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Cell Adhes Commun. 2000;7(6):477-90.
Localization of urokinase type plasminogen activator to focal adhesions requires ligation of vitronectin integrin receptors.

Wilcox-Adelman SA, Wilkins-Port CE, McKeown-Longo PJ.

Center for Cell Biology and Cancer Research, Albany Medical College, New York 12208, USA.

Previous studies have shown that the adhesion protein, vitronectin, directs the localization of urokinase-type plasminogen activator (uPA) to areas of cell-substrate adhesion, where uPA is thought to regulate cell migration as well as pericellular proteolysis. In the present study, HT-1080 cell lines expressing either wild-type vitronectin or vitronectin containing a single amino-acid substitution in the integrin binding domain were used to assess whether ligation of the alphavbeta5 integrin was required for uPA localization to focal adhesions. The synthesis of wild-type vitronectin by HT-1080 cells adherent to either collagen or fibronectin resulted in the redistribution of both the alphavbeta5 integrin as well as uPA to focal adhesion structures. In contrast, cells synthesizing mutant vitronectin, containing the amino-acid substitution in the integrin binding domain, were unable to direct the redistribution of either alphavbeta5 or uPA to focal adhesions. Recombinant forms of wild-type and mutant vitronectin were prepared in a baculovirus system and compared for their ability to direct the redistribution of vitronectin integrin receptors as well as uPA on human skin fibroblasts. In the absence of vitronectin, fibroblast cells adherent to fibronectin assemble focal adhesions which contain the beta1 integrin but do not contain uPA. Addition of recombinant wild-type, but not mutant, vitronectin to fibroblasts adherent to fibronectin resulted in the redistribution of alphavbeta3, alphavbeta5, and uPA into focal adhesions. However, when cells were plated directly onto antibodies directed against either the alphavbeta3 or alphavbeta5 integrins, uPA was not localized on the cell surface. These data indicate that ligation of vitronectin integrin receptors is necessary but not sufficient for the localization of uPA to areas of cell matrix adhesion, and suggest that vitronectin may promote cell migration by recruiting vitronectin integrin receptors and components of the plasminogen activator system to areas of cell matrix contact.


online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11051458&dopt=Abstract



Cell Adhes Commun. 2000;7(6):513-23.
Modulation of heart fibroblast migration and collagen gel contraction by IGF-I.

Kanekar S, Borg TK, Terracio L, Carver W.

Department of Developmental Biology and Anatomy, University of South Carolina, School of Medicine, Columbia 29208, USA.

Dynamic interactions between cells and the extracellular matrix are essential in the regulation of a number of cellular processes including migration, adhesion, proliferation and differentiation. A variety of factors have been identified which modulate these interactions including transforming growth factor-beta, platelet-derived growth factor and others. Insulin-like growth factors have been shown to regulate collagen production by heart fibroblasts; however, the effects of this growth factor on the interactions of heart fibroblasts with the extracellular matrix have not been examined. The present studies were carried out to determine the effects of IGF-I on the ability of fibroblasts to interact with the extracellular matrix and to begin to determine the mechanisms of this response. These experiments illustrate that IGF-I treatment results in increased migration, collagen reorganization and gel contraction by heart fibroblasts. IGF-I has been shown to activate both the mitogen-activated protein kinase and phophatidylinositol-3 kinase pathways in isolated cells. Experiments with pharmacological antagonists of these pathways indicate that the mitogen-activated protein kinase pathway is essential for IGF-I stimulated collagen gel contraction by fibroblasts. These studies illustrate that IGF-I modulates the ability of fibroblasts to interact with the collagen matrix and that activation of multiple signaling pathways by IGF-I may produce distinct downstream responses in these cells.


online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11051461&dopt=Abstract



Klin Med (Mosk). 2000;78(9):40-3.
[Diagnostic implications of extracellular matrix proteins in chronic hepatitis and hepatic cirrhosis]

[Article in Russian]

Dudanova OP.

