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Collagen Synthesis (collagen + synthesis)
Selected AbstractsEffects of protein-, peptide- and free amino acid-based diets in fish nutritionAQUACULTURE RESEARCH, Issue 5 2010Konrad Dabrowski In the present review, we summarize data related to the utilization of purified diets formulated with the purpose of determining the amino acid requirements in fish independent of the ontogenetic stage and the morphological characteristics of the digestive tract. Expanding present knowledge on the formulation of protein, free amino acid (FAA) and synthetic dipeptide-based diets can provide possible insights that might lead to a better understanding of the mechanism of amino acid utilization in the growth of fish. Differences exist in the utilization of protein, dipeptides or free amino acids for growth between stomach-possessing and stomachless fish with respect to their response to manipulating the proportion of protein and dipeptides in the formulas. Free amino acid-based diets are uniformly inferior. The effects of diet manipulation on indispensable FAA concentrations in the body (muscle) are not simply the result of deamination or the protein synthesis/degradation ratio. The hydroxyproline/proline ratio was confirmed to be of value in quantifying muscle collagen degradation/synthesis and can perhaps be used to quantify the amino acid requirement necessary to maximize the utilization (deposition) of dietary amino acids. In summary, indispensable amino acid requirements for maximum growth in fish can be addressed using diets formulated from protein/peptide/FAA sources. [source] Cryosurgery in the Treatment of Earlobe Keloids: Report of Seven CasesDERMATOLOGIC SURGERY, Issue 12 2005Tomas Fikrle MD Background. Keloids are benign cutaneous lesions that result from excessive collagen synthesis and deposition. Earlobe keloids in particular are seen as a complication of plastic surgery or piercing. Many different treatment modalities have been used, often with unsatisfactory results. Methods. We have made a retrospective analysis of seven young patients (ages 9 to 22 years) with earlobe keloids. Scarring followed plastic surgery in six cases and piercing in one case. All patients were treated with cryosurgery as the monotherapy. The freeze time and the number of sessions varied depending on the clinical findings, the effect of the treatment, and the patients' tolerance. Cryotherapy was started 6 to 24 months after keloid development. Results. Scar volume was reduced in all cases. Complete flattening in five patients and a pronounced reduction to a maximum of 25% of the previous thickness in one other patient were achieved. One patient discontinued the therapy because of soreness after only partial improvement. The procedure was painful for all patients; no further side effects were noticed. No recurrence was observed within 1 to 4.5 years of follow-up. Conclusion. We present an excellent effect of cryosurgery as the monotherapy for the treatment of earlobe keloid scars of young patients. TOMAS FIKRLE, MD, AND KAREL PIZINGER, MD, PHD, HAVE INDICATED NO SIGNIFICANT INTEREST WITH COMMERCIAL SUPPORTERS. [source] Occlusive Dressing versus Oxygen Mist Therapy Following CO2 Laser ResurfacingDERMATOLOGIC SURGERY, Issue 6 2000Teri Onouye BA Background. Oxygen is an essential element for collagen synthesis and reepithelialization. The use of topical oxygen after CO2 laser resurfacing has not been studied. Objective. To compare the rate and quality of healing in wounds treated with an oxygen mist to those treated with occlusive dressing following CO2 laser resurfacing. Methods. Three patients underwent CO2 laser resurfacing to each half of the face 3 weeks apart. Postoperatively, half of the face was treated with an oxygen mist protocol for 5 days, while the other half was treated with occlusive dressing for 4 days. Results. At postoperative day 5, significantly less crusting was observed on the half of the face treated with the oxygen mist protocol (p < 0.05). Conclusion. The oxygen mist postoperative protocol may offer patients similar overall healing rates and significantly less crusting compared to occlusive dressing. [source] Interaction of vitamins C and E as better cosmeceuticalsDERMATOLOGIC THERAPY, Issue 5 2007Karen E Burke ABSTRACT:, Although many cosmeceutical formulations contain vitamin C and/or vitamin E, very few are actually effective in topical application. First because there is only a low concentration, second because the stability is compromised as soon as the product is opened and exposed to air and light, and third because the form of the molecule (an ester or a mixture of isomers) is not absorbed or metabolized effectively by the skin. However, when a stable formulation delivers a high concentration of the nonesterified, optimal isomer of the antioxidant, vitamins C and E do indeed inhibit the acute ultraviolet (UV) damage of erythema, sunburn, and tanning as well as chronic UV photoaging and skin cancer. Both are highly effective depigmenting agents. Topical vitamin C also increases collagen synthesis in both young and old fibroblasts. Because vitamin C regenerates oxidized vitamin E, the combination in a cosmeceutical formulation is synergistic , particularly in UV protection. [source] ROCK inhibitor (Y27632) increases apoptosis and disrupts the actin cortical mat in embryonic avian corneal epitheliumDEVELOPMENTAL DYNAMICS, Issue 3 2004Kathy K.H. Svoboda Abstract The embryonic chicken corneal epithelium is a unique tissue that has been used as an in vitro epithelial sheet organ culture model for over 30 years (Hay and Revel [1969] Fine structure of the developing Avian cornea. Basel, Switzerland: S. Karger A.G.). This tissue was used to establish that epithelial cells could produce extracellular matrix (ECM) proteins such as collagen and proteoglycans (Dodson and Hay [1971] Exp Cell Res 65:215,220; Meier and Hay [1973] Dev Biol 35:318,331; Linsenmayer et al. [1977] Proc Natl Acad Sci U S A 74:39,43; Hendrix et al. [1982] Invest Ophthalmol Vis Sci 22:359,375). This historic model was also used to establish that ECM proteins could stimulate actin reorganization and increase collagen synthesis (Sugrue and Hay [1981] J Cell Biol 91:45,54; Sugrue and Hay [1982] Dev Biol 92:97,106; Sugrue and Hay [1986] J Cell Biol 102:1907,1916). Our laboratory has used the model to establish the signal transduction pathways involved in ECM-stimulated actin reorganization (Svoboda et al. [1999] Anat Rec 254:348,359; Chu et al. [2000] Invest Ophthalmol Vis Sci 41:3374,3382; Reenstra et al. [2002] Invest Ophthalmol Vis Sci 43:3181,3189). The goal of the current study was to investigate the role of ECM in epithelial cell survival and the role of Rho-associated kinase (p160 ROCK, ROCK-1, ROCK-2, referred to as ROCK), in ECM and lysophosphatidic acid (LPA) -mediated actin reorganization. Whole sheets of avian embryonic corneal epithelium were cultured in the presence of the ROCK inhibitor, Y27632 at 0, 0.03, 0.3, 3, or 10 ,M before stimulating the cells with either collagen (COL) or LPA. Apoptosis was assessed by Caspase-3 activity assays and visualized with annexin V binding. The ROCK inhibitor blocked actin cortical mat reformation and disrupted the basal cell lateral membranes in a dose-dependent manner and increased the apoptosis marker annexin V. In addition, an in vitro caspase-3 activity assay was used to determine that caspase-3 activity was higher in epithelia treated with 10 ,M Y-27632 than in those isolated without the basal lamina or epithelia stimulated with fibronectin, COL, or LPA. In conclusion, ECM molecules decreased apoptosis markers and inhibiting the ROCK pathway blocked ECM stimulated actin cortical mat reformation and increased apoptosis in embryonic corneal epithelial cells. Developmental Dynamics 229:579,590, 2004. © 2004 Wiley-Liss, Inc. [source] Quantitative analysis of the synthesis and secretion of type VII collagen in cultured human dermal fibroblasts with a sensitive sandwich enzyme-linked immunoassayEXPERIMENTAL DERMATOLOGY, Issue 2 2007Satoshi Amano Abstract:, Type VII collagen is the major component of anchoring fibrils in the epidermal basement membrane. Its expression has been analyzed by immunostaining or Northern blotting, but rarely at the protein level. In this study, we have quantitatively examined the effects of ascorbic acid and various cytokines/growth factors on the protein synthesis and secretion of type VII collagen by human dermal fibroblasts in culture, using a developed, highly sensitive sandwich enzyme-linked immunoassay with two kinds of specific monoclonal antibodies against the non-collagenous domain-1. Ascorbic acid and its derivative induced a twofold increase in type VII collagen synthesis, and markedly increased the secretion of type VII collagen into the medium when compared with the control culture. This effect was not influenced by the presence of transforming growth factor- ,1 (TGF- ,1). The synthesis of type VII collagen was elevated by TGF- ,1, platelet-derived growth factor, tumor necrosis factor- ,, and interleukin-1,, but not by TGF- ,. Thus, our data indicate that the synthesis and secretion of type VII collagen in human dermal fibroblasts are regulated by ascorbate and the enhancement of type VII collagen gene expression by cytokines/growth factors is accompanied with elevated production of type VII collagen at the protein level. [source] Effect of parathyroid hormone-related protein on fibroblast proliferation and collagen metabolism in human skinEXPERIMENTAL DERMATOLOGY, Issue 4 2002Emanuela Maioli Abstract: The parathyroid hormone-related protein (PTHrp), structurally similar to the parathyroid hormone (PTH) in its NH2 -terminal part, was first identified as a tumour-derived peptide responsible for a paraneoplastic syndrome known as humoral hypercalcemia of malignancy. The PTHrp gene is expressed not only in cancer but also in normal tissues during adult and/or fetal life, where it plays predominantly paracrine and/or autocrine roles. In the skin PTHrp produced by keratinocytes acts on fibroblasts by complex cooperative circuits involving cytokines and growth factors. In this report, we studied the direct effects of synthetic PTHrp 1,40 on proliferation and collagen synthesis and matrix metalloproteinase-2 (MMP-2) activity in cultures of fibroblasts isolated from normal human skin. Fibroblasts exposure to varying doses of PTHrp for 48 h, significantly and dose-dependently inhibited proliferation evaluated by [3H]-thymidine incorporation into DNA. A dose-dependent stimulation of cAMP released into the medium was concomitantly observed. In contrast, PTHrp had no effect on collagen synthesis evaluated either by [3H]-proline incorporation or by radioimmunoassay (RIA) of the carboxyterminal fragment of type I procollagen (PICP). MMP-2 activity, evaluated by quantitative zymographic analysis, was significantly increased by PTHrp treatment at doses of 160 and 320 nM. These findings indicate that PTHrp may play a role in normal dermal physiology by controlling both fibroblast proliferation and extracellular matrix degradation. [source] Preventive effects of ME3738 on hepatic fibrosis induced by bile duct ligation in ratsHEPATOLOGY RESEARCH, Issue 7 2008Kazunori Maeda Aim:, The aim of this study was to examine the preventive effects of ME3738 on hepatic fibrosis induced by bile duct ligation (BDL) in rats. Methods:, ME3738 (20 mg/day) was administered orally for 21 days immediately after BDL. Fibrosis was assessed by measuring hepatic hydroxyproline (Hyp) content. Activated hepatic stellate cells (HSCs) were assessed by ,-smooth muscle actin (,-SMA) immunostaining. Hepatic thiobarbituric acid-reactive substance (TBARS), 4-hydroxy-2-nonenal (4-HNE) and 8-hydroxy-2-deoxyguanosine (8-OHdG) immunostaining were used to analyze oxidative stress. The gene expressions of collagen-I, transforming growth factor-,1 (TGF-,1), tissue inhibitor of metalloproteinases-1 (TIMP-1), interleukin-6 (IL-6) and heme oxygenase-1 (HO-1) in the liver were examined by real-time reverse transcriptase polymerase chain reaction (RT,PCR). Results:, Hepatic Hyp content and the area of hepatic fibrosis in BDL rats treated with ME3738 were reduced by 24% and 39% compared with non-treated BDL rats (hepatic Hyp, 9.40 ± 2.85 vs. 12.39 ± 3.91 mg/liver; P = 0.036; area of hepatic fibrosis, 13.1 ± 3.8 vs. 21.5 ± 10.9; P = 0.045). Furthermore, ,-SMA-positive cells were significantly reduced by 40% (22.3 ± 14.8 vs. 37.6 ± 14.2; P = 0.011), collagen-I mRNA by 83% (6.5 ± 2.2 vs. 38.3 ± 9.1; P = 0.002), HO-1 mRNA by 58% (4.13 ± 1.22 vs. 9.73 ± 1.80; P = 0.018) and hepatic HO-1 content by 26% (2.13 ± 0.80 vs. 2.87 ± 0.19; P = 0.01) following ME3738 treatment. The hepatic expression of TBARS, 4-HNE, 8-OHdG and mRNA levels of TGF-,1, TIMP-1 and IL-6 in the liver were unchanged by ME3738 treatment. Conclusion:, Oral ME3738 administration may prevent the progression of hepatic fibrosis in BDL rats through suppression of the activation and collagen synthesis of HSC and, in part, oxidative stress. ME3738 has potential as a therapeutic drug for cholestatic liver fibrosis. [source] Alport syndrome: HLA association and kidney graft outcomeINTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 3 2004S. Barocci Summary Alport syndrome (AS) is a genetic disease of type IV collagen involving non-homogeneous patterns of inheritance characterized clinically by the presence of progressive haematuric nephritis leading to end-stage renal disease (ESRD), hearing loss and/or ophthalmologic abnormalities. The aim of this study was to investigate, in a cohort of AS patients who had undergone a kidney graft (KG) or who were still on a waiting list for a KG, (a) whether there is a correlation between AS and HLA antigen expression, and (b) long-term graft outcome in transplant patients. The AS cohort was represented by 34 ESRD patients, of whom 25 received a KG and the remaining nine were still on a waiting list. AS transplant patients represented 2.78% of 899 first KGs performed at our centre (Transplantation Department at S. Martino Hospital, Genoa) between 1983 and 