Ursula MIRASTSCHIJSKI's publications (49)

Reconstructive and Aesthetic Surgeries on the Female Genitalia. Guideline of the DGGG, DGPRÄC, OEGGG and SGGG (S2k-Level, AWMF Registry No. 009/019, May 2022).

Jul, 2023

This official guideline was coordinated and published by the German Society for Gynaecology and Obstetrics (DGGG), the German Society for Plastic, Reconstructive and Aesthetic Surgery (DGPRÄC), the Austrian Society for Gynaecology and Obstetrics (OEGGG), and the Swiss Society for Gynaecology and Obstetrics (SGGG). The guideline aims to provide a consensus-based overview of reconstructive and aesthetic surgeries on female genitalia based on an evaluation of the relevant literature. This S2k-guideline was developed by representative members from different medical professions on behalf of the guidelines commission of the DGGG, DGPRÄC, OEGGG and SGGG using a structured consensus process. Statements and recommendations on the epidemiology, aetiology, classification, symptoms, diagnosis, and treatment of acquired changes of the external genitalia are presented and special situations are discussed. read more

Geburtshilfe und Frauenheilkunde

Efficacy of topically applied rapamycin-loaded redox-sensitive nanocarriers in a human skin/T cell co-culture model.

Apr, 2023

Rapamycin, also known as Sirolimus, is a promising anti-proliferative drug, but its therapeutic use for the topical treatment of inflammatory, hyperproliferative skin disorders is limited by insufficient penetration rates due to its high molecular weight (MW of 914.172 g/mol) and high lipophilicity. We have shown that core multi-shell (CMS) nanocarriers sensitive to oxidative environment can improve drug delivery to the skin. In this study, we investigated the mTOR inhibitory activity of these oxidation-sensitive CMS (osCMS) nanocarrier formulations in an inflammatory ex vivo human skin model. In this model, features of inflamed skin were introduced by treating the ex vivo tissue with low-dose serine protease (SP) and lipopolysaccharide (LPS), while phorbol 12-myristate 13-acetate and ionomycin were used to stimulate IL-17A production in the co-cultured SeAx cells. Furthermore, we tried to elucidate the effects of rapamycin on single cell populations isolated from skin (keratinocytes, fibroblast) as well as on SeAx cells. Further, we measured possible effects of the rapamycin formulations on dendritic cell (DC) migration and activation. The inflammatory skin model enabled the assessment of biological readouts at both the tissue and T cell level. All investigated formulations successfully delivered rapamycin across the skin as revealed by reduced IL-17A levels. Nevertheless, only the osCMS formulations reached higher anti-inflammatory effects in the skin compared to the control formulations with a significant downregulation of mTOR activity. These results indicate that osCMS formulations could help to establish rapamycin, or even other drugs with similar physico-chemical properties, in topical anti-inflammatory therapy. read more

International immunopharmacology

Genital Wound Repair and Scarring.

Apr, 2022

Skin wound repair has been the central focus of clinicians and scientists for almost a century. Insights into acute and chronic wound healing as well as scarring have influenced and ameliorated wound treatment. Our knowledge of normal skin notwithstanding, little is known of acute and chronic wound repair of genital skin. In contrast to extra-genital skin, hypertrophic scarring is uncommon in genital tissue. Chronic wound healing disorders of the genitals are mostly confined to mucosal tissue diseases. This article will provide insights into the differences between extra-genital and genital skin with regard to anatomy, physiology and aberrant wound repair. In light of fundamental differences between genital and normal skin, it is recommended that reconstructive and esthetic surgery should exclusively be performed by specialists with profound expertise in genital wound repair. read more

Medical sciences (Basel, Switzerland) Load more  

Homophilic and heterophilic cadherin bond rupture forces in homo- or hetero-cellular systems measured by AFM-based single-cell force spectroscopy.

May, 2021

Cadherins enable intercellular adherens junctions to withstand tensile forces in tissues, e.g. generated by intracellular actomyosin contraction. In-vitro single molecule force spectroscopy experiments can reveal cadherin-cadherin extracellular region binding dynamics such as bond formation and strength. However, characterization of cadherin-presenting cell homophilic and heterophilic binding in the proteins' native conformational and functional states in living cells has rarely been done. Here, we used atomic force microscopy (AFM) based single-cell force spectroscopy (SCFS) to measure rupture forces of homophilic and heterophilic bond formation of N- (neural), OB- (osteoblast) and E- (epithelial) cadherins in living fibroblast and epithelial cells in homo- and hetero-cellular arrangements, i.e., between cells and cadherins of the same and different types. In addition, we used indirect immunofluorescence labelling to study and correlate the expression of these cadherins in intercellular adherens junctions. We showed that N/N and E/E-cadherin homophilic binding events are stronger than N/OB heterophilic binding events. Disassembly of intracellular actin filaments affects the cadherin bond rupture forces suggesting a contribution of actin filaments in cadherin extracellular binding. Inactivation of myosin did not affect the cadherin rupture force in both homo- and hetero-cellular arrangements, but particularly strengthened the N/OB heterophilic bond and reinforced the other cadherins' homophilic bonds. read more

European biophysics journal : EBJ

[Improvement in burn wound care: summary of the AWMF guideline for the treatment of thermal injuries in adults].

Dec, 2020

More than half a million patients suffer from minor burns in Germany per year. In 2018, almost 2000 patients needed intensive care for their burn injuries. Despite high standards of burn care, mortality remains high. Burn injuries may lead to long-term sequelae. In order to provide up-to-date burn care, guidelines are available online with public access. read more

Handchirurgie, Mikrochirurgie, plastische Chirurgie : Organ der Deutschsprachigen Arbeitsgemeinschaft fur Handchirurgie : Organ der Deutschsprachigen Arbeitsgemeinschaft fur Mikrochirurgie der Peripheren Nerven und Gefasse : Organ der V...

