DreamPharm Products:
Am J Physiol Lung Cell Mol Physiol. 2000 Nov;279(5):L895-902.
SB 239063, a p38 MAPK inhibitor, reduces neutrophilia, inflammatory cytokines, MMP-9, and fibrosis in lung.
Underwood DC, Osborn RR, Bochnowicz S, Webb EF, Rieman DJ, Lee JC, Romanic AM, Adams JL, Hay DW, Griswold DE.
Department of Pulmonary Pharmacology, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania 19406, USA.
The effects of a second generation p38 mitogen-activated protein kinase (MAPK) inhibitor, SB 239063 [trans-1-(4-hydroxycyclohexyl)-4-(4-fluorophenyl)-5-(2-methoxypyridim idi n-4-yl)imidazole; IC(50) = 44 nM vs. p38 alpha], were assessed in models that represent different pathological aspects of chronic obstructive pulmonary disease (COPD) [airway neutrophilia, enhanced cytokine formation and increased matrix metalloproteinase (MMP)-9 activity] and in a model of lung fibrosis. Airway neutrophil infiltration and interleukin (IL)-6 levels, assessed by bronchoalveolar lavage 48 h after lipopolysaccharide (LPS) inhalation, were inhibited dose dependently by 3-30 mg/kg of SB 239063 given orally twice a day. In addition, SB 239063 (30 mg/kg orally) attenuated IL-6 bronchoalveolar lavage fluid concentrations (>90% inhibition) and MMP-9 activity (64% inhibition) assessed 6 h after LPS exposure. In guinea pig cultured alveolar macrophages, SB 239063 inhibited LPS-induced IL-6 production (IC(50) of 362 nM). In a bleomycin-induced pulmonary fibrosis model in rats, treatment with SB 239063 (2.4 or 4.8 mg/day via osmotic pump) significantly inhibited bleomycin-induced right ventricular hypertrophy (indicative of secondary pulmonary hypertension) and increases in lung hydroxyproline synthesis (indicative of collagen synthesis and fibrosis). Therefore, SB 239063 demonstrates activity against a range of sequelae commonly associated with COPD and fibrosis, supporting the therapeutic potential of p38 MAPK inhibitors such as SB 239063 in chronic airway disease.
online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11053025&dopt=Abstract
J Lab Clin Med. 2002 Nov;140(5):342-50.
Interleukin-1beta stimulates human renal fibroblast proliferation and matrix protein production by means of a transforming growth factor-beta-dependent mechanism.
Vesey DA, Cheung C, Cuttle L, Endre Z, Gobe G, Johnson DW.
Department of Renal Medicine, Princess Alexandra Hospital, Brisbane, Qld, Australia. david_veseealth.qld.gov.au
One of the hallmarks of progressive renal disease is the development of tubulointerstitial fibrosis. This is frequently preceded by macrophage infiltration, raising the possibility that macrophages relay fibrogenic signals to resident tubulointerstitial cells. The aim of this study was to investigate the potentially fibrogenic role of interleukin-1beta (IL-1beta), a macrophage-derived inflammatory cytokine, on cortical fibroblasts (CFs). Primary cultures of human renal CFs were established and incubated for 24 hours in the presence or absence of IL-1beta. We found that IL-1beta significantly stimulated DNA synthesis (356.7% +/- 39% of control, P <.003), fibronectin secretion (261.8 +/- 11% of control, P <.005), collagen type 1 production, (release of procollagen type 1 C-terminal-peptide, 152.4% +/- 26% of control, P <.005), transforming growth factor-beta (TGF-beta) secretion (211% +/- 37% of control, P <.01), and nitric oxide (NO) production (342.8% +/- 69% of control, P <.002). TGF-beta (1 ng/mL) and the phorbol ester phorbol 12-myristate 13-acetate (PMA, 25 nmol/L) produced fibrogenic effects similar to those of IL-1beta. Neither a NO synthase inhibitor (N(G)-methyl-l-arginine, 1 mmol/L) nor a protein kinase C (PKC) inhibitor (bis-indolylmaleimide 1, 1 micromol/L) altered the enhanced level of fibronectin secretion or DNA synthesis seen in response to IL-1beta treatment. However, addition of a TGF-beta-neutralizing antibody significantly reduced IL-1beta-induced fibronectin secretion (IL-1beta + IgG, 262% +/- 72% vs IL-1beta + alphaTGF-beta 156% +/- 14%, P <.02), collagen type 1 production (IL-1beta + IgG, 176% +/- 28% vs IL-1beta + alphaTGF-beta, 120% +/- 14%, P <.005) and abrogated IL-1beta-induced DNA synthesis (245% +/- 49% vs 105% +/- 21%, P <.005). IL-1beta significantly stimulated CF DNA synthesis and production of fibronectin, collagen type 1, TGFbeta, and NO. The fibrogenic and proliferative action of IL-1beta on CF appears not to involve activation of PKC or production of NO but is at least partly TGFbeta-dependent.
