Systemic serum amyloid A in early (<24 h) diagnosis of acute synovial structure involvement in horses with penetrating limb injuries.

Synovial structure involvement secondary to limb injury is a common emergency in equine practice, requiring an accurate initial diagnosis for immediate treatment. This study aimed to investigate the clinical usefulness of Serum amyloid A (SAA) in the initial diagnosis of synovial structure involvement caused by acute (<24 h) penetrating limb injuries in horses and to correlate SAA with standard diagnostic parameters. Fifty-five horses with acute limb injuries were divided into two groups: Group 1 (G1, n = 26) with a diagnosis of penetrating synovial trauma and Group 2 (G2, n = 29) without synovial structure penetration. Serum SAA, white blood cell (WBC) count and fibrinogen as well as clinical criteria and synovial fluid parameters were assessed on admission. The two groups were compared using a two-sample t-test (metric parameters) or a Wilcoxon-Mann-Whitney test (ordinal parameters). Correlation was determined between serum SAA and the following parameters: WBC count, fibrinogen, synovial total nucleated cell count (TNCC) and percentage of neutrophils (% N), body temperature and the degree of lameness. Serum SAA concentrations were not different between G1 and G2; however, there were statistically significant differences in general health, the degree of lameness, and synovial fluid parameters. In G1, serum SAA concentrations positively correlated with fibrinogen concentrations and synovial fluid % N. Nonetheless, SAA cannot be used as a sole tool to diagnose synovial structure involvement caused by limb injuries. Synovial fluid parameters remain the most important tool in the diagnosis of synovial penetration. In cases where synoviocentesis fails or is not possible, serum SAA might support diagnosis.

5-Azacytidine and Resveratrol Enhance Chondrogenic Differentiation of Metabolic Syndrome-Derived Mesenchymal Stem Cells by Modulating Autophagy.

Recently, metabolic syndrome (MS) has gained attention in human and animal metabolic medicine. Insulin resistance, inflammation, hyperleptinemia, and hyperinsulinemia are critical to its definition. MS is a complex cluster of metabolic risk factors that together exert a wide range of effects on multiple organs, tissues, and cells in the body. Adipose stem cells (ASCs) are multipotent stem cell population residing within the adipose tissue that is inflamed during MS. Studies have indicated that these cells lose their stemness and multipotency during MS, which strongly reduces their therapeutic potential. They suffer from oxidative stress, apoptosis, and mitochondrial deterioration. Thus, the aim of this study was to rejuvenate these cells in vitro in order to improve their chondrogenic differentiation effectiveness. Pharmacotherapy of ASCs was based on resveratrol and 5-azacytidine pretreatment. We evaluated whether those substances are able to reverse aged phenotype of metabolic syndrome-derived ASCs and improve their chondrogenic differentiation at its early stage using immunofluorescence, transmission and scanning electron microscopy, real-time PCR, and flow cytometry. Obtained results indicated that 5-azacytidine and resveratrol modulated mitochondrial dynamics, autophagy, and ER stress, leading to the enhancement of chondrogenesis in metabolically impaired ASCs. Therefore, pretreatment of these cells with 5-azacytidine and resveratrol may become a necessary intervention before clinical application of these cells in order to strengthen their multipotency and therapeutic potential.

Static Magnetic Field (SMF) as a Regulator of Stem Cell Fate - New Perspectives in Regenerative Medicine Arising from an Underestimated Tool.

Tissue engineering and stem cell-based therapies are one of the most rapidly developing fields in medical sciences. Therefore, much attention has been paid to the development of new drug-delivery systems characterized by low cytotoxicity, high efficiency and controlled release. One of the possible strategies to achieve these goals is the application of magnetic field and/or magnetic nanoparticles, which have been shown to exert a wide range of effects on cellular metabolism. Static magnetic field (SMF) has been commonly used in medicine as a tool to increase wound healing, bone regeneration and as a component of magnetic resonance technique. However, recent data shed light on deeper mechanism of SMF action on physiological properties of different cell populations, including stem cells. In the present review, we focused on SMF effects on stem cell biology and its possible application as a tool for controlled drug delivery. We also highlighted the perspectives, in which SMF can be used in future therapies in tissue engineering due to its easy application and a wide range of possible effects on cells and organisms.

Tumescent local anaesthesia for early dermatosurgery in infants.