[Suitability of biological acellular dermal matrices as a skin replacement].

Dec, 2020

 Tissue defects are associated with loss of epidermal and dermal components of the skin. For full-thickness tissue defects, dermal equivalents are useful to enable rapid wound closure. Split-thickness skin grafts are associated with loss of tissue elasticity resulting in scar contractures that can impair joint mobility. Synthetic collagen matrices and allogeneic acellular dermal matrices (ADM) are commercially available and could serve as skin tissue replacement. The aim of this study was to investigate whether ADM of different dermal layers or bioartificial matrices can serve as cutaneous replacement. For this purpose, cellular migration, differentiation and the inflammatory reaction were studied in an established skin organ model. read more

Handchirurgie, Mikrochirurgie, plastische Chirurgie : Organ der Deutschsprachigen Arbeitsgemeinschaft fur Handchirurgie : Organ der Deutschsprachigen Arbeitsgemeinschaft fur Mikrochirurgie der Peripheren Nerven und Gefasse : Organ der V...

Body hair removal: Prevalence, demographics, and body experience among men and women in Germany.

Nov, 2020

Body hair removal is an increasing trend that has an impact on the individual's body image. read more

Journal of cosmetic dermatology

Injury triggers fascia fibroblast collective cell migration to drive scar formation through N-cadherin.

Nov, 2020

Scars are more severe when the subcutaneous fascia beneath the dermis is injured upon surgical or traumatic wounding. Here, we present a detailed analysis of fascia cell mobilisation by using deep tissue intravital live imaging of acute surgical wounds, fibroblast lineage-specific transgenic mice, and skin-fascia explants (scar-like tissue in a dish - SCAD). We observe that injury triggers a swarming-like collective cell migration of fascia fibroblasts that progressively contracts the skin and form scars. Swarming is exclusive to fascia fibroblasts, and requires the upregulation of N-cadherin. Both swarming and N-cadherin expression are absent from fibroblasts in the upper skin layers and the oral mucosa, tissues that repair wounds with minimal scar. Impeding N-cadherin binding inhibits swarming and skin contraction, and leads to reduced scarring in SCADs and in animals. Fibroblast swarming and N-cadherin thus provide therapeutic avenues to curtail fascia mobilisation and pathological fibrotic responses across a range of medical settings. read more

Nature communications

Interventional Surgical Treatment Options.

Sep, 2020

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Deutsches Arzteblatt international

Lung Surfactant Accelerates Skin Wound Healing: A Translational Study with a Randomized Clinical Phase I Study.

Feb, 2020

Lung surfactants are used for reducing alveolar surface tension in preterm infants to ease breathing. Phospholipid films with surfactant proteins regulate the activity of alveolar macrophages and reduce inflammation. Aberrant skin wound healing is characterized by persistent inflammation. The aim of the study was to investigate if lung surfactant can promote wound healing. Preclinical wound models, e.g. cell scratch assays and full-thickness excisional wounds in mice, and a randomized, phase I clinical trial in healthy human volunteers using a suction blister model were used to study the effect of the commercially available bovine lung surfactant on skin wound repair. Lung surfactant increased migration of keratinocytes in a concentration-dependent manner with no effect on fibroblasts. Significantly reduced expression levels were found for pro-inflammatory and pro-fibrotic genes in murine wounds. Because of these beneficial effects in preclinical experiments, a clinical phase I study was initiated to monitor safety and tolerability of surfactant when applied topically onto human wounds and normal skin. No adverse effects were observed. Subepidermal wounds healed significantly faster with surfactant compared to control. Our study provides lung surfactant as a strong candidate for innovative treatment of chronic skin wounds and as additive for treatment of burn wounds to reduce inflammation and prevent excessive scarring. read more

Scientific reports

Patch repair of deep wounds by mobilized fascia.

Dec, 2019

Mammals form scars to quickly seal wounds and ensure survival by an incompletely understood mechanism. Here we show that skin scars originate from prefabricated matrix in the subcutaneous fascia. Fate mapping and live imaging revealed that fascia fibroblasts rise to the skin surface after wounding, dragging their surrounding extracellular jelly-like matrix, including embedded blood vessels, macrophages and peripheral nerves, to form the provisional matrix. Genetic ablation of fascia fibroblasts prevented matrix from homing into wounds and resulted in defective scars, whereas placing an impermeable film beneath the skin-preventing fascia fibroblasts from migrating upwards-led to chronic open wounds. Thus, fascia contains a specialized prefabricated kit of sentry fibroblasts, embedded within a movable sealant, that preassemble together diverse cell types and matrix components needed to heal wounds. Our findings suggest that chronic and excessive skin wounds may be attributed to the mobility of the fascia matrix. read more

Nature

Matrix Metalloproteinase-3 is Key Effector of TNF-α-Induced Collagen Degradation in Skin.

Oct, 2019

Inflammatory processes in the skin augment collagen degradation due to the up-regulation of matrix metalloproteinases (MMPs). The aim of the present project was to study the specific impact of MMP-3 on collagen loss in skin and its interplay with the collagenase MMP-13 under inflammatory conditions mimicked by the addition of the pro-inflammatory cytokine tumor necrosis factor-α (TNF-α). Skin explants from MMP-3 knock-out (KO) mice or from transgenic (TG) mice overexpressing MMP-3 in the skin and their respective wild-type counterparts (WT and WTT) were incubated ex vivo for eight days. The rate of collagen degradation, measured by released hydroxyproline, was reduced ( < 0.001) in KO skin explants compared to WT control skin but did not differ ( = 0.47) between TG and WTT skin. Treatment with the MMP inhibitor GM6001 reduced hydroxyproline media levels from WT, WTT and TG but not from KO skin explants. TNF-α increased collagen degradation in the WT group ( = 0.0001) only. More of the active form of MMP-13 was observed in the three MMP-3 expressing groups (co-incubation with receptor-associated protein stabilized MMP-13 subforms and enhanced detection in the media). In summary, the innate level of MMP-3 seems responsible for the accelerated loss of cutaneous collagen under inflammatory conditions, possibly via MMP-13 in mice. read more

International journal of molecular sciences

[Tattoos in Germany: prevalence, demographics, and health orientation].

