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1.
J Cosmet Dermatol ; 2021 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-33825333

RESUMO

BACKGROUND: The treatment of facial erythema and subjective symptoms of rosacea patients remains challenging in clinical practice. Cosmeceuticals, care components containing active ingredients such as phytochemicals, play a growing role in treatment plans. However, well-designed studies on their efficacy and limitations are widely missing. OBJECTIVE: A foam and a cream for rosacea patients were assessed based on objective and subjective methodology. The tolerability of skin and eyes was evaluated. METHODS: A randomized, double blind, split-face, vehicle-controlled trial was conducted. At baseline and after four weeks of product use, dermatological and ophthalmological investigations were performed, employing image analysis of facial erythema, clinical assessments and questionnaires. RESULTS: The patient cohort comprised 33 females with persistent facial erythema due to rosacea. No significant differences were found between the vehicle and the verum. According to the analysis of facial erythema, a "less pronounced" or "much less pronounced" appearance was seen in two thirds of patients comparing V1 to V0. Especially the dryness of the skin improved by the use of the vehicle and the verum. Adverse subjective skin sensations decreased by 61.3% for the verum side and by 58.6% for the vehicle side. Subjective and objective analysis of ocular manifestation differed, with subjective manifestations reported more frequently, thus highlighting underdiagnosis of ocular rosacea. CONCLUSIONS: As no clear differences between the verum and the vehicle were found, an optimal skin care regime itself seems to have a superior effect in the relief of facial erythema and foremost of subjective symptoms, rather than certain active ingredients.

2.
BMC Urol ; 21(1): 60, 2021 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-33845814

RESUMO

BACKGROUND: CD276 is an immune checkpoint molecule. Elevated CD276 expression by urothelial carcinoma is associated with poor prognosis, but little is known about its expression across different tumor stages. We therefore investigated CD276 expression in bladder cancer (BC) cells and in tissue samples of BC stages from pT2 to pT4. METHODS: CD276 expression was explored in 4 urothelial cancer cell lines and 4 primary normal urothelial cell populations by quantitative RT-PCR, Western blot and flow cytometry. CD276 was investigated in bladder tumors from 98 patients by immunohistochemistry using a score (0-300) incorporating both, staining intensity and area of CD276 staining. Normal appearing urothelium in the bladder of the same patients served as controls. RESULTS: The urothelial carcinoma cell lines expressed significantly higher levels of CD276 on transcript (p < 0.006), total protein levels (p < 0.005), and on the cell surface (p < 0.02) when compared to normal urothelial cells. In pT2-T4 tumor tissue samples, CD276 was overexpressed (median score 185) when compared to corresponding healthy tissues from the same patients (median score 50; p < 0.001). No significant differences in CD276 expression were recorded in late, locally advanced ≥ pT3a tumors (median score 185) versus organ-confined < pT3a tumors (median score 190), but it was significantly lower in the normal urothelial tissue associated with ≥ pT3a tumors (median score 40) versus < pT3a tumors (median score 80; p < 0.05). CONCLUSION: CD276 expression is significantly elevated in urothelial carcinoma cells in all stages but varies between individuals considerably. Reduced CD276 expression in normal urothelial cells may imply that these cells would be protected from CD276-mediated immuno therapies.