BACKGROUND: Early paediatric dermatosurgery reveals excellent cosmetic results due to high skin elasticity and pronounced capacity to recover from trauma. Furthermore, the size of skin lesions increases during life proportionally to skin growth and therefore early removal is of major importance. Selected local anaesthetics like prilocaine can cause methaemoglobinemia. However, in contrast to general anaesthesia, many other local anaesthetics do not bare any major risks for infants. OBJECTIVE: In this retrospective study, we analysed infants aged less than 7 months receiving tumescent local anaesthesia (TLA) followed by dermatosurgery at our department between 2005 and 2015. The analysis is mainly based on our records. Additional information for a subset of patients was gained by a postoperative survey. METHODS: Ninety-two infants (39 male, 53 female) with a median age of 4.2 months (range: 1.5 months; 6.7 months) were included in this study. Additional postoperative information was available for 33 of the 92 studied patients (35%). RESULTS: Infants were mainly operated for removal of a melanocytic naevus (n = 54), followed by haemangioma (n = 23), naevus sebaceous (n = 6) and other lesions (n = 9). The lesions were located on the scalp or neck (n = 31), on the extremities (n = 31), on the trunk (n = 21), in the face (n = 6) or on the buttocks (n = 3). The median size of excision was 509 mm2 (range: 16 mm2 ; 3600 mm2 ). Primary defect closure was performed by intracutaneous (n = 68) or extracutaneous (n = 24) suture techniques. No side-effects of local anaesthesia were observed in any patient. Postoperative complications include pain (1/33; 3%), wound-healing disorder (1/33; 3%) and visible severe scarring (2/33; 6%). CONCLUSIONS: The combination of TLA and dermatosurgery in infants is a suitable outpatient treatment option for small lesions without any major risks or side-effects and the benefit of prolonged postoperative analgesia.

[Skin diseases due to systemic vasculitides and vasculopathies]. / Hauterkrankungen durch systemische Vaskulitiden und Vaskulopathien.

Vasculitis and vasculopathy are two distinct disease entities. Each entity comprises a large number of heterogeneous diseases, which can occur alone or associated with autoimmune, infectious or neoplastic diseases. The terms vasculitis and vasculopathy are often falsely used synonymously. A vasculitis initially causes inflammation of the vessel walls that may result in a secondary occlusion. In contrast, a vasculopathy is a primary occlusion of the vascular lumen, which is followed by inflammation after ischemia and ulceration. In most patients the distinction can be made based on the clinical presentation. A clear clinical diagnosis is then followed by targeted serological, histological and imaging procedures to confirm the clinical diagnosis. On this basis a well-founded treatment can be initiated. In the presence of vasculitis an anti-inflammatory therapy is indicated, whereas in the case of vasculopathy, removal of the vascular occlusion is the main focus. This article provides an overview of the various diseases and addresses the pathogenetic and clinical characteristics used to differentiate the individual disease entities. It also provides an insight into the therapy options and prophylaxis.

Canakinumab in adults with steroid-refractory pyoderma gangrenosum.

BACKGROUND: Pyoderma gangrenosum (PG) is a rare, neutrophilic, ulcerative skin disease that is difficult to treat, especially when unresponsive to steroids. OBJECTIVES: To determine whether canakinumab is an effective and safe treatment in PG. METHODS: Five adult patients with clinically and histologically confirmed steroid-refractory PG were enrolled in this prospective open-label study. They received canakinumab 150 mg subcutaneously at week 0 with an optional 150 mg at week 2 in case of an inadequate response [Physician's Global Assessment (PGA) ≥ 2], and an optional 150-300 mg at week 8 depending on PGA. The primary clinical end point was clinical improvement (PGA at least -1 from baseline) and/or complete remission (PGA 0 or 1) at week 16. Real-time quantitative polymerase chain reaction was performed on skin samples to quantify cytokine mRNA levels. RESULTS: Interleukin (IL)-1ß and its known target genes IL6, CXCL8 and IL36A were significantly increased in lesional skin of PG. Under canakinumab therapy, four of five patients showed a decrease in target-lesion size, PGA and Dermatology Life Quality Index (DLQI), and three of five achieved complete remission. The mean diameter of target lesions decreased from 4·32 ± 2·6 cm at visit 1 to 0·78 ± 1·3 cm at visit 7 (P = 0·03). Mean DLQI decreased from 15 ± 5 at visit 1 to 8 ± 4 by visit 7 (P = 0·01). Adverse effects were reported in two patients: fatigue in one and worsening of disease at a nontarget lesion in the other. CONCLUSIONS: Our data indicate that IL-1ß plays a key pathogenic role in PG and canakinumab may represent a therapeutic option for steroid-refractory PG.

