RESUMEN
Guidelines are systematically developed decision-making aids to ensure appropriate clinical care for specific medical conditions. In Germany, dermatological guidelines are developed under the aegis of the German Dermatological Society (DDG) and the Professional Association of German Dermatologists (BVDD), while European and international guidelines are published by organisations such as the European Centre for Guidelines Development (EuroGuiDerm), founded by the European Dermatology Forum (EDF) in cooperation with the Division of Evidence-Based Medicine at Charité-Universitätsmedizin Berlin. In 2021 and 2022, the German guidelines were revised or developed on topics such as the management of anticoagulation during dermatological procedures, chronic pruritus, contact dermatitis, laser therapy of the skin, psoriasis vulgaris, rosacea, extracorporeal photopheresis, onychomycosis, mucous membrane pemphigoid and prevention of skin cancer. A selection of the most important recommendations and innovations in the guidelines is summarized here.
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Dermatología , Psoriasis , Neoplasias Cutáneas , Humanos , Alemania , Psoriasis/tratamiento farmacológico , PielAsunto(s)
Dermatitis , Neoplasias Cutáneas , Humanos , Microscopía Confocal , Piel , Coloración y EtiquetadoRESUMEN
BACKGROUND: Ex vivo confocal laser scanning microscopy (CLSM) is a novel diagnostic tool for the fast examination of native tissue. However, CLSM produces black/white/green images, depending on the refraction indices of the tissue structures, complemented by nuclear fluorescence staining, which the vast majority of Mohs surgeons and dermatopathologists are not trained to interpret. Digital staining is applicable to ex vivo CLSM investigations to simulate the images of conventional slides stained with haematoxylin and eosin (H&E). OBJECTIVES: The aim of our study was to evaluate in detail the appearance of human skin structures using digitally stained ex vivo CLSM images and compare the results to that of conventional H&E slides of the same specimen. METHODS: After providing informed consent, 26 patients donated their Burow's triangles (healthy skin) that resulted from plastic reconstruction after the R0 excision of skin tumours. After being investigated by ex vivo CLSM, including automated digital staining (VivaScope 2500M-4G, MAVIG GmbH), the specimens were fixed in formalin, embedded in paraffin and stained with H&E. RESULTS: Almost all skin structures in the digitally stained ex vivo CLSM images morphologically resembled the structures in the histopathological images acquired from H&E slides. Due to the high refraction index of melanin, the hair shafts appeared bright pink, and the melanocytes and melanophages were poorly imaged, resulting in a strong pink appearance that vastly differed from the appearance of conventional H&E-stained histopathology. CONCLUSIONS: Digital staining of ex vivo CLSM images is an easy and highly useful tool to facilitate the interpretation of black-field images generated by confocal laser scanning microscopy for dermatopathologists and Mohs surgeons who are familiar with H&E staining. Unlike the pigmented structures, the cutaneous and subcutaneous structures had excellent visualization with only minimal differences from their appearance on H&E slides.
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Neoplasias Cutáneas , Humanos , Melanocitos , Microscopía Confocal , Piel/diagnóstico por imagen , Neoplasias Cutáneas/diagnóstico por imagen , Coloración y EtiquetadoRESUMEN
The standardization of outcome reporting is crucial for interpretation and comparison of studies related to laser treatment of skin disorders. In collaboration with the Cochrane Skin-Core Outcome Set Initiative (CS-COUSIN), a procedure has been proposed to find consensus on the most important generic outcome domains (what to measure) for implementation in the international Laser TrEAtment in Dermatology (LEAD) registry. As the first step in the development of a generic outcome set for the LEAD registry, we undertook a systematic review to identify outcomes, outcome measurement instruments, methods and definitions reported in recently published literature of laser treatments for skin disorders. A systematic search was conducted and generated a total of 707 papers. We assessed 150 studies including all types of studies involving laser treatments for the skin. Two researchers independently extracted the type, definition and frequency of all outcomes and used outcome measurement instruments. We identified 105 verbatim outcomes that were categorized into eight domains recommended by the COMET framework: appearance, long-term effects, physician and patient-reported physical signs, satisfaction, health-related quality of life, psychological functioning and adverse events. Heterogeneity in outcome reporting (e.g. categories and outcome measurement instruments) was high, and definitions were insufficiently reported. There was a clear under representation of life impact domains, including satisfaction (23%) quality of life (3%) and psychological functioning (1%). Outcome reporting concerning laser treatments for the skin is heterogeneous. Standardized outcomes are needed for improving evidence synthesis. Results of this review will be used in the next step to reach consensus between stakeholders on the outcome domains to be implemented in the LEAD registry.