3.
BMC Oral Health ; 21(1): 117, 2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-33711986

RESUMO

BACKGROUND: Xerostomia is associated with several diseases and is a side effect of certain drugs, resulting from reduced saliva secretion. Often, aged and sometimes younger people suffer from (idiopathic) xerostomia. Chewing gum and sucking pastilles may relieve symptoms of xerostomia by increasing the salivary flow rate due to the mechanical effect of sucking and gustatory stimulation. Swallowing problems and the urge to cough or experiencing a tickling sensation in the throat might be alleviated through a reduction in dry mouth symptoms. We investigated whether a pastille containing four polysaccharides increased the salivary flow rate and relieved the symptoms of dry mouth. METHODS: Participating subjects with xerostomia were randomized into two equally balanced treatment groups. Subjects received the pastille on Day 1 and a control product (Parafilm®) on Day 3, or vice versa. Unstimulated saliva was collected every 2.5 min for 0-10 min. Stimulated saliva was collected after subjects sucked the pastille or the control product. The salivary flow rate was determined gravimetrically, and, in parallel, the feeling of dry mouth was assessed using a visual analog scale. Saliva surface tension was measured in pooled saliva samples (0-5 min of sampling). Additionally, in stimulated saliva from six subjects who sucked the pastille, the presence of the main ingredient-gum arabic-was examined by Raman spectroscopy. RESULTS: Chewing the pastille significantly increased the mean salivary flow rate by 8.03 g/10 min compared to the mean changes after chewing the control product (+ 3.71 g/10 min; p < 0.0001). The mean score of dry mouth was significantly alleviated by the pastille (- 19.9 ± 17.9 mm) compared to the control product (- 3.3 ± 18.1 mm). No difference between the two products was seen regarding the saliva surface tension. Gum arabic was present in the saliva of all investigated subjects for up to 10 min after sucking the pastille. CONCLUSIONS: The pastille was well tolerated and effective in increasing the salivary flow rate and reducing mouth dryness after sucking. These results were in line with the detection of the main ingredient, gum arabic, in saliva for up to 10 min after sucking the pastille. Trial registration German Register Clinical Trials (Deutsches Register Klinische Studien, DRKS) DRKS-ID: DRKS00017393, Registered 29 May 2019, https://www.drks.de/drks_web/navigate.do?navigationId=trial . HTML&TRIAL_ID = DRKS00017393.

4.
Urologe A ; 2020 Dec 10.
Artigo em Alemão | MEDLINE | ID: mdl-33301070

RESUMO

White light cystoscopy and the concise documentation of pathological findings are standard diagnostic procedures in urology. Additional imaging modalities and technical innovations may support clinicians in the detection of bladder tumors. Modern endoscopy systems provide ultra-high-resolution imaging and the option of digital contrast enhancement. Photodynamic diagnostics and narrow band imaging are well-established in clinical routine and have shown significant benefits in the detection of bladder cancer. By means of multispectral imaging, different modalities can now be combined in real-time. Probe-based procedures such as optical coherence tomography (OCT) or Raman spectroscopy can further contribute to advanced imaging through an "optical biopsy" which may primarily improve diagnostics in the upper urinary tract. The aim of all techniques is to optimize the detection rate in order to achieve a more accurate diagnosis, resection and lower recurrence rates. Current research projects aim to digitalize the documentation of endoscopy and also make it more patient- and user-friendly. In the future, the use of image processing and artificial intelligence may automatically support the surgeon during endoscopy.

5.
Sci Rep ; 10(1): 16787, 2020 10 08.
Artigo em Inglês | MEDLINE | ID: mdl-33033281

RESUMO

The reprogramming of patient´s somatic cells into induced pluripotent stem cells (iPSCs) and the consecutive differentiation into cardiomyocytes enables new options for the treatment of infarcted myocardium. In this study, the applicability of a hydrojet-based method to deliver footprint-free iPSC-derived cardiomyocytes into the myocardium was analyzed. A new hydrojet system enabling a rapid and accurate change between high tissue penetration pressures and low cell injection pressures was developed. Iron oxide-coated microparticles were ex vivo injected into porcine hearts to establish the application parameters and the distribution was analyzed using magnetic resonance imaging. The influence of different hydrojet pressure settings on the viability of cardiomyocytes was analyzed. Subsequently, cardiomyocytes were delivered into the porcine myocardium and analyzed by an in vivo imaging system. The delivery of microparticles or cardiomyocytes into porcine myocardium resulted in a widespread three-dimensional distribution. In vitro, 7 days post-injection, only cardiomyocytes applied with a hydrojet pressure setting of E20 (79.57 ± 1.44%) showed a significantly reduced cell viability in comparison to the cells applied with 27G needle (98.35 ± 5.15%). Furthermore, significantly less undesired distribution of the cells via blood vessels was detected compared to 27G needle injection. This study demonstrated the applicability of the hydrojet-based method for the intramyocardial delivery of iPSC-derived cardiomyocytes. The efficient delivery of cardiomyocytes into infarcted myocardium could significantly improve the regeneration.