2002. Grafts were procured from cadaveric donors in 18 cases and from living, related donors in seven cases. All AS transplant patients had a post-transplant follow-up period of at least 12 months. Results showed that: (i) the frequency of the HLA-DRB1*16 antigen was significantly increased in the whole AS cohort as compared to 128 healthy subjects (HS) (corrected P -value 0.0026; relative risk 7.20) as well as to 232 non-AS ESRD patients on a waiting list for KG (corrected P -values 0.0156; relative risk 4.67); (ii) 5- and 10-year graft survivals in the AS transplant patients were 80 and 73%, respectively, and did not differ from those of a control group represented by 25 non-AS KG recipients matched for sex, age, number of HLA mismatches and immunosuppressive treatment. Increased frequency of HLA-DRB1*16 in AS patients may reflect a linkage disequilibrium with genes coding for collagen synthesis. [source] The characterization and optimization of injectable silicone resin particles in conjunction with dermal fibroblasts and growth factors: An in vitro studyJOURNAL OF BIOMEDICAL MATERIALS RESEARCH, Issue 1 2010Robert M. Crews Abstract Minimally invasive subdermal injection of liquid silicone has been used clinically to augment the soft tissue of the foot to mitigate high pressures that cause diabetic foot ulcers. However, implant migration has been a clinical issue. The objective of this study was to assess the effects of three specific concentrations of silicone resin particles (12 ,m average diameter) in conjunction with either platelet-derived growth factor (PDGF-BB) or basic fibroblast growth factor (bFGF) on fibroblast cell proliferation, collagen synthesis, cell morphology, and migration through in vitro assays and a monolayer scratch wound model. PDGF and bFGF enhanced the proliferation of fibroblasts 5.7-fold and fivefold, respectively, while the addition of silicone particles had no significant effect on proliferation. Collagen production was increased approximately twofold with the addition of bFGF and the medium concentration of particles over bFGF without particles and the PDGF groups. The addition of silicone particles had no significant effect on collagen production compared with control groups without particles. Fibroblast migration was enhanced by the addition of both PDGF and bFGF compared to controls, although slower scratch wound closure rates were observed in the presence of particles compared to controls without particles. Cell morphology suggested that particles induced cellular aggregation encircling silicone particles postwounding as well as migration into the wound area. These results suggest that silicone particles in combination with a growth factor might enhance fibroblast aggregation and implant stability, and could promote connective tissue ingrowth and implant encapsulation in the soft tissue of the diabetic foot. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2010 [source] Cellular repressor of E1A-stimulated genes attenuates cardiac hypertrophy and fibrosisJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 7 2009Zhouyan Bian Abstract Cellular repressor of E1A-stimulated genes (CREG) is a secreted glycoprotein of 220 amino acids. It has been proposed that CREG acts as a ligand that enhances differentiation and/or reduces cell proliferation. CREG has been shown previously to attenuate cardiac hypertrophy in vitro. However, such a role has not been determined in vivo. In the present study, we tested the hypothesis that overexpression of CREG in the murine heart would protect against cardiac hypertrophy and fibrosis in vivo. The effects of constitutive human CREG expression on cardiac hypertrophy were investigated using both in vitro and in vivo models. Cardiac hypertrophy was produced by aortic banding and infusion of angiotensin II in CREG transgenic mice and control animals. The extent of cardiac hypertrophy was quantitated by two-dimensional and M-mode echocardiography as well as by molecular and pathological analyses of heart samples. Constitutive over-expression of human CREG in the murine heart attenuated the hypertrophic response, markedly reduced inflammation. Cardiac function was also preserved in hearts with increased CREG levels in response to hypertrophic stimuli. These beneficial effects were associated with attenuation of the mitogen-activated protein kinase (MAPK)-extracellular signal-regulated kinase 1 (MEK-ERK1)/2-dependent signalling cascade. In addition, CREG expression blocked fibrosis and collagen synthesis through blocking MEK-ERK1/2-dependent Smad 2/3 activation in vitro and in vivo. Therefore, the expression of CREG improves cardiac functions and inhibits cardiac hypertrophy, inflammation and fibrosis through blocking MEK-ERK1/2-dependent signalling. [source] How do glucocorticoids compare to oligo decoys as inhibitors of collagen synthesis and potential toxicity of these therapeutics?JOURNAL OF CELLULAR BIOCHEMISTRY, Issue 1 2004Kenneth R. Cutroneo Abstract This article demonstrates how glucocorticoids decrease collagen synthesis. The parameters used to assess procollagen synthesis in our laboratory will be compared to those used by others. This article will note all the pertinent literature on the molecular mechanisms of this down regulation of procollagen synthesis. For example, what are the effects of glucocorticoids at the levels of transcription and translation of collagen mRNAs? Finally, we will define a molecular mechanism to inhibit Type I collagen synthesis by decreasing the binding of the TGF-, activator protein complex to the TGF-, element in the distal promoter of the pro,1 Type I collagen gene, preventing the 2:1 ratio of ,1 to ,2 chains in the processed Type I collagen molecule. We will next ask "How do sense oligo decoys decrease Type I collagen synthesis at the in vivo and at the cell levels?" In primary fibrotic cell culture, the double-stranded phosphorothioate oligodeoxynucleotide decoys were more effective than their sense single-stranded counterparts. The molecular mechanism for the decrease in Type I collagen synthesis is the same as glucocorticoids, that is by decreasing the binding of the TGF-, activator protein complex to the TGF-, element in the distal promoter of the pro,1 Type I collagen gene for the transcription of the pro,1 mRNAs. The reason for using sense oligo decoys as anti-fibrotic agents as compared to the anti-fibrotic glucocorticoids, is that presently marketed and FDA approved glucocorticoids have many untoward side effects which the sense oligo decoys do not have. © 2004 Wiley-Liss, Inc. [source] Effect of dexamethasone withdrawal on osteoblastic differentiation of bone marrow stromal cellsJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 1 2003Ryan M. Porter Abstract Dexamethasone is capable of directing osteoblastic differentiation of bone marrow stromal cells (BMSCs) in vitro, but its effects are not lineage-specific, and sustained exposure has been shown to down-regulate collagen synthesis and induce maturation of an adipocyte subpopulation within BMSC cultures. Such side effects might be reduced if dexamethasone is applied in a regimented manner, but the discrete steps in osteoblastic maturation that are stimulated by dexamethasone are not known. To examine this, dexamethasone was added to medium to initiate differentiation of rat BMSCs cultures and then removed after a varying number of days. Cell layers were analyzed for cell number, rate of collagen synthesis, expression of osteocalcin (OC), bone sialoprotein (BSP) and lipoprotein lipase (LpL), and matrix mineralization. Withdrawal of dexamethasone at 3 and 10 days was found to enhance cell number relative to continuous exposure, but did not affect to decrease collagen synthesis slightly. Late markers of osteoblastic differentiation, BSP expression and matrix mineralization, were also sensitive to dexamethasone and increased systematically with exposure while LpL systematically decreased. These results indicate that dexamethasone acts at both early and late stages to direct proliferative osteoprogenitor cells toward terminal maturation. J. Cell. Biochem. 