Efficacy of antifungal PACT in an in vitro model of onychomycosis.

BACKGROUND: The difficulty of antifungal substances to penetrate keratin and slow nail growth limit the efficacy of topical therapy in onychomycosis. One promising alternative is photodynamic antimicrobial chemotherapy, or PACT: an irradiated photosensitizer creates singlet oxygen molecules which destroy pathogens without damaging human cells. OBJECTIVE: As PACT has demonstrated strong antifungal capabilities, we wanted to investigate its efficacy in an in vitro model of onychomycosis. METHODS: PACT was tested in a microdilution assay, in an in vitro onychomycosis model as well as in a patient. RESULTS: PACT inhibited fungal growth in the microdilution assay with no colonies of T. rubrum detectable. Fungal growth was also inhibited in an onychomycosis model, after 30 min of LED irradiation. Subsequently, a patient with distolateral onychomycosis was treated on three consecutive days and showed significant and durable improvement of nail morphology 6 months after. CONCLUSION: PACT appears to be an effective treatment of onychomycosis in vitro. The promising results need to be validated by clinical trials.  

[Personalized molecular medicine: new paradigms in the treatment of cochlear implant and cancer patients]. / Molekulare personalisierte Medizin: Paradigmenwechsel in der Krankenversorgung von Cochlear-Implant- und Tumorpatienten.

OBJECTIVES: To evaluate present options for the indication of cochlear implants (CI) and new forms of treatment for head and neck cancer, melanomas and basal cell carcinomas, with emphasis on future perspectives. METHODS: A literature search was performed in the PubMed database. Search parameters were "personalized medicine", "individualized medicine" and "molecular medicine". RESULTS: Personalized medicine based on molecular-genetic evaluation of functional proteins such as otoferlin, connexin 26 and KCNQ4 or the Usher gene is becoming increasingly important for the indication of CI in the context of infant deafness. Determination of HER2/EGFR mutations in the epithelial growth factor receptor (EGFR) gene may be an important prognostic parameter for therapeutic decisions in head and neck cancer patients. In basal cell carcinoma therapy, mutations in the Hedgehog (PCTH1) and Smoothened (SMO) pathways strongly influence the indication of therapeutic Hedgehog inhibition, e.g. using small molecules. Analyses of c-Kit receptor, BRAF-600E and NRAS mutations are required for specific molecular therapy of metastasizing melanomas. The significant advances in the field of specific molecular therapy are best illustrated by the availability of the first gene therapeutic procedures for treatment of RPE65-induced infantile retinal degradation. CONCLUSION: The aim of personalized molecular medicine is to identify patients who will respond particularly positively or negatively (e.g. in terms of adverse side effects) to a therapy using the methods of molecular medicine. This should allow a specific therapy to be successfully applied or preclude its indication in order to avoid serious adverse side effects. This approach serves to stratify patients for adequate treatment.

Fumaderm® in daily practice for psoriasis: dosing, efficacy and quality of life.

BACKGROUND: Patients with psoriasis suffer from chronic skin disease and impaired quality of life. With a prevalence of 1-3% of the population, psoriasis is one of the most common chronic inflammatory autoimmune diseases. Fumaric acid esters (Fumaderm(®)) are approved for the treatment of psoriasis in Germany, but regular Fumaderm therapy with six tablets per day is often limited due to adverse events. OBJECTIVES: This observational study recorded data on quality of life, treatment efficacy and drug dosing in patients suffering from psoriasis treated with Fumaderm under conditions of daily practice in 78 dermatological centres. PATIENTS AND METHODS: In this prospective, multicentre, noninterventional trial we included adult patients with severe plaque psoriasis under outpatient conditions receiving Fumaderm according to the current summary of product characteristics for systemic treatment of psoriasis. At baseline and after 3, 6 and 12 months the dosing regimen under daily conditions, Dermatology Life Quality Index (DLQI) and clinical efficacy with the Psoriasis Area and Severity Index (PASI) were documented. RESULTS: A total of 249 patients were included. The mean DLQI score at study entry was 9·95; the mean PASI was 16·8. The average treatment dose of Fumaderm was 2·8 tablets daily. More than 70% of patients were treated with one to three tablets daily and < 30% were treated with a dose ranging from four to six tablets daily. DLQI and PASI improved in the entire study population by 67·2% and 66·6%, respectively. Specifically, when analysing patients who started Fumaderm within 4 weeks before baseline the mean DLQI score decreased from 11·8 to 2·9 (75% reduction) and the mean PASI score from 19·84 to 7·35 after 12 months (63% improvement). CONCLUSIONS: This is the first field study analysing the use of Fumaderm and the improvement of quality of life in patients with psoriasis under daily outpatient conditions. The improvement of DLQI obtained with Fumaderm was comparable with the improvement observed in patients with psoriasis treated with modern biologics. Importantly, in most patients with good clinical response, the treatment dose was one to three tablets daily.