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Terapia por Láser , Enfermedades de la Piel/terapia , Humanos , Evaluación de Resultado en la Atención de SaludRESUMEN
BACKGROUND: In recent years, various lasers have increasingly been applied during wound healing to minimize scar formation. However, no consensus regarding treatment procedures exists. OBJECTIVES: To assess scar formation clinically after three nonablative fractional laser (NAFL) exposures, targeting the inflammation, proliferation and remodelling wound healing phases in patients vs. untreated controls. METHODS: A randomized controlled trial was performed using a split-wound design to assess excisional wound halves treated with 1540-nm NAFL vs. no laser treatment. Three NAFL exposures were provided: immediately before surgery, at suture removal and 6 weeks after surgery. NAFL exposures were applied using two handpieces, sequentially distributing energy deeply and more superficially in the skin (40-50 mJ per microbeam). Evaluated at 3 months of follow-up, the primary outcome was blinded, on-site evaluation using the Patient Observer Scar Assessment Scale (POSAS total; range from 6, normal skin to 60, worst imaginable scar). Secondary outcomes comprised blinded evaluation on the Vancouver Scar Scale (VSS) and standardized assessment comparing scar sides, carried out by blinded on-site, photo and patient assessments. This trial was registered with ClinicalTrials.gov (NCT03253484). RESULTS: Thirty of 32 patients completed the trial. At the 3-month follow-up, the NAFL-treated scar halves showed improvement compared with the untreated control halves on POSAS total: NAFL treated, median 11, interquartile range (IQR) 9-12 vs. control, median 12, IQR 10-16; P = 0·001. The POSAS subitems showed that the NAFL-treated halves were significantly less red and more pliable, and presented with smoother relief than the untreated controls. VSS total correspondingly revealed enhanced appearance in the NAFL-treated halves: median 2, IQR 1-2·5 vs. control, median 2, IQR 1·75-3, P = 0·007. The standardized assessment comparing appearance of scar halves demonstrated a low degree of correspondence between on-site, photo and patient assessments. NAFL-treated scars were rated as superior to untreated scars by 21 of 29 patients. CONCLUSIONS: NAFL-treated scars showed subtle improvement compared with untreated control scars.
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Cicatriz/prevención & control , Terapia por Láser/instrumentación , Láseres de Estado Sólido/uso terapéutico , Cuidados Posoperatorios/instrumentación , Herida Quirúrgica/complicaciones , Anciano , Cicatriz/etiología , Cicatriz/patología , Femenino , Estudios de Seguimiento , Humanos , Terapia por Láser/efectos adversos , Terapia por Láser/métodos , Masculino , Persona de Mediana Edad , Satisfacción del Paciente , Cuidados Posoperatorios/efectos adversos , Cuidados Posoperatorios/métodos , Piel/patología , Piel/efectos de la radiación , Resultado del TratamientoRESUMEN
The ability of laser treatment to affect wound healing and subsequently minimize scar formation has been investigated in recent years. However, no systematic review links these clinical trials. The aim of this study was to systematically review and evaluate clinical evidence for early laser intervention to reduce scar formation in studies where laser treatment was introduced less than 3 months after wounding. We searched PubMed using relevant keywords in June 2017. Titles, abstracts and articles were sorted according to inclusion and exclusion criteria. Methodological quality was evaluated according to Cochrane Collaborations risk-of-bias assessment guideline by two independent authors. Twenty-five articles met the inclusion criteria. In total, 22 of 25 studies were controlled studies, and 17 of 25 studies compared laser treatment vs. untreated control scars. The following laser devices have been investigated: pulsed dye laser (PDL), potassium-titanyl-phosphate (KTP) laser, fractional erbium:glass 1540 nm/1550 nm, fractional/full ablation erbium-doped yttrium aluminium garnet (Er:YAG) laser or fractional CO2 laser. Eighteen studies applied laser treatments 2-4 times with 2- to 8-week intervals, while seven studies applied only one laser treatment. Follow-up time ranged from 1 to 12 months with 18 studies using a follow-up time ≤3 months. In general, laser-treated wounds and scars showed benefit from laser intervention, though not always reaching significance. Significant scar improvement was found in three of four studies using laser treatment in inflammation phase, in six of 16 studies with laser initiated in the proliferation phase and in two of five studies in the remodelling phase. High risk of bias was found in randomization and allocation concealment, and low risk of bias with regard to blinding of outcome assessment and lost to follow-up. In conclusion, laser intervention when introduced in inflammation, proliferation or remodelling phase has the potential to reduce cutaneous scar formation. Further, high-quality studies are needed before standard protocols can be implemented in clinical practice.