Sep, 2019

Tattooing has become very popular in recent years. In this context, socio-demographic information and health orientation is important. read more

Bundesgesundheitsblatt, Gesundheitsforschung, Gesundheitsschutz

Nano-mechanical mapping of interdependent cell and ECM mechanics by AFM force spectroscopy.

Aug, 2019

Extracellular matrix (ECM), as a dynamic component of the tissue, influences cell behavior and plays an important role in cell mechanics and tissue homeostasis. Reciprocally, this three-dimensional scaffold is dynamically, structurally and mechanically modified by cells. In the field of biophysics, the independent role of cell and ECM mechanics has been largely investigated; however, there is a lack of experimental data reporting the interdependent interplay between cell and ECM mechanics, measured simultaneously. Here, using Atomic Force Microscopy (AFM) we have characterized five different decellularized matrices diverse in their topography, ECM composition and stiffness and cultured them with normal and pathological fibroblasts (scar and Dupuytren's). We investigated the change in topography and elasticity of these matrices due to cell seeding, by using AFM peak force imaging and mechanical mapping, respectively. We found normal fibroblasts soften these matrices more than pathological fibroblasts, suggesting that pathological fibroblasts are profoundly influencing tissue stiffening in fibrosis. We detected different ECM composition of decellularized matrices used here influences fibroblast stiffness, thus highlighting that cell mechanics not only depends on ECM stiffness but also on their composition. We used confocal microscopy to assess fibroblasts invasion and found pathological fibroblasts were invading the matrices deeper than normal fibroblasts. read more

Scientific reports

Novel specific human and mouse stromelysin-1 (MMP-3) and stromelysin-2 (MMP-10) antibodies for biochemical and immunohistochemical analyses.

Jul, 2019

Matrix metalloproteinases (MMP) are a family of more than 25 zinc-dependent enzymes that are centrally involved in cellular migration, tissue remodeling, cancer invasion and metastasis. Besides degrading extracellular matrix proteins, MMPs are crucial for growth factor and cytokine release and activation. At the same time, they can inactivate inflammatory mediators and enzymes themselves through protein degradation. Subclasses of MMPs include collagenases, gelatinases, stromelysins, membrane-bound MMPs, and others. With regard to the stromelysin subfamily, three members exist, e.g., stromelysin-1 (MMP-3), stromelysin-2 (MMP-10), and stromelysin-3 (MMP-11). MMP-3, and MMP-10 share extensive similarities at the amino acid level that made it difficult to develop specific antibodies distinguishing between MMP-3 and MMP-10. Scrutinizing published data on and performing different analyses with detection of both stromelysins with commercially available or lab-made antibodies showed ambiguous results with regard to specificity of antibodies used to date. We developed new specific antibodies against the most divergent parts of the active forms of both proteins. We assessed the specificity of our novel specific anti-human and anti-mouse MMP-3 and MMP-10 antibodies in cell lysates and different human and murine skin tissues. Tests analyzing specificity of the novel antibodies included Western immunoblotting, immunofluorescence, and immunohistochemistry on paraffin sections. Analyses demonstrated specific detection of respective protein for human or mouse samples except for the anti-human MMP-3 antibody. The aim of this summary was to call attention the MMP research community to distinguish clearly between both enzymes. Our new specific anti-mouse MMP-3 and both MMP-10 antibodies allow us to address this detection problem and to enable comparative studies between both stromelysins with regard to their respective location and function in the tissue. read more

Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society

Response to the Letter to the Editor.

Oct, 2018

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Annals of plastic surgery

Mechanical and migratory properties of normal, scar, and Dupuytren's fibroblasts.

Sep, 2018

Mechanical properties of myofibroblasts play a key role in Dupuytren's disease. Here, we used atomic force microscopy to measure the viscoelastic properties of 3 different types of human primary fibroblasts derived from a same patient: normal and scar dermal fibroblasts and palmar fascial fibroblasts from Dupuytren's nodules. Different stiffness hydrogels (soft ~1 kPa and stiff ~ 50 kPa) were used as cell culture matrix to mimic the mechanical properties of the natural tissues, and atomic force microscopy step response force curves were used to discriminate between elastic and viscous properties of cells. Since transforming growth factor-β1 (TGF-β1) is known to induce expression of α-smooth muscle actin positive stress fibers in myofibroblasts, we investigated the behavior of these fibroblasts before and after applying TGF-β1. Finally, we performed an in vitro cell motility test, the wound healing or scratch assay, to evaluate the migratory properties of these fibroblasts. We found that (1) Dupuytren's fibroblasts are stiffer than normal and scar fibroblasts, the elastic modulus E ranging from 4.4, 2.1, to 1.8 kPa, for Dupuytren's, normal and scar fibroblasts, respectively; (2) TGF-β1 enhances the level of α-smooth muscle actin expression and thus cell stiffness in Dupuytren's fibroblasts (E, ~6.2 kPa); (3) matrix stiffness influences cell mechanical properties most prominently in Dupuytren's fibroblasts; and (4) Dupuytren's fibroblasts migrate slower than the other fibroblasts by a factor of 3. Taking together, our results showed that mechanical and migratory properties of fibroblasts might help to discriminate between different pathological conditions, helping to identify and recognize specific cell phenotypes. read more

Journal of molecular recognition : JMR

Body Image, Personality Traits, and Quality of Life in Botulinum Toxin A and Dermal Filler Patients.