online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12434136&dopt=Abstract
Am J Physiol Lung Cell Mol Physiol. 2000 Nov;279(5):L950-7.
Surfactant components modulate fibroblast apoptosis and type I collagen and collagenase-1 expression.
Vazquez de Lara L, Becerril C, Montano M, Ramos C, Maldonado V, Melendez J, Phelps DS, Pardo A, Selman M.
Universidad Autonoma de Puebla, Puebla, Puebla CP 72190, Mexico.
During lung injury, fibroblasts migrate into the alveolar spaces where they can be exposed to pulmonary surfactant. We examined the effects of Survanta and surfactant protein A (SP-A) on fibroblast growth and apoptosis and on type I collagen, collagenase-1, and tissue inhibitor of metalloproteinase (TIMP)-1 expression. Lung fibroblasts were treated with 100, 500, and 1,000 microg/ml of Survanta; 10, 50, and 100 microg/ml of SP-A; and 500 microg/ml of Survanta plus 50 microg/ml of SP-A. Growth rate was evaluated by a formazan-based chromogenic assay, apoptosis was evaluated by DNA end labeling and ELISA, and collagen, collagenase-1, and TIMP-1 were evaluated by Northern blotting. Survanta provoked fibroblast apoptosis, induced collagenase-1 expression, and decreased type I collagen affecting mRNA stability approximately 10-fold as assessed with the use of actinomycin D. Collagen synthesis and collagenase activity paralleled the gene expression results. SP-A increased collagen expression approximately 2-fold and had no effect on collagenase-1, TIMP-1, or growth rate. When fibroblasts were exposed to a combination of Survanta plus SP-A, the effects of Survanta were partially reversed. These findings suggest that surfactant lipids may protect against intraluminal fibrogenesis by inducing fibroblast apoptosis and decreasing collagen accumulation.
online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11053032&dopt=Abstract
Biophys J. 2000 Nov;79(5):2369-81.
A cell-based constitutive relation for bio-artificial tissues.
Zahalak GI, Wagenseil JE, Wakatsuki T, Elson EL.
Department of Biomedical Engineering, Washington University, St. Louis, Missouri 63130, USA. gie.wustl.edu
By using a combination of continuum and statistical mechanics we derive an integral constitutive relation for bio-artificial tissue models consisting of a monodisperse population of cells in a uniform collagenous matrix. This constitutive relation quantitatively models the dependence of tissue stress on deformation history, and makes explicit the separate contribution of cells and matrix to the mechanical behavior of the composite tissue. Thus microscopic cell mechanical properties can be deduced via this theory from measurements of macroscopic tissue properties. A central feature of the constitutive relation is the appearance of "anisotropy tensors" that embody the effects of cell orientation on tissue mechanics. The theory assumes that the tissues are stable over the observation time, and does not in its present form allow for cell migration, reorientation, or internal remodeling. We have compared the predictions of the theory to uniaxial relaxation tests on fibroblast-populated collagen matrices (FPMs) and find that the experimental results generally support the theory and yield values of fibroblast contractile force and stiffness roughly an order of magnitude smaller than, and viscosity comparable to, the corresponding properties of active skeletal muscle. The method used here to derive the tissue constitutive equation permits more sophisticated cell models to be used in developing more accurate representations of tissue properties.
online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11053116&dopt=Abstract
FASEB J. 2000 Nov;14(14):2329-38.
