Biomedical subjects

Stefan Beckert

Publications and source records attributed to Stefan Beckert.

11 recordsLinked to original sources

PubMed2006

Self-expanding nitinol stents for treatment of infragenicular arteries following unsuccessful balloon angioplasty.

The feasibility of self-expanding nitinol stents for treatment of infragenicular arteries following unsuccessful balloon angioplasty was assessed. Options for lower limb percutaneous revascularization are limited, especially for complex vessel obstruction. Depending on the lesion and the experience of the interventionalist, the failure rate of balloon angioplasty (PTA) ranges between 10 and 40%. Until recently, no self-expanding stent for the use in the infragenicular arteries was available. This is the first report of the results for 18 consecutive patients who received 4F sheath compatible self-expanding nitinol stents following unsuccessful PTA or early restenosis. Twenty-four stents were implanted in 21 lesions for various indications residual stenosis >50% due to heavy calcification, flow-limiting dissection, occluding thrombus resistant to thrombolyis, thrombaspiration, and PTA, and early restenosis after previous PTA. Stent implantation was feasible in all cases. No complications occurred. After the stent implantation, all primarily unsuccessful interventions could be transformed into successful procedures with no residual stenosis >30% in any case. After 6 +/- 2 months, two of the 18 patients died, and 14 of the 16 remaining patients improved clinically. At follow-up, the patency could be assessed in 14 stented arteries. Three stents were occluded, one stent showed some neointimal hyperplasia (50-70% restenosis), the remaining ten stents showed no restenosis (0-30%). The use of self-expanding nitinol stents in tibioperoneal and popliteal arteries is a safe and feasible option for the treatment of unsuccessful PTA. The 6-months patency is high.

Aged↗

PubMed2006

Stimulation of steroid-suppressed cutaneous healing by repeated topical application of IGF-I: different mechanisms of action based upon the mode of IGF-I delivery.

BACKGROUND: Insulin-like growth factor-I (IGF-I) is accepted as a potent stimulus of wound healing when applied in combination with its binding proteins. However, there is only one study published that has investigated the effect of repeated topical application of unbound IGF-I on ischemic wound healing. The aim of this study was to show the effect of daily topical IGF-I therapy on cutaneous ulcer healing in a steroid-suppressed wound model. MATERIALS AND METHODS: Full-thickness wounds were created on the back of 40 male Sprague-Dawley rats. Before surgery, animals received depot-steroids subcutaneously. Wounds were treated daily with either a standard hydrogel dressing (control), topical IGF-I dissolved in 0.2% methylcellulose gel (IGF-I gel), or a hydrogel dressing containing IGF-I (IGF-I dressing). After 7 days of treatment, wounds were excised and measured by photoplanimetry. SMA- and PCNA-expression as well as the formation of granulation tissue were assessed in tissue sections. Results are given as median(min-max). Differences between groups were calculated by the Mann-Whitney U test. RESULTS: Subcutaneous injection of depot-steroids induced a significant delay in healing, as shown by an enlarged wound size [44(33-65) versus 25(20-35)] mm(2); P = 0.001). In steroid-treated rats, both IGF-I gel and IGF-I dressing enhanced excisional healing, as shown by a significant reduction in wound size (P = 0.0001), with IGF-I released from the dressing being even more effective than IGF-I gel (P = 0.03). However, in these animals only IGF-I released from the hydrogel dressing stimulated SMA- (P = 0.03) as well as PCNA-expression (P = 0.001) and increased granulation tissue formation (P = 0.018). CONCLUSIONS: Our data indicate that a repeated application of topical IGF-I enhances cutaneous ulcer healing. In addition, only the controlled release of IGF-I from the hydrogel dressing is capable of reversing the steroid-induced delay of healing, suggesting different mechanisms of action with respect to the mode of IGF-I delivery.

Actins↗

PubMed2006

IGF-I-induced VEGF expression in HUVEC involves phosphorylation and inhibition of poly(ADP-ribose)polymerase.

Insulin-like growth factor-I (IGF-I) has been shown to promote angiogenesis by enhancing vascular endothelial growth factor (VEGF) expression. However, how IGF-I-induces VEGF expression is not yet fully understood. With this investigation, we propose a new possible mechanism involving downregulation of poly(ADP-ribosyl)ation (pADPR). We first demonstrated that IGF-I increased VEGF protein expression in endothelial cells. Inhibitors of mitogen activated kinase (PD 98059), phosphatidyl-3-inositol-kinase (LY 294002), and protein kinase C (staurosporine) diminished the IGF-I effect suggesting the involvement of signal transduction. Since there is an established link between pADPR and transcriptional activity, we focused on a possible role of poly(ADP-ribose)polymerase (PARP). The inhibition of PARP by 3-aminobenzamide or nicotinamide enhanced VEGF expression. Additionally, IGF-I markedly decreased PARP activity. Furthermore, the IGF-I-mediated inhibition of PARP could be demonstrated as a result of protein phosphorylation since phosphorylation of PARP decreased its activity in vitro and IGF-I treatment of endothelial cells induced PARP phosphorylation. The IGF-I-mediated phosphorylation and inhibition of PARP represent a novel mechanism of VEGF protein expression.