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Cicatriz/prevención & control , Terapia por Láser , Humanos , Cicatrización de HeridasRESUMEN
BACKGROUND: Ablative fractional laser (AFL) generates microchannels in skin surrounded by a zone of thermally altered tissue, termed the coagulation zone (CZ). The thickness of CZ varies according to applied wavelength and laser settings. It is well-known that AFL channels facilitate uptake of topically applied compounds, but the importance of CZ is unknown. METHODS: Franz Cells were used to investigate skin uptake and permeation of fluorescent labeled polyethylene glycols (PEGs) with mean molecular weights (MW) of 350, 1,000, and 5,000 Da. Microchannels with CZ thicknesses ranging from 0 to 80 µm were generated from micro-needles (0 µm, CZ-0), and AFL (10,600 nm) applied to -80°C deep frozen skin (20 µm, CZ-20) and skin equilibrated to room temperature (80 µm, CZ-80). Channels penetrated into similar mid-dermal skin depths of 600-700 µm, and number of channels per skin area was similar. At 4 hours incubation, skin uptake of PEGs into CZ and dermis was evaluated by fluorescence microscopy at specific skin depths of 150, 400, and 1,000 µm and the transcutaneous permeation was quantified by fluorescence of receptor fluids. RESULTS: Overall, the highest uptake of PEGs was reached through microchannels surrounded by CZ compared to channels with no CZ (CZ-20 and CZ-80>CZ-0).The thickness of CZ affected PEG distribution in skin. A thin CZ-20 favored significantly higher mean fluorescence intensities inside CZ areas compared to CZ-80 (PEG 350, 1,000, and 5,000; P < 0.001). In dermis, the uptake through CZ-20 channels was significantly higher than through CZ-80 and CZ-0 at all skin depths (PEG 350, 1,000 and 5,000, 150-1,000 µm; P < 0.001). Correspondingly, transcutaneous permeation of PEG 350 was highest in CZ-20 compared to CZ-80 and CZ-0 samples (P < 0.001). Permeation of larger molecules (PEG 1,000 and PEG 5,000) was generally low. CONCLUSION: Uptake of topical compounds is higher through microchannels surrounded by a CZ than without a CZ. Moreover, CZ thickness influences PEG distribution, with highest PEG uptake achieved from microchannels surrounded by a thin CZ. Lasers Surg. Med. 49:582-591, 2017. © 2017 Wiley Periodicals, Inc.
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Coagulación Sanguínea , Fármacos Dermatológicos/farmacocinética , Sistemas de Liberación de Medicamentos , Polietilenglicoles/farmacocinética , Piel/metabolismo , Administración Cutánea , Animales , Células Cultivadas , Fármacos Dermatológicos/administración & dosificación , Femenino , Microscopía Fluorescente , Polietilenglicoles/administración & dosificación , Distribución Aleatoria , Piel/diagnóstico por imagen , PorcinosRESUMEN
In Germany, the reported syphilis prevalence has increased continuously since 2010, with a total of 6834 syphilis cases being reported in 2015. The largest increase of reported syphilis occurred in men who have sex with men (MSM). The antibiotic agent of choice for treatment of syphilis is still penicillin. There are no penicillin-resistant Treponema pallidum strains. Alternatives are ceftriaxone and doxycycline. In Germany, azithromycin is not approved for treatment of syphilis; however, therapy failures are increasingly reported. Bacterial vaginosis is accompanied by vaginal discharge. The vaginal secretion exhibits an increased pH value higher than 4.5. Clinical symptoms are pruritus, burning, and the characteristic amine odor. The probability for bacterial vaginosis is highest in women with higher numbers of sexual partners, unmarried women, early first sexual intercourse, in commercial female sex workers, and those women who regularly apply vaginal douches. The main pathogen of bacterial vaginosis is Gardnerella vaginalis. For oral therapy metronidazole is given, alternatively clindamycin; the latter should be applied additionally as topical agent. Trichomoniasis is considered as the nonviral sexually transmitted infection with the highest prevalence worldwide. Other than direct microscopic detection of the protozoa (trophozoites) in vaginal secretion or urine, PCR has been approved as the diagnostic method with the highest sensitivity. Oral metronidazole represents the therapy of choice in trichomoniasis.
