RESUMEN
Against the background of the growing economization of clinical medicine, in the last decades the topics of risk and complication management have also become more important in surgical disciplines. The standardization and reproducible documentation of outcome and complication data play a key role for valid quality control. In this article a digital system implemented at the surgical clinic of the Charité University Medicine in Berlin is analyzed with respect to its practicability for perioperative and postoperative monitoring of complications within the framework of quality assurance.
Asunto(s)
Procedimientos Quirúrgicos del Sistema Digestivo , Complicaciones Posoperatorias , Berlin , Procedimientos Quirúrgicos del Sistema Digestivo/efectos adversos , Documentación , Humanos , Complicaciones Posoperatorias/etiologíaRESUMEN
BACKGROUND: Immunosuppression is essential after liver transplantation (LT). It, however, increases the risk for cancer. OBJECTIVE: To evaluate the prevalence and outcome of upper gastrointestinal (GI) tract cancer in LT patients and assess the perioperative risk of surgery for the upper GI malignancies post-LT. METHODS: 2855 patients underwent LT at our clinic from 1988 to 2018. 20 patients developed upper GI cancer. Data were retrospectively extracted from our database. Analysis included patients' specific data, tumor histopathology and stage, the treatment given and survival. RESULTS: 23 patients developed upper GI malignancies (2 gastric and 18 esophageal cancers; 3 excluded), translating to a incidence of 26.4 per 100,000 population per year. All patients were male. 80% showed alcohol-induced cirrhosis before LT. Most of the tumors were diagnosed at a stage ≥III. 70% underwent surgery and 78.6% developed postoperative complications. One-year-survival was 50%. Total survival rate was 28.6% with a median follow-up of 10 months (range: 0-184). CONCLUSION: Upper GI malignancies are more common after LT compared to the general population. Men after LT, due to alcohol-induced liver cirrhosis, are at a higher risk. Upper GI surgery after LT can be safe, but the severe risk for complications and a poor survival require strict indications.
RESUMEN
Aim: 20 years after establishment of the National Breastfeeding Committee, the present work, based on published data on breastfeeding, is aimed at providing insight into the development of breastfeeding behaviour in Germany. Methods: To identify relevant publications, a comprehensive literature search was conducted in PubMed and Web of Science using the search terms "breast feeding" or "breastfeeding" in combination with "Germany". The publication period was limited to the period 1995-2014. Results: A total of 35 studies with data on breastfeeding for the birth cohorts of 1990-2012 were identified. Most of the data had been collected in regional or local surveys, often retrospectively. About 60% of the studies had been conducted with the primary aim of collecting data on breastfeeding or infant nutrition. Over the past 2 decades, breastfeeding rates were always relatively high at the beginning (72-97%). However, they declined significantly within the first 2 months, and by the age of 6 months, only about 50% of infants were still breastfed. Conclusion: Breastfeeding support and early assistance should be offered to a greater extent in order to achieve sustainable improvement of breastfeeding frequency and duration in Germany. Regarding the quality of data collected on breastfeeding, it seems crucial to implement standardised approaches to monitor breastfeeding in Germany.
Asunto(s)
Lactancia Materna/estadística & datos numéricos , Lactancia Materna/tendencias , Conducta Materna , Adolescente , Adulto , Distribución por Edad , Femenino , Alemania/epidemiología , Humanos , Recién Nacido , Persona de Mediana Edad , Adulto JovenRESUMEN
The identification and development of novel nontoxic phytochemicals that target androgen and androgen receptor (AR) signaling remains a priority for prostate cancer (PCA) control. In the present study, we assessed the antiandrogenic efficacy of isosilybin B employing human PCA LNCaP (mutated AR), 22Rv1 (mutated AR) and LAPC4 (wild-type AR) cells. Isosilybin B (10-90 microM) treatment decreased the AR and prostate specific antigen (PSA) levels in LNCaP, 22Rv1 and LAPC4 cells, but not in non-neoplastic human prostate epithelial PWR-1E cells. Isosilybin B treatment also inhibited synthetic androgen R1881-induced nuclear localization of AR, PSA expression and cell growth, and caused G(1) arrest. In mechanistic studies identifying AR degradation, isosilybin B caused increased phosphorylation of Akt (Ser-473 and Thr-308) and Mdm2 (Ser-166), which was linked with AR degradation as pretreatment with PI3K inhibitor (LY294002)-restored AR level. Further, overexpression of kinase-dead Akt largely reversed isosilybin B mediated-AR degradation suggesting a critical role of Akt in AR degradation. Antibody pull-down results also indicated that isosilybin B treatment enhances the formation of complex between Akt, Mdm2 and AR, which promotes phosphorylation-dependent AR ubiquitination and its degradation by proteasome. Together, present findings identify a novel mechanism for isosilybin B-mediated anticancer effects in human PCA cells.
