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Biomedical subjects

S Werner

Publications and source records attributed to S Werner.

At least 91 records · Page 5Linked to original sources

Different types of ROS-scavenging enzymes are expressed during cutaneous wound repair.

Injury to the skin initiates a series of events including inflammation, new tissue formation, and matrix remodeling. During the early inflammatory phase, polymorphonuclear leukocytes and macrophages infiltrate the wounded tissue. Once activated, they produce large amounts of reactive oxygen species (ROS) as part of their defense mechanism. Although this process is beneficial, increased levels of ROS can inhibit cell migration and proliferation and can even cause severe tissue damage. Therefore, cells must develop strategies for the detoxification of these molecules. To gain insight into the mechanisms which underlie this process, we analyzed the temporal and spatial expression pattern of various ROS-scavenging enzymes during the healing process of full-thickness excisional wounds in mice. Here we demonstrate a strong mRNA expression of two types of superoxide dismutase (SOD), as well as of catalase, and the selenoenzymes glutathione peroxidase (SeGPx) and phospholipid hydroperoxide glutathione peroxidase in normal and wounded skin. Most importantly, mRNA levels of the SODs and of SeGPx increased strongly after skin injury. In situ hybridization and immunofluorescence studies revealed the presence of these transcripts at multiple places in the wound, whereby particularly high expression levels were detected in the hyperproliferative epithelium and the hair follicles at the wound edge. These data suggest an important role of ROS-scavenging enzymes in the detoxification of ROS during cutaneous wound repair.

Animals↗

Consequences of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor blockade during status epilepticus in the developing brain.

To investigate if AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptor activation contributes to acute manifestations and long term consequences of status epilepticus (SE), we administered the AMPA receptor antagonist NBQX to P35 rats undergoing kainic acid (KA)-induced SE. NBQX (30 mg/kg/dose) given intraperitoneally (i.p.) at 30, 60 and 90 min after i.p. KA injection (12 mg/kg) reduced severity of SE. When tested as adults, rats that had received KA and NBQX were similar to controls with no long term impairment in visuospatial memory (assessed by the water maze test), or histologic damage in the CA1 or CA3 hippocampal subfields. However, both P35 groups, those receiving KA alone and those receiving KA and NBQX, had similar rates of spontaneous recurrent seizures (SRS). In P15 rats, NBQX resulted in increased acute mortality from KA associated SE. These results indicate that the effects of NBQX on KA-induced SE are age dependent, and that non-NMDA receptor activation contributes to the acute manifestations and to the long term sequelae seen after KA-induced SE in the prepubescent rat brain.

Animals↗

Treatment of port-wine stains with a noncoherent pulsed light source: a retrospective study.

OBJECTIVE: We investigated whether a noncoherent intense pulsed light source (IPLS) would be effective in therapy of port-wine stains (PWSs). DESIGN: To evaluate the efficacy in treatment of PWSs with IPLS, a retrospective study was initiated. SETTING: The data were collected by physicians working in private practices and departments of university hospitals and medical centers, respectively. PATIENTS: A total of 37 randomly selected patients with a total of 40 PWSs were included in the study. Clinical PWS characteristics recorded were color and location of the PWS. INTERVENTIONS: All patients were treated with IPLS. MAIN OUTCOME MEASURES: Data collected included treatment parameter (filters, pulse duration, fluence, and pulse sequencing), percentage of clearance, and side effects (purpura, blisters, crusting, altered pigmentation, and scarring). RESULTS: Good and complete (70%-100%) clearance was achieved in 28 of 40 PWSs treated with IPLS. The average number of treatment sessions in PWSs reaching 100% clearance included 4.0 for pink PWSs and 1.5 for red PWSs. The average number of sessions for purple PWSs reaching good clearance (70%-99%) was 4.2 sessions. Parameters used most frequently were 515- and 550-nm cut-off filters, pulse duration of 2.5 to 5.0 milliseconds, and fluences of 24 to 60 J/cm2. Side effects included purpura in 133 (76%), superficial blisters in 14 (8%), and crusting in 35 (20%). Transient pigmentation changes were seen in 10.8% of patients (hypopigmentation in 3 [8.1%], hyperpigmentation in 1 [2.7%]). No scarring was observed. CONCLUSION: Intense pulsed light source presents an effective and safe method for treating PWSs, especially purple PWSs.