6.
Genes Dev ; 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33060136

RESUMO

Macrophages polarize into functionally distinct subtypes while responding to microenvironmental cues. The identity of proximal transcription factors (TFs) downstream from the polarization signals are known, but their activity is typically transient, failing to explain the long-term, stable epigenomic programs developed. Here, we mapped the early and late epigenomic changes of interleukin-4 (IL-4)-induced alternative macrophage polarization. We identified the TF, early growth response 2 (EGR2), bridging the early transient and late stable gene expression program of polarization. EGR2 is a direct target of IL-4-activated STAT6, having broad action indispensable for 77% of the induced gene signature of alternative polarization, including its autoregulation and a robust, downstream TF cascade involving PPARG. Mechanistically, EGR2 binding results in chromatin opening and the recruitment of chromatin remodelers and RNA polymerase II. Egr2 induction is evolutionarily conserved during alternative polarization of mouse and human macrophages. In the context of tissue resident macrophages, Egr2 expression is most prominent in the lung of a variety of species. Thus, EGR2 is an example of an essential and evolutionarily conserved broad acting factor, linking transient polarization signals to stable epigenomic and transcriptional changes in macrophages.

7.
BJU Int ; 2020 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-32940408

RESUMO

OBJECTIVES: To investigate the therapy of stress urinary incontinence in a preclinical setting cells were injected into the urethrae of minipigs; however, cells injected by William's needle were frequently misplaced or lost; thus, we investigated if needle-free cell injections using a novel waterjet technology facilitates precise injections in the urethral sphincter complex. MATERIALS AND METHODS: Porcine adipose tissue-derived stromal cells (pADSCs) were isolated from boars, expanded, labelled, and injected in the sphincter of female pigs by waterjet employing two different protocols. After incubation for 15 min or 3 days, the urethrae of the pigs were examined. Injected cells were visualised by imaging and fluorescence microscopy of tissue sections. DNA of injected male cells was verified by polymerase chain reaction (PCR) of the sex-determining region (SRY) gene. Cell injections by William's needle served as controls. RESULTS: The new waterjet technology delivered pADSCs faster and with better on-site precision than the needle injections. Bleeding during or after waterjet injection or other adverse effects, such as swelling or urinary retention, were not observed. Morphologically intact pADSCs were detected in the urethrae of all pigs treated by waterjet. SRY-PCR of chromosomal DNA and detection of recombinant green fluorescent protein verified the injection of viable cells. In contrast, three of four pigs injected by William's needle displayed no or misplaced cells. CONCLUSION: Transurethral injection of viable pADSCs by waterjet is a simple, fast, precise, and yet gentle new technology. This is the first proof-of-principle concept study providing evidence that a waterjet injects intact cells exactly in the tissue targeted in a preclinical in vivo situation. To further explore the clinical potential of the waterjet technology longer follow-up, as well as incontinence models have to be studied.

8.
BMC Urol ; 20(1): 59, 2020 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-32460737

RESUMO

BACKGROUND: During transurethral resection of bladder tumours (TURB), radio-frequency (RF) currents can lead to adverse neuromuscular stimulation (NMS). Here we present a novel ex vivo method to determine the risk of RF generators and their bipolar TURB modes to cause NMS. We aimed to develop an experimental platform for safety evaluation of new RF generators and their modes with a newly established test standard, suitable for replacement or reduction of animal testing. METHODS: We tested four contemporary RF generators with their bipolar modes for TURB in saline. A two-stage ex vivo approach was pursued: First, we recorded voltages at possible positions of the obturator nerve behind a porcine bladder wall in a TURB model using 18 RF applications per generator. Second, these voltage records were used as stimuli to evoke nerve compound action potentials (CAPs) in isolated porcine axillary nerves. The NMS potential was defined as the ratio between the observed area under the CAPs and the theoretical CAP area at maximum response and a firing rate of 250 Hz, which would reliably induce tetanic muscle responses in most human subjects. The measurement protocol was tailored to optimise reproducibility of the obtained NMS potentials and longevity of the nerve specimens. RESULTS: As prerequisite for the clinical translation of our results, the robustness of our test method and reproducibility of the NMS potential are demonstrated with an excellent correlation (r = 0.93) between two sets of identical stimuli (n = 72 each) obtained from 16 nerve segments with similar diameters (4.2 ± 0.37 mm) in the nerve model. The RF generators differed significantly (p < 0.0001) regarding NMS potential (medians: 0-3%). CONCLUSIONS: Our test method is suitable for quantifying the NMS potential of different electrosurgical systems ex vivo with high selectivity at a reasonable degree of standardization and with justifiable effort. Our results suggest that the clinical incidence of NMS is considerably influenced by the type of RF generator. Future generations of RF generators take advantage from the proposed test standard through higher safety and less animal testing. Health professionals and treated patients will benefit most from improved RF surgery using generators with a low NMS risk.