Aug, 2018

The demand for minimally invasive cosmetic procedures has continued to rise, especially in Germany, yet few studies have examined this patient population. The literature in Germany has repeatedly voiced the speculation that users of minimally invasive, skin-rejuvenating procedures displayed a higher tendency toward dysmorphic behavior patterns or, respectively, other abnormal personality traits. read more

Aesthetic plastic surgery

Classification and Treatment of the Adult Buried Penis.

Jun, 2018

In contrast to the concealed penis found in children, the adult buried penis (BP) is associated with obesity or found in patients after massive weight loss. Bariatric patients present with enormous prepubic fat masses into which the penile shaft retracts. As a consequence, urinating problems occur with wetting of the adjacent tissue. Many BP patients are circumcised with recurrence and worsening of the symptoms. In postbariatric patients, the penis is not engulfed into the prepubic tissue. In contrast to highly obese patients, the BP is covered underneath the cutaneous apron. Although all conditions are called BP, it is conceivable that plastic-surgical treatment differs. Hence, a novel classification for the adult BP was needed to adjust the procedures accordingly. We propose 3 types of the adult BP. The first type is termed "pseudo-BP." The penis is covered underneath the lax skin without signs of retraction. Here, an apronectomy and prepubic lift with tissue fixation are sufficient. The second type is the "intermediate-type BP" with partial penile invagination. After prepubic apronectomy, anchoring sutures secure the penile shaft from retraction. The third type is the "classical BP" seen in obese patients. The penile shaft is completely retracted into the prepubic fat. Often a stenotic scar tissue is found after previous circumcisions. The plastic-surgical reconstruction comprises scar excision, reduction of the prepubic fat masses with extraction of the penile shaft, anchoring sutures, and reconstruction of the penile envelope. In short, the etiology of the adult BP, a novel classification, and a treatment algorithm according to each type are presented in this comprehensive overview. read more

Annals of plastic surgery

Influence of MMP inhibitor GM6001 loading of fibre coated polypropylene meshes on wound healing: Implications for hernia repair.

May, 2018

Polypropylene meshes are standard for hernia repair. Matrix metalloproteinases play a central role in inflammation. To reduce the inflammatory response and improve remodelling with an associated reduction of hernia recurrence, we modified polypropylene meshes by nanofibre coating and saturation with the broad-spectrum matrix metalloproteinase inhibitor GM6001. The aim was to modulate the inflammatory reaction, increase collagen deposition and improve mesh biointegration. Polypropylene meshes were surface-modified with star-configured NCO-sP(EO -stat-PO) and covered with electrospun nanofibres (polypropylene-nano) and GM6001 (polypropylene-nano-GM). In a hernia model, defects were reconstructed with one of the meshes. Inflammation, neovascularization, bio-integration, proliferation and apoptosis were assessed histologically, collagen content and gelatinases biochemically. Mesh surface modification resulted in higher inflammatory response compared to polypropylene. Pro-inflammatory matrix metalloproteinase-9 paralleled findings while GM6001 reduced matrix metalloproteinase-9 significantly. Significantly increased matrix metalloproteinase-2 beneficial for remodelling was noted with polypropylene-nano-meshes. Increased vascular endothelial growth factor, neo-vascularization and collagen content were measured in polypropylene-nano-meshes compared to polypropylene. GM6001 significantly reduced myofibroblasts. This effect ended after d14 due to engineering limitations with release of maximal GM6001 loading. Nanofibre-coating of polypropylene-meshes confers better tissue vascularization to the cost of increased inflammation. This phenomenon can be only partially compensated by GM6001. Future research will enable higher GM6001 uptake in nano-coated meshes and may alter mesh biointegration in a more pronounced way. read more

Journal of biomaterials applications

Intra- or extra-exosomal secretion of HDGF isoforms: the extraordinary function of the HDGF-A N-terminal peptide.

Jun, 2017

Hepatoma-derived growth factor (HDGF) is a protein with diverse intracellular functions. Moreover, after non-conventional secretion, extracellular HDGF is able to influence different signaling pathways, leading for example to induction of processes like epithelial-mesenchymal transition (EMT) and cell migration. Intriguingly, in recent proteome studies, HDGF was also found secreted by special microvesicles called exosomes. Recently, we demonstrated the existence of two new HDGF isoforms (B and C). These isoforms are involved in different cellular processes than HDGF-A. Along this line, in the present study we discovered that full length HDGF-A clearly is located inside of exosomes, whereas the isoforms HDGF-B and HDGF-C are found exclusively on the outer surface. Furthermore, while HDGF-B and HDGF-C seem to use exosomes mediated pathway exclusively, HDGF-A was found also as unbound protein in the conditioned media. The new finding of an intra- or extra-exosomal localisation of protein splice variants opens a fascinating new perspective concerning functional diversity of HDGF isoforms. Dysregulation of HDGF expression during cancer development and tumor progression is a commonly known fact. With our new findings, unraveling the potential functional impact according to physiological versus pathophysiologically altered levels and compositions of intra- and extra-exosomal HDGF has to be addressed in future studies. read more

Biological chemistry

[Buried Penis: A Comprehensive Review on Aetiology, Classification and Plastic-Surgical Reconstruction].

Apr, 2017

The buried penis, also called hidden or concealed penis, is associated with morbid obesity or seen after massive weight loss in adults. In highly obese, bariatric patients, the penile shaft invaginates into the pre-pubic fat masses, resulting in voiding problems and urine wetting of the surrounding tissue. This leads to infection, skin maceration, lichen sclerosus and eczema. Sole circumcision without mons pubis plasty or penile fixation does not suffice to alleviate the discomfort and leads to recurrence. In post-bariatric patients, penile retraction is only partially present or absent, but abundant pre-pubic skin tissue forms an apron covering the genitals with problems in hygiene and sexual intercourse. In these cases, plastic-reconstructive interventions include mons pubis plasty with or without penile fixation. This article provides a comprehensive overview on aetiology, a novel classification of the buried penis and plastic-surgical reconstructive interventions matched to the stages of the condition. read more

Handchirurgie, Mikrochirurgie, plastische Chirurgie : Organ der Deutschsprachigen Arbeitsgemeinschaft fur Handchirurgie : Organ der Deutschsprachigen Arbeitsgemeinschaft fur Mikrochirurgie der Peripheren Nerven und Gefasse : Organ der V...

