OBJECTIVETo investigate type I collagen metabolism in patients with arsenic poisoning in Dazhuyuan town, Ankang area in southern Shaanxi province known for high-level exposure to arsenic (As), fluoride (F) and selenium (Se).

METHODSThis case-control study involved 29 patients with arsenic poisoning from Dazhuyuan, a town in Ankang area of Shaanxi province affected by coal-borne endemic arsenicosis. Thirty individuals without arsenic poisoning from Chang'an county of Xi'an city were included as the control group. The serum concentrations of As and Se were determined using a graphite furnace atomic absorption spectrophotometer, and the levels of F detected with a fluoride ion-selective electrode. Enzyme-linked immunosorbent assay (ELISA) was used for assessing serum contents of PICP and PINP, and the sequence of COL1alpha1 gene was analyzed with ABI sequence analyzer.

RESULTSThe contents of PICP and PINP were similar between the two groups, which had also identical COL1alpha1 DNA sequences. After controlling for all the other factors, an inverse correlation was noted between PICP and serum F contents (r=-0.4, P<0.05) and between PINP and hair F content (r=-0.5, P<0.05), but a positive correlation was found between PINP and hair Se content (r=0.5, P<0.05).

CONCLUSIONHair F and Se levels are the major factors affecting PINP synthesis, and increased hair F level is associated with elevated PINP content, whereas hair Se level is inversely correlated to PINP content. But in the patients with arsenic poisoning from Dazhuyuan town, the PICP, PINP contents and COL1alpha1 DNA sequence show no significant alterations, suggesting that hair Se increment abolishes the effect of hair F increment in inducing the decrease in PINP content.

Adult ; Aged ; Aged, 80 and over ; Arsenic Poisoning ; blood ; genetics ; Case-Control Studies ; China ; Collagen Type I ; genetics ; Female ; Humans ; Male ; Middle Aged ; Peptide Fragments ; blood ; Procollagen ; blood ; Sequence Analysis, DNA

BACKGROUNDS/AIMS: The serum level of hyaluronic acid (HA) has been suggested as a useful serologic marker for hepatic fibrosis. However, the relationship between serum HA levels and quantitative markers of fibrosis from liver tissue has not been reported. The aim of this study was to determine the correlation between serum HA level and quantitative measurement of hepatic fibrosis in a cirrhotic rat model. METHODS: Cirrhosis was produced by common bile duct ligation (BDL) in adult Sprague-Dawley rats. The animals were classified into four groups: (1) G1, sham operated (n=5); (2) G2, BDL for 2 weeks (n=6); (3) G3, BDL for 3 weeks (n=6); and (4) G4, BDL for 4 weeks (n=6). Hepatic fibrosis was analyzed histomorphologically using the Batts and Ludwig scoring system. Serum HA level and hepatic hydroxyproline content were quantified. The gene expressions in the liver of procollagen, collagen, and transforming growth factor-beta (TGF-beta) were measured by reverse transcriptase-polymerase chain reaction. RESULTS: In groups G1, G2, G3, and G4, the Batts and Ludwig scores (mean+/-SD) were 0, 1.3+/-0.5, 2.6+/-0.5, and 3.4+/-0.5, respectively (P<0.05), serum HA levels were 12.5+/-3.2, 30.0+/-4.3, 228.6+/-157.7, and 391.3+/-207.7 ng/mL (P<0.05), and the concentration of hydroxyproline was 12.4+/-2.8, 17.6+/-3.8, 17.9+/-2.4, and 33.4+/-3.4 microgram/g liver tissue, and it was significantly higher in group G4 than in the other groups (P<0.05). The gene expressions of collagen, procollagen, and TGF-beta1 in the liver were also significantly higher in group G4 compared with the other groups (P<0.05). Direct linear correlations were observed between serum HA level and hepatic hydroxyproline content, hepatic gene expressions of collagen, procollagen, TGF-beta1, and histomorphological grade of hepatic fibrosis (P<0.001). CONCLUSIONS: These results indicate that serum HA is a useful and noninvasive serologic marker for the evaluation of advanced hepatic fibrosis.
Animals ; Bile Ducts/pathology/surgery ; Biological Markers/blood ; Collagen/analysis/genetics ; Hyaluronic Acid/*blood ; Hydroxyproline/blood ; Ligation ; Liver/metabolism/*pathology ; Liver Cirrhosis, Experimental/*diagnosis/metabolism/pathology ; Male ; Models, Animal ; Procollagen/analysis/genetics ; RNA, Messenger/analysis ; Rats ; Rats, Sprague-Dawley ; Sickness Impact Profile ; Transforming Growth Factor beta/analysis/genetics

