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1.
Am J Physiol Gastrointest Liver Physiol ; 317(4): G493-G507, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31411503

RESUMO

Genetically modified mice have been successfully used as models for inflammatory bowel diseases; however, dietary effects were poorly examined. Here, we studied the impact of particular nutrients and supplements on gut functions related to the knockout of the epithelial caspase-8 gene. Caspase-8 knockout (Casp8∆IEC) and control (Casp8fl) mice were fed for 4 wk a control diet (CD) enriched with 10% inulin (CD-Inu) or 5% sodium butyrate (CD-But) while having free access to plain water or water supplemented with 30% fructose (+F). Body weight changes, intestinal inflammation, and selected markers for barrier function and of liver steatosis were assessed. Casp8∆IEC mice developed ileocolitis accompanied by changes in intestinal barrier morphology and reduced expression of barrier-related genes such as mucin-2 (Muc2) and defensins in the ileum and Muc2 in the colon. Casp8∆IEC mice fed a CD also showed impaired body weight gain compared with Casp8fl mice, which was even more pronounced in mice receiving water supplemented with fructose. Furthermore, we observed a marked liver steatosis and inflammation in some but not all Casp8∆IEC mice under a CD, which was on average similar to that observed in control mice under a fructose-rich diet. Hepatic lipid accumulation, as well as markers of ileal barrier function, but not intestinal pathohistology or body weight loss, were attenuated by diets enriched with inulin or butyrate, especially in the absence of fructose supplementation. Our data show that ileocolitis, barrier dysfunction, and malassimilation in Caspase-8 knockout mice can be partially attenuated by oral inulin or butyrate supplementation.NEW & NOTEWORTHY Genetic mouse models for ileocolitis are important to understand inflammatory bowel disease in humans. We examined dietetic factors that might aggravate or attenuate ileocolitis and related pathologies in such a model. Deletion of the caspase-8 gene results not only in ileocolitis but also in gut barrier dysfunction, liver steatosis, and malassimilation, which can be partially attenuated by oral inulin or sodium butyrate. Our data indicate that diet modifications can contribute to disease variability and therapy.

2.
J Neurol ; 266(10): 2488-2494, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31250103

RESUMO

BACKGROUND: Facial nerve palsy is the most common cranial nerve disorder. There is no consensus on a single diagnostic tool deemed as the 'gold standard' for distinguishing between idiopathic (Bell's palsy) and symptomatic causes. The diagnosis is one of exclusion and most often made on physical examination. In the present study, we describe the etiological background of peripheral facial palsy in N = 509 patients and evaluate the relevance of cerebrospinal fluid (CSF) analysis and magnetic resonance imaging (MRI) in differential diagnosis. METHODS: We carried out a retrospective data analysis of 509 patients with the clinical diagnosis of peripheral facial palsy admitted to our emergency unit between January 2006 and January 2017. All patients were seen clinically; their CSF was analyzed and MRI was performed. RESULTS: Of N = 526 patients with isolated facial palsy, 17 patients were excluded because they did not consent to CSF analysis. Of the remaining N = 509 patients, 383 patients (75.2%) were diagnosed with idiopathic facial palsy. In the remaining 126 patients (24.8%), the following etiologies for facial palsy could be found: Ramsay-Hunt-Syndrome (N = 34), Lyme Neuroborreliosis (N = 32), other viral/bacterial central nervous system (CNS) infections (N = 8), neoplasias (N = 18), autoimmune disease (N = 12), otogenous processes (N = 6), or other etiologies (N = 16). Analysis of the CSF showed 85% sensitivity for Ramsay-Hunt-Syndrome and 100% for Lyme Neuroborreliosis and other viral/bacterial CNS infections. CSF analysis proved a reliable diagnostic tool for identifying these subgroups. MRI with contrast compounds, as performed in 409 patients, was the most important tool in diagnosing neoplasias (88% sensitivity) and otogenous processes (83% sensitivity). MRI with contrast-enhancing compounds did not reveal additional information concerning inflammatory facial nerve lesions when performed the same day as hospital admission. CONCLUSIONS: Although peripheral facial palsy was predominantly idiopathic (75.3%) in our cohort, the disease was caused in approximately 25% of the patients by factors which require specific treatment. In the present study, CSF analysis proved to be the leading method for the diagnosis of Ramsay-Hunt-Syndrome, Lyme Neuroborreliosis, and other CNS infections. These subgroups made up approximately 15% of our cohort. To detect these subgroups reliably, routine use of CSF analysis in peripheral facial palsy may be advisable, whereas MRI proved to be useful for exclusion of otogenic and neoplastic processes with a sensitivity of 83% and 88%. We found that the use of MRI with contrast-enhancing compounds does not provide additional diagnostic information on the day of hospital admission. Hence, the potential benefits of routine use of MRI in patients with facial nerve palsy should be weighed against health care cost factors.

