Search results for " Phase I"
showing 10 items of 89 documents
Cellular and humoral immune responses against autoreactive T cells in multiple sclerosis patients after T cell vaccination.
1999
Myelin basic protein (MBP)-reactive T cells may play an important role in the autoimmune pathogenesis of multiple sclerosis (MS). MBP-reactive T cells can be specifically targeted by T cell vaccination, a procedure whereby MS patients are immunized with attenuated autologous MBP reactive T cells. T cell vaccination induces immune responses to the vaccine cells together with a depletion of MBP reactive T cells. Forty-nine MS patients were treated with T cell vaccination in an extended phase I trial to study the safety, immune responses and clinical effects of T cell vaccination. In the present paper the immune responses towards the vaccine cells were characterized. Substantial long-term in v…
Advances in haploidentical stem cell transplantation for hematologic malignancies
2016
One of the most important advances in allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the use of alternative donors and cell sources, such as haploidentical transplants (haplo-HSCT) from family donors. Several approaches have been developed to overcome the challenging bidirectional alloreactivity. We discuss these approaches, including ex vivo T-cell-depleted grafts with megadose of CD34(+) cells, not requiring immunosuppression after allogeneic transplantation for graft-versus-host disease (GVHD) prophylaxis, and other strategies using unmanipulated T-cell-replete grafts with intensive immunosuppression or post-transplantation cyclophosphamide to minimize the GVHD. We als…
In vitro and in vivo purging of B lymphoma cells from stem-cell products using anti-CD20 Abs.
2000
Background Autologous stem-cell transplantation has proved curative therapy for relapsed NHL. However, recurrence of underlying disease remains the major cause of treatment failure in this setting. Methods Development of effective MAb therapy directed against the B cell surface antigen CD20 has added a valuable tool of clearing contaminating lymphoma cells from stem-cell products by either in vitro or in vivo application. Results Transplantation of successfully in vitro purged bone marrow using Mabs has been correlated with prolonged survival in large Phase-II study. So far, no randomized trial could demonstrate a therapeutic benefit for in vitro purging. The anti-CD20 Mab rituximab has bee…
Coordinated induction of drug transporters and phase I and II metabolism in human liver slices
2008
Although regulation of phase I drug metabolism in human liver is relatively well studied, the regulation of phase II enzymes and of drug transporters is incompletely characterized. Therefore, we used human liver slices to investigate the PXR, CAR and AhR-mediated induction of drug transporters and phase I and II metabolic enzymes. Precision-cut human liver slices were incubated for 5 or 24 h with prototypical inducers: phenobarbital (PB) (50 mu M) for CAR, beta-naphthoflavone (BNF) (25 mu M) for AhR, and rifampicin (RIF) (10 mu M) for PXR, and gene expression of the phase I enzymes CYP1A1, 1A2, 3A4, 3A5, 2136, 2A6, the phase II enzymes UGT1A1 and 1A6, and the transporters MRP2, MDR1, BSEP, …
Multiple solutions for parametric double phase Dirichlet problems
2020
We consider a parametric double phase Dirichlet problem. Using variational tools together with suitable truncation and comparison techniques, we show that for all parametric values [Formula: see text] the problem has at least three nontrivial solutions, two of which have constant sign. Also, we identify the critical parameter [Formula: see text] precisely in terms of the spectrum of the [Formula: see text]-Laplacian.
Drug-metabolizing enzymes in the skin of man, rat, and pig.
2007
The mammalian skin has long been considered to be poor in drug metabolism. However, many reports clearly show that most drug metabolizing enzymes also occur in the mammalian skin albeit at relatively low specific activities. This review summarizes the current state of knowledge on drug metabolizing enzymes in the skin of human, rat, and pig, the latter, because it is often taken as a model for human skin on grounds of anatomical similarities. However only little is known about drug metabolizing enzymes in pig skin. Interestingly, some cytochromes P450 (CYP) have been observed in the rat skin which are not expressed in the rat liver, such as CYP 2B12 and CYP2D4. As far as investigated most d…
Spark ignition feedback control by means of combustion phase indicators on steady and transient operation
2014
In order to reduce fuel cost and CO2 emissions, modern spark ignition (SI) engines need to lower as much as possible fuel consumption. A crucial factor for efficiency improvement is represented by the combustion phase, which in an SI engine is controlled acting on the spark advance. This fundamental engine parameter is currently controlled in an open-loop by means of maps stored in the electronic control unit (ECU) memory: such kind of control, however, does not allow running the engine always at its best performance, since optimal combustion phase depends on many variables, like ambient conditions, fuel quality, engine aging, and wear, etc. A better choice would be represented by a closed-…
Pulse trains produced by phase-modulation of ultrashort optical pulses: tailoring and characterization
2009
1094-4087; In this paper, creation of pulse doublets and pulse trains by spectral phase modulation of ultrashort optical pulses is investigated. Pulse doublets with specific features are generated through step-like and triangular spectral phase modulation, whereas sequences of pulses with controllable delay and amplitude are produced via sinusoidal phase modulations. A temporal analysis of this type of tailored pulses is exposed and a complete characterization with the SPIDER technique (Spectral Phase Interferometry for Direct Electric-field Reconstruction) is presented. (C) 2004 Optical Society of America.
Biomonitoring of Enniatin B1 and Its Phase I Metabolites in Human Urine: First Large-Scale Study
2020
Enniatins (Enns) are mycotoxins produced by Fusarium spp. which are a fungus widely spread throughout cereals and cereal-based products. Among all the identified enniatins, Enn B1 stands as one of the most prevalent analogues in cereals in Europe. Hence, the aim of this study was to evaluate for the first time the presence of Enn B1 and its phase I metabolites in 300 human urine samples using an ultrahigh-performance liquid chromatography high resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS) methodology. Enn B1 was detected in 94.3% of samples ranging from 0.007 to 0.429 ng/mL (mean value: 0.065 ng/mL). In accordance with previous in vitro and in vivo analysis, hydroxylated metabolites …
Should cirrhosis change our attitude towards treating non-hepatic cancer?
2011
Cirrhosis is a major cause of morbidity and mortality and is the end stage of any chronic liver disease. Cancer, a leading cause of death worldwide, is a growing global health issue. There are limited data in the literature on the incidence, prevalence and management of non-hepatic cancers (NHC) in cirrhotic patients. The aim of this brief review was to underline the main concerns, pitfalls and warnings regarding practice for these patients. Survival of patients with compensated cirrhosis is significantly longer than that of decompensated cirrhosis and patients with NHC and in Child-Pugh class C should not be candidates for cytotoxic chemotherapy. It is important before starting cytotoxic c…