Extremely Obese Patients With Buried Penis.

Jan, 2017

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Deutsches Arzteblatt international

[Current Perceptions of Lipofilling on the Basis of the New Guideline on "Autologous Fat Grafting"].

Dec, 2016

Autologous fat transfer has recently become an increasingly popular surgical procedure and comprises harvesting, processing and transplantation of adipose tissue, as well as professional follow-up care. This method, as a surgical procedure, can be utilised for trauma-, disease- or age-related soft tissue volume deficits and soft tissue augmentation. As usage is increasing, but the variables of fat harvest, specific indications and fashion of fat transfer are poorly defined, there is a great demand for development of a guideline in the field of reconstructive and aesthetic surgery. All relevant points were discussed within the scope of a consensus conference including a nominal group process of all societies involved in the procedure and ratified with a strong consensus (>95%). Literature from the standard medical databases over the last 10 years was retrieved, studied and specific guidelines were concluded. Consensus was achieved among all professionals involved on the following points: 1. definition 2. indication/contraindication, 3. preoperative measures 4. donor sites 5. techniques of processing 6. transplantation 7. follow-up care 8. storage 9. efficacy 10. documentation 11. evaluation of patient safety. Definite indications and professional expertise are paramount for autologous fat tissue transfer. Successful transfers are based on the use of correct methods as well as specific instruments and materials. Autologous adipose tissue transplantation is considered to be a safe procedure in reconstructive and aesthetic surgery, due to the low rate of postoperative complications and sequelae. read more

Handchirurgie, Mikrochirurgie, plastische Chirurgie : Organ der Deutschsprachigen Arbeitsgemeinschaft fur Handchirurgie : Organ der Deutschsprachigen Arbeitsgemeinschaft fur Mikrochirurgie der Peripheren Nerven und Gefasse : Organ der V...

Two new isoforms of the human hepatoma-derived growth factor interact with components of the cytoskeleton.

May, 2016

Hepatoma-derived growth factor (HDGF) is involved in diverse, apparently unrelated processes, such as cell proliferation, apoptosis, DNA-repair, transcriptional control, ribosome biogenesis and cell migration. Most of the interactions of HDGF with diverse molecules has been assigned to the hath region of HDGF. In this study we describe two previously unknown HDGF isoforms, HDGF-B and HDGF-C, generated via alternative splicing with structurally unrelated N-terminal regions of their hath region, which is clearly different from the well described isoform, HDGF-A. In silico modeling revealed striking differences near the PHWP motif, an essential part of the binding site for glycosaminoglycans and DNA/RNA. This observation prompted the hypothesis that these isoforms would have distinct interaction patterns with correspondingly diverse roles on cellular processes. Indeed, we discovered specific associations of HDGF-B and HDGF-C with cytoskeleton elements, such as tubulin and dynein, suggesting previously unknown functions of HDGF in retrograde transport, site directed localization and/or cytoskeleton organization. In contrast, the main isoform HDGF-A does not interact directly with the cytoskeleton, but via RNA with messenger ribonucleoprotein (mRNP) complexes. In summary, the discovery of HDGF splice variants with their discrete binding activities and subcellular distributions opened new avenues for understanding its biological function and importance. read more

Biological chemistry

The cost of post-burn scarring.

Sep, 2015

Deep burns lead to scarring and contractures for which there is little or no published data on treatment costs. The purpose of this study was to fill this gap by analysing treatment costs for burn sequelae. To do this, German-DRG for in-patient treatment was collected from the Burn Centre Lower Saxony. DRG-related T95.-coding served as a tool for burn-associated sequelae. Data on scar occurrence, plastic-reconstructive surgery and sick leave were collected by a questionnaire. The findings showed that 44.6% patients reported post-burn scarring and 31% needed surgical intervention. The expected risk for readmission was significantly higher (p=0.0002) with scars compared to without. Significantly higher costs for pressure garments were noted for scarred patients (p=0.04). No differences were found for ointments, silicone dressings or pain medication. Treatment costs for patients with scars were 5.6 times higher compared with no scar assessed by G-DRG. No differences were stated subsuming multiple readmissions for post-burn treatment per individual. Significantly higher costs (p=0.03) were noted for patients with burn sequelae other than scars with regard to individual readmissions. It has been revealed that treatment of scars causes higher costs than for other burn sequelae because of multiple surgical interventions. To reduce post-burn scarring and costs, specialized burn centres provide optimal and state-of-the-art treatment. As well as this, more emphasis should be laid on promoting research for the development of novel anti-scarring therapies. read more

Annals of burns and fire disasters

Tumor necrosis factor-α-accelerated degradation of type I collagen in human skin is associated with elevated matrix metalloproteinase (MMP)-1 and MMP-3 ex vivo.