3.
Arch Gynecol Obstet ; 300(1): 201-206, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31044301

RESUMO

PURPOSE: To assess the change of body mass index (BMI), muscle mass, visceral and subcutaneous fat in patients with metastatic breast cancer. METHODS: In this retrospective chart analysis, patients with metastatic breast cancer as initial diagnosis between 2012 and 2016 were analyzed. Patients had received either chemotherapy (CTH) or endocrine therapy (ETH) according to the German S3 Guideline. BMI was calculated from the patients' weight and height. Change of muscle mass, visceral and subcutaneous fat was determined by comparing the surface area of these tissues on transverse CT images at the level of the third lumbar vertebrae (L3) at baseline and during treatment. RESULTS: A total of 45 patients were included in the study, 29 on CTH and 16 on ETH. BMI, visceral and subcutaneous fat remained stable over time for both treatment groups. When taking both treatment groups together, muscle mass decreased significantly by 5.0 ± 2.5 cm2 per year (p < 0.05). CONCLUSION: In patients with metastatic breast cancer, a slight reduction of muscle mass was observed, independent of therapy regimes.

4.
Dev Psychol ; 55(5): 1072-1087, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30702311

RESUMO

Residential mobility-the change of residence within a country-is a pervasive phenomenon in 21st century societies, with the peak clearly being in young adulthood. Placing the self in geographical space has now become a major challenge for young adults, making region a key identity domain. Little is known, however, about the correlates of regional identity development. In line with the dynamic-transactional paradigm, we expected longitudinal associations between regional identity and the geographical dispersion of personal relationships. We specifically assumed that both individual experiences-such as moving-and personal relationship experiences-such as emotional closeness toward relationship partners-moderate these associations over time. Using longitudinal multilevel analyses, we found support for these hypotheses in a 3-wave longitudinal study over 1 year with 1,059 postsecondary graduates from Germany (73% female, mean age 24.53 years). Most notably, changes in regional identity were related to changes in geographical distance from personal relationship partners. Effects were robust and confirmed when controlling for diverse reasons for moving. We conclude that regional identity and personal relationships share a common developmental pathway. This pathway also points toward the relevance of geographical distance from personal relationships, even in young adults' mobile and connected world. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Assuntos
Geografia , Relações Interpessoais , Dinâmica Populacional , Autoimagem , Identificação Social , Adulto , Feminino , Amigos/psicologia , Alemanha , Humanos , Individuação , Estudos Longitudinais , Masculino , Desenvolvimento da Personalidade , Parceiros Sexuais/psicologia , Adulto Jovem
5.
Artigo em Inglês | MEDLINE | ID: mdl-30176354

RESUMO

The objective of this study was to investigate the impact of cold atmospheric-pressure plasma (CAP) produced by a surface micro-discharge plasma source as a new strategy to combat the transmission of five multidrug-resistant (MDR) pathogens and Yersinia enterocolitica on typical hospital- and food-producing surfaces, e.g. stainless-steel. Approximately 106 CFU/cm2 of vancomycin-resistant Enterococcus faecium, methicillin-resistant Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli and Y. enterocolitica were inoculated on a 3.14-cm2 stainless-steel surface. Bovine serum albumin (BSA) (3%) was used as a disruptive factor simulating natural organic material. The inoculated surfaces were subsequently exposed to CAP, generated by a peak-to-peak voltage of 10 kV with sinusoidal waveform and a frequency of 2 kHz, for 5, 10 and 20 min, respectively. Fluorescent staining with propidium iodide and SYTOTM 9 was used to demonstrate the manner of bacterial cell damage. Significant (P < 0.05) inactivation of 1.68 ± 0.17 up to 2.80 ± 0.17 log steps was achieved after 5 min of CAP treatment. However, bacterial reduction could be increased to 3.35 ± 0.1 up to 5.17 ± 0.67 log steps after 20 min of CAP treatment. Bacterial cells covered with BSA were statistically significantly less inactivated by CAP. Fluorescent staining showed a predominant level of orange-stained, sublethally damaged bacterial cells after 10 min of CAP treatment. In conclusion, CAP has the ability to inactivate MDR bacterial pathogens on stainless-steel surfaces. Further research is required to investigate the clinical features of CAP.

