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1.
Neuroradiology ; 62(6): 763, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32215681

RESUMEN

The above article was published with one author name being incorrect. The published paper states "H. von Tengg", whereas it should be "H. von Tengg-Kobligk". The author name has been corrected above.

2.
AJNR Am J Neuroradiol ; 40(5): 769-775, 2019 05.
Artículo en Inglés | MEDLINE | ID: mdl-31000524

RESUMEN

BACKGROUND AND PURPOSE: Predicting motor outcome following intracerebral hemorrhage is challenging. We tested whether the combination of clinical scores and DTI-based assessment of corticospinal tract damage within the first 12 hours of symptom onset after intracerebral hemorrhage predicts motor outcome at 3 months. MATERIALS AND METHODS: We prospectively studied patients with motor deficits secondary to primary intracerebral hemorrhage within the first 12 hours of symptom onset. Patients underwent multimodal MR imaging including DTI. We assessed intracerebral hemorrhage and perihematomal edema location and volume, and corticospinal tract involvement. The corticospinal tract was considered affected when the tractogram passed through the intracerebral hemorrhage or/and the perihematomal edema. We also calculated affected corticospinal tract-to-unaffected corticospinal tract ratios for fractional anisotropy, mean diffusivity, and axial and radial diffusivities. Motor impairment was graded by the motor subindex scores of the modified NIHSS. Motor outcome at 3 months was classified as good (modified NIHSS 0-3) or poor (modified NIHSS 4-8). RESULTS: Of 62 patients, 43 were included. At admission, the median NIHSS score was 13 (interquartile range = 8-17), and the median modified NIHSS score was 5 (interquartile range = 2-8). At 3 months, 13 (30.23%) had poor motor outcome. Significant independent predictors of motor outcome were NIHSS and modified NIHSS at admission, posterior limb of the internal capsule involvement by intracerebral hemorrhage at admission, intracerebral hemorrhage volume at admission, 72-hour NIHSS, and 72-hour modified NIHSS. The sensitivity, specificity, and positive and negative predictive values for poor motor outcome at 3 months by a combined modified NIHSS of >6 and posterior limb of the internal capsule involvement in the first 12 hours from symptom onset were 84%, 79%, 65%, and 92%, respectively (area under the curve = 0.89; 95% CI, 0.78-1). CONCLUSIONS: Combined assessment of motor function and posterior limb of the internal capsule damage during acute intracerebral hemorrhage accurately predicts motor outcome.


Asunto(s)
Hemorragia Cerebral/patología , Trastornos Motores/etiología , Tractos Piramidales/patología , Recuperación de la Función , Anciano , Hemorragia Cerebral/complicaciones , Imagen de Difusión por Resonancia Magnética , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Tractos Piramidales/diagnóstico por imagen
3.
Pharmacol Res ; 133: 318-327, 2018 07.
Artículo en Inglés | MEDLINE | ID: mdl-29530601

RESUMEN

The ABCC4/MRP4 exporter has a clinical impact on membrane transport of a broad range of xenobiotics. It is expressed at key locations for drug disposition or effects such as in the liver, the kidney and blood cells. Several polymorphisms and mutations (e.g., p.Gly187Trp) leading to MRP4 dysfunction are associated with an increased risk of toxicity of some drugs. So far, no human MRP4 structure has been elucidated, precluding rationalization of these dysfunctions at a molecular level. We constructed an atomistic model of the wild type (WT) MRP4 and the p.Gly187Trp mutant embedded in different lipid bilayers and relaxed them for hundreds of nanoseconds by molecular dynamics simulations. The WT MRP4 molecular structure confirmed and ameliorated the general knowledge about the transmembrane helices and the two nucleotide binding domains. Moreover, our model elucidated positions of three generally unresolved domains: L1 (linker between the two halves of the exporter); L0 (N-terminal domain); and the zipper helices (between the two NBDs). Each domain was thoroughly described in view of its function. The p.Gly187Trp mutation induced a huge structural impact on MRP4, mainly affecting NBD 1 structure and flexibility. The structure of transporter enabled rationalization of known dysfunctions associated with polymorphism of MRP4. This model is available to the pharmacology community to decipher the impact of any other clinically observed polymorphism and mutation on drug transport, giving rise to in silico predictive pharmacogenetics.