Previous studies have demonstrated that enalapril and verapamil seem to attenuate the cyclosporine nephrotoxicity. However, the mechanisms have not been completely understood, especially on molecular events. The aim of this study was to examine the effect of individual or combined treatment on osteopontin, TGF-beta, endothelin-1 and procollagen alpha 1(I) mRNA expressions. Enalapril (50 mg/L in drinking water) and verapamil (0.5 mg/kg/day, subcutaneously), alone or in combination, were administered to rats with chronic cyclosporine nephrotoxicity (cyclosporine, 25 mg/kg/day, subcutaneously) (n = 5 each). Five rats treated with olive oil vehicle were used as control. After 4 weeks, biochemical parameters were measured, and renal cortical mRNA levels were evaluated by Northern blot analysis. Cyclosporine reduced renal creatinine clearance significantly and induced renal cortical osteopontin, TGF-beta, endothelin-1 and procollagen alpha 1(I) gene expressions around 13.5 +/- 1.3, 2.4 +/- 0.2, 1.5 +/- 0.1, 1.9 +/- 0.1 folds, respectively. Individual treatment with enalapril or verapamil significantly suppressed the osteopontin and TGF-beta mRNA expression, but not endothelin-1 and procollagen alpha 1(I). Combined treatment also inhibited the osteopontin and TGF-beta mRNA expression but there was no difference between combined and individual treatment. In conclusion, enalapril or verapamil significantly blunted the cyclosporine-induced osteopontin and TGF-beta gene expressions. However, combined treatment did not show any additive effect.
Angiotensin-Converting Enzyme Inhibitors/therapeutic use* ; Animal ; Calcium Channel Blockers/therapeutic use* ; Cyclosporine/adverse effects ; Drug Therapy, Combination ; Enalapril/therapeutic use* ; Enalapril/administration & dosage ; Endothelin-1/metabolism ; Endothelin-1/genetics ; Gene Expression Regulation/drug effects ; Immunosuppressive Agents/adverse effects ; Kidney Cortex/metabolism ; Male ; Nephritis/drug therapy* ; Nephritis/chemically induced ; Procollagen/metabolism ; Procollagen/genetics ; RNA, Messenger/analysis ; Rats ; Rats, Wistar ; Sialoglycoproteins/metabolism ; Sialoglycoproteins/genetics ; Transforming Growth Factor beta/metabolism ; Transforming Growth Factor beta/genetics ; Verapamil/therapeutic use* ; Verapamil/administration & dosage

BACKGROUNDLower fluence of 585-nm flashlamp-pumped pulsed dye laser has been successfully used as a nonablative technique in the treatment of wrinkles. The objective of this study was to evaluate the effect of the pulsed dye laser (585 nm) on the production of collagen and the mRNA expression of collagen related gene in fibroblasts in vitro.

METHODSCultured fibroblasts were treated with a 585-nm flashlamp-pumped pulsed dye laser (fluence 3 J/cm(2), 4 J/cm(2), spot size 7 mm, pulse duration 450 micros). The production of collagen and the mRNA expression of transforming growth factor (TGF)-beta1, SMAD2, SMAD3, SMAD4, SMAD7 and type I procollagen alpha1, alpha2 in fibroblasts were investigated by colorimetry or real time polymerase chain reaction.

RESULTSThe production of collagen was significantly up-regulated after treatment with a 585-nm flashlamp-pumped pulsed dye laser with a fluence of 3 J/cm(2) (P < 0.001). The mRNA expression of TGF-beta1, SMAD2, SMAD3, SMAD4, SMAD7 and procollagen I was significantly up-regulated after treatment with a 585-nm flashlamp-pumped pulsed dye laser with a fluence of 3 J/cm(2) (P < 0.001). No significant difference of mRNA expression of SMAD2, SMAD3, SMAD4, SMAD7 and type I procollagen was found between controls and fibroblasts treated with pulsed dye laser with a fluence of 4 J/cm(2) (P > 0.05).

CONCLUSIONSLower fluence (3 J/cm(2)) pulsed dye laser increased the collagen production in fibroblasts by up-regulating TGF-beta1, SMAD2, SMAD3, SMAD4, SMAD7 and type I procollagen mRNA expression. These may be the reason it can be effectively used in the treatment of wrinkles.

Analysis of Variance ; Cells, Cultured ; Collagen ; biosynthesis ; Fibroblasts ; cytology ; metabolism ; radiation effects ; Gene Expression ; radiation effects ; Humans ; Lasers ; Procollagen ; genetics ; RNA, Messenger ; genetics ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Smad2 Protein ; genetics ; Smad3 Protein ; genetics ; Smad4 Protein ; genetics ; Smad7 Protein ; genetics ; Transforming Growth Factor beta ; genetics ; Transforming Growth Factor beta1