Adolescent↗

Xanthelasma palpebrarum: treatment with the ultrapulsed CO2 laser.

BACKGROUND AND OBJECTIVE: Due to its delicate location near the eye and the high recurrence rate, the therapy of xanthelasma palpebrarum is a difficult surgical task. Besides chemical, physical, and surgical procedures, various laser systems have been used to treat these lesions (argon laser, pulsed dye laser, and CO2 laser). This study was designed to critically evaluate the use of the ultrapulsed CO2 laser for the treatment of xanthelasma palpebrarum. STUDY DESIGN/MATERIALS AND METHODS: We report about the standardized treatment of 23 patients (52 periorbital xanthelasmas) and the results obtained after one treatment with a new generation, ultrapulsed CO2 laser (COHERENT Ultrapulse 5000C, Palo Alto, CA; 250-500 mJ; 600-900 microsec; 10,600 nm). The followup time was 10 months. RESULTS: All lesions could be removed completely with a single laser treatment. As for side effects, only transient pigmental changes (4% hyperpigmentations, 13% hypopigmentations) and no visible scarring was observed. Three patients (13%) developed a recurrence of xanthelasma. CONCLUSIONS: The ultrapulsed CO2 laser is an effective and safe therapeutic alternative to the hitherto described approaches.

Adult↗

Treatment of venous malformations with an intense pulsed light source (IPLS) technology: A retrospective study.

BACKGROUND AND OBJECTIVE: The intense pulsed light source (IPLS) technology provides an innovative concept in the treatment of vascular lesions. We investigated the effectiveness of IPLS in the treatment of venous malformations. STUDY DESIGN/MATERIALS AND METHODS: A retrospective study of 11 patients with venous malformations (VMA) treated with IPLS was initiated. Clinical VMA characteristics recorded were size and location. Data collected included treatment parameters (filters, pulse duration, fluence, and pulse sequencing), % clearance, and side effects (e.g., swelling, blisters, crusting, pain, altered pigmentation, and scarring). RESULTS: Good and very good (70-100%) clearance was achieved in 8 malformations smaller than 100 cm(2). Especially small lesions needed only 2-3 treatments. Three VMA larger than 100 cm(2) could be cleared well in an average of 18 sessions. The most frequently used parameters were the 590 nm filter in long pulse mode, triple pulses, and fluences at an average of 80.4 J/cm(2). Side effects included prolonged erythema in 23.6, swelling in 17.9%, crusting in 4.7%. Bleeding, hypo-, hyperpigmentation, and scarring were rare (0.9% respectively). CONCLUSION: IPLS presents an effective method for treating VMA, especially small malformations, with a justifiable rate of side effects when optimal parameters are chosen.

Adolescent↗

[Tattoo removal Q-switched ruby laser (694 nm) and the Q-switched Nd:YAG laser (532 and 1064 nm). A retrospective study].

In a retrospective study 47 patients with 68 amateur and 25 professional tattoos were examined, considering clearance of tattoo pigments and the frequency of side effects after finished treatments with the Q-switched ruby (694 nm) and the Q-switched Nd:YAG laser (532 and 1064 nm). Black amateur tattoos were found to lighten faster than professional tattoos (13.2 and 18.6 treatments respectively). For the clearance of multicolored tattoos (amateur or professional), similar numbers of laser treatments were needed. Green pigments were removed with the Q-switched ruby laser and red pigments with the frequency-doubled Nd:YAG laser (532 nm). Compared to the Q-switched Nd:YAG laser (1064 nm), the Q-switched ruby laser and the frequency-doubled Nd:YAG laser (532 nm) more often caused blistering and transient hypopigmentation (5.4% and 7.5% vs. 1.1% (blisters); 8.6% and 15.1% vs. 4.3% (hypopigmentation).