9.
Horm Behav ; 122: 104762, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32353446

RESUMO

Women's voices reportedly sound more attractive during the fertile days compared to the non-fertile days of their menstrual cycle. Here we investigated whether the speech content modulates the cyclic changes in women's voices. We asked 72 men and women to rate how interested they were in getting to know the speaker based on her voice. Forty-two naturally cycling women were recorded once during the late follicular phase (high fertility) and once during the luteal phase (low fertility) while speaking sentences of neutral and social content. Listeners were more interested in getting to know the speakers when hearing sentences with social content. Furthermore, raters were more interested in getting to know the speakers when these were recorded in the late follicular than in the luteal phase, but only in sentences with social content. Notably, levels of reproductive hormones (EP ratio) across the cycle phases did not significantly predict the preference for late follicular voices, but echoing the perceptual ratings, there was a significant EP ratio x speech content interaction. Phonetic analyses of mean fundamental frequency (F0) revealed a main effect of menstrual cycle phase and speech content but no interaction. Employing an action-oriented task, the present study extends findings of cycle-dependent voice changes by emphasising that speech content critically modulates fertility effects.

10.
Nat Rev Urol ; 17(11): 650, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32457430

RESUMO

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

11.
Int J Cosmet Sci ; 42(4): 328-335, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32279349

RESUMO

OBJECTIVE: During the development of cosmetic formulations, in vitro and in vivo methods are essential tools used to reliably assess the skin irritation potential of a product or ingredient. Epicutaneous patch testing (single and/or multiple application protocols) has long been used as an initial in vivo method to screen for possible skin irritation properties of a substance or formulation. To confirm the mildness and dermatological and/or consumer acceptance of a product, use tests are often subsequently conducted. A study was therefore initiated to see how well patch test results correlate with use tests with respect to irritation elicited by skincare (leave-on) products. METHODS/RESULTS: A number of different cosmetic formulations were assessed in both tests. Although the patch test results did not indicate substantial irritation potentials, immediate-type reactions (stinging and redness) were observed in some volunteers which disappeared within approx. 1 h. Although transient, these reactions suggested that consumer acceptance would probably be low and the studies were discontinued. Immediate-type reactions are rare but have been described for some substances used in cosmetics. These unexpected results were nevertheless intriguing and prompted the start of a journey to see if patch test protocols could be modified to assess these reactions. An occlusive short-term patch test protocol with an application period of 20 min was developed. Successful identification of the spontaneous reactions became possible. Furthermore, there was a correlation between the intensity of reactions observed in the short-term patch test and those observed in the controlled in-use studies. Short-term patch testing using the developed protocol can therefore reliably be used as a screening method, for example in the development and optimization of cosmetic formulations containing ingredients that could cause spontaneous reactions, for instance of non-immunological contact urticaria type. CONCLUSION: The lessons learned from this studies indicate that simple modifications of existing test protocols can lead to important insights into skin reactions. These modifications can then be used to create further building blocks in the development and optimization of test strategies for cosmetic formulations which offer reliable study designs for possible reactions product developers may encounter.

12.
Mater Sci Eng C Mater Biol Appl ; 110: 110710, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32204022

RESUMO

The study is aimed to synthesize potent metal oxide based biomimetic nanocomposites to overcome the risk associated with artificial bone tissue engineering. High purity TiO2 nanoparticles are synthesized via hydrothermal route. A biomimetic nanocomposite scaffolds containing chitosan-sodium alginate (4: 4) blended with three different (0.5, 1, and 1.5 wt%) concentrations of hydrothermally synthesized TiO2 nanoparticles are obtained by solvent casting technique. The physico-chemical and thermal degradation properties of as-synthesized TiO2 nanoparticles and their nanocomposite scaffolds are analyzed. In-vitro cytotoxicity and biocompatibility of the prepared TiO2 nanoparticles and nanocomposites are tested against human bladder tumor (UC6) and osteosarcoma (MG-63) cell lines. Antibacterial property is tested against Escherichia coli and Staphylococcus aureus. These studies reveal that TiO2 nanoparticles and polymeric nanocomposites contain good physico-chemical and mechanical properties for enhanced in-vitro biocompatibility suitable for biomedical applications. Biomimetically prepared chitosan-sodium alginate scaffold containing TiO2 nanoparticles (1 wt%) is found to exhibit superior biocompatibility for bone tissue engineering applications.