Enzyme immunoassay measured concentrations of basic extracellular matrix proteins, collagen type 3 (C-3) and fibronectin, in blood plasm of 119 patients with chronic hepatic diseases. 30, 16, 18, 6 and 49 of them had chronic hepatitis of minimal activity (MiACH), that of moderate activity (MACH), intermediate activity (CHIA), high activity (HACH) and hepatic cirrhosis (HC), respectively. The highest C-3 level occurred in C-stage HC, the lowest--in MiACH. Fibronectin was the highest in HACH, minimal--in C-stage HC. C-3 and fibronectin levels correlated with severity of mesenchymal-inflammatory syndrome in CH and HC; in CHIA, HACH and in B-stage HC--with cytolysis markers. A direct relationship was found between protein-synthetizing function of hepatocytes and fibronectin levels in CHIA, HACH and HC while it was inverse in relation to C-3 amount in HC. Thus, tests for plasm C-3 and finronectin expand potentialities of laboratory diagnosis of the process activity in CH and HC, allow prediction of probability of CH transformation into HC.


online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11051739&dopt=Abstract



J Dermatol. 2000 Sep;27(9):573-5.
Soluble thrombomodulin, a possible predictor of thrombotic crisis in thrombotic disease.

Fujita H.

Department of Dermatology, National Tosei Hospital, Shizuoka, Japan.

Serum soluble thrombomodulin is known to be a factor in visceral vascular disorders such as organic vasculitis in collagen diseases, but recently it has also been reported as a predictor of thrombotic crisis in thrombotic diseases. In this report, serum soluble thrombomodulin levels and events of thrombotic crises in clinical patients were studied retrospectively in our dermatology department over the past five years. I found an increase in soluble thrombomodulin one to two months before the crisis in eight of ten patients including three with anti-phospholipid syndrome, two with lupus anticoagulant-positive systemic lupus erythematosus, four patients with chronic disseminated intravascular coagulation syndrome and one patient with thrombotic thrombocytopenic purpura. A decrease was found after treatment. Other tested parameters did not respond as soluble thrombomodulin, and they were not useful for predicting the crisis one to two months before the crisis. These results suggest the possibility that soluble thrombomodulin might be an important factor in predicting thrombotic crisis.


online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11052232&dopt=Abstract



Histochem Cell Biol. 2000 Aug;114(2):157-65.
Temporospatial expression of tissue inhibitors of matrix metalloproteinases-1, -2 and -3 during development, growth and aging of the mouse skeleton.

Joronen K, Salminen H, Glumoff V, Savontaus M, Vuorio E.

Department of Medical Biochemistry and Molecular Biology, University of Turku, Finland.

Proteolytic degradation of collagen-rich extracellular matrices is a key feature in the development, growth and aging of skeleton. Matrix metalloproteinases (MMPs) are a family of enzymes capable of performing this function, whereas tissue inhibitors of MMPs (TIMPs) are believed to play an important role in regulating their activity. To better understand the roles of TIMP-1, -2 and -3, we have studied their mRNA levels in several different mouse tissues with special emphasis on the skeleton and the developing eye. A systematic analysis of TIMP-1, -2 and -3 mRNA levels in mouse knee joints during growth and aging demonstrated markedly different expression patterns for each TIMP. Immunohistochemical analysis revealed several time-dependent changes in the distribution of TIMP-1 and -2 in articular and growth cartilages, synovial tissue and bone. The data suggest that upon aging synovial tissue becomes the major source of synovial fluid TIMPs. In articular cartilage these inhibitors were mainly found in the deep layer and in subchondral bone. Compared with epiphyseal growth plate, the amounts of TIMP-1 and -2 in articular cartilage were quite low. These findings suggest that the capacity of articular cartilage chondrocytes to inhibit MMP activities by local production of TIMPs is limited, which may be of consequence during osteoarthritic cartilage degeneration.


online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11052264&dopt=Abstract








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