6.
Auris Nasus Larynx ; 2018 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-30098846

RESUMO

OBJECTIVE: Ear, nose and throat infections are among the most common reasons for absence from work. They are usually caused by various bacteria like Haemophilus influenzae, Staphylococcus aureus, Streptococcus pneumoniae and Streptococcus pyogenes. Cold atmospheric plasma (CAP) can effectively eliminate even multi-resistant bacteria and has no cytotoxic or mutagenic effects on the mucosa when applied for less than 60s. Aim of the study was to evaluate the effects of CAP on common ENT bacteria and on the mucosa of the upper aerodigestive tract. METHODS: The bactericidal effects of CAP against the bacteria most commonly causing ENT infections were investigated using the colony-forming units assay (CFU) on a Müller-Hinton agar plate after applying CAP for 30, 60, 90 and 120s. To evaluate the interaction of CAP with mucosal cells, 3D mini organ cultures were treated for up to 180s, after which cell viability and necrosis induction were evaluated. RESULTS: Treatment with CAP for 60s or longer induced at least a 3-log10 reduction in the bacterial load (> 99.9%). Treatment times shorter than 60s had only slight cytotoxic effects on cell viability and necrosis whereas treatment times above 60s showed a fast increase of cytotoxic side effects. CONCLUSION: CAP exhibited strong bactericidal effects on the most common ENT pathogens. Treatment times of up to 60s showed only minimal adverse reactions in healthy mucosa. CAP could be a promising new therapeutic modality for ENT infections.

7.
Sci Rep ; 8(1): 10048, 2018 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-29968804

RESUMO

Cold atmospheric plasma (CAP) is a promising approach in anti-cancer therapy, eliminating cancer cells with high selectivity. However, the molecular mechanisms of CAP action are poorly understood. In this study, we investigated CAP effects on calcium homeostasis in melanoma cells. We observed increased cytoplasmic calcium after CAP treatment, which also occurred in the absence of extracellular calcium, indicating the majority of the calcium increase originates from intracellular stores. Application of previously CAP-exposed extracellular solutions also induced cytoplasmic calcium elevations. A substantial fraction of this effect remained when the application was delayed for one hour, indicating the chemical stability of the activating agent(s). Addition of ryanodine and cyclosporin A indicate the involvement of the endoplasmatic reticulum and the mitochondria. Inhibition of the cytoplasmic calcium elevation by the intracellular chelator BAPTA blocked CAP-induced senescence. This finding helps to understand the molecular influence and the mode of action of CAP on tumor cells.

8.
Biol Chem ; 400(1): 111-122, 2018 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-29908123

RESUMO

Plasma oncology is a relatively new field of research. Recent developments have indicated that cold atmospheric plasma (CAP) technology is an interesting new therapeutic approach to cancer treatment. In this study, p53 wildtype (LoVo) and human p53 mutated (HT29 and SW480) colorectal cancer cells were treated with the miniFlatPlaSter - a device particularly developed for the treatment of tumor cells - that uses the Surface Micro Discharge (SMD) technology for plasma production in air. The present study analyzed the effects of plasma on colorectal cancer cells in vitro and on normal colon tissue ex vivo. Plasma treatment had strong effects on colon cancer cells, such as inhibition of cell proliferation, induction of cell death and modulation of p21 expression. In contrast, CAP treatment of murine colon tissue ex vivo for up to 2 min did not show any toxic effect on normal colon cells compared to H2O2 positive control. In summary, these results suggest that the miniFlatPlaSter plasma device is able to kill colorectal cancer cells independent of their p53 mutation status. Thus, this device presents a promising new approach in colon cancer therapy.