Cells, Cultured↗

PubMed2006

Efficacy of topical pale sulfonated shale oil in the treatment of venous leg ulcers: a randomized, controlled, multicenter study.

BACKGROUND: Venous leg ulcers are a growing socioeconomic burden. Pale sulfonated shale oils (PSSO) are used for therapy of inflammatory skin diseases and have been shown to enhance wound healing in vitro and in vivo. The aim of this study was to investigate whether PSSO is capable of enhancing venous ulcer healing beyond compression therapy alone. METHODS: One hundred nineteen patients were enrolled in this randomized, multicenter, observer-blind study. In the treatment group, PSSO 10% was applied daily for 20 weeks, and the control group received the vehicle only. Wounds were covered by a nonadherent gauze dressing, and compression therapy with short-stretch elastic bandages was performed in an outpatient setting. The primary study end point was defined as cumulative reduction in wound area; the secondary study end point was treatment success as assessed by both physicians and patients. Additionally, adverse events, including changes with respect to physical examination and vital signs, were documented. RESULTS: At the end of the study period, ulcer size was significantly more reduced in the PSSO group compared with the vehicle group (15 +/- 15.9 to 6.2 +/- 12.9 cm(2) vs 11.4 +/- 14.5 to 10.8 +/- 15.7 cm(2); P = .0005). The cumulative relative reduction in ulcer area was significantly higher in the PSSO group (-4391 +/- 4748.7 vs -231.9 +/- 6283.6 % x days; P < .0001). Relative reduction in wound area was significantly greater in the PSSO group as early as 6 weeks after the beginning of treatment (-47.4 +/- 28.4 vs -23.8 +/- 42.2%; P < .001). PSSO was judged successful both by physicians and patients. There were no significant differences in adverse events (PSSO, 9 [12.2%]; vehicle, 7 [11.1%]. Similarly, tolerability of PSSO was equal to the tolerability of the vehicle. CONCLUSION: Pale sulfonated shale oils were capable of favoring venous ulcer healing in addition to compression therapy. PSSO should be considered for future wound care protocols for treatment of venous leg ulcers.

Administration, Topical↗

PubMed2006

A new wound-based severity score for diabetic foot ulcers: A prospective analysis of 1,000 patients.

OBJECTIVE: Several well-accepted classification systems are available for diabetic foot ulcers. However, there are only a few and scientifically not validated severity scores. The aim of this study was to establish a new wound-based clinical scoring system for diabetic foot ulcers suitable for daily clinical practice anticipating chances for healing and risk of amputation. RESEARCH DESIGN AND METHODS: Four clinically defined parameters, namely palpable pedal pulses, probing to bone, ulcer location, and presence of multiple ulcerations, were prospectively assessed in 1,000 consecutive patients. In the next step, a new diabetic ulcer severity score (DUSS) was created from these parameters. Palpable pedal pulses were categorized by the absence (scored as 1) or presence (scored as 0) of pedal pulses, while probing to bone was defined as yes (scored as 1) or no (scored as 0). The site of ulceration was defined as toe (scored as 0) or foot (scored as 1) ulcer. Patients with multiple ulcerations were graded as 1 compared with those with single ulcers (scored as 0). The DUSS was calculated by adding these separate gradings to a theoretical maximum of 4. Wounds were followed-up for 365 days or until healing or amputation if earlier. Probability of healing and risk of amputation were calculated by the Kaplan-Meier method. RESULTS: Uni- and multivariate analyses showed a significantly higher probability of healing for patients with palpable pulses, no probing to bone, toe ulcers, and absence of multiple ulcerations. When patients were divided into subgroups with the same DUSS, we found significantly different probabilities for healing. We showed a decreasing probability of healing for ulcers with a high DUSS, concurrent with increasing amputation rates. An increase in the DUSS by one score point reduced the chance for healing by 35%. Similarly, the higher the ulcer score, the larger the initial wound area, the longer the wound history, and the more likely the need for surgery or hospitalization. CONCLUSIONS: The DUSS categorizes different ulcers into subgroups with specific severity and similar clinical outcome. Using this score, the probabilities for healing, amputation, need for surgery, and hospitalization are predictable with high accuracy. This might be useful for the anticipation of health care costs and for comparison of subgroups of patients in clinical studies.

