral density, biochemical markers of bone turnover and hip fracture occurrence in Belgian older postmenopausal women. The gene polymorphisms were evaluated by restriction fragment length polymorphism analyses, using the restriction enzymes BsmI (VDR), AccB7I (COLIA1), and PvuII and XbaI (ER), respectively. As expected, bone mineral density and biochemical analyses demonstrated significant differences between hip fracture patients and elderly controls. However, no significant differences in genotype distributions or allele frequencies were observed between the cases (n = 135, age 78 +/- 9 years) and controls (n = 239, age 76 +/- 4 years) for any of the gene polymorphisms. Stratification of both study populations according to VDR, COLIA1 or ER genotype did not reveal any statistically significant difference in bone density or bone turnover between subgroups with different genotypes. In conclusion, despite its limited statistical power the outcome of this study does not support the hypothesis of a major contribution of the VDR, COLIA1 or ER polymorphisms to explain variations in bone mineral density or bone turnover, or to identify elderly women at risk of osteoporotic hip fracture.
online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11069192&dopt=Abstract
J Biol Chem. 2003 Feb 7;278(6):4238-49. Epub 2002 Nov 14.
Endorepellin, a novel inhibitor of angiogenesis derived from the C terminus of perlecan.
Mongiat M, Sweeney SM, San Antonio JD, Fu J, Iozzo RV.
Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
Perlecan, a ubiquitous basement membrane heparan sulfate proteoglycan, plays key roles in blood vessel growth and structural integrity. We discovered that the C terminus of perlecan potently inhibited four aspects of angiogenesis: endothelial cell migration, collagen-induced endothelial tube morphogenesis, and blood vessel growth in the chorioallantoic membrane and in Matrigel plug assays. The C terminus of perlecan was active at nanomolar concentrations and blocked endothelial cell adhesion to fibronectin and type I collagen, without directly binding to either protein; henceforth we have named it "endorepellin." We also found that endothelial cells possess a significant number of high affinity (K(d) of 11 nm) binding sites for endorepellin and that endorepellin binds endostatin and counteracts its anti-angiogenic effects. Thus, endorepellin represents a novel anti-angiogenic product, which may retard tumor neovascularization and hence tumor growth in vivo.
online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12435733&dopt=Abstract
Matrix Biol. 2000 Nov;19(6):489-500.
Structure of the mouse type XV collagen gene, Col15a1, comparison with the human COL15A1 gene and functional analysis of the promoters of both genes.
Eklund L, Muona A, Lietard J, Pihlajaniemi T.
Collagen Research Unit, Biocenter and Department of Medical Biochemistry, University of Oulu, Aapistie 7, P.O. Box 5000, 90014, Oulu, Finland.
Isolation and characterization of the mouse gene for the alpha1 chain of type XV collagen (Col15a1) revealed it to be approximately 110 kb in length and contain 40 exons. Analysis of the proximal 5'-flanking region showed properties characteristic of a housekeeping gene promoter, such as an absence of TATA and CAAT boxes, the presence of several transcriptional start sites and a high G+C content. The general organization of the mouse Col15a1 gene was found to be highly similar to that of its human homologue, but the genomic area encoding the end of the N-terminal non-collagenous domain showed marked divergence from the human form. Furthermore, two exons coding for the N-terminal collagenous domain of the human alpha1(XV) chain are lacking in the mouse Col15a1 gene. Due to the lack of two exons and a codon divergence in one exon, the mouse alpha1(XV) chain contains seven collagenous domains, whereas the human equivalent contains nine. Comparison of 5'-flanking sequences indicated four domains that were conserved between the mouse and human genes. Functional analysis of the mouse promoter identified cis-acting elements for both positive and negative regulation of Col15a1 gene expression in mouse NIH/3T3 cells.
online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11068203&dopt=Abstract
Am J Clin Nutr. 2000 Nov;72(5):1206-13.
Alcohol intake and bone metabolism in elderly women.
Rapuri PB, Gallagher JC, Balhorn KE, Ryschon KL.
Bone Metabolism Unit and the Cardiac Center, Creighton University, School of Medicine, Omaha, NE 68131, USA. thiyyarreighton.edu
BACKGROUND: Published reports on the effect of alcohol consumption on bone mineral density (BMD) are inconsistent. OBJECTIVE: The objective of this study was to examine the relation between alcohol intake and BMD, calcitropic hormones, calcium absorption, and other biochemical indexes of bone and mineral metabolism in elderly women. DESIGN: The results presented are derived from baseline observations of 489 elderly women (aged 65-77 y) recruited for an osteoporosis study. The nondrinking group comprised 297 women and the drinking group comprised 148 women. Furthermore, the effect of different alcohol intakes (</=28.6, >28.6 to </=57.2, >57.2 to </=142.9, and >142.9 g/wk) was studied. RESULTS: Women who consumed alcohol had significantly higher spine (10%), total body (4.5%), and midradius (6%) BMD than did nondrinkers. An alcohol intake >28.6 g/wk was associated with higher BMD; maximum effect was seen with an intake of >28.6 to </=57.2 g/wk (16%, 12%, and 14% increase in spine, total body, and midradius BMD, respectively). There was a marked reduction in bone remodeling markers, serum osteocalcin, and the ratio of urinary cross-linked N:-telopeptides of type 1 collagen to creatinine with alcohol consumption, suggesting that increased BMD with alcohol consumption could be due to reduced bone remodeling. Further, serum parathyroid hormone concentrations were significantly lower in alcohol drinkers than in nondrinkers and could be one of the causes of decreased bone resorption. CONCLUSIONS: Moderate alcohol intake was associated with higher BMD in postmenopausal elderly women. The protective effect of alcohol may have been a result of lower bone remodeling due to reduced parathyroid hormone concentrations or factors such as increased estrogen concentrations.
online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11063451&dopt=Abstract
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