Bimodal immune activation in psoriasis.

Psoriasis is an immune-regulated skin disease with various clinical subtypes and disease activities. The majority of patients present with predominantly stable plaques. At the onset of new lesions, plaque-type psoriasis frequently demonstrates pin-sized and highly inflammatory papules sometimes with an inflammatory border. The histopathology of initial psoriasis differs from stable plaque-type psoriasis. Early lesions demonstrate innate immune cells with neutrophils, degranulating mast cells and macrophages. These are followed by interleukin (IL)-1-dependent T helper (Th)17 cells, finally resulting in the Th1-dominated immunopathology of stable plaque-type psoriasis, where mononuclear cells predominate with interspersed neutrophilic (Munro) microabscesses. These features suggest a bimodal immune pathway where alternate activation of either innate (autoinflammatory) or adaptive (autoimmune) immunity predominates. Neutrophilic infiltrations appear during early psoriasis with Munro abscesses. They are time limited and occur periodically, clinically best seen in linear nail pitting. These features strongly suggest a critical role for an IL-1-Th17-dominated autoinflammation in the initiation of psoriasis, followed by a Th1-dominated late-phase reaction. The concept of bimodal immune activation helps to explain results from therapeutic interventions that are variable and previously only partly understood.

Efficacy of bath psoralen plus ultraviolet A (PUVA) vs. system PUVA in psoriasis: a prospective, open, randomized, multicentre study.

BACKGROUND: Plaque psoriasis is an inflammatory disease affecting approximately 2% of the population. The clinical hallmarks of psoriasis are sharply demarcated, erythematous plaques with thick scales. Photochemotherapy (psoralen plus ultraviolet A, PUVA) is one of the most effective therapies of psoriasis. The photosensitizer 8-methoxypsoralen (8-MOP) can be applied either orally (system PUVA) or topically in a warm water bath (bath PUVA). OBJECTIVES: To compare bath PUVA and system PUVA in the treatment of plaque psoriasis. METHODS: This was a randomized, open, prospective, multicentre trial. We included 74 patients with moderate-to-severe plaque psoriasis during a 6-week treatment and a 4-week follow-up period. Of the patients enrolled in the study, 38 received bath PUVA and 36 system PUVA. RESULTS: Both treatment modalities significantly reduced the median Psoriasis Area and Severity Index (PASI) score in the intention-to-treat population. Within 6 weeks bath PUVA reduced the median PASI by 74% (16·4 to 4·2) while system PUVA did so by 62% (15·3 to 5·8). The difference between the two modalities was not significant with regard to treatment efficacy (P = 0·389). CONCLUSION: There is no difference between bath PUVA and system PUVA in the treatment of psoriasis.

[Delayed appearance of symptoms in immediate hypersensitivity: type I sensitization to galactose-α-1,3-galactose]. / Verzögert auftretende Symptome einer Soforttypallergie: Typ-I-Sensibilisierung gegenüber Galaktose-α-1,3-Galaktose.

Delayed immediate-type allergy to innards and red meat can be mediated by IgE antibodies to galactose-α-1, 3-galactose (α-Gal). Apart from humans and Old World apes, α-Gal is ubiquitously expressed in glycoproteins and glycolipids. Thus, as α-Gal is immunogenic for humans, they can be easily sensitized even through a tick bite. Anti-α-Gal IgG represents approximately 1% of total IgG; IgE antibodies to α-Gal are comparably rare. However, in these patients, consuming red meat and especially innards can lead to the development of immediate type reactions such as urticaria. Cetuximab is a humanized IgG1 antibody containing murine α-Gal. Therefore, allergic reactions may occur with its first administration.