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Enfermedades de Transmisión Sexual/diagnóstico , Enfermedades de Transmisión Sexual/tratamiento farmacológico , Tricomoniasis/diagnóstico , Tricomoniasis/tratamiento farmacológico , Vaginosis Bacteriana/diagnóstico , Vaginosis Bacteriana/tratamiento farmacológico , Antibacterianos/administración & dosificación , Antiprotozoarios/administración & dosificación , Medicina Basada en la Evidencia , Femenino , Alemania/epidemiología , Humanos , Masculino , Prevalencia , Factores de Riesgo , Enfermedades de Transmisión Sexual/epidemiología , Evaluación de Síntomas/métodos , Resultado del Tratamiento , Infecciones por Treponema/diagnóstico , Infecciones por Treponema/epidemiología , Infecciones por Treponema/terapia , Tricomoniasis/epidemiologíaRESUMEN
Approximately 1 million people are infected per day worldwide by one or more sexually transmitted infections (STI) as estimated by the World Health Organization (WHO). Gonorrhoea represents an almost exclusively sexually transmitted infection, which predominantly affects mucous membranes of the genitourinary tract. Extragenital localization of infections is also possible, e. g. in the anorectal region. Currently, only syphilis and human immunodeficiency virus (HIV) are notifiable diseases according to the Infection Protection Act in Germany. In Saxony, an extended registration ordinance according to the German Infection Protection Act is in force, which means that besides syphilis the laboratory detection of Neisseria gonorrhoeae, Chlamydia trachomatis and genital mycoplasms are also notifiable infections. In particular, beginning in 2009 in Saxony a spectacular increase of registered infections due to N. gonorrhoeae was observed and in 2015 altogether 824 infections due to N. gonorrhoeae were reported. Alarming is the increase in resistance of N. gonorrhoeae against penicillin, doxycycline, ciprofloxacin and recently also against azithromycin and third generation cephalosporins. The so-called superbug of N. gonorrhoeae, which originated in Japan with multidrug resistance against most of the currently available oral antibiotics, has now arrived in Europe. Intramuscular or intravenous injection of ceftriaxone plus oral azithromycin, each given as single dose is the standard therapy for gonorrhoea.
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Azitromicina/administración & dosificación , Ceftriaxona/administración & dosificación , Gonorrea/diagnóstico , Gonorrea/tratamiento farmacológico , Neisseria gonorrhoeae/aislamiento & purificación , Administración Oral , Antibacterianos/administración & dosificación , Combinación de Medicamentos , Medicina Basada en la Evidencia , Alemania , Gonorrea/epidemiología , Humanos , Inyecciones Intramusculares , Inyecciones Intravenosas , Neisseria gonorrhoeae/clasificación , Prevalencia , Factores de Riesgo , Resultado del Tratamiento , Virosis/diagnóstico , Virosis/tratamiento farmacológico , Virosis/epidemiologíaRESUMEN
Chlamydia trachomatis is the most common pathogen of sexually transmitted bacterial infections worldwide. Every year in Germany approximately 300,000 new infections are to be expected. Chlamydia infections occur nearly exclusively in the postpubertal period. The peak age group is 15-25 years. The infection usually runs an asymptomatic course and the diagnosis is made by nucleic acid amplification techniques (NAAT) often after chlamydial screening or if complications occur. For treatment of chlamydial infections oral doxycycline 100 mg twice daily over 7 days is initially used or alternatively oral azithromycin 1.5 g as a single dose is recommended. The sexual partner should also be investigated and treated. Genital Mycoplasma infections are caused by Ureaplasma urealyticum (pathogen of urethritis and vaginitis), Ureaplasma parvum (mostly saprophytic and rarely a cause of urethritis) and Mycoplasma hominis (facultative pathogenic). Mycoplasma genitalium represents a relatively new sexually transmitted Mycoplasma species. Doxycycline is effective in Ureaplasma infections or alternatively clarithromycin and azithromycin. Doxycycline can be ineffective in Mycoplasma hominis infections and an alternative is clindamycin. Non-gonococcal and non-chlamydial urethritis due to Mycoplasma genitalium can now be diagnosed by molecular biological techniques using PCR and should be treated by azithromycin.
