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1.
J Eur Acad Dermatol Venereol ; 33 Suppl 8: 52-56, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31833606

RESUMO

Evasion of immune recognition by the innate and acquired immune system is a major principle of tumour cells and belongs to the hallmarks of cancer. Immune checkpoint inhibitor-based cancer therapies targeting the co-inhibitory receptors CTLA-4 or PD-1 have received enormous scientific and clinical attention during the last few years, because of promising clinical results observed in the treatment of different cancer entities including melanoma and cutaneous squamous cell carcinoma. However, the enthusiasm about the effects of the immune checkpoint inhibitors is muted as only a subfraction of patients shows a stable clinical response. To predefine the patient cohorts that may benefit from immune checkpoint therapy, rigorous biomarker analyses, which predict the response to these novel therapies, need to be performed. In addition, combination of immune checkpoint therapy with classical DNA-damaging chemotherapy or radiotherapy, which positively affects tumour neo-antigen presentation, appears to be a promising approach in optimizing patients' response. In this review, we briefly summarize important biomarkers for patient stratification and discuss the current limitations of these biomarkers in defining responders vs. non-responders to immune checkpoint therapy.

2.
Chirurg ; 2019 Oct 25.
Artigo em Alemão | MEDLINE | ID: mdl-31654103

RESUMO

BACKGROUND: Minimally invasive gastrectomy is increasingly becoming established worldwide as an alternative to open gastrectomy (OG); however, the majority of available articles in the literature refer to Asian populations and early stages of gastric cancer. This makes an international comparison difficult due to a discrepancy in patient populations and tumor biology as well as Asian and western treatment approaches. Little is known, therefore, whether laparoscopic gastrectomy (LG) can be performed in advanced cancer, in particular with respect to laparoscopic D2 lymphadenectomy, with sufficient radicality and safety in this country. MATERIAL AND METHODS: All gastrectomies performed for the treatment of advanced gastric cancer with clinical UICC stages 2 and 3 between 2005 and 2017 were analyzed. A case match by age, gender and UICC stage was performed to compare the operative and early postoperative results of LG and OG. RESULTS: A total of 243 patients with advanced gastric cancer were analyzed. Of these 81 patients (33.3%) underwent LG. The operative time for LG was around 74 min longer (279.2 min vs. 353.4 min, OG vs. LG; p < 0.001), the hospital stay after LG was around 4 days shorter (22.9 days vs. 18.4 days, OG vs. LG; p < 0.001). Significantly more lymph nodes were resected by LG (24.1 lymph nodes vs. 28.8 lymph nodes, OG vs. LG; p < 0.001). In terms of morbidity and mortality there were no differences between the groups. CONCLUSION: The present study showed that minimally invasive gastrectomy can be performed safely and with comparable histopathological results to open surgery, even in advanced gastric cancer in western populations; however, larger case series and evidence from high-quality studies are urgently needed especially to compare short-term and long-term survival.

3.
Phys Med Biol ; 64(10): 105022, 2019 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-30970340

RESUMO

Range verification is one of the most relevant tasks in ion beam therapy. In the case of carbon ion therapy, positron emission tomography (PET) is the most widely used method for this purpose, which images the [Formula: see text]-activation following nuclear interactions of the ions with the tissue nuclei. Since the positron emitter activity profile is not directly proportional to the dose distribution, until today only its comparison to a prediction of the PET profile allows for treatment verification. Usually, this prediction is obtained from time-consuming Monte Carlo simulations of high computational effort, which impacts the clinical workflow. To solve this issue in proton therapy, a convolution approach was suggested to predict positron emitter activity profiles from depth dose distributions analytically. In this work, we introduce an approach to predict positron emitter distributions from depth dose profiles in carbon ion therapy. While the distal fall-off position of the positron emitter profile is predicted from a convolution approach similar to the one suggested for protons, additional analytical functions are introduced to describe the characteristics of the positron emitter distribution in tissue. The feasibility of this approach is demonstrated with monoenergetic depth dose profiles and spread out Bragg peaks in homogeneous and heterogeneous phantoms. In all cases, the positron emitter profile is predicted with high precision and the distal fall-off position is reproduced with millimeter accuracy.