Jan, 2015

Tumor necrosis factor (TNF)-α induces matrix metalloproteinases (MMPs) that may disrupt skin integrity. We have investigated the effects and mechanisms of exogenous TNF-α on collagen degradation by incubating human skin explants in defined serum-free media with or without TNF-α (10ng/ml) in the absence or presence of the nonselective MMP inhibitor GM6001 for 8 days. The basal culture conditions promoted type I collagen catabolism that was accelerated by TNF-α (p<0.005) and accomplished by MMPs (p<0.005). Levels of the collagenases MMP-8 and MMP-13 were insignificant and neither MMP-2 nor MMP-14 were associated with increased collagen degradation. TNF-α increased secretion of MMP-1 (p<0.01) but had no impact on MMP-1 quantities in the tissue. Immunohistochemical analysis confirmed similar tissue MMP-1 expression with or without TNF-α with epidermis being the major source of MMP-1. Increased tissue-derived collagenolytic activity with TNF-α exposure was blocked by neutralizing MMP-1 monoclonal antibody and was not due to down-regulation of tissue inhibitor of metalloproteinase-1. TNF-α increased production (p<0.01), tissue levels (p<0.005) and catalytic activity of the endogenous MMP-1 activator MMP-3. Type I collagen degradation correlated with MMP-3 tissue levels (rs=0.68, p<0.05) and was attenuated with selective MMP-3 inhibitor. Type I collagen formation was down-regulated in cultured compared with native skin explants but was not reduced further by TNF-α. TNF-α had no significant effect on epidermal apoptosis. Our data indicate that TNF-α augments collagenolytic activity of MMP-1, possibly through up-regulation of MMP-3 leading to gradual loss of type I collagen in human skin. read more

European journal of cell biology

[Impact of Martian and Lunar dust simulants on cellular inflammation in human skin wounds ex vivo].

Dec, 2014

In 2006 NASA published its plans to build a manned lunar station in order to undertake missions to Mars in the future. Thus research projects have been conducted on the influence of Lunar and Martian dust on human health. The present study investigated the effect of Lunar and Martian dust simulants (LDS, MDS) in comparison with earth dust (ED) on viability, migration and inflammatory reaction during wound closure in an ex vivo human skin wound model. read more

Handchirurgie, Mikrochirurgie, plastische Chirurgie : Organ der Deutschsprachigen Arbeitsgemeinschaft fur Handchirurgie : Organ der Deutschsprachigen Arbeitsgemeinschaft fur Mikrochirurgie der Peripheren Nerven und Gefasse : Organ der V...

Biomechanics and biocompatibility of woven spider silk meshes during remodeling in a rodent fascia replacement model.

Apr, 2014

The aim of this study was to investigate biomechanical and immunogenic properties of spider silk meshes implanted as fascia replacement in a rat in vivo model. read more

Annals of surgery

Complete horizontal skin cell resurfacing and delayed vertical cell infiltration into porcine reconstructive tissue matrix compared to bovine collagen matrix and human dermis.

Oct, 2013

Xenogenous dermal matrices are used for hernia repair and breast reconstruction. Full-thickness skin replacement is needed after burn or degloving injuries with exposure of tendons or bones. The authors used a human skin organ culture model to study whether porcine reconstructive tissue matrix (Strattice) is effective as a dermal tissue replacement. read more

Plastic and reconstructive surgery

Zinc, copper, and selenium tissue levels and their relation to subcutaneous abscess, minor surgery, and wound healing in humans.

Jun, 2013

Trace element involvement in wounds left to heal by secondary intention needs clarification. We have previously reported faster healing of wounds following acute surgery compared with elective excision of pilonidal sinus disease. The effect of topical zinc on the closure of the excisional wounds was mediocre compared with placebo. In contrast, parenteral zinc, copper, and selenium combined appear effective for wound healing in humans. We have investigated zinc, copper, and selenium with respect to (a) impact of acute versus chronic pilonidal sinus and (b) regional concentrations within granulating wounds treated topically with placebo or zinc in 42 (33 males) pilonidal disease patients. Baseline serum and skin concentrations of copper correlated (r S = 0.351, p = 0.033, n = 37), but not of zinc or selenium. Patients with abscesses had elevated serum C-reactive protein (CRP) and copper levels (+29 %; p < 0.001) compared with the elective patients consistent with the strong correlation between serum copper and CRP (r S = 0.715, p < 0.0005, n = 41). Seven days after elective surgery, serum CRP and copper levels were elevated (p = 0.010) versus preoperative values. The copper concentration in wound edges was higher than in periwound skin (p < 0.0005) and wound base (p = 0.010). Selenium levels were increased in wound edge compared to wound base (p = 0.003). Topical zinc oxide treatment doubled (p < 0.050) zinc concentrations in the three tissue localizations without concomitant significant changes of copper or selenium levels. In conclusion, copper and selenium are mobilized to injured sites possibly to enhance host defense and early wound healing mechanisms that are complementary to the necessity of zinc for matrix metalloproteinase activity. read more

Biological trace element research

Rehabilitation of burn patients: an underestimated socio-economic burden.

Mar, 2013

Patients with burns utilise intensive medical care and rehabilitation. Deep dermal burns lead to scar contractures. Virtually no published data exists on costs for treatment of acute burns in comparison to burn sequelae. Our purpose was to collect financial data on burn therapy to estimate the socio-economic burden of thermal injuries. read more

Burns : journal of the International Society for Burn Injuries

Too little appreciation for great expenditure? Workload and resources in ICUs.

Oct, 2012

The aim of this study was providing descriptive information and the comparative examination of job strain and mental health of nurses and physicians in different intensive care units (ICU). read more

International archives of occupational and environmental health

Syndromes with focal overgrowth in infancy: diagnostic approach and surgical treatment.

Feb, 2012

Syndromes with focal overgrowth are sporadic diseases and comprise Proteus syndrome and congenital lipomatous overgrowth, vascular malformations, and epidermal naevi (CLOVE) syndrome, and isolated hemihyperplasia. We describe 3 children classified according to standard criteria with dysregulated growth of various tissues that was excised, together with excess toes, and tumours. Correct classification facilitates diagnosis and operations. Interdisciplinary treatment and follow-up are recommended to prevent disfiguration. read more

Journal of plastic surgery and hand surgery

An isolated hand tumour as primary manifestation of sarcoidosis.