Asunto(s)
Modelos Moleculares , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/química , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/fisiología , Membrana Dobles de Lípidos/metabolismo , Mutación , Polimorfismo Genético
4.
Am J Transplant ; 17(1): 201-209, 2017 01.
Artículo en Inglés | MEDLINE | ID: mdl-27272414

RESUMEN

Acute renal rejection is a major risk factor for chronic allograft dysfunction and long-term graft loss. We performed a genome-wide association study to detect loci associated with biopsy-proven acute T cell-mediated rejection occurring in the first year after renal transplantation. In a discovery cohort of 4127 European renal allograft recipients transplanted in eight European centers, we used a DNA pooling approach to compare 275 cases and 503 controls. In an independent replication cohort of 2765 patients transplanted in two European countries, we identified 313 cases and 531 controls, in whom we genotyped individually the most significant single nucleotide polymorphisms (SNPs) from the discovery cohort. In the discovery cohort, we found five candidate loci tagged by a number of contiguous SNPs (more than five) that was never reached in iterative in silico permutations of our experimental data. In the replication cohort, two loci remained significantly associated with acute rejection in both univariate and multivariate analysis. One locus encompasses PTPRO, coding for a receptor-type tyrosine kinase essential for B cell receptor signaling. The other locus involves ciliary gene CCDC67, in line with the emerging concept of a shared building design between the immune synapse and the primary cilium.


Asunto(s)
Rechazo de Injerto/diagnóstico , Fallo Renal Crónico/cirugía , Trasplante de Riñón/efectos adversos , Proteínas Asociadas a Microtúbulos/genética , Polimorfismo de Nucleótido Simple , Proteínas Tirosina Fosfatasas Clase 3 Similares a Receptores/genética , Proteínas Supresoras de Tumor/genética , Enfermedad Aguda , Adulto , Estudios de Casos y Controles , Femenino , Marcadores Genéticos , Estudio de Asociación del Genoma Completo , Rechazo de Injerto/etiología , Rechazo de Injerto/genética , Humanos , Masculino , Persona de Mediana Edad , Pronóstico
5.
Am J Transplant ; 17(5): 1370-1379, 2017 May.
Artículo en Inglés | MEDLINE | ID: mdl-27862923

RESUMEN

The aim of this study (ClinicalTrials.gov, NCT01744470) was to determine the efficacy and safety of two different doses of extended-release tacrolimus (TacER) in kidney transplant recipients (KTRs) between 4 and 12 mo after transplantation. Stable steroid-free KTRs were randomized (1:1) after 4 mo: Group A had a 50% reduction in TacER dose with a targeted TacER trough level (C0 ) >3 µg/L; group B had no change in TacER dose (TacER C0 7-12 µg/L). The primary outcome was estimated GFR at 1 year. Of 300 patients, the intent-to-treat analysis included 186 patients (group A, n = 87; group B, n = 99). TacER C0 was lower in group A than in group B at 6 mo (4.1 ± 2.7 vs. 6.7 ± 3.9 µg/L, p < 0.0001) and 12 mo (5.6 ± 2.0 vs. 7.4 ± 2.1 µg/L, p < 0.0001). Estimated GFR was similar in both groups at 12 mo (group A, 56.0 ± 17.5 mL/min per 1.73 m²; group B, 56.0 ± 22.1 mL/min per 1.73 m²). More rejection episodes occurred in group A than group B (11 vs. 3; p = 0.016). At 1 year, subclinical inflammation occurred more frequently in group A than group B (inflammation score [i] >0: 21.4% vs. 8.8%, p = 0.047; tubulitis score [t] >0: 19.6% vs. 8.7%, p = 0.076; i + t: 1.14 ± 1.21 vs. 0.72 ± 1.01, p = 0.038). Anti-HLA donor-specific antibodies appeared only in group A (6 vs. 0 patients, p = 0.008). TacER C0 should be maintained >7 µg/L during the first year after transplantation in low-immunological-risk, steroid-free KTRs receiving a moderate dose of mycophenolic acid.