Asunto(s)
Fosfatidilinositol 3-Quinasas/metabolismo , Neoplasias de la Próstata/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Proto-Oncogénicas c-mdm2/metabolismo , Receptores Androgénicos/metabolismo , Silimarina/análogos & derivados , Línea Celular Tumoral , Núcleo Celular/metabolismo , Citoplasma/metabolismo , Humanos , Masculino , Modelos Biológicos , Fosforilación , Antígeno Prostático Específico/metabolismo , Complejo de la Endopetidasa Proteasomal/metabolismo , Silimarina/fisiologíaRESUMEN
The dynamic structure factor, vorticity and entropy density dynamic correlation functions are measured for stochastic rotation dynamics (SRD), a particle based algorithm for fluctuating fluids. This allows us to obtain unbiased values for the longitudinal transport coefficients such as thermal diffusivity and bulk viscosity. The results are in good agreement with earlier numerical and theoretical results, and it is shown for the first time that the bulk viscosity is indeed zero for this algorithm. In addition, corrections to the self-diffusion coefficient and shear viscosity arising from the breakdown of the molecular chaos approximation at small mean free paths are analyzed. In addition to deriving the form of the leading correlation corrections to these transport coefficients, the probabilities that two and three particles remain collision partners for consecutive time steps are derived analytically in the limit of small mean free path. The results of this paper verify that we have an excellent understanding of the SRD algorithm at the kinetic level and that analytic expressions for the transport coefficients derived elsewhere do indeed provide a very accurate description of the SRD fluid.
RESUMEN
Here, we assessed and compared the anticancer efficacy and associated mechanisms of silymarin and silibinin in human prostate cancer (PCA) PC3 cells; silymarin is comprised of silibinin and its other stereoisomers, including isosilybin A, isosilybin B, silydianin, silychristin and isosilychristin. Silymarin and silibinin (50-100 microg/ml) inhibited cell proliferation, induced cell death, and caused G1 and G2-M cell cycle arrest in a dose/time-dependent manner. Molecular studies showed that G1 arrest was associated with a decrease in cyclin D1, cyclin D3, cyclin E, cyclin-dependent kinase (CDK)4, CDK6 and CDK2 protein levels, and CDK2 and CDK4 kinase activity, together with an increase in CDK inhibitors (CDKIs) Kip1/p27 and Cip1/p21. Further, both agents caused cytoplasmic sequestration of cyclin D1 and CDK2, contributing to G1 arrest. The G2-M arrest by silibinin and silymarin was associated with decreased levels of cyclin B1, cyclin A, pCdc2 (Tyr15), Cdc2, and an inhibition of Cdc2 kinase activity. Both agents also decreased the levels of Cdc25B and cell division cycle 25C (Cdc25C) phosphatases with an increased phosphorylation of Cdc25C at Ser216 and its translocation from nucleus to the cytoplasm, which was accompanied by an increased binding with 14-3-3beta. Both agents also increased checkpoint kinase (Chk)2 phosphorylation at Thr68 and Ser19 sites, which is known to phosphorylate Cdc25C at Ser216 site. Chk2-specific small interfering RNA largely attenuated the silymarin and silibinin-induced G2-M arrest. An increase in the phosphorylation of histone 2AX and ataxia telangiectasia mutated was also observed. These findings indicate that silymarin and silibinin modulate G1 phase cyclins-CDKs-CDKIs for G1 arrest, and the Chk2-Cdc25C-Cdc2/cyclin B1 pathway for G2-M arrest, together with an altered subcellular localization of critical cell cycle regulators. Overall, we observed comparable effects for both silymarin and silibinin at equal concentrations by weight, suggesting that silibinin could be a major cell cycle-inhibitory component in silymarin. However, other silibinin stereoisomers present in silymarin also contribute to its efficacy, and could be of interest for future investigation.