Jul, 2011

Sarcoidosis is a systemic disorder with unknown etiology, characterized by non-caseating granulomas in numerous organs and tissues. In 90% of patients lung and lymph nodes are involved. The incidence of sarcoidal granulomas in the upper extremities is low. Here we present the case of a primary hand manifestation of sarcoidosis without clinical systemic involvement. read more

Sarcoidosis, vasculitis, and diffuse lung diseases : official journal of WASOG

Intraaxonal uptake and transport of marker proteins: novel ways of tracing peripheral nerve regeneration.

Jan, 2011

Disruption of peripheral nerve continuity occurs after accidents or in obstetrics. Brachial plexus palsy is accompanied by loss of function of the upper extremity. For optimal regeneration, surgical reconstruction should be performed within 6 months after injury. Postoperative monitoring is difficult because reliable diagnostic tools are not available. Here we present a hypothesis how to monitor peripheral nerve regeneration taking into account two intriguing features of nerve repair. First, the nerve itself with its numerous axons has been neglected as transportation pathway hitherto. Second, growth associated proteins are exclusively upregulated during peripheral nerve repair and development providing excellent target molecules. Contrast media could be designed using truncated forms of these proteins. Previous studies showed that peripheral nerves have the ability to incorporate proteins with a size up to 240 kDa. After wounding, growth associated proteins are transported intraaxonally and incorporated into growth cone membranes. We hypothesize that injection of contrast media close to nerve cell bodies or into the end organ of the injured nerve would lead to protein uptake and transport to the injury site. Sprouting of peripheral nerves could be monitored by magnetic resonance imaging or single photon emission computer tomography using adequate tracer-coupled proteins. By this new method, nerve repair could be monitored non-invasively, selectively and repeatedly. Less contrast media at lower price would be needed and only the injured part of the body would be exposed to the diagnostic apparatus. Aberrant nerve repair could be detected easily followed by surgical therapy within the critical time frame of sustained nerve regeneration. read more

Medical hypotheses

Novel plant metalloproteinase from Dieffenbachia seguine causes fingertip necrosis.

May, 2010

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The British journal of dermatology

Myopathic changes in bilateral hypertrophy of the first dorsal interosseus muscle of the hand.

Sep, 2009

A 43-year-old healthy man presented with bilateral hypertrophy of the first dorsal interosseus muscles of both hands. Neurophysiologic and laboratory examinations revealed no pathologic findings. Doubled muscle width was found by ultrasound. Myopathic changes were present in muscle biopsy with varying fiber sizes but without inflammatory features. The clinical impression of massive bilateral symmetric enlargement of the first dorsal interosseus muscles was characterized by subtle, non-specific muscular pathology. read more

Journal of neurology

Magnetic resonance imaging monitoring of peripheral nerve regeneration following neurotmesis at 4.7 Tesla.

Jun, 2009

The preoperative diagnostic imaging of peripheral nerve lesions and the postoperative monitoring of microsurgically coapted nerves remain unsolved problems. The aim of this study was to investigate peripheral nerve regeneration after complete neurotmesis with magnetic resonance imaging techniques. read more

Plastic and reconstructive surgery

Ileal J-pouch vaginoplasty: reconstruction of a physiologic vagina with an ileal J-pouch.

Jun, 2009

Vaginal reconstruction has been performed for more than a century. Main complications are vaginal stenosis requiring dilatation, dyspareunia, excessive mucus secretion, and poor aesthetic and functional outcome. Here we report a new operation method modified after Baldwin for intestinal vaginoplasty in a patient with pelvic exenteration after spinal cell carcinoma of the vagina. Because of balanced liquid resorption and mucus secretion with sufficient vessel length in the terminal ileum, this intestinal segment was chosen. A J-pouch of distal ileum was constructed pedicled on the ileocolic artery and accompanying nervous plexus, transferred into the lower pelvis and sutured to the vaginal stump. One year follow-up showed a highly satisfied, sexually active patient, with adequate vaginal size, optimal lubrication and no molesting fecal odor. Terminal ileum J-pouch vaginoplasty is an optimal method for vaginal reconstruction providing a sufficient vaginal lumen and lubrication and thereby restoring patients' sexual life and increasing life quality. read more

American journal of obstetrics and gynecology

Neurological picture. Bilateral idiopathic hypertrophy of the first dorsal interosseous muscles in a 43-year-old man.

Sep, 2008

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Journal of neurology, neurosurgery, and psychiatry

Action of matrix metalloproteinases at restricted sites in colon anastomosis repair: an immunohistochemical and biochemical study.

Jul, 2006

Dehiscence of colon anastomosis is a common, serious and potentially life-threatening complication after colorectal operation. In experimental models, impaired biomechanic strength of colon anastomoses is preventable by general inhibitors of matrix metalloproteinases (MMPs) and associated with collagen loss, which indicates a possible link between MMP-mediated collagen degradation and dehiscence. The precise localization of collagen degradation within the anastomotic area and the specific MMPs responsible are unknown. read more

Surgery

Lung Surfactant for Pulmonary Barrier Restoration in Patients With COVID-19 Pneumonia.

2020

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Frontiers in medicine

Panta Rhei: Neovascularization, Angiogenesis and Nutritive Perfusion in Wound Healing.

2018

In response to tissue damage, angiogenesis is an extremely dynamic process that is finely regulated by signals from cells, the surrounding extracellular matrix (ECM), and derived mediators. As the only process, angiogenesis remains of decisive importance in the context of the entire wound healing process and is subject to constant change. The dissolution of the endothelial basement membrane, the migration of endothelial cells, and the development of new capillary vessels during wound healing depend not only on the cells and cytokines present, but also on the production and organization of ECM components in the immediate wound. read more

European surgical research. Europaische chirurgische Forschung. Recherches chirurgicales europeennes

Transcriptome Study of an Mutant on an Skin Model: Is Melanin Important for Infection?