Asunto(s)
Rechazo de Injerto/etiología , Isoanticuerpos/sangre , Fallo Renal Crónico/cirugía , Trasplante de Riñón/efectos adversos , Tacrolimus/farmacología , Donantes de Tejidos , Receptores de Trasplantes , Adolescente , Adulto , Anciano , Femenino , Estudios de Seguimiento , Tasa de Filtración Glomerular , Rechazo de Injerto/sangre , Rechazo de Injerto/tratamiento farmacológico , Supervivencia de Injerto/efectos de los fármacos , Humanos , Inmunosupresores/farmacología , Isoanticuerpos/inmunología , Pruebas de Función Renal , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias , Pronóstico , Estudios Prospectivos , Factores de Riesgo , Adulto Joven
6.
Curr Oncol ; 23(4): e383-91, 2016 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-27536188

RESUMEN

The management of high-grade gliomas (hggs) is complex and ever-evolving. The standard of care for the treatment of hggs consists of surgery, chemotherapy, and radiotherapy. However, treatment options are influenced by multiple factors such as patient age and performance status, extent of tumour resection, biomarker profile, and tumour histology and grade. Follow-up cranial magnetic resonance imaging (mri) to differentiate treatment response from treatment effect can be challenging and affects clinical decision-making. An assortment of advanced radiologic techniques-including perfusion imaging with dynamic susceptibility contrast mri, dynamic contrast-enhanced mri, diffusion-weighted imaging, proton spectroscopy, mri subtraction imaging, and amino acid radiotracer imaging-can now incorporate novel physiologic data, providing new methods to help characterize tumour progression, pseudoprogression, and pseudoresponse. In the present review, we provide an overview of current treatment options for hgg and summarize recent advances and challenges in imaging technology.

7.
Eur J Obstet Gynecol Reprod Biol ; 205: 7-10, 2016 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-27552172

RESUMEN

OBJECTIVE: Uterine infertility (UI), which can be caused by a variety of congenital or acquired factors, affects several thousand women in Europe. Uterus transplantation (UTx), at the current stage of research, offers hope for these women to be both the biological mother and the carrier of their child. However, the indications of UTx still need to be defined. The main aim of the study was to describe the different etiologies of UI and other data as marital and parental status from women requesting UTx who contacted us in the framework of a UTx clinical trial. Secondarily, we discussed the potential indications of UTx and their feasibility. STUDY DESIGN: This is an observational study. RESULTS: Of a total of 139 patients with UI, 105 patients (75.5%) had uterine agenesis, making it the leading cause of UI in this sample. Among the patients with uterine agenesis, 25% had a solitary kidney and 44.7% had undergone vaginal reconstruction. Peripartum hysterectomy, hysterectomy for cancer, and hysterectomy for benign pathologies accounted for 9.4%, 7.2% and 5% of cases, respectively. Less common causes of UI included complete androgen insensitivity syndrome (2.2% of patients) and prenatal diethylstilbestrol exposure (0.7%). Approximately 14% of the women already had at least one child and 66% were in a couple living together for at least 2 years. CONCLUSION: UTx is still under evaluation and further research is under way. Nulliparous patients with no major medical or surgical history and with normal ovarian function, who meet the legal criteria for medically assisted reproduction, represent the best indications for UTx at this stage of its development.