Adult↗

[Current status of laser therapy of hemangioma in infants. Case reports and review of the literature].

Today the management of hemangiomas is still a great challenge for physicians, even for the most experienced of clinicians. With the introduction of lasers, new ways of treating hemangiomas have been found. Four case reports document the importance of early treatment. In addition, the differentiated use of various laser systems and their effects, limitations, and side effects are shown and discussed.

Child↗

Vascular endothelial growth factor (VEGF) in Crohn's disease: increased production by peripheral blood mononuclear cells and decreased VEGF165 labeling of peripheral CD14+ monocytes.

Recently, increased serum levels of vascular endothelial growth factor (VEGF) have been shown in patients with inflammatory bowel disease. The origins of the circulating VEGF are still not described. Monocytes play an important role in the inflammatory process. VEGF binding to monocytes mediates monocyte recruitment and activation. The present study investigates the VEGF production of peripheral blood mononuclear cells and the ability of peripheral monocytes to bind VEGF165 in patients with Crohn's disease. Nineteen patients with Crohn's disease and 10 healthy volunteers were studied. VEGF165 labeling of CD14+ monocytes was measured using two-color flow cytometry. Density of VEGF labeling was expressed as the mean fluorescence intensity (MFI). Furthermore, VEGF levels were determined in culture supernatants of unstimulated peripheral blood mononuclear cells. VEGF in culture supernatants was measured using a solid-phase enzyme-linked immunosorbent assay. There was a significantly decreased VEGF165 labeling of monocytes of patients with active Crohn's disease (MFI: 369.9+/-121.6, N = 7, P < 0.002) compared to patients with inactive disease (MFI: 457.7+/-74.5, N = 6) and healthy controls (MFI: 542.9+/-96.2, N = 10). Unstimulated peripheral blood mononuclear cells of patients with active Crohn's disease produced significantly higher amounts of VEGF (1142.6+/-483.9 pg/ml, N = 12, P < 0.001) compared with peripheral blood mononuclear cells of healthy volunteers (113.4+/-101.8 pg/ml, N = 10). VEGF production by peripheral blood mononuclear cells of patients with active disease was significantly increased compared to patients with quiescent disease (261.6+/-254.8 pg/ml, N = 7, P < 0.001). In conclusion, our data describe peripheral blood mononuclear cells as one of the origins of the elevated VEGF serum levels in patients with active Crohn's disease. Furthermore, a decrease in VEGF165 binding sites on peripheral monocytes of patients with active Crohn's disease has been shown. The study underlines the important role of VEGF in Crohn's disease.

Adolescent↗

Paradoxical role of PGE2 and cAMP in Actinobacillus actinomycetemcomitants strain Y4-induced lymphocyte proliferation.

An immune mechanism has been suggested in the pathogenesis of periodontal disease. Actinobacillus actinomycetemcomitants (Aa) has been implicated as one of the etiological agents that induces the major immune response together with a dense infiltrate of inflammatory cells. But the exact role of these immune cells in periodontal disease has not yet been clarified. In this study the T lymphocyte (TL) proliferative response was evaluated after having being exposed to free cell supernatant (SN) from Aa. Aa SN increased TL proliferation. This mitogenic effect of Aa SN was attenuated by pretreating TL with indomethacin (INDO) or acetylsalicylic acid (ASA) but not by polymyxin B. The inhibitory effect of INDO on cell proliferation was reversed by the addition of prostaglandin E2 (PGE2) to the culture assay. Moreover, when immune cells were exposed to Aa SN they were able to generate PGE2 at the same time as intracellular levels of cAMP decreased. Both, PGE2 release and decrease accumulation of cAMP in TL were blunted by treated lymphocytes with INDO. In this paper we demonstrate that cell free SN from Aa induces a mitogenic effect on murine lymphocytes. The mechanism involves the host's immunecompetent cells and the release of PGE2 and appears not to be induced by capsular-like polysaccharide antigen. Results show a paradoxical mitogenic effect of Aa SN accompanied by increased generation of PGE2 and decreased production of cAMP by lymphocytes.