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Ceftriaxona/administración & dosificación , Infecciones por Chlamydia/diagnóstico , Infecciones por Chlamydia/tratamiento farmacológico , Doxiciclina/administración & dosificación , Infecciones por Mycoplasma/diagnóstico , Infecciones por Mycoplasma/tratamiento farmacológico , Administración Oral , Antibacterianos/administración & dosificación , Chlamydia/clasificación , Chlamydia/aislamiento & purificación , Infecciones por Chlamydia/epidemiología , Combinación de Medicamentos , Medicina Basada en la Evidencia , Alemania , Humanos , Mycoplasma/clasificación , Mycoplasma/aislamiento & purificación , Infecciones por Mycoplasma/epidemiología , Prevalencia , Factores de Riesgo , Resultado del Tratamiento , Virosis/diagnóstico , Virosis/epidemiología , Virosis/terapiaRESUMEN
High amounts of nicotinamide phosphoribosyltransferase (NAMPT) were found in human seminal plasma. This enzyme influences energy metabolism and apoptosis and is essential for the regulation of cellular nicotinamide adenine dinucleotide (NAD)+ levels in somatic cells. NAD+ is required as a co-substrate for dehydrogenases, which are potentially important for spermatogenesis. The functional significance of intra- and extracellular NAMPT in human reproduction, however, has not been defined yet. The objectives of the study were therefore to determine NAMPT protein expression in human spermatozoa and testes, the secretion of NAMPT by spermatozoa depending on their maturation stage and the impact of NAMPT enzymatic function on sperm viability, motility, fertilisation capacity and induction of apoptosis. Firstly, we detected NAMPT protein in different cell types of human testes. NAMPT protein was also detected in spermatozoa, with significantly higher amounts in immature than in mature ejaculated spermatozoa. Additionally, NAD+ levels were significantly higher in immature than in mature spermatozoa. Secondly, NAMPT was released into the supernatant of human spermatozoa, with significantly higher NAMPT levels in supernatant of immature spermatozoa compared with mature cells. Finally, the specific inhibition of the enzyme by FK866 did not influence motility, capacitation or apoptosis signalling. In summary, NAMPT is produced in human spermatozoa in a maturation-dependent manner.
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Nicotinamida Fosforribosiltransferasa/metabolismo , Maduración del Esperma/fisiología , Espermatozoides/metabolismo , Acrilamidas/farmacología , Inhibidores Enzimáticos/farmacología , Fertilidad/efectos de los fármacos , Fertilidad/fisiología , Humanos , Masculino , Piperidinas/farmacología , Transducción de Señal/efectos de los fármacos , Transducción de Señal/fisiología , Capacitación Espermática/efectos de los fármacos , Capacitación Espermática/fisiología , Motilidad Espermática/efectos de los fármacos , Motilidad Espermática/fisiología , Espermatozoides/efectos de los fármacos , Testículo/efectos de los fármacos , Testículo/metabolismoRESUMEN
STUDY QUESTION: Is the Leydig cell function of young European men associated with semen quality? SUMMARY ANSWER: Compensated reduction in Leydig cell function, defined as increased LH concentration combined with adequate testosterone production is associated with lower semen quality. WHAT IS ALREADY KNOWN: Semen quality of young European men shows a heterogeneous pattern. Many have sperm counts below and in the lower WHO reference where there nevertheless is a significant risk of subfecundity. Little is known about differences in Leydig cell function between men with semen quality below and within the WHO reference range. STUDY DESIGN, SIZE AND DURATION: A coordinated, cross-sectional population-based study of 8182 men undertaken in 1996-2010. PARTICIPANTS, SETTING AND METHOD: Young men (median age 19.1 years) were investigated in centres in Denmark, Estonia, Finland, Germany Latvia, Lithuania, and Spain. The men originated from the general populations, all were young, almost all were unaware of their fecundity and each provided a semen and blood sample. Associations between semen parameters and serum levels of testosterone and luteinising hormone (LH), calculated free testosterone, and ratios between serum testosterone and LH were determined. MAIN RESULT AND ROLE OF CHANCE: Serum testosterone levels were not associated with sperm concentrations, total sperm counts, or percentage of motile or morphologically normal spermatozoa. There was an inverse association between the semen parameters and serum LH levels, and accordingly a positive association to testosterone/LH ratio and calculated-free-testosterone/LH ratio. LIMITATIONS, REASON FOR CAUTION: The size of the study mitigates the intra-individual variability concern. The