Asunto(s)
Infertilidad Femenina/cirugía , Selección de Paciente , Anomalías Urogenitales/cirugía , Útero/anomalías , Útero/trasplante , Adulto , Femenino , Francia , Humanos , Infertilidad Femenina/etiología , Estado Civil , Resultado del Tratamiento , Anomalías Urogenitales/complicaciones , Útero/cirugía
8.
Ultraschall Med ; 36(6): 566-80, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26669869

RESUMEN

This is the second part of the series on interventional ultrasound guidelines of the Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB). It deals with the diagnostic interventional procedure. General points are discussed which are pertinent to all patients, followed by organ-specific imaging that will allow the correct pathway and planning for the interventional procedure. This will allow for the appropriate imaging workup for each individual interventional procedure (Long version/ short version; the long version is published online).


Asunto(s)
Abdomen/diagnóstico por imagen , Sociedades Médicas , Ultrasonografía Intervencional/métodos , Ultrasonografía/métodos , Europa (Continente) , Humanos , Imagen por Resonancia Magnética , Imagen Multimodal , Sensibilidad y Especificidad , Tomografía Computarizada por Rayos X
9.
Ultraschall Med ; 36(6): E15-35, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26669871

RESUMEN

This is the second part of the series on interventional ultrasound guidelines of the Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB). It deals with the diagnostic interventional procedure. General points are discussed which are pertinent to all patients, followed by organ-specific imaging that will allow the correct pathway and planning for the interventional procedure. This will allow for the appropriate imaging workup for each individual interventional procedure (Long version).


Asunto(s)
Abdomen/diagnóstico por imagen , Sociedades Médicas , Ultrasonografía Intervencional , Ultrasonografía , Europa (Continente) , Medicina Basada en la Evidencia , Humanos
10.
Gynecol Obstet Fertil ; 43(2): 133-8, 2015 Feb.
Artículo en Francés | MEDLINE | ID: mdl-25595943

RESUMEN

OBJECTIVES: To study the demand there is for uterus transplantation (UTx). PATIENTS AND METHODS: Recent media coverage of developments in UTx prompted associations of patients with Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome and of women suffering from UI to contact us. We sent them anonymous questionnaires devised to sound out their attitude towards UTx and towards adoption and gestational surrogacy (GS). A clinical psychologist also carried out a qualitative discourse analysis. RESULTS: Sixty patients answered the questionnaire. Thirty-eight patients were married or living with a male partner. Seven patients had had a hysterectomy. Fifty-one patients had uterine agenesis. Of the 60 patients, 19 and 21, respectively, had ruled out the option of adoption or GS, and 11 would not envisage either possibility. Thirty-five patients were willing to take part in a clinical study into UTx despite the uncertainty of the outcome and the potential risks involved. Of these 35 volunteers, 23 were in a heterosexual relationship and aged ≤35 years. DISCUSSION AND CONCLUSION: For women with UI the condition is all the more distressing because there is no medical solution for it. UTx could hold out hope for some of these patients despite the complexity of the procedure and the attendant risks. Because of the feelings of vulnerability engendered by UI, any UTx programme should provide full information to patients and ensure they are carefully screened and selected.


Asunto(s)
Necesidades y Demandas de Servicios de Salud , Útero/trasplante , Trastornos del Desarrollo Sexual 46, XX/complicaciones , Adolescente , Adulto , Actitud Frente a la Salud , Anomalías Congénitas , Femenino , Humanos , Infertilidad Femenina/etiología , Infertilidad Femenina/cirugía , Conductos Paramesonéfricos/anomalías , Encuestas y Cuestionarios , Útero/anomalías , Adulto Joven
11.
J Neuroradiol ; 42(4): 236-44, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-24996569