Asunto(s)
Carcinoma/tratamiento farmacológico , Proteínas de Ciclo Celular/metabolismo , Quinasas Ciclina-Dependientes/metabolismo , Flavonas/uso terapéutico , Neoplasias de la Próstata/tratamiento farmacológico , Silimarina/uso terapéutico , Ciclo Celular/efectos de los fármacos , Proteínas de Ciclo Celular/análisis , Núcleo Celular/química , Proliferación Celular/efectos de los fármacos , Quinasas Ciclina-Dependientes/análisis , Citoplasma/química , Humanos , Masculino , Fosforilación , Silibina , Células Tumorales CultivadasRESUMEN
A recently introduced particle-based model for fluid flow, called stochastic rotation dynamics, can be made Galilean invariant by introducing a random shift of the computational grid before collisions. In this paper, it is shown how the Green-Kubo relations derived previously can be resummed to obtain exact expressions for the collisional contributions to the transport coefficients. It is also shown that the collisional contribution to the microscopic stress tensor is not symmetric, and that this leads to an additional viscosity. The resulting identification of the transport coefficients for the hydrodynamic modes is discussed in detail, and it is shown that this does not impose restrictions on the applicability of the model. The collisional contribution to the thermal conductivity, which becomes important for small mean free path and small average particle number per cell, is also derived.
RESUMEN
A recently introduced stochastic model for fluid flow can be made Galilean invariant by introducing a random shift of the computational grid before collisions. This grid shifting procedure accelerates momentum transfer between cells and leads to a collisional contribution to transport coefficients. By resumming the Green-Kubo relations derived in a previous paper, it is shown that this collisional contribution to the transport coefficients can be determined exactly. The resummed Green-Kubo relations also show that there are no mixed kinetic-collisional contributions to the transport coefficients. The leading correlation corrections to the transport coefficients are discussed, and explicit expressions for the transport coefficients are presented and compared with simulation data.
RESUMEN
Explicit expressions for the transport coefficients of a recently introduced stochastic model for simulating fluctuating fluid dynamics are derived in three dimensions by means of Green-Kubo relations and simple kinetic arguments. The results are shown to be in excellent agreement with simulation data. Two collision rules are considered and their computational efficiency is compared.
RESUMEN
A detailed analytical and numerical analysis of a recently introduced stochastic model for fluid dynamics with continuous velocities and efficient multi-particle collisions is presented. It is shown how full Galilean invariance can be achieved for arbitrary Mach numbers and how other low temperature anomalies can be removed. The relaxation towards thermal equilibrium is investigated numerically, and the relaxation time is measured. Equations of motions for the correlation functions of coarse-grained hydrodynamic variables are derived using a discrete-time projection operator technique, and the Green-Kubo relations for all relevant transport coefficients are given. In the following paper (Part 2), analytic expressions for the transport coefficients are derived and compared with simulation results. Long-time tails in the velocity and stress autocorrelation functions are measured and shown to be in good agreement with previous mode-coupling theories for continuous systems.
RESUMEN
A discrete-time projection operation technique was used to derive the Green-Kubo relations for the transport coefficients of a recently introduced stochastic model for fluid dynamics in a previous paper (Part 1). The most important feature of the analysis was the incorporation of a new grid shifting procedure which was shown to guarantee Galilean invariance for arbitrary Mach number and temperature. This paper (Part 2) contains a detailed analysis of the transport coefficients of this model. An exact calculation of the first terms in the stress correlation function in the limit of infinite particle density is presented, which explicitly accounts for the cell structure introduced to define the collision environment. It is also shown that this cell structure can lead to additional contributions to the transport coefficients even at large mean free paths. Explicit expressions for all transport coefficients are derived and compared with simulation results. Long-time tails in the velocity, stress, and heat-flux autocorrelation functions are measured and shown to be in excellent agreement with the predictions of mode-coupling theory.
RESUMEN
Crystalline domains embedded in fluid membrane vesicles are studied by Monte Carlo simulations of dynamically triangulated surfaces and by scaling arguments. A budding transition from a caplike state to a budded shape is observed for increasing spontaneous curvature C0 of the crystalline domain as well as increasing line tension lambda. The location of the budding transition is determined as a function of C0, lambda, and the radius R(A) of the crystalline domain. In contrast to previous theoretical predictions, it is found that budding occurs at a value of the spontaneous curvature C0, that is always a decreasing function of the domain size R(A). Several characteristic scaling regimes are predicted. The distribution of five- and sevenfold disclinations as the budding transition is approached is determined, and the dynamics of the generation of defects is studied.
Asunto(s)
Clatrina/química , Animales , Fenómenos Biofísicos , Biofisica , Pollos , Fibroblastos/metabolismo , Concentración de Iones de Hidrógeno , Modelos Moleculares , Modelos Estadísticos , Método de Montecarlo , Temperatura , Termodinámica , Factores de TiempoRESUMEN
The effective longitudinal dispersion constant, D(L)(eff), in cylindrical packed beds is larger than in the bulk due to the existence of radial inhomogeneities induced by the cylinder walls. For dense random packed beds, D(L)(eff) can be several times larger than the bulk value, even for arbitrarily large cylinder radius, R. The time-scale for attaining asymptotic dispersion rates in a cylindrical geometry is neither the convective nor the diffusive time-scale, but rather D(T)/R(2), where D(T) is the bulk transverse dispersion rate. Similar effects are predicted for packed beds confined in ducts of any cross-sectional geometry. The case of a rectangular duct, compared with an infinite slit, provides an intuitive model for the influence of walls in the limit as R goes to infinity.