90: 13,22, 2003. © 2003 Wiley-Liss, Inc. [source] Toothbrushing promotes gingival fibroblast proliferation more effectively than removal of dental plaqueJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 9 2002Masazumi Horiuchi Abstract Objectives: Removal of dental plaque is an essential element of periodontal treatment. However, there have also been studies of the effects of the mechanical stimulation provided by toothbrushing on gingival host-defense mechanisms. The aim of the study was to evaluate the effects of toothbrushing on gingival fibroblast proliferation in dogs over time, compared to effects of plaque removal without brushing. Methods: The mouths of six mongrel dogs were divided into four quadrants: two for daily toothbrushing, and two for daily plaque removal with a curette. After 1, 3 and 5 weeks of treatment, histometrical analyses were performed to assess inflammatory cell infiltration, proliferating cell nuclear antigen (PCNA)-positive fibroblasts, procollagen type I-positive fibroblasts in the subepithelial connective tissue of junctional epithelium. Results: Toothbrushing increased the number of PCNA-positive fibroblasts in the first week, increased the number of type I procollagen-positive fibroblasts at the fifth week, and reduced inflammatory cell infiltration at the third week. Conclusion: These findings suggest that mechanically stimulated fibroblasts begin proliferating within a week, and this cell division results in an increased number of fibroblasts at the third week. It takes 5 weeks before differences in collagen synthesis between brushing and plaque removal areas are detectable. Zusammenfassung Die Proliferation der gingivalen Fibroblasten wird durch Zähneputzen wirkungsvoller gefördert als durch Plaqueentfernung Ziele: Die Entfernung von Zahnplaque ist ein essenzieller Bestandteil der Parodontalbehandlung. Es gibt jedoch auch Studien über die Wirkung einer durch Zähneputzen bewirkten mechanischen Stimulation der gingivalen Abwehrmechanismen. Ziel dieser Studie war es, bei Hunden die Wirkung des Zähneputzen auf die Proliferation der gingivalen Fibroblasten über eine gewisse Zeit zu untersuchen und mit der Wirkung einer Plaqueentfernung ohne Zähneputzen zu vergleichen. Methoden: Das Maul von 6 Mischlingshunden wurde in vier Quadranten unterteilt: zwei mit täglichem Zähneputzen und zwei mit täglicher Plaqueentfernung mittels Kürette. 1, 3 und 5 Wochen nach der Behandlung wurden histometrische Analysen durchgeführt um das entzündliche Zellinfiltrat, die proliferierenden Cell-Nuclear-Antigen (PCNA)-positiven Fibroblasten und die Prokollagen-I-positiven Fibroblasten des subgingivalen Bindegewebes des Saumepithels zu bestimmen. Ergebnisse: Zähneputzen erhöhte in der ersten Woche die Anzahl der PCNA-positiven Fibroblasten, erhöhte bis zur fünften Woche die Anzahl der Type-I-Prokollagen-positiven Fibroblasten und reduzierte das entzündliche Zellinfiltrat bis zur dritten Woche. Schlussfolgerung: Diese Ergebnisse lassen annehmen, dass mechanisch stimulierte Fibroblasten während einer Woche zu proliferieren beginnen und diese Zellteilung eine erhöhte Anzahl von Fibroblasten in der dritten Woche zum Ergebnis hat. Es dauert fünf Wochen bevor zwischen den Bereichen mit Zähneputzen und Plaqueentfernung Unterschiede in der Kollagensynthese nachweisbar sind. Résumé Le brossage dentaire favorise la prolifération des fibroblastes gingivaux d'une manière plus efficace que l'enlèvement de la plaque dentaire L'enlèvement de la plaque dentaire est un élément essentiel dans le traitement parodontal. Cependant, des études ont été menées sur les effets de la stimulation mécanique produit par le brossage dentaire sur les mécanismes de défense de l'hôte au niveau gingival. Le but de l'étude présente a été d'évaluer les effets du brossage dentaire sur la prolifération des fibroblastes gingivaux chez les chiens dans le temps, comparés aux effets de l'enlèvement de la plaque dentaire sans brossage. Les bouches de six chiens bâtards ont été divisés en quatre quadrants : deux pour un brossage dentaire journalier et deux pour l'enlèvement journalier de la plaque à l'aide d'une curette. Après une, trois et cinq semaines de traitement, les analyses histométriques ont été effectuées pour évaluer l'infiltration cellulaire inflammatoire, les fibroblastes positifs à l'antigène du noyau cellulaire proliférant (PCNA), les fibroblastes positifs au procollagène-I dans le tissu conjonctif sous-épithélial de l'épithélium de jonction. Le brossage dentaire augmentait le nombre de fibroblastes positifs (PCNA) durant la première semaine, augmentait le nombre de fibroblastes positifs au collagène type-1 à la cinquième semaine et réduisait l'infiltration cellulaire inflammatoire à la troisième semaine. Ces découvertes suggèrent que les fibroblastes stimulés mécaniquement commencent à proliférer en une semaine, et cette division cellulaire abouti en un nombre plus important de fibroblastes à la troisième semaine. Il faut attendre cinq semaines avant que des différences dans la synthèse du collagène entre les zones de brossage et d'enlèvement de la plaque dentaire ne soient détectables. [source] The use of light-emitting diode therapy in the treatment of photoaged skinJOURNAL OF COSMETIC DERMATOLOGY, Issue 3 2007FACCS, FRACGP, Fabien Baez MBBS, MAACS, MCPSA Summary Background, Light-emitting diode (LED) therapy is an increasingly popular methodology for the treatment of sun damage. Combination use of light wavelengths reported to stimulate collagen synthesis and accelerate fibroblast,myofibroblast transformation may display a composite rejuvenative effect. Objective, To clinically assess reduction in sun damage signs following a 5-week course of LED therapy and to assess subject's perception of the treatment. Methods, Thirteen subjects with wrinkles or fine lines in the periorbital and nasolabial region and those presenting Glogau scale photodamage grade II,III received nine 20-min duration light treatments using the OmniluxÔ LED system. The treatments combined wavelengths of 633 and 830 nm