RESUMEN

OBJECTIVE: To prove superiority of blood pool contrast agent gadofosveset over conventional contrast agent gadobenate dimeglumine for assessment of stenotic internal carotid artery (ICA). METHODS: Eleven patients with high-grade ICA stenosis (≥75%), confirmed by duplex sonography, underwent MR angiography (MRA) with gadofosveset and gadobenate dimeglumine. RESULTS: Agreement in stenosis grade was reached in 7 of 10 stenotic ICAs. In two ICAs, gadobenate dimeglumine led to underestimation of stenosis grade. There was a significant difference in signal intensity (pre-/post-stenotic segments), showing higher values for gadofosveset (P<0.01; P<0.05). Impression of contrast intensity with gadofosveset was better in 8 ICAs and only in 1 ICA with gadobenate dimeglumine (P<0.05). CONCLUSION: Gadofosveset-enhanced MR angiography may be superior for assessment of high-grade ICA stenosis compared with gadobenate dimeglumine MR angiography.


Asunto(s)
Estenosis Carotídea/patología , Angiografía Cerebral/métodos , Gadolinio , Aumento de la Imagen/métodos , Angiografía por Resonancia Magnética/métodos , Meglumina/análogos & derivados , Compuestos Organometálicos , Reconocimiento de Normas Patrones Automatizadas/métodos , Adulto , Anciano , Anciano de 80 o más Años , Medios de Contraste , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Sensibilidad y Especificidad
13.
Clin Pharmacol Ther ; 96(4): 508-15, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-24968086

RESUMEN

A time-to-event model was developed to study the predictive factors of immunosuppressive efficacy in renal transplant patients and to investigate longitudinal calcineurin inhibitor (CNI) and mycophenolic acid (MPA) coexposures and patient characteristics as potential covariates. The efficacy end point included acute rejection (AR), graft loss, and death. Data from 222 patients were analyzed: 23 events were observed in 126 patients receiving cyclosporine as compared with 15 events in 96 patients receiving tacrolimus (P = 0.61) in the first 2 years posttransplantation. Each 1-mg·h/l increase of MPA area under the plasma concentration vs. time curve was associated with a 4% decreased risk of an event (hazard ratio (HR) = 0.96; 95% confidence interval (CI): 0.93-0.99). The onset of cytomegalovirus infection/disease significantly increased this risk (HR = 10.9; 95% CI: 6.5-21.7). Within the observed ranges, CNI exposures were not significantly associated with efficacy (i.e., AR, graft loss, and death). This work advocates the avoidance of unnecessary high CNI dosing and puts forward new arguments for MPA concentration monitoring.


Asunto(s)
Inhibidores de la Calcineurina , Inmunosupresores/uso terapéutico , Trasplante de Riñón , Ácido Micofenólico/uso terapéutico , Ciclosporina/uso terapéutico , Infecciones por Citomegalovirus/prevención & control , Quimioterapia Combinada , Rechazo de Injerto/prevención & control , Humanos , Modelos Logísticos , Modelos Biológicos , Estudios Multicéntricos como Asunto , Ensayos Clínicos Controlados Aleatorios como Asunto , Tacrolimus/uso terapéutico
15.
Transplant Proc ; 45(4): 1603-7, 2013 May.
Artículo en Inglés | MEDLINE | ID: mdl-23726629

RESUMEN

Maribavir (MBV), a UL97 inhibitor, shows good oral bioavailability, low host cell toxicity, and theoretical benefits to inhibit cross-resistant viruses. We herein examined clinical and virological outcomes of 12 patients, including 3 bone marrow recipients and 9 organ recipients infected with resistant cytomegalovirus (CMV) and treated with MBV during 2011-2012. All received at least 800-mg daily doses. They had developed clinical (12/12) and/or virological (11/12) resistance to CMV infection. Based on a decrease of viral load in blood >1.5 log copies/mL half of them responded to MBV treatment. The individual changes varied from a rapid decrease in viral load (n = 4) to no response (n = 3) with some late response slowly decreasing viremia (n = 3). In 2 cases MBV was used as secondary prophylaxis. No clear parameter emerged as a clinical surrogate for nonresponse to MBV. These results contrast with the lack of efficacy in phase III trials of MBV prophylaxis among stem cell recipients, which were possibly due to low doses or inadequate timing of drug initiation in the study. Additional clinical and surrogate laboratory markers are needed to determine antiviral responses to guide MBV use. Dosage ranging studies might benefit future MBV use.