4.
Phys Med Biol ; 64(2): 025011, 2019 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-30524026

RESUMO

Dose and range verification have become important tools to bring carbon ion therapy to a higher level of confidence in clinical applications. Positron emission tomography is among the most commonly used approaches for this purpose and relies on the creation of positron emitting nuclei in nuclear interactions of the primary ions with tissue. Predictions of these positron emitter distributions are usually obtained from time-consuming Monte Carlo simulations or measurements from previous treatment fractions, and their comparison to the current, measured image allows for treatment verification. Still, a direct comparison of planned and delivered dose would be highly desirable, since the dose is the quantity of interest in radiation therapy and its confirmation improves quality assurance in carbon ion therapy. In this work, we present a deconvolution approach to predict dose distributions from PET images in carbon ion therapy. Under the assumption that the one-dimensional PET distribution is described by a convolution of the depth dose distribution and a filter kernel, an evolutionary algorithm is introduced to perform the reverse step and predict the depth dose distribution from a measured PET distribution. Filter kernels are obtained from either a library or are created for any given situation on-the-fly, using predictions of the [Formula: see text]-decay and depth dose distributions, and the very same evolutionary algorithm. The applicability of this approach is demonstrated for monoenergetic and polyenergetic carbon ion irradiation of homogeneous and heterogeneous solid phantoms as well as a patient computed tomography image, using Monte Carlo simulated distributions and measured in-beam PET data. Carbon ion ranges are predicted within less than 0.5 mm and 1 mm deviation for simulated and measured distributions, respectively.


Assuntos
Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Neoplasias de Cabeça e Pescoço/radioterapia , Radioterapia com Íons Pesados/métodos , Processamento de Imagem Assistida por Computador/métodos , Imagens de Fantasmas , Tomografia por Emissão de Pósitrons/métodos , Planejamento da Radioterapia Assistida por Computador/métodos , Algoritmos , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Método de Monte Carlo
5.
World J Urol ; 37(7): 1415-1420, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30341450

RESUMO

PURPOSE: To analyze and compare preoperative patient characteristics and postoperative results in men with stress urinary incontinence (SUI) selected for an adjustable male sling system or an artificial urinary sphincter (AUS) in a large, contemporary, multi-institutional patient cohort. METHODS: 658 male patients who underwent implantation between 2010 and 2012 in 13 participating institutions were included in this study (n = 176 adjustable male sling; n = 482 AUS). Preoperative patient characteristics and postoperative outcomes were analyzed. For statistical analysis, the independent T test and Mann-Whitney U test were used. RESULTS: Patients undergoing adjustable male sling implantation were less likely to have a neurological disease (4.5% vs. 8.9%, p = 0.021), a history of urethral stricture (21.6% vs. 33.8%, p = 0.024) or a radiation therapy (22.7% vs. 29.9%, p = 0.020) compared to patients that underwent AUS implantation. Mean pad usage per day (6.87 vs. 5.82; p < 0.00) and the ratio of patients with a prior incontinence surgery were higher in patients selected for an AUS implantation (36.7% vs. 22.7%; p < 0.001). At maximum follow-up, patients that underwent an AUS implantation had a significantly lower mean pad usage during daytime (p < 0.001) and nighttime (p = 0.018). Furthermore, the patients' perception of their continence status was better with a subjective complete dry rate of 57.3% vs. 22.0% (p < 0.001). CONCLUSIONS: Patients selected for an AUS implantation showed a more complex prior history and pathogenesis of urinary incontinence as well as a more severe grade of SUI. Postoperative results reflect a better continence status after AUS implantation, favoring the AUS despite the more complicated patient cohort.