9.
PLoS One ; 13(5): e0197773, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29795627

RESUMO

The application of cold atmospheric pressure plasma (CAP) for decontamination of sliced ready-to-eat (RTE) meat products (in this case, rolled fillets of ham), inoculated with Salmonella (S.) Typhimurium and Listeria (L.) monocytogenes was investigated. Cold atmospheric plasma (CAP) is an ionised gas that includes highly reactive species and ozone, interacting with cell membranes and DNA of bacteria. The mode of action of CAPs includes penetration and disruption of the outer cell membrane or intracellular destruction of DNA located in the cytoplasm. Inoculated ham was treated for 10 and 20 min with CAP generated by a surface-micro-discharge-plasma source using cost-effective ambient air as working gas with different humidity levels of 45-50 and 90%. The chosen plasma modes had a peak-to-peak voltage of 6.4 or 10 kV and a frequency of 2 and 10 kHz. Under the tested conditions, the direct effectiveness of CAP on microbial inactivation was limited. Although all treated samples showed significant reductions in the microbial load subsequent to plasma treatment, the maximum inactivation of S. Typhimurium was 1.14 lg steps after 20 min of CAP-treatment (p<0.05), and L. monocytogenes was reduced by 1.02 lg steps (p<0.05) using high peak-to-peak voltage of 10 kV and a frequency of 2 kHz regardless of moisture content. However, effective inactivation was achieved by a combination of CAP-treatment and cold storage at 8°C ± 0.5°C for 7 and 14 days after packaging under sealed high nitrogen gas flush (70% N2, 30% CO2). Synergistic effects of CAP and cold storage for 14 days led to a clearer decrease in the microbial load of 1.84 lg steps for S. Typhimurium (p<0.05) and 2.55 lg steps for L. monocytogenes (p<0.05). In the case of L. monocytogenes, subsequent to CAP-treatment (10 kV, 2 kHz) and cold storage, microbial counts were predominantly below the detection limit. Measurement showed that after CAP-treatment, surface temperature of ham did not exceed the room temperature of 22°C ± 2°C. With the application of humidity levels of 45-50%, the colour distance ΔE increased in CAP treated samples due to a decrease in L* values. In conclusion, effectiveness of CAP-treatment was limited. However, the combination of CAP-treatment and cold storage of samples under modified-atmospheric-conditions up to 14 days could significantly reduce microorganisms on RTE ham. Further investigations are required to improve effectiveness of CAP-treatment.


Assuntos
Listeria monocytogenes/efeitos dos fármacos , Produtos da Carne/microbiologia , Gases em Plasma/farmacologia , Salmonella typhimurium/efeitos dos fármacos , Pressão Atmosférica , Temperatura Baixa , Conservação de Alimentos/métodos , Umidade , Viabilidade Microbiana/efeitos dos fármacos , Nitrogênio/química , Espécies Reativas de Oxigênio/química , Espécies Reativas de Oxigênio/farmacologia , Propriedades de Superfície
10.
J Mech Behav Biomed Mater ; 77: 578-585, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29096123

RESUMO

Biomechanical in vitro tests analysing screw loosening often include high standard deviations caused by high variabilities in bone mineral density and pedicle geometry, whereas standardized mechanical models made of PU foam often do not integrate anatomical or physiological boundary conditions. The purpose of this study was to develop a most realistic mechanical model for the standardized and reproducible testing of pedicle screws regarding the resistance against screw loosening and the holding force as well as to validate this model by in vitro experiments. The novel mechanical testing model represents all anatomical structures of a human vertebra and is consisting of PU foam to simulate cancellous bone, as well as a novel pedicle model made of short carbon fibre filled epoxy. Six monoaxial cannulated pedicle screws (Ø6.5 × 45mm) were tested using the mechanical testing model as well as human vertebra specimens by applying complex physiological cyclic loading (shear, tension, and bending; 5Hz testing frequency; sinusoidal pulsating forces) in a dynamic materials testing machine with stepwise increasing load after each 50.000 cycles (100.0N shear force + 20.0N per step, 51.0N tension force + 10.2N per step, 4.2Nm bending moment + 0.8Nm per step) until screw loosening was detected. The pedicle screw head was fixed on a firmly clamped rod while the load was applied in the vertebral body. For the in vitro experiments, six human lumbar vertebrae (L1-3, BMD 75.4 ± 4.0mg/cc HA, pedicle width 9.8 ± 0.6mm) were tested after implanting pedicle screws under X-ray control. Relative motions of pedicle screw, specimen fixture, and rod fixture were detected using an optical motion tracking system. Translational motions of the mechanical testing model experiments in the point of load introduction (0.9-2.2mm at 240N shear force) were reproducible within the variation range of the in vitro experiments (0.6-3.5mm at 240N shear force). Screw loosening occurred continuously in each case between 140N and 280N, while abrupt failures of the specimen were observed only in vitro. In the mechanical testing model, no translational motion was detected in the screw entry point, while in vitro, translational motions of up to 2.5mm in inferior direction were found, leading to a slight shift of the centre of rotation towards the screw tip. Translational motions of the screw tip of about 5mm in superior direction were observed both in vitro and in the mechanical testing model, while they were continuous in the mechanical testing model and rapidly increasing after screw loosening initiation in vitro. The overall pedicle screw loosening characteristics were qualitatively and quantitatively similar between the mechanical testing model and the human vertebral specimens as long as there was no translation of the screw at the screw entrance point. Therefore, the novel mechanical testing model represents a promising method for the standardized testing of pedicle screws regarding screw loosening for cases where the screw rotates around a point close to the screw entry point.