distinction between different sub-categories of sperm motility and sperm morphology is subjective despite training. However, inter-observer variation would tend towards non-differential misclassification and would decrease the likelihood of detecting associations between reproductive hormone levels and semen variables, suggesting that the presented associations might in reality be even stronger than shown. Although we adjusted for confounders, we cannot of course exclude that our results can be skewed by selection bias or residual confounding. WIDER IMPLICATIONS OF THE FINDINGS: Compensated reduction in Leydig cell function, defined as increased LH concentration combined with adequate testosterone production is associated with lower semen quality. This is apparent even within the WHO reference range of semen quality. It is unknown whether impaired Leydig cell function in young men may confer an increased risk of acquired testosterone deficiency later in life. STUDY FUNDING/COMPETING INTERESTS: Support from The Research Fund of Rigshospitalet (grant no. R42-A1326) to N.J. made this study possible. The background studies of young men have been supported economically by several grants. ITALIC! Denmark: The European Union (contract numbers BMH4-CT96-0314, QLK4-CT-1999-01422, QLK4-CT-2002-00603 and most recently FP7/2007-2013, DEER Grant agreement no. 212844), The Danish Research Council (grants nos. 9700833 2107-05-0006), The Danish Agency for Science, Technology and Innovation (Grant no. 271070678), Rigshospitalet (Grant no. 961506336), The University of Copenhagen (Grant no. 211-0357/07-3012), The Danish Ministry of Health and the Danish Environmental Protection Agency, A.P. Møller and wife Chastine McKinney Møllers foundation, and Svend Andersens Foundation. ITALIC! Finland: European Union (contract numbers BMH4-CT96-0314, QLK4-CT-1999-01422, QLK4-CT- 2002-00603 and most recently FP7/2008-2012, DEER Grant agreement no. 212844), The Academy of Finland, Turku University Hospital Funds, Sigrid Juselius Foundation. ITALIC! Estonia, Latvia and Lithuania: European Union (QLRT-2001-02911), the Estonian Science Foundation, grant number 2991, Lithuanian Foundation for Research, Organon Agencies B.V. and the Danish Research Council, grant no. 9700833. ITALIC! Germany: European Union (contract numbers QLK4-CT-2002-00603). ITALIC! Spain: European Commission QLK4-1999-01422. M.F. received support from the Spanish Ministry of Science and Innovation (Program Ramon y Cajal). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. None of the authors have any competing interests to declare.
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Células Intersticiales del Testículo/fisiología , Análisis de Semen , Adulto , Estudios Transversales , Europa (Continente) , Fertilidad , Humanos , Hormona Luteinizante/sangre , Masculino , Estudios Prospectivos , Valores de Referencia , Testosterona/sangreRESUMEN
BACKGROUND AND OBJECTIVE: Ablative fractional laser (AFXL) facilitates delivery of topical methotrexate (MTX). This study investigates impact of laser-channel depth on topical MTX-delivery. MATERIALS AND METHODS: MTX (1% [w/v]) diffused for 21 hours through AFXL-exposed porcine skin in in vitro Franz Cells (n = 120). A 2,940 nm AFXL generated microscopic ablation zones (MAZs) into epidermis (11 mJ/channel, MAZ-E), superficial-dermis (26 mJ/channel, MAZ-DS), and mid-dermis (256 mJ/channel, MAZ-DM). High performance liquid chromatography (HPLC) was used to quantify MTX deposition in full-thickness skin, biodistribution profiles at specific skin levels, and transdermal permeation. Fluorescence microscopy was used to visualize UVC-activated MTX-fluorescence (254 nm) and semi-quantify MTX distribution in skin. RESULTS: AFXL increased topical MTX-delivery (P < 0.001). Without laser exposure, MTX-concentration in full-thickness skin was 0.07 mg/cm(2) , increasing sixfold (MAZ-E), ninefold (MAZ-DS), and 11-fold (MAZ-DM) after AFXL (P < 0.001). Deeper MAZs increased MTX-concentrations in all skin layers (P < 0.038) and favored maximum accumulation in deeper skin layers (MAZ-E: 1.85 mg/cm(3) at 500 µm skin-level vs. MAZ-DM: 3.75 mg/cm(3) at 800 µm, P = 0.002). Ratio of skin deposition versus transdermal permeation remained constant, regardless of MAZ depth (P = 0.172). Fluorescence intensities confirmed MTX biodistribution through coagulation zones and into surrounding skin, regardless of thickness of coagulation zones (6-47 µm, P ≥ 0.438). CONCLUSION: AFXL greatly increases topical MTX-delivery. Deeper MAZs deliver higher MTX-concentrations than superficial MAZs, which indicates that laser channel depth may be important for topical delivery of hydrophilic molecules. Lasers Surg. Med. 48:519-529, 2016. © 2016 Wiley Periodicals, Inc.