Assuntos
Slings Suburetrais , Incontinência Urinária por Estresse/cirurgia , Esfíncter Urinário Artificial , Procedimentos Cirúrgicos Urológicos Masculinos/métodos , Idoso , Estudos de Coortes , Humanos , Masculino , Medidas de Resultados Relatados pelo Paciente , Seleção de Pacientes , Radioterapia/estatística & dados numéricos , Estudos Retrospectivos , Índice de Gravidade de Doença , Resultado do Tratamento , Estreitamento Uretral/epidemiologia
6.
Opt Lett ; 43(19): 4711-4714, 2018 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-30272721

RESUMO

One-dimensional (1D) photonic crystals (PCs) were fabricated by three-dimensional (3D) direct laser writing using a single polymer to obtain reflectance values approaching that of a gold reference in the near-infrared (near-IR) spectral range. The PCs are composed of alternating compact and low-density polymer layers that provide the necessary periodic variation of the refractive index. The low-density polymer layers are composed of subwavelength-sized pillars which simultaneously serve as a scaffold while also providing refractive index contrast to the adjacent compact polymer layers. The Bruggemann effective medium theory and stratified-layer optical-model calculated reflectivity profiles were employed to optimize the PC's design to operate at a desired wavelength of 1.55 µm. After the fabrication, the PC's structure was compared to the nominal geometry using complementary scanning electron microscopy and optical microscopy micrographs identifying a true-to-form fabrication. The performance of the PCs was investigated experimentally using FTIR reflection and transmission measurements. A good agreement between stratified-layer optical-model calculated and measured data is observed. Therefore, we demonstrate the ease of predictive design and fabrication of highly efficient 1D PCs for the IR spectral range using 3D direct laser writing of a single polymer.

7.
Opt Lett ; 43(2): 239-242, 2018 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-29328249

RESUMO

Three-dimensional direct laser writing via two-photon polymerization is used to fabricate anti-reflective structured surfaces (ARSSs) composed of subwavelength conicoid features optimized to operate over a wide bandwidth in the near-infrared range from 3700 cm-1 to 6600 cm-1 (2.7-1.52 µm). Analytic Bruggemann effective medium calculations are used to predict nominal geometric parameters such as the fill factor of the constitutive conicoid features of the anti-reflective structured surfaces (ARSSs) presented here. The performance of the ARSSs was investigated experimentally using infrared reflection and transmission measurements. An enhancement of the transmittance by 1.35%-2.14% over a broadband spectral range from 3700 cm-1 to 6600 cm-1 (2.7-1.52 µm) was achieved. We further report on finite-element-based reflection and transmission data using three-dimensional (3D) model geometries for comparison. A good agreement between experimental results and the finite-element-based numerical analysis is observed once as-fabricated deviations from the nominal conicoid forms are included in the model. 3D direct laser writing is demonstrated here as an efficient method for the fabrication and optimization of ARSSs designed for the infrared spectral range.

8.
Transplant Proc ; 49(8): 1947-1955, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28923653

RESUMO

BACKGROUND: The influence of immunosuppressants on hepatitis C virus (HCV) re-infection after liver transplantation, particularly mammalian target of rapamycin inhibitors, remains unclear. The aim of our study was to analyze the influence of everolimus (EVR) on HCV replication activity in the context of underlying molecular mechanisms, with focus on the pro-myelocytic leukemia protein (PML). METHODS: HCV viral load was recorded in 40 patients with post-transplant HCV re-infection before and 8 weeks after introduction of EVR. An HCV cell culture replicon system for genotype (GT) 1b, GT2b, and GT3a was used to compare the influence of EVR on HCV replication for the respective genotypes in vitro. Fluorescence-activated cell-sorting analysis was used to test for effects on cell proliferation. PML expression was silenced with the use of small hairpin RNA constructs, and PML expression was quantified by means of quantitative real-time polymerase chain reaction. RESULTS: In patients with HCV, the viral load of GT1a and GT1b was hardly affected by EVR, whereas the viral load was reduced in patients with GT2a (P ≤ .0001) or GT3 infection (P ≤ .05). In vitro EVR impairs HCV replication activity of GT2a and GT3a up to 60% (P ≤ .0005), whereas in GT1b cells, HCV replication activity is increased by 50% (P ≤ .005). Replicon cell viability was not impaired. HCV replication activity is impaired in the absence of PML, which can be reversed by overexpression of PML isoforms. Furthermore, in the absence of PML, the effect of EVR on HCV replication activity is nearly abrogated. CONCLUSIONS: The mammalian target of rapamycin inhibitor EVR influences HCV replication via PML. The herein presented results suggest a genotype-dependent benefit for an EVR-based immunosuppressive regimen in patients with GT2a or GT3 re-infection after liver transplantation.