Assuntos
Carbono/química , Vértebras Lombares/fisiologia , Parafusos Pediculares , Idoso , Fenômenos Biomecânicos , Densidade Óssea , Cadáver , Simulação por Computador , Desenho de Equipamento , Feminino , Humanos , Técnicas In Vitro , Modelos Lineares , Masculino , Teste de Materiais , Pessoa de Meia-Idade , Movimento (Física) , Reprodutibilidade dos Testes , Rotação , Fusão Vertebral , Estresse Mecânico , Resistência à Tração , Tomografia Computadorizada por Raios X
11.
Psychol Sci ; 29(1): 3-13, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29155616

RESUMO

The notion of person-environment fit implies that personal and contextual factors interact in influencing important life outcomes. Using data from 8,458 employed individuals, we examined the combined effects of individuals' actual personality traits and jobs' expert-rated personality demands on earnings. Results from a response surface analysis indicated that the fit between individuals' actual personality and the personality demands of their jobs is a predictor of income. Conclusions of this combined analysis were partly opposite to conclusions reached in previous studies using conventional regression methods. Individuals can earn additional income of more than their monthly salary per year if they hold a job that fits their personality. Thus, at least for some traits, economic success depends not only on having a "successful personality" but also, in part, on finding the best niche for one's personality. We discuss the findings with regard to labor-market policies and individuals' job-selection strategies.

12.
Obes Surg ; 28(5): 1232-1239, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29101717

RESUMO

OBJECTIVE: Ileal transposition (IT) procedure leads to higher secretion of incretin hormones what is associated with a beneficial metabolic effect. However, IT will also have an influence on the related jejunum and ileum function. The aim of this research was to investigate the morphology of the jejunum and transposed ileum with the use of light and transmission electron microscopy (TEM) in order to determine the local alternations in the intestine resulting from the transposition. METHODS: Twenty male, 8-week-old, obese Zucker rats underwent IT and six of them sham surgery. To compare both groups, the transection was made at all corresponding ileum positions among both groups of animals. The ileal anastomoses among the rats of sham procedure were subsequently formed accordingly without IT. Three months following the surgery, the tissue samples of jejunum and ileum were harvested. RESULTS: A significant increase in villus length, a decrease in the crypt depth, and an increased thickness of mucosa-muscularis-serosa (MMS) as well as cellular hyperplasia, with increased mitochondrial density of the transposed ileum segment, were observed among the group of rats which underwent IT comparing to the ones undergoing sham surgery. In rats undergoing IT, microvillus degeneration in jejunum regions was observed. CONCLUSIONS: Ileal transposition alters the morphology and ultrastructure of the ileum as well as the jejunum. Given that the microvillus membrane represents an important aspect of the enterocyte functions, a further biochemical and molecular research is necessary in order to assess whether the observed changes are beneficial or not and to explore the phenomenon of gut adaptability after metabolic surgery.