at fluences of 126 and 66 J/cm2, respectively. Sun-damage reduction was assessed at 6, 9, and 12 weeks by clinical photography and patient satisfaction scores. Results, The majority of subjects displayed "moderate" (50%) or "slight" (25%) response to treatment at investigator assessment. Treatment of the periorbital region was reported more effective than the nasolabial region. At 12-week follow-up, 91% of subjects reported improved skin tone, and 82% reported enhanced smoothness of skin in the treatment area. Conclusion, Good response to LED therapy has been shown in this modest sample. Larger trials are needed to assess optimum frequency of light treatments and overall treatment time. [source] Effects of lipopolysaccharide on platelet-derived growth factor isoform and receptor expression in cultured rat common bile duct fibroblasts and cholangiocytesJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 7 2009Tae-Hyeon Kim Abstract Background and Aim:, Little is known about the role of platelet-derived growth factor (PDGF) in biliary fibrosis in the setting of bacterial colonization of the biliary tree. We therefore sought to investigate whether exposure to bacterial lipopolysaccharide (LPS) alters PDGF isoform and receptor expression in cultured rat common bile duct fibroblasts (CBDF) and normal rat cholangiocytes (NRC). Methods:, Collagen content in cells and media was assessed by colorimetric assay and gel electrophoresis. mRNA levels of PDGF-A and -B, and PDGF-Receptors (PDGF-R) , and , were measured by relative quantitative real-time PCR. Protein levels of PDGF-AA, AB and BB were measured by ELISA, and PDGF-R, and PDGF-R, by Western blot. Results:, In CBDF, LPS increased total soluble collagen synthesis and secretion. PDGF-R, and , mRNA and protein were also increased by LPS treatment in CBDF. Lipopolysaccharide treatment elicited an increase in PDGF-A and -B mRNA levels in CBDF. In NRC, levels of PDGF-A mRNA increased in a dose-dependent fashion following LPS treatment, whereas PDGF-B mRNA showed no response. PDGF-AA secretion was higher by CBDF than by NRC. PDGF-BB levels were also higher in CBDF than in NRC. While PDGF-BB levels did not respond to LPS treatment in CBDF, there was a dose-dependent response of this isoform to LPS in NRC. Intracellular and secreted PDGF-AB increased with LPS treatment in NRC. Conclusions:, These results support a model in which chronic bacterial colonization of the biliary tree induces fibrosis through PDGF-dependent mechanisms. [source] Induced hypothyroidism accelerates the regression of liver fibrosis in ratsJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 12 2007Rafael Bruck Abstract Background and Aim:, It has been shown in previous studies that hypothyroidism prevents the development of liver fibrosis in bile duct ligated rats and in rats chronically treated with thioacetamide (TAA). In recent years, regression of liver fibrosis (occurring spontaneously or during treatment) has been demonstrated in rodent models such as bile duct ligation and CCl4 administration. Therefore, in the present study, the potential therapeutic effect of hypothyroidism on liver fibrosis was investigated. Methods:, Liver fibrosis was induced in rats by administration of TAA (200 mg/kg, i.p., twice weekly) for 12 weeks. Hypothyroidism was then induced by either methimazole (0.04%) or propylthiouracil (0.05%) administered in drinking water for 8 weeks. Control euthyroid rats received normal drinking water. Hypothyroidism was confirmed by a significant elevation of serum thyroid-stimulating hormone levels. Results:, Eight weeks after the cessation of TAA administration, spleen weight, histological score of liver fibrosis, and hepatic hydroxyproline content were significantly lower in both groups of hypothyroid rats as compared to euthyroid controls (P < 0.001). In vitro studies using the rat hepatic stellate cell line HSC-T6 using northern blot analysis and zymography, respectively, showed that high concentrations of triiodotyronine (T3) enhanced transforming growth factor (TGF)-,-induced collagen I gene expression, and reduced metalloproteinase (MMP)-2 secretion, implying that reducing the levels of T3 may contribute to resolution of fibrosis. Additionally, low T3 concentration inhibited HSC-T6 proliferation. Conclusion:, Pharmacologically induced hypothyroidism accelerates the resolution of liver fibrosis in rats. This beneficial effect may in part be due to prevention of T3 -induced stimulation of collagen synthesis and reduction of MMP-2 secretion. [source] Copper stimulates human oral fibroblasts in vitro: a role in the pathogenesis of oral submucous fibrosisJOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 8 2001C. Trivedy Abstract: Copper is implicated in the pathogenesis of several fibrotic disorders. Areca nut has been shown to have a high copper content and areca chewing is associated with oral submucous fibrosis (OSF). The effects of copper on human oral fibroblasts were investigated in vitro. Human oral fibroblasts were incubated with copper chloride (CuCl2) at concentrations ranging from 0.01 ,M to 500 ,M for 24 h, and in vitro cell proliferation was assayed by incorporation of tritiated,thymidine; soluble and non-soluble collagen synthesis was assayed using tritiated-proline. Addition of copper chloride at concentrations ranging from 0.1 ,M to 50 ,M increased the collagen synthesis by the oral fibroblasts compared with growth without copper (P<0.05). The addition of copper chloride neither increased the synthesis of non-collagenous proteins by the fibroblasts nor influenced their proliferation rate. We conclude that copper upregulates collagen production in oral fibroblasts. This appears to be concentration dependent, with peak collagen synthesis at 50 ,M CuCl2. These in vitro results taken together with the recent findings of copper in oral biopsies from OSF subjects support the hypothesis that copper in areca nut acts as a mediator of OSF. [source] Interferon gamma (IFN-,) may reverse oral submucous fibrosisJOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 1 2001M. F. Haque Abstract: Oral submucous fibrosis (OSF) is a chronic disease of the oral cavity and oropharyngx characterised by fibrosis in the submucosa leading to progressive limitation of the mouth opening. Interferon gamma (IFN-,) is a known anti-fibrotic cytokine. In this study we have investigated: a) the effect of IFN-, on collagen synthesis by arecoline-stimulated OSF fibroblasts in vitro (n=5), b) the effect of intra-lesional IFN-, on the fibrosis of OSF patients (n=29) and c) the immunohistochemical analysis of pre- and post-treatment inflammatory cell infiltrates and cytokine levels in the lesional tissue (n=29). The results show that the increased collagen synthesis in vitro in response to arecoline was inhibited in the presence of IFN-, (0.01,10.0 U/ml) in a dose-related way. In an open uncontrolled study intra-lesional IFN-, treatment showed improvement in the patients mouth opening from an inter-incisal distance before treatment of 21±7 mm, to 30±7 mm immediately after