Asunto(s)
Antivirales/uso terapéutico , Bencimidazoles/uso terapéutico , Infecciones por Citomegalovirus/tratamiento farmacológico , Trasplante de Órganos , Ribonucleósidos/uso terapéutico , Adulto , Antivirales/farmacología , Bencimidazoles/farmacología , Citomegalovirus/efectos de los fármacos , Francia , Genotipo , Humanos , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Fosfotransferasas (Aceptor de Grupo Alcohol)/genética , Ribonucleósidos/farmacología
16.
Pharmacol Res ; 72: 52-60, 2013 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-23557931

RESUMEN

This study aimed to investigate the association between longitudinal exposure to mycophenolic acid (MPA) and acute rejection (AR) risk in the first year after renal transplantation, and to propose MPA exposure targets conditionally to this association. A joint model, adjusted for monitoring strategy (fixed-dose versus concentration-controlled) and recipient age, was developed; it combined a mixed-effects model to describe the whole pattern of MPA exposure (i.e. area under the concentration-time curve (AUC)) and a survival model. MPA AUC thresholds were determined using time-dependent receiver-operating characteristics (ROC) curves. Data from 490 adult renal-transplant recipients, representative of the general population of adult renal-transplant patients (i.e. including patients considered at low immunological risk-enrolled in the OPERA trial as well as second renal transplant and patients co-treated by either cyclosporine or tacrolimus), were analyzed. A significant association was found between the longitudinal exposure to MPA (MPA AUCs=f(t)) and AR (p=0.0081), and validated by bootstrapping. A significant positive correlation was observed between time post-transplantation and ROC thresholds which increased in average from 35 mg h/L in the first days to 41 mg h/L beyond six months post-transplantation (p<0.001). Using a new modeling approach which recognizes the repeated measures in a same patient, this study supports the association between MPA exposure and AR.


Asunto(s)
Rechazo de Injerto/inducido químicamente , Inmunosupresores/efectos adversos , Trasplante de Riñón , Ácido Micofenólico/efectos adversos , Adulto , Factores de Edad , Anciano , Humanos , Inmunosupresores/administración & dosificación , Inmunosupresores/uso terapéutico , Trasplante de Riñón/métodos , Persona de Mediana Edad , Modelos Biológicos , Ácido Micofenólico/administración & dosificación , Ácido Micofenólico/uso terapéutico , Curva ROC
17.
Gynecol Obstet Fertil ; 40(11): 691-4, 2012 Nov.
Artículo en Francés | MEDLINE | ID: mdl-23084737

RESUMEN

Except adoption, absolute uterine factor infertility lacks solution in case of motherhood desire. Gestational surrogacy is still not approved in France. Over the last decade, uterus transplantation experimentation made advances. Data from animal research, progress in immunosuppressive treatment and knowledge about pregnancy after transplantation provide a scenario in which a human allotransplantation project can become reality.


Asunto(s)
Infertilidad Femenina/etiología , Infertilidad Femenina/cirugía , Enfermedades Uterinas/complicaciones , Útero/trasplante , Animales , Modelos Animales de Enfermedad , Femenino , Francia , Humanos , Terapia de Inmunosupresión , Embarazo , Madres Sustitutas/legislación & jurisprudencia
18.
Transpl Infect Dis ; 14(6): E134-6, 2012 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-22998023

RESUMEN

Bordetella holmesii is a gram-negative rod that was initially identified in 1995. It causes bacteremia, pneumonia, and endocarditis mostly in patients with anatomical or functional asplenia. We report here, to the best of our knowledge, the first case of B. holmesii bacteremia in a renal transplant recipient following rituximab therapy for recurrence of membranoproliferative glomerulonephritis.