Aggregatibacter actinomycetemcomitans↗

Activin: a novel player in tissue repair processes.

Recent studies have demonstrated a strong expression of activin in repair processes of various tissues and organs, including the skin, the lung, the intestine, the cardiovascular system, and even the brain. Although little is as yet known about the function of activin in tissue repair, first results suggest a role of activin in epithelial differentiation, fibroblast proliferation and expression of matrix molecules by these cells, and also in neuroprotection. Whereas a transient overexpression of activin after tissue injury might be beneficial for the repair process, sustained expression of activin could lead to fibrotic processes. Therefore, the modulation of the availability or biological activity of activin could be of particular importance for the treatment of impaired tissue repair on the one hand and tissue fibrosis on the other hand.

Activins↗

Dexamethasone is a novel potent inducer of connective tissue growth factor expression. Implications for glucocorticoid therapy.

Due to its potent effect on fibroblast proliferation and extracellular matrix deposition, connective tissue growth factor (CTGF) seems to play an important role in the pathogenesis of fibrotic disease. Since glucocorticoids are frequently used for the therapy of these disorders, we determined a potential effect of these steroids on CTGF expression. In cultured fibroblasts, a striking induction of CTGF expression was observed after dexamethasone treatment and occurred in a time- and dose-dependent manner. This effect was obviously not mediated by the CTGF inducer transforming growth factor-beta1, since expression of this factor was down-regulated by the glucocorticoid. Most importantly, CTGF expression levels also increased substantially in various tissues and organs by systemic glucocorticoid treatment of mice. After cutaneous injury, a strong induction of CTGF expression was seen in the wounds of nontreated mice. However, no further increase in the levels of CTGF mRNA occurred in wounded skin compared with unwounded skin of glucocorticoid-treated animals, suggesting the presence of other factors in the wound that might compensate for the effect of the steroids. Tumor necrosis factor-alpha was identified as a possible mediator of this effect because this factor suppressed CTGF expression in cultured fibroblasts and also blocked the glucocorticoid-induced CTGF production by these cells. These findings indicate that glucocorticoids stimulate CTGF expression in normal tissues and organs but not in highly inflamed areas.

3T3 Cells↗

Matrix metalloproteinases (MMPs) and their physiological inhibitors (TIMPs) are differentially expressed during excisional skin wound repair.

During cutaneous wound healing a number of migratory and remodeling events occur that require the action of matrix metalloproteinases (MMPs) and their natural inhibitors (TIMPs). In this study, we analyzed the temporal and spatial expression patterns of these molecules during the healing of murine excisional skin wounds. Our data imply that defined phases of repair rely on distinct repertoires of MMP activity and TIMP counterregulation. Reepithelialization was found to be associated with active production of collagenase, 92-kDa gelatinase, and stromelysins-1 and -2 by distinct subpopulations of keratinocytes at the migrating border. Notably, no TIMP transcripts were expressed in the epidermis, but TIMP-1 expression in the wound colocalized with expression of collagenase, 92-kDa gelatinase, and stromelysin-1, albeit in distinct cells. Concomitant with the formation of an extensive hyperproliferative epithelium, TIMP-1 transcripts accumulated at the mesenchymal/epidermal border of the granulation tissue. During later phases of wound repair, we observed an increase in 72-kDa gelatinase and MT1-MMP expression, whereby the transcripts of these colocalizing MMPs were detected exclusively and at high levels in the granulation tissue. At completion of reepithelialization, the expression levels of the MMPs and TIMP-1 seen in epidermal and dermal compartments declined to near-basal levels, whereas the macrophage-specific metalloelastase (MME) reached maximum expression. In reepithelialized wound tissue, MME transcripts were detected in deep layers of reconstituted dermis and seemed to cluster around vascular structures. Systemic glucocorticoid treatment, which is known to result in impaired wound healing, led to a nearly complete shut-off of MME expression. These observations imply an additional role of macrophage-related proteolysis, independent of its classical roles during earlier, inflammatory phases of cutaneous wound repair.