treatment and 30±8 mm 6-months later, giving a net gain of 8±4 mm (42%) (range 4,15 mm). Patients also reported reduced burning dysaesthesia and increased suppleness of the buccal mucosa. The post-treatment immunohistochemistry showed a decreased amount of inflammatory cell infiltrate and an altered level of cytokines compared with the pre-treatment lesional tissue. The effect of IFN-, on collagen synthesis appears to be a key to the treatment of these patients, and intra-lesional injections of the cytokine may have a significant therapeutic effect on OSF. [source] Low-intensity pulsed ultrasound (LIPUS) increases the articular cartilage type II collagen in a rat osteoarthritis modelJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 3 2010Kiyohito Naito Abstract In this study, the effect of low-intensity pulsed ultrasound (LIPUS) on cartilage was evaluated in a rat osteoarthritis (OA) model using serum biomarkers such as CTX-II (type II collagen degradation) and CPII (type II collagen synthesis) as well as histological criteria (Mankin score and immunohistochemical type II collagen staining). OA was surgically induced in the knee joint of rats by anterior cruciate/medial collateral ligament transection and medial meniscus resection (ACLT,+,MMx). Animals were divided into three groups: sham-operated group (Sham), ACLT,+,MMx group without LIPUS (,LIPUS), and ACLT,+,MMx group with LIPUS (+LIPUS; 30 mW/cm2, 20 min/day for 28 days). CTX-II levels were elevated in both ,LIPUS and +LIPUS groups compared to that in the Sham group after the operation, but there was no significant difference between +LIPUS and ,LIPUS groups, suggesting that LIPUS does not affect the degradation of type II collagen in this model. In contrast, CPII was significantly increased in +LIPUS group compared to ,LIPUS and Sham. Moreover, histological damage on the cartilage (Mankin score) was ameliorated by LIPUS, and type II collagen was immunohistochemically increased by LIPUS in the cartilage of an OA model. Of interest, mRNA expression of type II collagen was enhanced by LIPUS in chondrocytes. Together these observations suggest that LIPUS is likely to increase the type II collagen synthesis in articular cartilage, possibly via the activation of chondrocytes and induction of type II collagen mRNA expression, thereby exhibiting chondroprotective action in a rat OA model. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:361,369, 2010 [source] Treatment of cartilage with ,-aminopropionitrile accelerates subsequent collagen maturation and modulates integrative repairJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 3 2005Kevin B. McGowan Abstract Integrative repair of cartilage was previously found to depend on collagen synthesis and maturation. ,-aminopropionitrile (BAPN) treatment, which irreversibly blocks lysyl oxidase, inhibited the formation of collagen crosslinks, prevented development of adhesive strength, and caused a buildup of GuHCl-extractable collagen crosslink precursors. This buildup of crosslink precursor in the tissue may be useful for enhancing integrative repair. We tested in vitro the hypothesis that pre-treatment of cartilage with BAPN, followed by washout before implantation, could be a useful therapeutic strategy to accelerate subsequent collagen maturation. In individual cartilage disks, collagen processing was reversibly blocked by BAPN treatment (0.1 mM) as indicated by a BAPN-induced increase in the total and proportion of incorporated radiolabel that was extractable by 4 M guanidine-HCl, followed by a decrease, within 3,4 days of BAPN washout, in the proportion of extractable radiolabel to control levels. With a similar pattern, integration between pairs of apposed cartilage blocks was reversibly blocked by BAPN treatment, and followed by an enhancement of integration after BAPN washout. The low and high levels of integration were associated with enrichment in [3H]proline in a form that was susceptible and resistant, respectively, to extraction. With increasing duration up to 7 days after BAPN pre-treatment, the levels of [3H]proline extraction decreased, and the development of adhesive strength increased. Thus, BAPN can be used to modulate integrative cartilage repair. © 2004 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved. [source] Repeated intraarticular injections of triamcinolone acetonide alter cartilage matrix metabolism measured by biomarkers in synovial fluidJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 3 2005Christophe Céleste Abstract Although intraarticular (IA) corticosteroids are frequently used to treat joint disease, the effects of their repeated use on articular cartilage remains controversial. The aim of our study was to determine the effects of a clinically recommended dose of IA triamcinolone acetonide (TA), on synovial fluid (SF) biomarkers of cartilage metabolism. Ten adult horses, free of osteoarthritis (OA) in their radiocarpal joints, were studied. One radiocarpal joint of each horse was randomly chosen for treatment and the contralateral anatomically paired joint acted as the control. Aseptic arthrocentesis was performed weekly on both joints for 13 weeks. The initial results from the first 3 weeks of the experimental period established baseline untreated control marker levels for each joint, each being its own control. On weeks 3, 5, and 7, a sterile suspension of 12mg of TA was injected into the treated joint and an equivalent volume of sterile saline solution (0.9%) was injected into the control joint. SF was immunoassayed for biomarkers of aggrecan turnover (CS 846 & KS), types I and II collagen cleavage (C1,2C) and type II collagen synthesis (CPII). In treated joints, there was a significant increase in CS 846, KS, C1,2C and CPII epitope concentrations following IA TA injections when compared to baseline levels. There was also a significant increase in C1,2C and CPII epitope concentrations in the contralateral control joints following IA TA injections in the treated joint. Significant differences were observed between treated and control joints for all markers except CPII. These findings indicate that TA alters articular cartilage and collagen metabolism in treated and, interestingly, also in control joints, suggesting a systemic effect of the drug. Though intuitively the observed findings would favor the hypothesis that long-term IA TA treatment changes joint metabolism and this may have detrimental effects; further studies would be necessary to confirm this. © 2004 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved. [source] Curcumin inhibits collagen synthesis and hepatic stellate cell activation in-vivo and in-vitroJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 1 2002Hee-Chul Kang We previously demonstrated that curcumin, a well-known antioxidant, inhibits collagen deposition in carbon tetrachloride-induced liver injury in rats. The major effector cells responsible for collagen synthesis in the liver are activated hepatic stellate cells. In this study, we investigated the inhibitory effects of curcumin on the collagen synthesis and