Leptin promotes invasiveness of kidney and colonic epithelial cells via phosphoinositide 3-kinase-, rho-, and rac-dependent signaling pathways.
Attoub S, Noe V, Pirola L, Bruyneel E, Chastre E, Mareel M, Wymann MP, Gespach C.
INSERM U482, Signal Transduction and Cellular Functions in Diabetes and Digestive Cancers, and IFR65, Hopital Saint-Antoine, 75571 Paris Cedex 12, France.
Leptin plays a key role regulating food intake, body weight and fat mass. These critical parameters are associated with an increased risk for digestive and mammary gland cancer in the Western population. Here we determined whether leptin contributes to the invasive phenotype of colonic and kidney epithelial cells at various stages of the neoplastic progression. First, leptin potently (EC50 = 10-30 ng/ml) induces invasion of collagen gels by premalignant familial adenomatous colonic cells PC/AA/C1 and nontumorigenic MDCK kidney epithelial cells, their src-transformed counterparts, and the human adenocarcinoma colonic cells LoVo and HCT-8/S11. Leptin and its Ob-Rb receptors were consistently identified by RT-PCR and immunoblotting in these cell lines, as well as in human colonic epithelial crypts, polyps, colonic tumor resections, and adjacent mucosa. Leptin-induced invasion was effectively blocked by pharmacological inhibitors of several downstream signaling pathways involved in cell transformation, namely, JAK2 tyrosine kinase (AG490), phosphoinositide PI3'-kinase (wortmannin and LY294002), mTOR kinase (rapamycin), and protein kinases C (GF109203X, Go6976). Accordingly, leptin induces transient elevation of the PI3'-kinase lipid products in JAK2 immunoprecipitates prepared from parental MDCK cells. The leptin effect on invasion was potentiated by the activated form of the small GTPase RhoA and was abrogated by dominant negative mutants of RhoA, Rac1, and the p110alpha of PI3'-K. Our data indicate that leptin may exert a local and beneficial effect on migration of normal colonic epithelial cells and reparation of the inflamed or wounded digestive mucosa. We also emphasize a new role for leptin, linking the nutritional and body fat status to digestive cancer susceptibility by stimulating the invasive capacity of colonic epithelial cells at early stages of neoplasia. This finding has potential clinical implications for colon cancer progression and management of obesity.
online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11053255&dopt=Abstract
Is your hair shedding prematurely? Are you losing hair gradually or all of a sudden, or just as you are aging?
Numerous anecdotal cases, and personal testimonies indicate that this herbal formula based on Chinese herbs actually
improves the conditions of hair thinning and hair loss for a significant fraction of people taking it regularly.
The biology of hair growth is complex and a field still under exploration.
hair restoration, despite all the supporting anecdotal cases.
Neither scientific research nor placebo controlled clinical trials has been conducted due to the cost. Shortage of scientific
and clinical research data is not uncommon in herbal and nutritional arena. Important merits of Hair Million is that it is relatively
inexpensive compared with surgical transplantation or prescription drugs, and secondly, it is made only of traditional herbs that
promote hair growth and are widely known to be safe in regular quantities. If you are interested in clinically tested prescription
medication, check Propecia.
LipitorTramadol
Natural Herbal Supplements||
Constipation relief, laxative, colon cleansing ||
Best Realtor in Glendale, California: Residential Home and Commercial Property ||
Related Web pages ||
Viagra ||
Herbs and Pharmaceuticals Online ||