Assuntos
Everolimo/farmacologia , Hepacivirus/efeitos dos fármacos , Hepatite C Crônica/virologia , Imunossupressores/farmacologia , Transplante de Fígado , Sirolimo/antagonistas & inibidores , Serina-Treonina Quinases TOR/antagonistas & inibidores , Replicação Viral/efeitos dos fármacos , Genótipo , Hepacivirus/genética , Hepacivirus/fisiologia , Humanos , Técnicas In Vitro , RNA Viral , Reação em Cadeia da Polimerase em Tempo Real , Carga Viral/efeitos dos fármacos
9.
Rev Sci Instrum ; 87(11): 113701, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27910407

RESUMO

An optical microscope is described that reveals contrast in the Mueller matrix images of a thin, transparent, or semi-transparent specimen located within an anisotropic object plane (anisotropic filter). The specimen changes the anisotropy of the filter and thereby produces contrast within the Mueller matrix images. Here we use an anisotropic filter composed of a semi-transparent, nanostructured thin film with sub-wavelength thickness placed within the object plane. The sample is illuminated as in common optical microscopy but the light is modulated in its polarization using combinations of linear polarizers and phase plate (compensator) to control and analyze the state of polarization. Direct generalized ellipsometry data analysis approaches permit extraction of fundamental Mueller matrix object plane images dispensing with the need of Fourier expansion methods. Generalized ellipsometry model approaches are used for quantitative image analyses. These images are obtained from sets of multiple images obtained under various polarizer, analyzer, and compensator settings. Up to 16 independent Mueller matrix images can be obtained, while our current setup is limited to 11 images normalized by the unpolarized intensity. We demonstrate the anisotropic contrast optical microscope by measuring lithographically defined micro-patterned anisotropic filters, and we quantify the adsorption of an organic self-assembled monolayer film onto the anisotropic filter. Comparison with an isotropic glass slide demonstrates the image enhancement obtained by our method over microscopy without the use of an anisotropic filter. In our current instrument, we estimate the limit of detection for organic volumetric mass within the object plane of ≈49 fg within ≈7 × 7 µm2 object surface area. Compared to a quartz crystal microbalance with dissipation instrumentation, where contemporary limits require a total load of ≈500 pg for detection, the instrumentation demonstrated here improves sensitivity to a total mass required for detection by 4 orders of magnitude. We detail the design and operation principles of the anisotropic contrast optical microscope, and we present further applications to the detection of nanoparticles, to novel approaches for imaging chromatography and to new contrast modalities for observations on living cells.


Assuntos
Microscopia/métodos , Modelos Teóricos , Anisotropia
10.
J Physiol Pharmacol ; 67(2): 195-203, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27226179

RESUMO

Irisin has recently been proposed to act as a myokine secreted from skeletal muscle following exercise and to exert several health-beneficial effects, although its role is far from being established. In contrast to the growing body of literature on the biological regulation and function of irisin, there is no evidence on potential associations with mental functions. Since physical activity has been reported to have favorable impact on mental functions, we investigated the association of irisin with depressiveness, perceived stress, and anxiety as well as eating disorder symptoms in obese women. We included 98 female obese inpatients (age: mean ± S.D. 43.9 ± 12.5 years; body mass index 49.2 ± 8.3 kg/m(2)) covering a broad spectrum of psychopathology. Depressiveness (PHQ-9), perceived stress (PSQ-20), anxiety (GAD-7), and eating disorder symptoms (EDI-2) were assessed psychometrically. Plasma irisin obtained at the same time was determined by ELISA. Irisin did not correlate with depressiveness (r = -0.03, P = 0.80), anxiety (r = 0.14, P = 0.17) and perceived stress (r = -0.14, P = 0.18) as well as eating disorder symptoms in general (r = -0.09, P = 0.39). No correlation of irisin was observed with any subscales of the PSQ-20 and EDI-2 (after Bonferroni correction). In conclusion, irisin is not associated with depressiveness, anxiety and perceived stress in female obese patients. These results do not support the assumption of irisin being involved in psychoendocrine pathways of the regulation of depression or other mental functions such as anxiety and perceived stress.