Asunto(s)
Infecciones por Bordetella/microbiología , Bordetella/clasificación , Trasplante de Riñón/efectos adversos , Adulto , Antibacterianos/uso terapéutico , Anticuerpos Monoclonales de Origen Murino/uso terapéutico , Infecciones por Bordetella/tratamiento farmacológico , Humanos , Huésped Inmunocomprometido , Inmunosupresores/uso terapéutico , Masculino , Rituximab
19.
J Proteomics ; 75(12): 3674-87, 2012 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-22564819

RESUMEN

Nephrotoxicity is an adverse event that strongly limits the use of the immunosuppressant cyclosporine in solid organ transplantation and the precise molecular mechanisms underlying this toxicity remain unclear. MS-based proteomic analysis of the secretome of HEK-293 renal cells exposed to cyclosporine was performed to identify changes in protein secretion, as a first step to discover potential biomarkers of such nephrotoxicity. To detect and quantify the perturbed proteins in the culture medium we used SILAC and nano-scale liquid chromatography followed by MALDI-TOF/TOF mass spectrometry. Among 106 proteins identified, 80 were quantified in both forward/reverse SILAC experiments and quantitative proteomic analysis revealed altered levels of expression for 24 secreted proteins. These included the down-regulation of a number of extracellular matrix/cell adhesion components, and the up-regulation of secreted cyclophilins A and B, macrophage inhibition factor and phosphatidylethanolamine-binding protein 1. These changes in protein secretion were not prevented by co-incubation with the antioxidant N-acetylcysteine, suggesting that they were not triggered by cyclosporine-induced oxidative stress. The results from the present study provide important new knowledge to gain insights into the molecular mechanisms of cyclosporine-related toxicity. Some of the proteins identified here should be tested as potential biomarkers of cyclosporine nephrotoxicity in subsequent clinical studies.


Asunto(s)
Moléculas de Adhesión Celular/metabolismo , Ciclosporina/toxicidad , Proteínas de la Matriz Extracelular/metabolismo , Riñón/efectos de los fármacos , Riñón/metabolismo , Proteoma/metabolismo , Aminoácidos/farmacocinética , Células Cultivadas , Ciclofilina A/metabolismo , Ciclofilinas/metabolismo , Regulación hacia Abajo , Regulación de la Expresión Génica/efectos de los fármacos , Células HEK293 , Humanos , Inmunosupresores/farmacología , Marcaje Isotópico/métodos , Riñón/citología , Regulación hacia Arriba
20.
Radiologe ; 52(3): 229-34, 2012 Mar.
Artículo en Alemán | MEDLINE | ID: mdl-22476705

RESUMEN

Therapy-related side effects, which are detectable with magnetic resonance imaging (MRI) at high sensitivity, are one of the most frequent causes of morbidity in cancer patients. They can be observed in the treatment of central nervous system (CNS) diseases as well as in systemic therapy, including whole brain irradiation and chemotherapy and are more often seen due to the better overall survival. This review describes the most frequent acute and chronic therapy-related changes in the CNS and the imaging findings. Acute changes are often reversible while chronic changes can be observed up to several years after treatment.The differentiation of treatment-related from tumor-related changes might be very difficult, although modern imaging modalities such as MR spectroscopy or MR perfusion measurements supply helpful differential diagnostic information.


Asunto(s)
Lesiones Encefálicas/etiología , Lesiones Encefálicas/patología , Encéfalo/efectos de la radiación , Imagen por Resonancia Magnética/métodos , Traumatismos por Radiación/etiología , Traumatismos por Radiación/patología , Radioterapia/efectos adversos , Encéfalo/patología , Humanos , Resultado del Tratamiento
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