13.
Int J Cosmet Sci ; 42(3): 277-288, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32181499

RESUMO

Cellulite occurs in females and is a common condition of altered connective tissue matrix and increased adipogenicity with visible dimples and orange-peel appearance on the skins surface. Whilst advancements in methods continue to help our understanding, attempts to correct the appearance of cellulite topically have yielded limited success. Various kinds of non-invasive body contouring methods such as whole body vibration have been reported with demonstrable visible improvements in the cellulite condition. The aim of this study was to evaluate volume reduction and improvement of the visible appearance of cellulite as judged both objectively (AEVA-HE phase-shift 3-D fringe projection, macrophotography image grading) and subjectively (questionnaires) after application of a hand-held localized vibrational device over 24-weeks. The study was conducted on 40 healthy female volunteers who were instructed how to use the device on defined areas of cellulite of the outside and rear of the thighs (iliotibial band, and over biceps femoris region respectively). The initial 12 weeks of continuous massage application of the study were followed by a 12 week phase in which volunteers were split into 2 subgroups - one for assessment of regression effects and one for continuous application effects. AEVA (skin surface volume) measurements of cellulite-related dimples correlated with questionnaires and visual image evaluation scoring, in that in the iliotibial region cellulite was significantly reduced at 12 weeks. In the regression subgroup cellulite returned to initial values soon after cessation of treatment, whereas in the continuous application subgroup, cellulite remained diminished. The effect of this device to reduce cellulite as observed in this study proves that continuous use of vibrational massage is beneficial to mitigate visible signs of cellulite.

14.
Nat Rev Urol ; 17(3): 151-161, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31974507

RESUMO

Stress urinary incontinence (SUI) is a common and bothersome condition. Anti-incontinence surgery has high cure rates, but concerns about mesh tapes have resulted in the resurgence of surgical procedures that involve increased abdominopelvic dissection and morbidity. Injection therapy with urethral bulking agents or stem cell formulations have been developed as minimally invasive alternatives. Many synthetic and biological bulking agents have been trialled, but several have been discontinued owing to safety concerns. The use of Macroplastique and Contigen has the largest evidence base, but, overall, success rates seem to be similar between the various agents and positive outcomes are poorly sustained for more than 6 months. Furthermore, subjective cure rates, although initially high, also deteriorate over time. The available data consistently demonstrate manifestly poorer outcomes for injection therapies than for surgery. Stem cell treatments are thought to functionally regenerate the urethral sphincter in patients with suspected intrinsic sphincter deficiency. Autologous adipose and muscle-derived stem cells seem to be the intuitive cell source, as they are comparatively abundant, can be harvested and cause minimal donor site morbidity. To date, only a few small clinical studies have been reported and most data are derived from animal models. The success rates of stem cell injection therapies seem to be comparable with those of bulking agents.


Assuntos
Materiais Biocompatíveis/administração & dosagem , Doenças Uretrais/terapia , Incontinência Urinária por Estresse/terapia , Humanos , Injeções Intralesionais , Medicina Regenerativa/métodos , Transplante de Células-Tronco
15.
Nervenarzt ; 91(2): 156-160, 2020 Feb.
Artigo em Alemão | MEDLINE | ID: mdl-31900515

RESUMO

Neurological disorders can occur before the diagnosis of a malignoma is set. These disorders are induced by a misguided immune response with antibodies against intracellular or cell surface antigens. One of the most common paraneoplastic diseases is the subacute degeneration of the cerebellum. In most of the cases antibodies against Anti Hu, CRMP5/CV2, Amphiphysin and Ma/Ta are found and small cell bronchial carcinoma, breast cancer and lymphoma are diagnosed. We report about a 67 years old man with cerebellar symptoms and a weight loss of 10 kg who was treated in our clinic. After our diagnostic work up we found a non small cell cancer and diagnosed a subacute degeneration of the cerebellum as a paraneoplastic disorder. We found a high positive titer for Anti-Tr3 antibodies while the rest of the paraneoplastic antibodies described as typically associated with the subacute degeneration of the cerebellum were negative. The Anti-Tr3 antibodies are usually found in patients with Hodgkin and less often Non-Hodgkin disease. After initiation of a tumor specific therapy and intravenous immunoglobulin therapy the cerebellar symptoms decreased. In future follow up examinations we will see if the anti-Tr3 antibodies were associated with the non small cell bronchial carcinoma or if a lymphoma will occur in our patient.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Doenças do Sistema Nervoso , Degeneração Paraneoplásica Cerebelar , Idoso , Autoanticorpos , Carcinoma Pulmonar de Células não Pequenas/complicações , Cerebelo/patologia , Humanos , Neoplasias Pulmonares/complicações , Masculino , Degeneração Paraneoplásica Cerebelar/etiologia
16.
Neurourol Urodyn ; 39(2): 594-602, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31873953