13.
Psychother Psychosom Med Psychol ; 67(11): 477-484, 2017 Nov.
Artigo em Alemão | MEDLINE | ID: mdl-29121683

RESUMO

Introduction The ICD-10 symptom rating (ISR) is a self-rating instrument that is based on ICD-10 syndromes. Can previous findings concerning its validity be replicated in a non-clinical sample? Material & Methods N=428 study participants - mainly students - completed the ISR and the SCL-90-R in an online survey. Results The assumed factorial structure was replicated with a good model fit. The correlations between the content-related scales of the two instruments ranged from rmin=0.60 to rmax=0.85. Study participants indicated that they did not find completing the ISR stressful. Discussion and Conclusions These results indicate good validity and applicability of the ISR.


Assuntos
Classificação Internacional de Doenças/estatística & dados numéricos , Adolescente , Adulto , Idoso , Análise Fatorial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Psicometria/estatística & dados numéricos , Reprodutibilidade dos Testes , Inquéritos e Questionários , Adulto Jovem
14.
Int J Psychol ; 52(6): 425-435, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26729421

RESUMO

Although international student mobility has become a ubiquitous phenomenon in many parts of the world, the goals that student sojourners pursue when moving abroad have received little systematic attention in psychological research. Likewise, their effects on psychological outcomes such as sojourners' psychological and sociocultural adaptation abroad have not yet been examined. Hence, the purpose of the present research was twofold: First, we established the parsimonious Sojourn Goals Scale and confirmed its psychometric quality and construct validity. Second, we used a longitudinal sample of student sojourners to investigate the role of sojourn goals for sojourners' sociocultural (i.e., sojourners' social relationships) and psychological (i.e., sojourn satisfaction) adaptation abroad at 3 months into the sojourn. Regression analyses revealed substantial effects of sojourn goals on measures of sociocultural adaptation. Response surface analyses served to examine the interplay of sojourn goals and respective sojourn experiences on sojourn satisfaction. We discuss implications for both psychological and applied research and identify future research needs.


Assuntos
Adaptação Psicológica/fisiologia , Estudantes/psicologia , Feminino , Metas , Humanos , Estudos Longitudinais , Masculino , Adulto Jovem
15.
J Adolesc ; 54: 104-109, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27930938

RESUMO

The U-MICS is a self-report questionnaire designed to assess the identity dimensions from a domain-specific perspective. The present study reports on the development of a short-form version for the domains of job and romantic relationship in young adults from Germany and extends this scale to include the domain of region (nSample1 = 95, 84% female, mean age 22.45 years; nSample2 = 1,795, 71% female, mean age 24.53 years). We found the short form to possess adequate psychometric properties and to demonstrate a factor structure congruent to the long-form version. Regarding validity, the small correlations across domains within dimensions support a domain-specific approach to identity. The associations between the different identity domains with personality traits are similar, indicating a consistent pattern of convergent validity for all domains. We conclude that "region" provides a valuable complement to the established domains that can all be reliably assessed with the U-MICS-Short Form.


Assuntos
Inventário de Personalidade , Autoimagem , Adulto , Feminino , Alemanha , Humanos , Masculino , Psicometria , Reprodutibilidade dos Testes , Inquéritos e Questionários , Adulto Jovem
16.
Crit Rev Oncog ; 21(3-4): 253-267, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27915975

RESUMO

The induction of apoptosis, a physiological type of cell death, is currently the primary therapeutic aim of most cancer therapies. As resistance to apoptosis is an early hallmark of developing cancer, the success of this treatment strategy is already potentially compromised at treatment initiation. In this review, we discuss the tumor in Darwinian terms and describe it as a complex, yet highly unstable, ecosystem. Current therapeutic strategies often focus on directly killing the dominant subclone within the population of mutated cancer cells while ignoring the subclonal complexity within the ecosystem tumor, the complexity of the direct tumor/ microenvironment interaction and the contribution of the ecosystem human - that is, the global environment which provides the tumor with both support and challenges. The Darwinian view opens new possible therapeutic interventions, such as the disruption of the microenvironment by targeting nonmutated cells within the tumor or the interaction points of mutant tumor cells with their environment, and it forces us to reevaluate therapeutic endpoints. It is our belief that a central future challenge of apoptosis-inducing therapies will be to understand better under which preconditions which treatment strategy and which therapeutic endpoint will lead to the highest quality and quantity of a patient's life.