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Fármacos Dermatológicos/administración & dosificación , Sistemas de Liberación de Medicamentos/métodos , Láseres de Estado Sólido , Metotrexato/administración & dosificación , Piel/metabolismo , Administración Cutánea , Animales , Cromatografía Líquida de Alta Presión , Fármacos Dermatológicos/farmacocinética , Femenino , Metotrexato/farmacocinética , Microscopía Fluorescente , Permeabilidad , Absorción Cutánea , PorcinosRESUMEN
Dermatologists administer a broad spectrum of systemic medications. However, our current knowledge of potential risks to male fertility is still limited, particularly with the new emerging therapies in dermato-oncology. Individual differences in susceptibility and a history of andrological disorders influence prognostic values. For fertility protection, a thoughtful selection of medication and/or sperm cryopreservation remain the best options.
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Fármacos Dermatológicos/efectos adversos , Fármacos Dermatológicos/uso terapéutico , Infertilidad Masculina/inducido químicamente , Infertilidad Masculina/prevención & control , Preservación de Semen/métodos , Enfermedades de la Piel/tratamiento farmacológico , Humanos , Infertilidad Masculina/diagnóstico , Masculino , Enfermedades de la Piel/complicaciones , Resultado del TratamientoRESUMEN
Topically applied ingenol mebutate (IngMeb) is approved for field-treatment of actinic keratosis and is currently being investigated for treatment of non-melanoma skin cancer (NMSC). Ablative fractional lasers (AFXLs) generate microscopic ablation zones (MAZs) in the skin, which may help induce a deep penetration needed for effective treatment of NMSC. Using Franz diffusion cells, uptake and bio-distribution were investigated over 21 h in intact (n = 9) and AFXL-exposed porcine skin (n = 58). A 2940-nm fractional Er:YAG laser generated intraepidermal (11.2 mJ/MAZ; 66 µm deep, 177 µm wide) and intradermal (128 mJ/MAZ; 570 µm deep, 262 wide) MAZ's with 16, 97, and 195 MAZs/cm(2). Surface ablation densities corresponded to 0.5, 2.5, and 5 % for intraepidermal MAZs, and corresponded to 1, 5, and 10.5 % for intradermal MAZs. Liquid-chromatography-mass-spectrometry quantified deposition of IngMeb in stratum corneum, epidermis, dermis, and receiver chamber. In intact skin, IngMeb readily penetrated to the epidermal layer (1,314 ng, 41 % of the applied IngMeb), while dermal deposition was limited (508 ng, 16 %). In AFXL-exposed skin, a profound dermal deposition of IngMeb was achieved, while less accumulated in SC and epidermis. Uptake depended entirely on laser density; increasing coverage from 0 % to 0.5 %, 1 %, 2.5 %, 5 %, and 10.5 % enhanced dermal uptake 1.6-, 2.1-, 3.1-, 3.4-, and 3.9-fold, respectively (p < 0.0001). Channel depth did not influence drug uptake; at 5 % density, dermal deposition with intraepidermal and intradermal MAZs was analogous (1801 vs. 1744; p = 0.447). In conclusion, IngMeb readily distributes to superficial layers of intact skin, whereas dermal uptake is limited. Independent of channel depth, AFXL enhances dermal drug deposition, providing for customized topical delivery and potential use of IngMeb for treatment of NMSC.
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Diterpenos/metabolismo , Terapia por Láser/métodos , Absorción Cutánea , Piel/metabolismo , Administración Cutánea , Animales , Cromatografía Liquida , Sistemas de Liberación de Medicamentos , Humanos , Queratosis Actínica/tratamiento farmacológico , Láseres de Estado Sólido , Espectrometría de Masas , Porcinos , Distribución TisularRESUMEN
BACKGROUND: Photodynamic therapy (PDT) is approved for selected nodular basal cell carcinomas (nBCC) but efficacy is reduced for large and thick tumours. Ablative fractional lasers (AFXL) facilitate uptake of methyl aminolaevulinate (MAL) and may thus improve PDT outcome. OBJECTIVES: To evaluate efficacy and safety of AFXL-mediated PDT (AFXL-PDT) compared with conventional PDT of high-risk nBCC. METHODS: Patients with histologically verified facial nBCC (n = 32) defined as high-risk tumours were included; diameter > 15 mm, tumours located in high-risk zones, or on severely sun-damaged skin. Tumours were debulked and patients randomized to either AFXL-PDT (n = 16) or PDT (n = 16). Fractional CO2 laser treatment was applied at 5% density and 1000 µm (80 mJ) ablation depth. MAL was applied under occlusion for 3 h and illuminated with a 633-nm light-emitting diode source, 37 J cm(-2) . Clinical assessments were performed at 3, 6, 9 and 12 months and biopsies were taken at 12 months. RESULTS: Clinical cure rates at 3 months were 100% (16 of 16 AFXL-PDT) and 88% (14 of 16 PDT, P = 0·484). Recurrences tended to occur later and in lower numbers after AFXL-PDT at 6, 9 and 12 months (6%, 19%, 19%) than PDT (25%, 38%, 44%) (P = 0·114). Histology at 12 months documented equal tumour clearance after AFXL-PDT (63%, 10 of 16) and PDT (56%, 9 of 16). Cosmetic outcomes were highly satisfactory after both treatments (P > 0·090). CONCLUSIONS: Long-term efficacy was similar after PDT and AFXL-PDT with a trend for a favourable short-term cure rate after AFXL-PDT. AFXL-PDT needs further refinement for nBCC and at present is not recommended over PDT.