Assuntos
Exercício Físico , Fibronectinas/sangue , Obesidade/sangue , Adulto , Ansiedade/sangue , Índice de Massa Corporal , Depressão/sangue , Transtornos da Alimentação e da Ingestão de Alimentos/sangue , Feminino , Humanos , Pessoa de Meia-Idade , Estresse Psicológico/sangue
11.
Colorectal Dis ; 18(6): O194-8, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26999764

RESUMO

AIM: The use of a loose seton for complex anal fistulae can cause perianal discomfort and reduced quality of life. The aim of this study was to assess the impact of the novel knot-free Comfort Drain on quality of life, perianal comfort and faecal continence compared to conventional loose setons. METHOD: Forty-four patients treated for complex anal fistula at a single institution between July 2013 and September 2014 were included in the study. A matched-pair analysis was performed to compare patients with a knot-free Comfort Drain and controls who were managed by conventional knotted setons. The 12-item Short Form survey (SF-12) questionnaire was used to assess quality of life. Additionally, patients reported perianal comfort and faecal incontinence using a Visual Analog Scale (VAS) and the St Mark's Incontinence Score. RESULTS: The Comfort Drain was associated with improved quality of life with significant higher median physical (P = 0.001) and mental (P = 0.04) health scores compared with a conventional loose seton. According to the VAS, patients with a Comfort Drain in situ reported greater perianal comfort with significantly less burning sensation (P < 0.001) and pruritus (P < 0.001). Faecal continence was similar in each group. CONCLUSION: The Comfort Drain offers improved perianal comfort and better quality of life compared with a conventional loose seton and therefore facilitates long-term therapy in patients with complex fistula-in-ano.


Assuntos
Qualidade de Vida , Fístula Retal/cirurgia , Técnicas de Sutura , Adulto , Estudos de Casos e Controles , Drenagem/instrumentação , Incontinência Fecal/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dor/etiologia , Dor/cirurgia , Fístula Retal/etiologia , Estudos Retrospectivos , Inquéritos e Questionários
12.
Cell Death Differ ; 23(1): 110-22, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26113041

RESUMO

Upon severe DNA damage a cellular signalling network initiates a cell death response through activating tumour suppressor p53 in association with promyelocytic leukaemia (PML) nuclear bodies. The deacetylase Sirtuin 1 (SIRT1) suppresses cell death after DNA damage by antagonizing p53 acetylation. To facilitate efficient p53 acetylation, SIRT1 function needs to be restricted. How SIRT1 activity is regulated under these conditions remains largely unclear. Here we provide evidence that SIRT1 activity is limited upon severe DNA damage through phosphorylation by the DNA damage-responsive kinase HIPK2. We found that DNA damage provokes interaction of SIRT1 and HIPK2, which phosphorylates SIRT1 at Serine 682 upon lethal damage. Furthermore, upon DNA damage SIRT1 and HIPK2 colocalize at PML nuclear bodies, and PML depletion abrogates DNA damage-induced SIRT1 Ser682 phosphorylation. We show that Ser682 phosphorylation inhibits SIRT1 activity and impacts on p53 acetylation, apoptotic p53 target gene expression and cell death. Mechanistically, we found that DNA damage-induced SIRT1 Ser682 phosphorylation provokes disruption of the complex between SIRT1 and its activator AROS. Our findings indicate that phosphorylation-dependent restriction of SIRT1 activity by HIPK2 shapes the p53 response.


Assuntos
Apoptose/genética , Proteínas de Transporte/biossíntese , Leucemia Promielocítica Aguda/genética , Proteínas Serina-Treonina Quinases/biossíntese , Sirtuína 1/biossíntese , Proteína Supressora de Tumor p53/biossíntese , Acetilação , Proteínas de Transporte/genética , Linhagem Celular Tumoral , Dano ao DNA/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Leucemia Promielocítica Aguda/patologia , Fosforilação , Ligação Proteica , Proteínas Serina-Treonina Quinases/genética , Sirtuína 1/genética , Proteína Supressora de Tumor p53/genética
13.
J Physiol Pharmacol ; 66(4): 493-503, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26348074