Adult↗

PubMed2005

TGF-beta3 inhibits pentagastrin-stimulated gastric acid secretion in rats.

BACKGROUND: Transforming growth factor beta3 (TGF-beta3) has been shown to accelerate gastric ulcer healing in rats. However, little is known about the mechanism. In this study we investigated the influence of TGF-beta3 on gastric acid secretion, since gastric hyperacidity is a major cause of gastroduodenal ulcer disease. MATERIAL/METHODS: Male Sprague Dawley rats were equipped with gastric Thomas cannulas and jugular vein catheters. The acute effect of either intravenous TGF-beta3 (400 and 1200 pg/kg/h) or saline (0.15 M) on pentagastrin-stimulated (10 pg/kg/h) gastric acid secretion was evaluated by gastric acid back-titration after 5 days of recovery. Additionally, pentagastrin-stimulated gastric acid secretion was assessed after 48 hours following TGF-beta3 (1200 microg/kg/h) or saline treatment. RESULTS: Pentagastrin significantly increased gastric acid production. TGF-beta3 significantly reduced pentagastrin-stimulated gastric acid secretion in a dose-dependent manner as early as 15 minutes after application (saline: 124.9+/-14.9 microEq H+/15 min, TGF-beta3: 97.7+/-13.1 9 microEq H+/15 min, p<0.002). Additionally, pretreatment with TGF-beta3 abolished the effect of pentagastrin on gastric acid production. This effect lasted throughout the entire recording period of 48 hours. However, baseline physiological gastric acid production was not altered by TGF-beta3. CONCLUSIONS: TGF-beta3 inhibits gastric acid secretion when given prior to as well as after pentagastrin treatment. This implicates both a preventive and a therapeutic role of TGF-beta3 in gastroduodenal ulcer disease.

Animals↗

PubMed2004

Growth hormone enhances gastric ulcer healing in rats.

BACKGROUND: Gastric ulcer healing requires the reconstitution of epithelial structures and underlying connective tissue through cellular proliferation, migration, and differentiation. The systemic application of growth hormone (GH) has shown anabolic effects in postoperative and burn therapy by increasing protein synthesis and attenuating protein catabolism. There is also evidence that GH stimulates cell proliferation and differentiation. In this study we evaluated the impact of GH on gastric ulcer healing. MATERIAL/METHODS: Gastric ulcers were induced with a cryoprobe in male Wistar rats (285+/-11 g). The first group of rodents (n=10) received a daily subcutaneous dose of 2.5 mg/kg growth hormone for seven days. The second group (n=10) received only vehicle. After 7 days, ulcer size was determined photoplanimetrically. Cell proliferation and new vessel growth in the ulcer margin were evaluated by quantitative immunohistochemical staining for proliferating cell nuclear antigen (PCNA) and smooth muscle actin (SMA), respectively. RESULTS: The systemic application of GH caused a significant increase in body weight (332+/-7 g vs. 289+/-13 g; p=0.007). Ulcer size was also reduced significantly compared with controls (5.6+/-0.8 mm2 vs. 9.9+/-1 mm2; p=0.005). Immunohistochemical analysis revealed a significant increase in cell proliferation (79.7+/-0.9% pos. cells vs. 64.7+/-1.9% pos. cells; p=0.0001) as shown by PCNA expression, and a significant increase in new vessel growth as demonstrated by SMA expression (1762+/-124 cells/mm2 vs. 1067+/-77 cells/mm2; p=0.0001). CONCLUSIONS: Growth hormone accelerates gastric ulcer healing by stimulating cell proliferation and angiogenesis.

Animals↗

PubMed2004

The impact of the Micro-Lightguide O2C for the quantification of tissue ischemia in diabetic foot ulcers.