Asunto(s)
Coloides/química , Difusión , Gases/química , Modelos Químicos , Reología/métodos , Simulación por Computador , Cinética , Movimiento (Física) , Tamaño de la Partícula , PorosidadAsunto(s)
Antibacterianos/efectos adversos , Sistema Enzimático del Citocromo P-450/efectos de los fármacos , Hypericum/química , Oxigenasas de Función Mixta/efectos de los fármacos , Terpenos/efectos adversos , Compuestos Bicíclicos con Puentes , Citocromo P-450 CYP3A , Depresión/tratamiento farmacológico , Humanos , Neoplasias/complicaciones , Neoplasias/tratamiento farmacológico , Floroglucinol/análogos & derivados , Fitoterapia , Extractos Vegetales/uso terapéuticoRESUMEN
St. John's wort (Hypericum perforatum) is the most widely used herbal medicine for the treatment of depression. However, concerns have arisen about the potential of its interaction with other drugs due to the induction of cytochrome P450 isozymes 1A2 and 3A4 by the components hypericin and hyperforin, respectively. Structurally similar natural products are often employed as antitumor agents due to their action as inhibitors of DNA topoisomerases, nuclear enzymes that modify DNA during cellular proliferation. Preliminary findings that hypericin inhibited the DNA relaxation activity of topoisomerase IIalpha (topo II; EC 5.99.1.3) led us to investigate the mechanism of enzyme inhibition. Rather than stabilizing the enzyme in covalent complexes with DNA (cleavage complexes), hypericin inhibited the enzyme prior to DNA cleavage. In vitro assays indicate that hypericin is a potent antagonist of cleavage complex stabilization by the chemotherapeutics etoposide and amsacrine. This antagonism appears to be due to the ability of hypericin to intercalate or distort DNA structure, thereby precluding topo II binding and/or DNA cleavage. Supporting its non-DNA damaging, catalytic inhibition of topo II, hypericin was shown to be equitoxic to both wild-type and amsacrine-resistant HL-60 leukemia cell lines. Moreover, hypericin was incapable of stimulating DNA damage-responsive gene promoters that are activated by etoposide. As with the in vitro topo II assay, antagonism of DNA damage stimulated by 30 microM etoposide was evident in leukemia cells pretreated with 5 microM hypericin. Since many cancer patients experience clinical depression and concomitantly self-medicate with herbal remedies, extracts of St. John's wort should be investigated further for their potential to antagonize topo II-directed chemotherapy regimens.
Asunto(s)
ADN-Topoisomerasas de Tipo II , Inhibidores Enzimáticos/farmacología , Hypericum/química , Isoenzimas/antagonistas & inhibidores , Perileno/análogos & derivados , Perileno/farmacología , Plantas Medicinales , Inhibidores de Topoisomerasa II , Antracenos , Antígenos de Neoplasias , Catálisis , Daño del ADN , Fragmentación del ADN/efectos de los fármacos , ADN-Topoisomerasas de Tipo II/metabolismo , Proteínas de Unión al ADN , Antagonismo de Drogas , Células HL-60 , Humanos , Isoenzimas/metabolismo , FitoterapiaRESUMEN
Chronic exposure to benzene is associated with hematotoxicity and acute myelogenous leukemia. Inhibition of topoisomerase IIalpha (topo II) has been implicated in the development of benzene-induced cytogenetic aberrations. The purpose of this study was to determine the mechanism of topo II inhibition by benzene metabolites. In a DNA cleavage/relaxation assay, topo II was inhibited by p-benzoquinone and hydroquinone at 10 microM and 10 mM, respectively. On peroxidase activation, inhibition was seen with 4,4'-biphenol, hydroquinone, and catechol at 10 microM, 10 microM, and 30 microM, respectively. But, in no case was cleavable complex stabilization observed and the metabolites appeared to act at an earlier step of the enzyme cycle. In support of this conclusion, several metabolites antagonized etoposide-stabilized cleavable complex formation and inhibited topo II-DNA binding. It is therefore unlikely that benzene-induced acute myelogenous leukemia stems from events invoked for leukemogenic topo II cleavable complex-stabilizing antitumor agents. (Blood. 2001;98:830-833)