RESUMO

AIMS: In a recent preclinical study, we noticed that injection of cells in the urethral sphincter by needle through a cystoscope under visual control frequently yielded in misplacement or loss of cells. We, therefore, investigated if a needle-free waterjet device delivers viable cells under defined settings, including injection volume and pressure, fluid velocity and transportation media, precisely through the urothelium and connective tissue close to the sphincter muscle without full penetration of the sphincter apparatus. METHODS: Mesenchymal stromal cells (MSCs) were prepared for needle-free waterjet injections. Upon injections into liquids cell viability and yield were investigated by trypan blue dye exclusion. Upon injection into cadaveric urethral tissue samples, cells were isolated from the urethrae and expanded to prove that this novel method delivered viable cells into the tissue. MSC injections by William's needle served as controls. RESULTS: Waterjet injections of MSCs into isotonic cell culture medium resulted in equal or better yields of viable cells when compared with needle injections. Upon injection in urethral tissue samples, the waterjet technology facilitated fast and precise injections of viable cells through urothelial, mucosal and submucosal layers to reach the sphincter muscle. By controlling the injection pressure, loss of cells due to insufficient thrust or unintended full penetration was avoided. CONCLUSIONS: Needle-free waterjet injections deliver cells in the urethra faster and more precisely when compared with needle injections without compromising their viability. This is the first proof-of-concept study providing evidence that a waterjet transports viable cells precisely into the targeted tissue.


Assuntos
Injeções/instrumentação , Células-Tronco Mesenquimais , Uretra/fisiologia , Cistoscopia , Humanos
17.
Ecotoxicol Environ Saf ; 184: 109621, 2019 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-31520953

RESUMO

ZnO nanoparticles (NPs) possess a wide range of biological functions in pharmaceutical and cosmetic applications due to their excellent antimicrobial, optical and UV protective properties. This study first reports the toxicological assessment of ZnO NPs green synthesized from Jatropha curcas shells for multifunctional biomedical applications. The hot water extract of J.curcas shells is utilized as a chelating agent for the reduction of zinc acetate and then, the prepared ZnO NPs are broadly characterized using X-ray spectroscopic and electron microscopic observations. The prepared ZnO NPs acquire high purity (100%) wurtzite crystal with hexagonal structure with the average particle size of 53 nm. In vitro and in vivo toxicity evaluation against human tumor cell lines and zebrafish embryos have ascertained the purpose of ZnO NPs in clinical research. Toxic effects of ZnO NPs were observed by a dose-dependent reduction of bacterial growth at ≥1   µg ml-1, by teratogenicity and genotoxicity in zebrafish embryos (from 3 to 90 µg ml-1) and by a significant nanoparticle uptake (0.5 ng µl-1) by a fish serum. In contrast, ZnO NPs fail to reduce the proliferation of human bladder tumor cells (UC6) and cell viability of A549 cells in vitro up to 500 µg ml-1. All these observations limit the unobstructed application of ZnO NPs at higher concentrations. Thus, abundantly used metal oxide nanoparticles like ZnO NPs examined in our present study in different animal models under in vitro and in vivo conditions will be the significant screening strategy to determine the nanotoxicity.