Assuntos
Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Neoplasias/tratamento farmacológico , Microambiente Tumoral , Animais , Antineoplásicos/farmacologia , Humanos , Acúmulo de Mutações , Neoplasias/genética , Neoplasias/fisiopatologia
17.
Nucleic Acid Ther ; 26(6): 355-362, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27736370

RESUMO

Activated protein C (APC) is a critical regulator of thrombin formation and thereby protects against thrombosis. On the other hand, overwhelming formation of APC increases the risk of bleeding such as in trauma-induced coagulopathy. Thus, pharmacological inhibition of APC activity may improve blood clottability in certain clinical situations. In this study, we demonstrate that the DNA aptamer HS02-52G binds with fast onset (1.118 ± 0.013 × 105 M-1 s-1) to APC and possesses a long residence time of 13.5 min within the aptamer-APC complex. Functional analysis revealed HS02-52G as a highly potent and specific inhibitor of APC in plasma and whole blood with IC50 values ≤30 nM, whose activity can be readily neutralized by the short complementary DNA molecule AD22. These features qualify the novel aptamer-antidote pair as a candidate treatment option for acute APC-related bleedings.


Assuntos
Anticoagulantes/química , Aptâmeros de Nucleotídeos/química , Oligonucleotídeos Antissenso/química , Proteína C/antagonistas & inibidores , Trombina/química , Anticoagulantes/síntese química , Aptâmeros de Nucleotídeos/síntese química , Pareamento de Bases , Humanos , Cinética , Conformação de Ácido Nucleico , Oligonucleotídeos Antissenso/síntese química , Tempo de Tromboplastina Parcial , Ligação Proteica , Proteína C/química , Proteínas Recombinantes/química , Termodinâmica , Trombina/agonistas , Trombina/antagonistas & inibidores , Tempo de Coagulação do Sangue Total
18.
Int J Syst Evol Microbiol ; 66(12): 5288-5293, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27666312

RESUMO

A Gram-stain-positive, rod-shaped bacterium (strain JZ16T) was isolated from raw cow's milk from the bulk tank of a dairy farm in Germany. The 16S rRNA gene sequence of the isolate showed a similarity of 98.3 % to the nearest related type strain Corynebacterium glutamicum ATCC 13032T, a similarity of 97.6 % to Corynebacterium deserti GIMN1.010T and a similarity of 97.4 % to Corynebacterium callunae DSM 20147T. Determination of chemotaxonomic characteristics revealed oleic acid (18 : 1 cis 9) as the predominant fatty acid, major amounts of hexadecanoic acid (16 : 0) and minor amounts of heptadecanoic acid (17 : 0). The isolate showed an acetyl type of peptidoglycan and corynemycolic acids. The menaquinones MK-8(H2) and MK-9(H2) and the phospholipids diphosphatidylglycerol, phosphatidylglycerol, phosphatidylinositol and phosphatidylinositol mannoside were detected, which was in agreement with the description of the genus Corynebacterium. Strain JZ16T was positive for reduction of nitrate to nitrite, pyrazinamidase, ß-glucuronidase, ß-glucosidase and urease activities. Acid was produced from d-glucose, d-ribose and d-mannitol, but not from d-xylose, maltose, lactose, sucrose and glycogen. The results of phylogenetic, phenotypic and chemotaxonomic analyses enabled the differentiation of the isolated strain from other closely related species of the genus Corynebacterium. Therefore, strain JZ16T represents a novel species of the genus Corynebacterium, for which the name Corynebacterium crudilactis sp. nov. is proposed. The type strain is JZ16T (=DSM 100882T=CCUG 69192T=LMG 29813T).