OBJECTIVE: Tissue oxygen supply is crucial for wound healing. Especially in diabetic foot lesions, the chances for healing are mainly dependent on the presence or absence of ischemia. This study investigates the impact of the tissue O2 analysis system "O2C" for noninvasive quantification of tissue oxygenation in diabetic foot ulcer patients. RESEARCH DESIGN AND METHODS: O2C assessed relative blood flow (flow), flow velocity (velo), and hemoglobin concentration (rHb) and hemoglobin oxygenation (SO2) at 2 and 6 mm depth (means +/- SE). 1) Measurements were performed on intact skin of the forefoot and forearm of 20 healthy volunteers on 2 consecutive days. 2) Parameters were assessed on intact skin of the forefoot of diabetic foot ulcer patients (n=14). 3) Measurements were performed directly at the wound site in diabetic patients (n = 14). RESULTS: 1) Flow, velo, rHb, and SO2 at 2 and 6 mm depth were not significantly different when measured at 2 consecutive days. 2) There were no significant differences between diabetic subjects and healthy volunteers. Only flow in 6 mm depth was significantly higher in diabetic subjects (75 +/- 13 vs. 51 +/- 0.4 arbitrary units [AU], P <0.05). When diabetic foot ulcer patients were split into healers and nonhealers, initial readings of SO2 at 2 mm (32 +/- 6 vs. 44 +/- 3%, P <0.05) and flow in 6 mm (28 +/- 1 vs. 51 +/- 0.6 AU, P <0.05) were significantly reduced in nonhealers compared with control subjects, whereas in healers flow in 6 mm (70 +/- 0.6 vs. 51 +/- 0.6 AU, P <0.05) was significantly higher than that in control subjects. 3) Initial SO2, rHb, flow, and velo were significantly lower in nonhealing compared with healing wounds. CONCLUSIONS: O2C is a new reliable and valid method for noninvasive measurement of tissue oxygenation and microvascular blood flow in patients with diabetic foot ulcers.

Adult↗

PubMed2002

Skin grafting of venous ulcers: a review of its current role.

As a therapeutic option, grafting of venous ulcers has not been very successfully received despite the different types of grafting methods. Currently, there are only a few controlled randomized trials offering clear guidance to clinicians. The development of artificially bioengineered skin constructs has led to a renewed interest in wound bed preparation, and preliminary successes suggest that the role of skin grafting could be studied in the current context.

Journal Article↗

PubMedDate not supplied

Experimental ischemic wounds: correlation of cell proliferation and insulin-like growth factor I expression and its modification by different local IGF-I release systems.

We investigated cell proliferation and local insulin-like growth factor-I (IGF-I) expression in ischemic wounds after topical application of IGF-I through different delivery systems. IGF-I dressings were fabricated from an IGF-I containing polyvinyl alcohol film placed on a standard hydrogel dressing. In vitro, the release of IGF-I from this dressing was assessed by enzyme-linked immunosorbent assay. For animal experiments, a standardized ischemic skin flap containing a full-thickness wound was created on the back of male Sprague-Dawley rats. An identical wound outside the flap served as control. We initially investigated intracutaneous pO2 (p(ti)O2), cell proliferation, and local IGF-I expression. In a second setting, wounds were treated either with IGF-I dissolved in methylcellulose gel or with an IGF-I dressing, and ulcer size and cell proliferation were assessed. In vitro, approximately 60% of IGF-I was released from the IGF-I dressing, compared to a 97% release from methylcellulose gel. In vivo, ischemic wounds showed less cell proliferation and decreased IGF-I expression than nonischemic wounds. A lower local p(ti)O2 correlated with larger wound size, less cell proliferation, and decreased IGF-I expression. Ulcer size was reduced after treatment with either IGF-I dressing or methylcellulose gel. However, cell proliferation only increased after treatment with IGF-I dressing, but not after methylcellulose gel treatment. We conclude that IGF-I expression is decreased in ischemic wounds and correlates with low cell proliferation. This can be reversed by local IGF-I application, but the efficacy of treatment depends on the delivery system.

Administration, Topical↗

PubMedDate not supplied

Lactate stimulates endothelial cell migration.

The significance of the high lactate levels that characterize healing wounds is not fully understood. Lactate has been shown to enhance collagen synthesis by fibroblasts and vascular endothelial growth factor (VEGF) production by macrophages and endothelial cells. VEGF has been shown to induce endothelial cell migration. However, it has not been shown whether accumulated lactate correlates with the biological activity of VEGF. Therefore, we investigated the effect of lactate on migration of endothelial cells. Human umbilical vein endothelial cells and human microvascular endothelial cells were cultured to subconfluent monolayers in standard six-well tissue culture plates. Following a 24-hour serum starvation, cells were treated with the indicated concentrations of l-lactate. Cell migration was assessed using a modified Boyden chamber. VEGF protein in the cell culture supernatant was measured by enzyme-linked immunoassay. Lactate-enhanced VEGF protein synthesis in a time- and dose-dependent manner. Lactate added into the bottom well did not stimulate cellular migration from the upper well. However, lactate when added together with endothelial cells to the bottom well of the Boyden chamber increased cellular migration in a dose-dependent manner. This effect was blocked by anti-VEGF and by cycloheximide. Lactate enhances VEGF production in endothelial cells, although lactate, itself, is not a chemoattractant. We conclude that the lactate-mediated increase in cellular migration is regulated by VEGF.

Cell Movement↗