2018

The black yeast is a polyextremophilic human pathogen, especially known for growing in man-made extreme environments. Reported diseases caused by this fungus range from benign cutaneous to systemic infections with 40% fatality rate. While the number of cases steadily increases in both immunocompromised and immunocompetent people, detailed knowledge about infection mechanisms, virulence factors and host response are scarce. To understand the impact of the putative virulence factor melanin on the infection, we generated a polyketide synthase () mutant using CRISPR/Cas9 resulting in a melanin deficient strain. The mutant and the wild-type fungus were inoculated onto skin explants using an skin organ culture model to simulate cutaneous infection. The difference between the mutant and wild-type transcriptional landscapes, as assessed by whole RNA-sequencing, were small and were observed in pathways related to the copper homeostasis, cell wall genes and proteases. Seven days after inoculation the wild-type fungus completely colonized the stratum corneum, invaded the skin and infected keratinocytes while the mutant had only partially covered the skin and showed no invasiveness. Our results suggest that melanin dramatically improves the invasiveness and virulence of during the first days of the skin infection. read more

Frontiers in microbiology

Skin Wound Healing: An Update on the Current Knowledge and Concepts.

2017

The integrity of healthy skin plays a crucial role in maintaining physiological homeostasis of the human body. The skin is the largest organ system of the body. As such, it plays pivotal roles in the protection against mechanical forces and infections, fluid imbalance, and thermal dysregulation. At the same time, it allows for flexibility to enable joint function in some areas of the body and more rigid fixation to hinder shifting of the palm or foot sole. Many instances lead to inadequate wound healing which necessitates medical intervention. Chronic conditions such as diabetes mellitus or peripheral vascular disease can lead to impaired wound healing. Acute trauma such as degloving or large-scale thermal injuries are followed by a loss of skin organ function rendering the organism vulnerable to infections, thermal dysregulation, and fluid loss. read more

European surgical research. Europaische chirurgische Forschung. Recherches chirurgicales europeennes

The Transcriptome of during Skin Model Infection.

2016

The black yeast is a widespread polyextremophile and human pathogen, that is found in extreme natural habitats and man-made environments such as dishwashers. It can cause various diseases ranging from phaeohyphomycosis and systemic infections, with fatality rates reaching 40%. While the number of cases in immunocompromised patients are increasing, knowledge of the infections, virulence factors and host response is still scarce. In this study, for the first time, an artificial infection of an skin model with was monitored microscopically and transcriptomically. Results show that is able to actively grow and penetrate the skin. The analysis of the genomic and RNA-sequencing data delivers a rich and complex transcriptome where circular RNAs, fusion transcripts, long non-coding RNAs and antisense transcripts are found. Changes in transcription strongly affect pathways related to nutrients acquisition, energy metabolism, cell wall, morphological switch, and known virulence factors. The L-Tyrosine melanin pathway is specifically upregulated during infection. Moreover the production of secondary metabolites, especially alkaloids, is increased. Our study is the first that gives an insight into the complexity of the transcriptome of during artificial skin infections and reveals new virulence factors. read more

Frontiers in cellular and infection microbiology

Matrix metalloproteinase inhibition delays wound healing and blocks the latent transforming growth factor-beta1-promoted myofibroblast formation and function.

2010

The ability to regulate wound contraction is critical for wound healing as well as for pathological contractures. Matrix metalloproteinases (MMPs) have been demonstrated to be obligatory for normal wound healing. This study examined the effect that the broad-spectrum MMP inhibitor BB-94 has when applied topically to full-thickness skin excisional wounds in rats and its ability to inhibit the promotion of myofibroblast formation and function by the latent transforming-growth factor-beta1 (TGF-beta1). BB-94 delayed wound contraction, as well as all other associated aspects of wound healing examined, including myofibroblast formation, stromal cell proliferation, blood vessel formation, and epithelial wound coverage. Interestingly, BB-94 dramatically increased the level of latent and active MMP-9. The increased levels of active MMP-9 may eventually overcome the ability of BB-94 to inhibit this MMP and may explain why wound contraction and other associated events of wound healing were only delayed and not completely inhibited. BB-94 was also found to inhibit the ability of latent TGF-beta1 to promote the formation and function of myofibroblasts. These results suggest that BB-94 could delay wound closure through a twofold mechanism; by blocking keratinocyte migration and thereby blocking the necessary keratinocyte-fibroblast interactions needed for myofibroblast formation and by inhibiting the activation of latent TGF-beta1. read more

Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society

Zinc in wound healing: theoretical, experimental, and clinical aspects.

2007

Zinc is an essential trace element in the human body and its importance in health and disease is appreciated. It serves as a cofactor in numerous transcription factors and enzyme systems including zinc-dependent matrix metalloproteinases that augment autodebridement and keratinocyte migration during wound repair. Zinc confers resistance to epithelial apoptosis through cytoprotection against reactive oxygen species and bacterial toxins possibly through antioxidant activity of the cysteine-rich metallothioneins. Zinc deficiency of hereditary or dietary cause can lead to pathological changes and delayed wound healing. Oral zinc supplementation may be beneficial in treating zinc-deficient leg ulcer patients, but its therapeutic place in surgical patients needs further clarification. Topical administration of zinc appears to be superior to oral therapy due to its action in reducing superinfections and necrotic material via enhanced local defense systems and collagenolytic activity, and the sustained release of zinc ions that stimulates epithelialization of wounds in normozincemic individuals. Zinc oxide in paste bandages (Unna boot) protects and soothes inflamed peri-ulcer skin. Zinc is transported through the skin from these formulations, although the systemic effects seem insignificant. We present here the first comprehensive account of zinc in wound management in relation to current concepts of wound bed preparation and the wound-healing cascade. This review article suggests that topical zinc therapy is underappreciated even though clinical evidence emphasizes its importance in autodebridement, anti-infective action, and promotion of epithelialization. read more

Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society