RESUMO

The ghrelin acylating enzyme ghrelin-O-acyltransferase (GOAT) was recently identified and implicated in several biological functions. However, the effects on food intake warrant further investigation. While several genetic GOAT mouse models showed normal food intake, acute blockade using a GOAT inhibitor resulted in reduced food intake. The underlying food intake microstructure remains to be established. In the present study we used an automated feeding monitoring system to assess food intake and the food intake microstructure. First, we validated the basal food intake and feeding behavior in rats using the automated monitoring system. Afterwards, we assessed the food intake microstructure following intraperitoneal injection of the GOAT inhibitor, GO-CoA-Tat (32, 96 and 288 µg/kg) in freely fed male Sprague-Dawley rats. Rats showed a rapid habituation to the automated food intake monitoring system and food intake levels were similar compared to manual monitoring (P = 0.43). Rats housed under these conditions showed a physiological behavioral satiety sequence. Injection of the GOAT inhibitor resulted in a dose-dependent reduction of food intake with a maximum effect observed after 96 mg/kg (-27%, P = 0.03) compared to vehicle. This effect was delayed in onset as the first meal was not altered and lasted for a period of 2 h. Analysis of the food intake microstructure showed that the anorexigenic effect was due to a reduction of meal frequency (-15%, P = 0.04), whereas meal size (P = 0.29) was not altered compared to vehicle. In summary, pharmacological blockade of GOAT reduces dark phase food intake by an increase of satiety while satiation is not affected.


Assuntos
Aciltransferases/antagonistas & inibidores , Depressores do Apetite/farmacologia , Ingestão de Alimentos/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Peptídeos/farmacologia , Animais , Depressores do Apetite/administração & dosagem , Relação Dose-Resposta a Droga , Comportamento Alimentar/efeitos dos fármacos , Grelina/metabolismo , Injeções Intraperitoneais , Masculino , Peptídeos/administração & dosagem , Ratos , Ratos Sprague-Dawley , Resposta de Saciedade/efeitos dos fármacos
14.
Opt Lett ; 40(12): 2688-91, 2015 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-26076237

RESUMO

The effect of a tunable, externally coupled Fabry-Perot cavity to resonantly enhance the optical Hall effect signatures at terahertz frequencies produced by a traditional Drude-like two-dimensional electron gas is shown and discussed in this Letter. As a result, the detection of optical Hall effect signatures at conveniently obtainable magnetic fields, for example, by neodymium permanent magnets, is demonstrated. An AlInN/GaN-based high-electron mobility transistor structure grown on a sapphire substrate is used for the experiment. The optical Hall effect signatures and their dispersions, which are governed by the frequency and the reflectance minima and maxima of the externally coupled Fabry-Perot cavity, are presented and discussed. Tuning the externally coupled Fabry-Perot cavity strongly modifies the optical Hall effect signatures, which provides a new degree of freedom for optical Hall effect experiments in addition to frequency, angle of incidence, and magnetic field direction and strength.

15.
Klin Monbl Augenheilkd ; 232(4): 375-9, 2015 Apr.
Artigo em Alemão | MEDLINE | ID: mdl-25902079

RESUMO

BACKGROUND: Corneal endothelial cell density is an important factor in maintaining corneal transparency. It is generally assumed that corneal endothelial cell density continuously decreases from birth. MATERIAL AND METHODS: On healthy eyes of 191 subjects, images of the endothelium were taken using a specular endothelial microscope. Statistical analyses were done on corneal endothelial cell density, polymegatism and proportion of hexagonal cells in relation to age. RESULTS: Extrapolated endothelial cell density at birth was 2957 cells/mm2. Using linear regression, the calculated annual cell loss was 7.58 cells/mm2. With age, polymegatism is increasing and the proportion of hexagonal cells is decreasing. Based on our data, the decrease in corneal endothelial cell density can be described in two different time periods: from birth until 35 years of age, endothelial cell density is considerably and continuously decreasing; after this corneal endothelial cell density is decreasing at a much slower rate. CONCLUSIONS: Our data suggest that changes in the structure of the corneal endothelium are different in the first three decades of life compared to later decades. Reasons for this could be mechanical and physical influences, changing biochemical properties of the cornea and aqueous humor, or the embryological origin of the endothelium. This observation shows that age generally is not a deciding factor for intraocular surgeries.