Asunto(s)
Carcinoma Basocelular/tratamiento farmacológico , Neoplasias Faciales/tratamiento farmacológico , Fotoquimioterapia/métodos , Neoplasias Cutáneas/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Ácido Aminolevulínico/análogos & derivados , Ácido Aminolevulínico/uso terapéutico , Terapia Combinada , Femenino , Fluorescencia , Humanos , Terapia por Láser/efectos adversos , Terapia por Láser/instrumentación , Terapia por Láser/métodos , Láseres de Gas/efectos adversos , Láseres de Gas/uso terapéutico , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/etiología , Fotoquimioterapia/efectos adversos , Fármacos Fotosensibilizantes/uso terapéutico , Factores de Riesgo , Resultado del TratamientoRESUMEN
After leaving the testis, spermatozoa undergo several important steps of biochemical maturation during the passage through the epididymis, increasing their motility and fertilizing ability. These changes comprise (among others) the modification of the phospholipid composition of the sperm membrane. This process is thought to be important for the achievement of motility and fertilizing capacity. The lipids of the sperm membrane are characterized by a significant content of unsaturated fatty acyl residues, resulting in a high sensitivity against oxidative stress. This is evidenced by the appearance of lysolipids, for example, lysophosphatidylcholine, which acts like a detergent and is normally present in only very small amounts in biological membranes. The epididymis represents a tubular system comprising three main parts (caput, corpus, and cauda), through which the spermatozoa are consecutively transported undergoing distinct maturation stages. Using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, we established three striking differences in the lipid composition of murine spermatozoa from the different epididymal regions: in comparison to the caput sperm, sperm from the cauda are characterized by (1) a higher degree of unsaturation (PC 18:0/22:5 and 18:0/22:6 vs. 18:0/20:4 and 18:0/18:1), (2) an enhanced plasmalogen content, and (3) an enhanced content of lysolipids. These changes are likely to be of physiological relevance and potentially useful as diagnostic markers of sperm maturation and acquisition of motility.
Asunto(s)
Fosfolípidos/metabolismo , Espermatozoides/metabolismo , Animales , Epidídimo/crecimiento & desarrollo , Epidídimo/metabolismo , Masculino , Ratones , Ratones Endogámicos BALB C , Espectrometría de Masa por Láser de Matriz Asistida de Ionización DesorciónRESUMEN
Infections of the finger and the toe nails are most frequently caused by fungi, primarily dermatophytes. Causative agents of tinea unguium are mostly anthropophilic dermatophytes. Both in Germany, and worldwide, Trichophyton rubrum represents the main important causative agent of onychomycoses. Yeasts are isolated from fungal nail infections, both paronychia and onychomycosis far more often than generally expected. This can represent either saprophytic colonization as well as acute or chronic infection of the nail organ. The main yeasts causing nail infections are Candida parapsilosis, and Candida guilliermondii; Candida albicans is only in third place. Onychomycosis due to molds, or so called non-dermatophyte molds (NDM), are being increasingly detected. Molds as cause of an onychomycosis are considered as emerging pathogens. Fusarium species are the most common cause of NDM onychomycosis; however, rare molds like Onychocola canadensis may be found. Bacterial infections of the nails are caused by gram negative bacteria, usually Pseudomonas aeruginosa (recognizable because of green or black coloration of the nails) but also Klebsiella spp. and gram positive bacteria like Staphylococcus aureus. Treatment of onychomycosis includes application of topical antifungal agents (amorolfine, ciclopirox). If more than 50 % of the nail plate is affected or if more than three out of ten nails are affected by the fungal infection, oral treatment using terbinafine (in case of dermatophyte infection), fluconazole (for yeast infections), or alternatively itraconazole are recommended. Bacterial infections are treated topically with antiseptic agents (octenidine), and in some cases with topical antibiotics (nadifloxacin, gentamicin). Pseudomonas infections of the nail organ are treated by ciprofloxacin; other bacteria are treated according to the results of culture and sensitivity testing.