[Chronic actinic dermatitis. Therapy with systemic PUVA and mycophenolate mofetil]. / Chronisch aktinische Dermatitis. Therapie mit systemischer PUVA und Mycophenolatmofetil.

A 66-year-old man was diagnosed with psoriasis in 2001 and treated accordingly; in 2007, the diagnosis was switched to atopic dermatitis and the therapy modified. Initially he improved with fumarates and methotrexate, but then experienced recurrent exacerbations with erythroderma and severe superinfection requiring hospitalization. Based on the modified clinical picture with striking accentuation on the head and back of the hands, we diagnosed chronic actinic dermatitis. In September 2008 immunosuppressive therapy with mycophenolate mophetil (2×500 mg/d) was started. Since the response was modest, photo-hardening with systemic photochemotherapy (PUVA) was added, producing close to complete recovery within 6 months.

Effects of nonpathogenic gram-negative bacterium Vitreoscilla filiformis lysate on atopic dermatitis: a prospective, randomized, double-blind, placebo-controlled clinical study.

BACKGROUND: Atopic dermatitis (AD) is associated with elevated IgE levels and Th2 responses. The oral administration of nonpathogenic bacteria such as probiotics may improve the course of atopic diseases. It is believed that nonpathogenic bacteria prevent the development of allergic diseases by modulating intestinal immune responses. However, the effects of oral probiotics on AD could not be reproduced in all studies and the direct immunomodulation of the skin-associated immune response by nonpathogenic bacteria has not yet been investigated. OBJECTIVES: We performed a prospective, double-blind, placebo-controlled clinical study with a cream containing a 5% lysate of the nonpathogenic bacteria Vitreoscilla filiformis. PATIENTS AND METHODS: Seventy-five volunteers with AD (6-70 years of age) were randomized to receive either V. filiformis cream 5% or vehicle cream daily for 30 days. Efficacy was evaluated by the SCORe of Atopic Dermatitis (SCORAD), transepidermal water loss (TEWL), assessment of microflora, and the patient's assessment of itch and loss of sleep. RESULTS: Compared with placebo, V. filiformis lysate significantly decreased SCORAD levels (P=0.0044) and pruritus (P=0.0171). Active cream significantly decreased loss of sleep from day 0 to day 29 (P=0.0074). Qualitative and quantitative assessment of cutaneous microbial colonization revealed that V. filiformis lysate reduced Staphylococcus aureus colonization of the skin. The skin barrier as determined by TEWL also improved significantly with the cream alone. CONCLUSIONS: V. filiformis lysate significantly improved AD. This may be in part due to reduction of S. aureus, but seems to relate in most parts to a direct immunomodulatory effect on skin-associated immune responses.

Pimecrolimus cream 1% in erosive oral lichen planus--a prospective randomized double-blind vehicle-controlled study.

BACKGROUND: Erosive oral lichen planus (EOLP) is a T-cell mediated inflammatory disease leading to severe pain and impairment. As current therapies are of limited efficacy, application of calcineurin inhibitors is considered to be a potential option. OBJECTIVES: To investigate the efficacy of pimecrolimus cream 1% (Elidel) compared with vehicle cream in the treatment of EOLP. METHODS: Twenty patients were enrolled in a prospective, double-blind, randomized, vehicle-controlled trial and assigned to either pimecrolimus or vehicle group. Study medication was applied for 30 days followed by 30 days of observation without therapy. In case of unresponsiveness, treatment was continued for 30 days with open-label pimecrolimus. EOLP was monitored on days 0, 30 and 60. Safety was assessed by patient documentation, measurement of pimecrolimus levels and blood counts. RESULTS: Within 30 days erosions cleared completely in seven of 10 patients treated with pimecrolimus and in two of 10 patients treated with vehicle. The clinical EOLP 'composite score' including mucosal erosions and pain sensation was significantly reduced in the pimecrolimus-treated group compared with vehicle (P = 0.025). In the three of 10 patients not responding to pimecrolimus, EOLP cleared after an additional 30 days of treatment with pimecrolimus. Following termination of the therapy, sustained remission of EOLP was detected in 83% of patients demonstrating long-lasting effects of pimecrolimus treatment. No severe adverse events were observed. In five patients pimecrolimus blood levels were detected, all of which stayed below 4 ng mL(-1). CONCLUSIONS: Pimecrolimus cream 1% effectively treats EOLP with long-lasting therapeutic effects and is therefore a promising therapeutic option for EOLP.