activation of rat hepatic stellate cells in-vitro, and on hepatic stellate cell activation in-vivo. The effects of curcumin on the production of collagen and smooth muscle ,-actin proteins and of ,1(I) collagen mRNA were studied in-vivo and in-vitro. The effect of curcumin on DNA synthesis was also determined in-vitro. In-vivo, treatment with curcumin reduced collagen deposition and smooth muscle ,-actin-positive areas and lowered mRNA levels of type I collagen in the liver. In-vitro, curcumin at a concentration of 5 ,g mL,1 reduced DNA synthesis, and downregulated smooth muscle ,-actin and type I collagen expression, and ,1(I) collagen mRNA expression. We concluded that curcumin inhibits collagen synthesis and hepatic stellate cell activation in-vivo and in-vitro, and thus may prove a valuable anti-fibrogenic agent. [source] Effects of mechanical loading on collagen propeptides processing in cartilage repairJOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE, Issue 1 2010Rosmarie Hardmeier Abstract Injured articular cartilage has poor reparative capabilities and if left untreated may develop into osteoarthritis. Unsatisfactory results with conventional treatment methods have brought as an alternative treatment the development of matrix autologous chondrocyte transplants (MACTs). Recent evidence proposes that the maintenance of the original phenotype by isolated chondrocytes grown in a scaffold transplant is linked to mechanical compression, because macromolecules, particularly collagen, of the extracellular matrix have the ability to ,self-assemble'. In load-bearing tissues, collagen is abundantly present and mechanical properties depend on the collagen fibre architecture. Study of the active changes in collagen architecture is the focus of diverse fields of research, including developmental biology, biomechanics and tissue engineering. In this review, the structural model of collagen assembly is presented in order to understand how scaffold geometry plays a critical role in collagen propeptide processing and chondrocyte development. When physical forces are applied to different cell-based scaffolds, the resulting specific twist of the scaffolds might be accompanied by changes in the fibril pattern synthesis of the new collagen. The alteration in the scaffolds due to mechanical stress is associated with cellular signalling communication and the preservation of N-terminus procollagen moieties, which would regulate both the collagen synthesis and the diameter of the fibre. The structural difference would also affect actin stabilization, cytoskeleton remodelling and proteoglycan assembly. These effects seemed to be dependent on the magnitude and duration of the physical stress. This review will contribute to the understanding of mechanisms for collagen assembly in both a natural and an artificial environment. Copyright © 2009 John Wiley & Sons, Ltd. [source] Aldosterone induces collagen synthesis via activation of extracellular signal-regulated kinase 1 and 2 in renal proximal tubulesNEPHROLOGY, Issue 8 2008GUOSHUANG XU SUMMARY: Aim: Aldosterone plays a crucial role in renal fibrosis by inducing mesangial cell proliferation and promoting collagen synthesis in renal fibroblasts. However, renal proximal tubule involvement in aldosterone-induced collagen synthesis has not yet been identified. The aim of this study was to examine the potential role of aldosterone in collagen expression and its possible mineralocorticoid receptor (MR)-dependent pathway, mediated by activation of extracellular signal-regulated kinase 1 and 2 (ERK1/2) in cultured human renal proximal tubular epithelial (HKC) cells. Methods: After HKC cells were stimulated by aldosterone with different concentrations for various time and periods, the gene expression and protein synthesis of collagen I, II, III and IV were measured by real-time polymerase chain reaction and western blot, respectively. ERK1/2 activation, ,-smooth muscle actin (,-SMA), and E-cadherin were also detected by western blot. Results: Aldosterone can increase ERK1/2 phosphorylation of human renal proximal tubular epithelial cells in a time- and dose-dependent manner. Although aldosterone had no effect on collagen I and II expression, it increased expression of ,-SMA and collagen III and IV and decreased that of E-cadherin in HKC cells after 48 h. These effects could be prevented by a ERK pathway inhibitor, U0126, or by a selective MR antagonist, spironolactone. Conclusion: The results suggest that aldosterone plays a pivotal role in tubulointerstitial fibrosis by promoting tubular epithelial,mesenchymal transition and collagen synthesis in proximal tubular cells. The process is MR-dependent, and mediated by ERK1/2 mitogen-activated protein kinase pathway. [source] Glycosaminoglycans and the peritoneaumNEPHROLOGY, Issue 5 2002Susan YUNG SUMMARY: The introduction of peritoneal dialysis (PD) over two decades ago has allowed us to manipulate the peritoneal membrane to perform as a continuous dialysing organ. to maximize the efficacy of solute transport and waste removal, conventional PD fluids require unphysiological concentrations of glucose to provide the osmotic drive, lactate to alleviate metabolic acidosis, and a low pH to prevent the caramelization of glucose during the preparation of the solutions. These factors either alone or in combination, are irritants to the peritoneal membrane. Thus, continuous exposure of the peritoneum to PD solutions, together with frequent episodes of peritonitis confers a chronic inflammatory response within the peritoneum. It is, therefore, not unexpected that with time, long-term PD patients develop structural and functional changes within the peritoneum, which in many cases develop into peritoneal fibrosis of varying degrees and compromises the peritoneal membrane as a dialysing organ. to date, numerous studies have investigated methods to improve the efficiency of PD and preserve the structure of the peritoneal membrane. Recently, a number of reports have documented the beneficial effects of intraperitoneal administration of glycosaminoglycans (GAGs) on both the structural and functional qualities of the peritoneum. In this context, GAGs have been demonstrated to inhibit collagen synthesis within the peritoneum, decrease peritoneal advanced glycosylated end-products (AGE) deposition, and modulate cytokine and growth factor synthesis. This review will examine the available data with regards to the potential role of GAGs in maintaining ultrafiltration, solute transport and the structural integrity of the peritoneum. [source] IFN-, gene therapy by intrasplenic hepatocyte transplantation: a novel strategy for reversing hepatic fibrosis in Schistosoma japonicum -infected micePARASITE IMMUNOLOGY, Issue 1 2001Lihuang Zhang Liver-targeted gene therapy using hepatocyte as recipient cells has recently been documented to be effective in treatment of numerous hepatic diseases, such as metabolic diseases and liver carcinoma. IFN-, elicits antipreliferative and antifibrogenic activity in a variety of mesenchymal cells, including hepatic