Animals↗

Connective tissue growth factor: a novel regulator of mucosal repair and fibrosis in inflammatory bowel disease?

Inflammatory bowel disease (IBD) is a multifactorial disorder which is characterized by massive damage of the epithelium and the underlying mesenchyme of the intestine. Due to the potent effect of connective tissue growth factor (CTGF) on fibroblast proliferation and connective tissue deposition we speculated about a possible role of this mitogen in IBD. Here we demonstrate a strikingly increased expression of CTGF mRNA in surgical specimens of patients suffering from two forms of IBD, Crohn's disease and ulcerative colitis. In most specimens, the levels of CTGF mRNA correlated with the degree of inflammation as assessed by histological analysis of adjacent tissue samples and by expression analysis of the pro-inflammatory cytokine interleukin-1 beta. However, areas of little inflammation which were characterized by severe fibrosis also revealed high levels of CTGF mRNA. Expression of transforming growth factor beta-1 (TGF-beta 1), the only known inducer of CTGF so far, as well as of the CTGF target genes collagen I alpha 1, fibronectin and integrin alpha 5 revealed a strong correlation with the expression of CTGF. These data suggest a prominent role of CTGF in the repair of mucosal injury in IBD and in the aberrant deposition of extracellular matrix leading to fibrosis and stenosis, one major complication in IBD, especially in Crohn's disease.

Animals↗

Keratinocyte growth factor: a unique player in epithelial repair processes.

Keratinocyte growth factor (KGF) is a member of the rapidly growing fibroblast growth factor (FGF) family of mitogens. Whereas most FGFs influence proliferation and/or differentiation of various cell types, KGF seems to act specifically on epithelial cells. It has been demonstrated that KGF stimulates proliferation and migration of these cells, but it also affects differentiation processes. Finally, recent studies have demonstrated a protective function of this growth factor in vitro and in vivo. Due to these properties, KGF could play an important role in repair processes. Indeed a series of studies have provided insight into the expression and function of KGF in inflammation and repair of various tissues and organs, and a therapeutic potential of this growth factor has been demonstrated.

Animals↗

Induction of inducible nitric oxide synthase and its corresponding tetrahydrobiopterin-cofactor-synthesizing enzyme GTP-cyclohydrolase I during cutaneous wound repair.

Recent work has suggested a possible role of nitric oxide, a free radical gas, during the wound healing process. In this study we investigated the regulation of inducible nitric oxide synthase (iNOS) and GTP-cyclohydrolase I (GTP-CH I), the rate-limiting enzyme in the biosynthesis of the iNOS cofactor (6R) 5,6,7,8-tetrahydrobiopterin (6-BH4), during the repair process. We found a similar time course of induction of iNOS and GTP-CH I expression, whereas absolute expression levels were different for both genes. Immunohistochemical analysis revealed colocalization of iNOS and GTP-CH I proteins in the wound. Systemic treatment with glucocorticoids significantly altered the expression levels of iNOS and GTP-CH I. Expression of iNOS and GTP-CH I was suppressed by glucocorticoids in normal, and to a much greater extent in wounded skin. Furthermore, a role of nitric oxide as a novel mediator of gene regulation during healing is suggested by the demonstration of nitric oxide-mediated induction of vascular endothelial growth factor expression in keratinocytes. These findings may provide an explanation for the beneficial effects of orally supplemented L-arginine on wound healing, and suggest that a disturbed induction of iNOS and GTP-CH I expression may at least partially underlie the wound healing defect seen in glucocorticoid-treated animals.

Animals↗