Assuntos
Envelhecimento/patologia , Perda de Células Endoteliais da Córnea/patologia , Células Endoteliais/patologia , Epitélio Posterior/patologia , Adolescente , Adulto , Idoso , Contagem de Células/estatística & dados numéricos , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Adulto Jovem
16.
Eur J Nutr ; 54(1): 149-56, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24740588

RESUMO

PURPOSE: Coffee consumption has been reported to decrease oxidative damage in peripheral white blood cells (WBC). However, effects on the level of spontaneous DNA strand breaks, a well established marker of health risk, have not been specifically reported yet. We analyzed the impact of consuming a dark roast coffee blend on the level of spontaneous DNA strand breaks. METHODS: Healthy men (n = 84) were randomized to consume daily for 4 weeks either 750 ml of fresh coffee brew or 750 ml of water, subsequent to a run in washout phase of 4 weeks. The study coffee was a blend providing high amounts of both caffeoylquinic acids (10.18 ± 0.33 mg/g) and the roast product N-methylpyridinium (1.10 ± 0.05 mg/g). Before and after the coffee/water consumption phase, spontaneous strand breaks were determined by comet assay. RESULTS: At baseline, both groups exhibited a similar level of spontaneous DNA strand breaks. In the intervention phase, spontaneous DNA strand breaks slightly increased in the control (water only) group whereas they significantly decreased in the coffee group, leading to a 27% difference within both arms (p = 0.0002). Food frequency questionnaires indicated no differences in the overall diet between groups, and mean body weight during the intervention phases remained stable. The consumption of the study coffee substantially lowered the level of spontaneous DNA strand breaks in WBC. CONCLUSION: We conclude that regular coffee consumption contributes to DNA integrity.


Assuntos
Antioxidantes/administração & dosagem , Café , Quebras de DNA , Manipulação de Alimentos , Leucócitos/metabolismo , Adulto , Alcaloides/administração & dosagem , Alcaloides/análise , Alcaloides/urina , Antioxidantes/análise , Biomarcadores/sangue , Cafeína/administração & dosagem , Cafeína/análise , Coffea/química , Café/química , Estudos de Coortes , Ensaio Cometa , Alemanha , Temperatura Alta , Humanos , Masculino , Cooperação do Paciente , Compostos de Piridínio/administração & dosagem , Compostos de Piridínio/análise , Compostos de Piridínio/urina , Ácido Quínico/administração & dosagem , Ácido Quínico/análogos & derivados , Ácido Quínico/análise , Sementes/química
17.
Adv Exp Med Biol ; 839: 13-24, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25252902

RESUMO

Systemic antibiotic treatment is established for many pulmonary diseases, e.g., cystic fibrosis (CF), bronchiectasis and chronic obstructive pulmonary disease (COPD) where recurrent bacterial infections cause a progressive decline in lung function. In the last decades inhalative administration of antibiotics was introduced into clinical routine, especially tobramycin, colistin, and aztreonam for treatment of CF and bronchiectasis. Even though they are important in systemic treatment of these diseases due to their antimicrobial spectrum and anti-inflammatory and immunomodulatory properties, macrolides (e.g., azithromycin, clarithromycin, erythromycin, and telithromycin) up to now are not administered by inhalation. The number of in vitro aerosol studies and in vivo inhalation studies is also sparse. We analyzed publications on preparation and administration of macrolide aerosols available in PUBMED focusing on recent publications. Studies with solutions and dry powder aerosols were published. Publications investigating physicochemical properties of aerosols demonstrated that macrolide aerosols may serve for inhalation and will achieve sufficient lung deposition and that the bitter taste can be masked. In vivo studies in rats demonstrated high concentrations and areas under the curve sufficient for antimicrobial treatment in alveolar macrophages and epithelial lining fluid without lung toxicity. The obtained data demonstrate the feasibility of macrolide inhalation which should be further investigated.