satellite cells. To investigate the antifibrogenic response of liver gene therapy mediated by intrasplenic transplantation of gene-modified hepatocytes, normal mouse liver cell line BNL CL.2 cells were transfected with murine IFN-, gene (BNL.IFN-,) in vitro, and transplanted intrasplenically into Schistosoma japonicum -infected mice. The amounts and distribution of IFN-, (which inhibits collagen synthesis), TGF-, (which stimulates collagen synthesis) and extracellular matrix, including type I and III collagen, were detected. In mice infected with S. japonicum and then treated with BNL.IFN-,, an increase of IFN-, and decrease of TGF-,1 were detected at 20 weeks postinfection compared to untreated S. japonicum -infected mice. Immunohistochemical analysis showed that S. japonicum infection induced a marked increase of type I and III collagen synthesis. Whereas, 4 weeks after treatment with BNL.IFN-,, net synthesis rates of type I and III collagen were markedly decreased in the liver of infected mice. In addition, a decreased expression of TGF-,1 and its receptor TGF-,RII in the liver of BNL.IFN-,-treated mice was also observed. Moreover, the decrease in TGF-,1 and TGF-,RII protein approximately paralleled the decrease in their mRNA expression, which was detected by RNA dot blotting. The data indicate that intrasplenic transplantation of IFN-, gene-modified hepatocyte can be a candidate approach to treat hepatic fibrosis. [source] Role of heat shock protein 47 on tubulointerstitium in experimental radiation nephropathyPATHOLOGY INTERNATIONAL, Issue 5-6 2002Diange Liu The molecular mechanisms of fibrosis in radiation nephropathy have received scant attention. Heat shock protein 47 (HSP47), a collagen-binding stress protein, helps in the intracellular processing of procollagen molecules during collagen synthesis. We investigated the role of HSP47 in the progression of radiation nephropathy using experimental radiation nephropathy. Experimental rat groups were as follows: (i) group I, sham operated (n = 12); (ii) group II, single doses of irradiation, either 7, 15 or 25 Gy to left kidney (n = 60); and (iii) group III, a similar irradiation procedure as group II after right nephrectomy (n = 60). The rats were followed up until 9 months after renal exposure to radiation. Renal dysfunction (as determined by serum creatinine and blood urea nitrogen) and hypertension were noted in group III rats, along with inflammatory cell infiltration and interstitial fibrosis (as determined by increased deposition of collagens). Compared to control rat kidneys, an increased expression of HSP47 was noted in kidneys obtained from irradiated rats. By double immunostaining, HSP47-expressing cells were identified as ,-smooth muscle actin-positive myofibroblasts and vimentin-positive tubular epithelial cells. Increased expression of HSP47 was closely associated with increased deposition of collagens in the widened interstitium of irradiated rats. Overexpression of HSP47 by phenotypically altered tubulointerstitial cells might play a role in excessive assembly/synthesis of collagens and could contribute to tubulointerstitial fibrosis in radiation nephropathy. [source] Anti-wrinkling effects of the mixture of vitamin C, vitamin E, pycnogenol and evening primrose oil, and molecular mechanisms on hairless mouse skin caused by chronic ultraviolet B irradiationPHOTODERMATOLOGY, PHOTOIMMUNOLOGY & PHOTOMEDICINE, Issue 5 2007Ho-Song Cho Background: Naturally occurring antioxidants were used to regulate the skin damage caused by ultraviolet (UV) radiation because several antioxidants have demonstrated that they can inhibit wrinkle formation through prevention of matrix metalloproteinases (MMPs) and/or increase of collagen synthesis. Objective: We examined the effect of oral administration of the antioxidant mixture of vitamin C, vitamin E, pycnogenol, and evening primrose oil on UVB-induced wrinkle formation. In addition, we investigated the possible molecular mechanism of photoprotection against UVB through inhibition of collagen-degrading MMP activity or through enhancement of procollagen synthesis in mouse dorsal skin. Methods: Female SKH-1 hairless mice were orally administrated the antioxidant mixture (test group) or vehicle (control group) for 10 weeks with UVB irradiation three times a week. The intensity of irradiation was gradually increased from 30 to 180 mJ/cm2. Microtopographic and histological assessment of the dorsal skins was carried out at the end of 10 weeks to evaluate wrinkle formation. Western blot analysis and EMSA were also carried out to investigate the changes in the balance of collagen synthesis and collagen degradation. Results: Our antioxidant mixture significantly reduced UVB-induced wrinkle formation, accompanied by significant reduction of epidermal thickness, and UVB-induced hyperplasia, acanthosis, and hyperkeratosis. This antioxidant mixture significantly prevented the UVB-induced expressions of MMPs, mitogen-activated protein (MAP) kinase, and activation of activator protein (AP)-1 transcriptional factor in addition to enhanced type I procollagen and transforming growth factor-,2 (TGF-,2) expression. Conclusion: Oral administration of the antioxidant mixture significantly inhibited wrinkle formation caused by chronic UVB irradiation through significant inhibition of UVB-induced MMP activity accompanied by enhancement of collagen synthesis. [source] Inhibition of nifedipine-induced proliferation of cultured human gingival fibroblasts by Saiko, a Chinese herbal medicinePHYTOTHERAPY RESEARCH, Issue 8 2006Toshimi Hattori Abstract Saiko is predominantly contained in Saireito, a Chinese herbal medicine. The present study was conducted to determine whether or not Saiko is involved in the inhibition by Saireito of nifedipine-induced proliferation and collagen synthesis in gingival fibroblasts. Nifedipine (10 µm) significantly enhanced the proliferation starting on day 5 of the culture period. When added together with nifedipine, Saiko at concentrations of 0.05%,0.2% (w/v) dose-dependently inhibited the nifedipine-induced proliferation, and at the highest concentration tested (0.2%), Saiko inhibited the nifedipine-induced proliferation by about 40%. Moreover, Saiko (0.2%) also inhibited the normal proliferation at days 11 and 14. Sole application of nifedipine (10 µm) augmented the release of bFGF, and Saiko concentration-dependently reduced the level of bFGF in the nifedipine-containing culture medium. Nifedipine (10 µm) increased the production of type I collagen to almost twice that of the control (normal medium), and Saiko at concentrations above 0.1% significantly reduced the nifedipineinduced production of collagen. In conclusion, the present findings demonstrate that Saiko inhibited the nifedipine-induced proliferation of gingival fibroblasts by reducing the release of bFGF and that Saiko is involved in the Saireito-induced inhibition of nifedipine-stimulated proliferation and collagen synthesis in gingival fibroblasts. Copyright © 2006 John Wiley & Sons, Ltd. [source] | ||||||||||||||||||||||||||||||||||