Assuntos
Corynebacterium/classificação , Leite/microbiologia , Animais , Técnicas de Tipagem Bacteriana , Composição de Bases , Bovinos , Corynebacterium/genética , Corynebacterium/isolamento & purificação , DNA Bacteriano/genética , Ácidos Graxos/química , Genes Bacterianos , Alemanha , Hibridização de Ácido Nucleico , Peptidoglicano/química , Fosfolipídeos/química , Filogenia , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Vitamina K 2/química
19.
J Surg Res ; 203(2): 424-33, 2016 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-27363652

RESUMO

OBJECTIVES: Severe bleeding related to cardiac surgery is associated with increased morbidity and mortality. Thromboelastography (TEG) and thromboelastometry (ROTEM) are point-of-care tests (POCT). Bedside ROTEM/TEG can rapidly detect changes in blood coagulation and therefore provide a goal-directed, individualized coagulation therapy. In this meta-analysis, we aimed to determine the current evidence for or against POCT-guided algorithm in patients with severe bleeding after cardiac surgery. METHODS: We performed a meta-analysis of randomized controlled trials and observational trials retrieved from a literature search in PubMed, EMBASE, and Cochrane Library. Only trials comparing transfusion strategy guided by TEG/ROTEM with a standard of care control group undergoing cardiac surgery were included. In addition, at least one clinical outcome had to be mentioned: mortality, surgical re-exploration rate, sternal wound infection, and acute kidney injury (AKI). Also, surrogate parameters such as transfusion requirements and amount of blood loss were analyzed. The pooled treatment effects (odds ratio [OR] and 95% confidence intervals [CI]) were assessed using a fixed or random-effects model. RESULTS: The literature search retrieved a total of 17 trials (nine randomized controlled trial and eight observational trials) involving 8332 cardiac surgery patients. POCT-guided transfusion management significantly decreased the odds for patients to receive allogeneic blood products (OR 0.63, 95% CI 0.56-0.71; P < 0.00001) and the re-exploration rate due to postoperative bleeding (OR 0.56, 95% CI 0.45-0.71; P < 0.00001). Furthermore, the incidence of postoperative AKI (OR 0.77, 95% CI 0.61-0.98; P = 0.0278) and thromboembolic events (OR 0.44, 95% CI 0.28-0.70; P = 0.0006) was significantly decreased in the TEG/ROTEM group. No statistical differences were found with regard to inhospital mortality, cerebrovascular accident, or length of intensive care unit and hospital stay. CONCLUSIONS: TEG/ROTEM-based coagulation management decreases the risk of allogeneic blood product exposure after cardiac surgery. Furthermore, it results in significantly lower re-exploration rate, decreased incidence of postoperative AKI, and thromboembolic events in cardiac surgery patients. Results of this meta-analysis indicate that POCT-guided transfusion therapy is superior to the current standard of care.


Assuntos
Transfusão de Sangue/métodos , Procedimentos Cirúrgicos Cardíacos , Sistemas Automatizados de Assistência Junto ao Leito , Hemorragia Pós-Operatória/terapia , Tromboelastografia/métodos , Algoritmos , Tomada de Decisão Clínica/métodos , Técnicas de Apoio para a Decisão , Humanos , Modelos Estatísticos , Hemorragia Pós-Operatória/complicações , Hemorragia Pós-Operatória/diagnóstico , Resultado do Tratamento
20.
PLoS One ; 10(11): e0141827, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26588072

RESUMO

Head and neck squamous cell cancer (HNSCC) is the 7th most common cancer worldwide. Despite the development of new therapeutic agents such as monoclonal antibodies, prognosis did not change for the last decades. Cold atmospheric plasma (CAP) presents the most promising new technology in cancer treatment. In this study the efficacy of a surface micro discharging (SMD) plasma device against two head and neck cancer cell lines was proved. Effects on the cell viability, DNA fragmentation and apoptosis induction were evaluated with the MTT assay, alkaline microgel electrophoresis (comet assay) and Annexin-V/PI staining. MTT assay revealed that the CAP treatment markedly decreases the cell viability for all tested treatment times (30, 60, 90, 120 and 180 s). IC 50 was reached within maximal 120 seconds of CAP treatment. Comet assay analysis showed a dose dependent high DNA fragmentation being one of the key players in anti-cancer activity of CAP. Annexin-V/PI staining revealed induction of apoptosis in CAP treated HNSCC cell lines but no significant dose dependency was seen. Thus, we confirmed that SMD Plasma technology is definitely a promising new approach on cancer treatment.


Assuntos
Carcinoma de Células Escamosas/terapia , Neoplasias de Cabeça e Pescoço/terapia , Gases em Plasma/uso terapêutico , Apoptose/efeitos da radiação , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos da radiação , Fragmentação do DNA/efeitos da radiação , Neoplasias de Cabeça e Pescoço/patologia , Humanos
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