Assuntos
Materiais Biocompatíveis/química , Materiais Biocompatíveis/toxicidade , Jatropha/química , Óxido de Zinco/química , Óxido de Zinco/toxicidade , Células A549 , Animais , Bactérias/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Química Verde , Humanos , Nanopartículas Metálicas/química , Nanopartículas Metálicas/toxicidade , Testes de Toxicidade , Peixe-Zebra/embriologia
18.
Urologe A ; 58(9): 1029-1038, 2019 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-31451881

RESUMO

The demographic developments of western society and the resulting increase in the number of very old patients in urology represents a challenge for the design of clinical studies and, consequently, recommendations of guidelines. While in internal medicine there is already a subspecialization with a focus on the treatment of elderly and multimorbid patients, in urology there is hardly any subspecialization into the problems of geriatric patients. Thus, using a case study as an example, the treatment decisions for benign prostatic hyperplasia (BPH) in geriatric patients are discussed. In addition the available evidence from the literature and guidelines are presented in order to assiste in daily management of geriatric patients with lower urinary tract symptoms and to critically discuss potential fields of application and limitations of the existing guidelines. In this context, we also examine the challenges when choosing a drug therapy and in deciding which of the many surgical options should be used.


Assuntos
Sintomas do Trato Urinário Inferior/diagnóstico , Sintomas do Trato Urinário Inferior/terapia , Guias de Prática Clínica como Assunto , Hiperplasia Prostática/diagnóstico , Hiperplasia Prostática/terapia , Urologia/normas , Idoso , Humanos , Sintomas do Trato Urinário Inferior/etiologia , Masculino , Hiperplasia Prostática/etiologia
19.
Int J Cosmet Sci ; 41(3): 281-291, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31002377

RESUMO

OBJECTIVE: Lip treatment products often incorporate oils and waxes in their formulations, and a desired outcome of their use is to prevent lip dryness and roughness as well as help to repair this condition. The objective of this study was to combine confocal Raman spectroscopy with skin capacitance (corneometry) and transepidermal water loss (closed chamber Aquaflux system) measurements, in the evaluation of the degree of moisturization and lip skin penetration of a fruit wax (Rhus vernicula peel cera) and natural oil-based (Cocos nucifera fruit oil and Olea europea oil) lip care product, following a single application. METHODS: The study was conducted on a total of 15 healthy female volunteers. Instrumental measurements were performed before and 30 min, 2 h and 6 h after a single application of the product. RESULTS: Lip skin barrier function as well as lip hydration were significantly improved and penetration of olive oil was maintained for at least 6 h post product application. The deposition of the three component lipids (berry fruit wax, coconut oil and olive oil) into the stratum corneum after a single application of the lip care product was maintained and data significant for 2-6 h post product application. Lipid deposition was regarded as a positive long-lasting skin care (depot-) effect combined with a profound hydrating effect for about 6 h. CONCLUSION: The tri-method approach taken in this study is deemed relevant and valid for measuring lip hydration offering a complimentary assessment of the barrier function of lip skin and interactive effects of cosmetic ingredients.


Assuntos
Cosméticos , Lábio , Metabolismo dos Lipídeos , Plantas/metabolismo , Análise Espectral Raman/métodos , Perda Insensível de Água , Adolescente , Adulto , Idoso , Emolientes/administração & dosagem , Feminino , Humanos , Pessoa de Meia-Idade , Pele/metabolismo , Adulto Jovem
20.
Science ; 364(6436): 188-193, 2019 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-30975888

RESUMO

Notch signaling is a core patterning module for vascular morphogenesis that codetermines the sprouting behavior of endothelial cells (ECs). Tight quantitative and temporal control of Notch activity is essential for vascular development, yet the details of Notch regulation in ECs are incompletely understood. We found that ubiquitin-specific peptidase 10 (USP10) interacted with the NOTCH1 intracellular domain (NICD1) to slow the ubiquitin-dependent turnover of this short-lived form of the activated NOTCH1 receptor. Accordingly, inactivation of USP10 reduced NICD1 abundance and stability and diminished Notch-induced target gene expression in ECs. In mice, the loss of endothelial Usp10 increased vessel sprouting and partially restored the patterning defects caused by ectopic expression of NICD1. Thus, USP10 functions as an NICD1 deubiquitinase that fine-tunes endothelial Notch responses during angiogenic sprouting.


Assuntos
Endotélio Vascular/metabolismo , Neovascularização Fisiológica/fisiologia , Proteólise , Receptor Notch1/metabolismo , Ubiquitina Tiolesterase/fisiologia , Animais , Células HEK293 , Células Endoteliais da Veia Umbilical Humana , Humanos , Camundongos , Camundongos Knockout , Neovascularização Fisiológica/genética , Domínios Proteicos , Estabilidade Proteica , RNA Interferente Pequeno/genética , Transdução de Sinais , Ubiquitina Tiolesterase/genética
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