Assuntos
Antibacterianos/uso terapêutico , Bronquiectasia/tratamento farmacológico , Fibrose Cística/tratamento farmacológico , Pulmão/efeitos dos fármacos , Macrolídeos/uso terapêutico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Administração por Inalação , Aerossóis , Animais , Azitromicina/uso terapêutico , Bronquiectasia/microbiologia , Bronquiectasia/fisiopatologia , Claritromicina/uso terapêutico , Fibrose Cística/microbiologia , Fibrose Cística/fisiopatologia , Eritromicina/uso terapêutico , Humanos , Cetolídeos/uso terapêutico , Pulmão/microbiologia , Pulmão/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/microbiologia , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Ratos
19.
Rev Sci Instrum ; 85(7): 071301, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25085120

RESUMO

We report on the development of the first integrated mid-infrared, far-infrared, and terahertz optical Hall effect instrument, covering an ultra wide spectral range from 3 cm(-1) to 7000 cm(-1) (0.1-210 THz or 0.4-870 meV). The instrument comprises four sub-systems, where the magneto-cryostat-transfer sub-system enables the usage of the magneto-cryostat sub-system with the mid-infrared ellipsometer sub-system, and the far-infrared/terahertz ellipsometer sub-system. Both ellipsometer sub-systems can be used as variable angle-of-incidence spectroscopic ellipsometers in reflection or transmission mode, and are equipped with multiple light sources and detectors. The ellipsometer sub-systems are operated in polarizer-sample-rotating-analyzer configuration granting access to the upper left 3 × 3 block of the normalized 4 × 4 Mueller matrix. The closed cycle magneto-cryostat sub-system provides sample temperatures between room temperature and 1.4 K and magnetic fields up to 8 T, enabling the detection of transverse and longitudinal magnetic field-induced birefringence. We discuss theoretical background and practical realization of the integrated mid-infrared, far-infrared, and terahertz optical Hall effect instrument, as well as acquisition of optical Hall effect data and the corresponding model analysis procedures. Exemplarily, epitaxial graphene grown on 6H-SiC, a tellurium doped bulk GaAs sample and an AlGaN/GaN high electron mobility transistor structure are investigated. The selected experimental datasets display the full spectral, magnetic field and temperature range of the instrument and demonstrate data analysis strategies. Effects from free charge carriers in two dimensional confinement and in a volume material, as well as quantum mechanical effects (inter-Landau-level transitions) are observed and discussed exemplarily.

20.
Pflugers Arch ; 466(12): 2177-89, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24633576

RESUMO

Transient receptor potential cation channel, subfamily M, member 7 (TRPM7) is a cation channel covalently linked to a protein kinase domain. TRPM7 is ubiquitously expressed and regulates key cellular processes such as Mg(2+) homeostasis, motility, and proliferation. TRPM7 is involved in anoxic neuronal death, cardiac fibrosis, and tumor growth. The goal of this work was to identify small molecule activators of the TRPM7 channel and investigate their mechanism of action. We used an aequorin bioluminescence-based assay to screen for activators of the TRPM7 channel. Valid candidates were further characterized using patch clamp electrophysiology. We identified 20 drug-like compounds with various structural backbones that can activate the TRPM7 channel. Among them, the δ opioid antagonist naltriben was studied in greater detail. Naltriben's action was selective among the TRP channels tested. Naltriben activates TRPM7 currents without prior depletion of intracellular Mg(2+) even under conditions of low PIP2. Moreover, naltriben interfered with the effect of the TRPM7 inhibitor NS8593. Finally, our experiments with TRPM7 variants carrying mutations in the pore, TRP, and kinase domains indicate that the site of TRPM7 activation by this small-molecule ligand is most likely located in or near the TRP domain. In conclusion, we identified the first organic small-molecule activators of TRPM7 channels, thus providing new experimental tools to study TRPM7 function in native cellular environments.


Assuntos
Bibliotecas de Moléculas Pequenas/farmacologia , Canais de Cátion TRPM/agonistas , Potenciais de Ação , Animais , Células HEK293 , Humanos , Magnésio/metabolismo , Camundongos , Naltrexona/análogos & derivados , Naltrexona/farmacologia , Fosfatidilinositol 4,5-Difosfato/metabolismo , Bibliotecas de Moléculas Pequenas/química , Canais de Cátion TRPM/metabolismo
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