Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 32
Filtrar
Más filtros










Base de datos
Intervalo de año de publicación
1.
Br J Radiol ; : 20200881, 2020 Dec 04.
Artículo en Inglés | MEDLINE | ID: mdl-33252986

RESUMEN

OBJECTIVE: Diagnosis of female pelvic congestion syndrome (PCS) is challenging. Although invasive venography is the gold-standard for diagnosis, however, CT and MRI are important in the assessment. In this study, we tried to highlight the role of CT and MRI as non-invasive tools in the diagnosis and management of PCS. METHODS AND MATERIAL: This was a retrospective study of 50 patients confirmed clinically to have PCS. These patients had already done CT and MRI before venography or surgery. RESULTS: The mean age of the patients was 48 years ± 12 years SD. Vaginal discharge and pelvic heaviness were the commonest symptoms (46 and 42% respectively). The commonest risk factor was multiparity (56%) followed by the RVF uterus (26%). No significant difference was found between CT, MRI, and venography as regarding the diameter of the ovarian vein, diameter, and the number of the varicose veins. The sensitivity of CT and MRI was 94.8 and 96%. CT and MRI discovered five cases with local pelvic obstructing cause,14 cases with evidence of vascular compression syndrome, and the rest 31 cases diagnosed to have primary non-obstructing PCS which was effective in decision-making with the surgery indicated in the first group while stenting of the vascular obstruction followed by bilateral ovarian veins coiling was the better option for the second group and only bilateral coiling was needed for the last group. CONCLUSION: CT and MRI play important roles in the diagnosis and even management decision in cases of PCS. ADVANCES IN KNOWLEDGE:: Identification of the importance of diagnostic radiology before management decisions of cases with PCS.

2.
Qual Life Res ; 29(12): 3185-3186, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33201389
3.
Artículo en Inglés | MEDLINE | ID: mdl-32909145

RESUMEN

The purpose of this study is to test the capability of a commercially available feature tracking-cardiac magnetic resonance (FT-CMR) strain analysis software module in differentiating between viable and non-viable myocardium in chronic ischemic patients. Thirty chronic ischemic patients and 10 healthy volunteers were enrolled. Cine images were used for peak circumferential and radial strains quantification using dedicated FT-CMR software. Global strain was compared between patients and controls. In patients, segmental strain was compared in viable and non-viable myocardium determined by late gadolinium enhancement (LGE); and in segments with wall abnormalities. Among 480 myocardial segments analyzed in patients, 76 segments were non-viable on LGE. The mean left ventricular ejection fraction (LVEF) of the patients (87% males, mean age 55 ± 12 years) was 40 ± 12% vs. 61 ± 5% for the controls (80% males, mean age 39 ± 11 years). Peak global circumferential strain (GCS) and global radial strain (GRS) were significantly impaired in patients compared to controls (-13.89 ± 4.12% vs. -19.84 ± 1.47%), p < 0.001 and (23.11 ± 6.59% vs. 31.72 ± 5.52%), p = 0.001. Segmental circumferential strain (SCS) and segmental radial strain (SRS) were significantly impaired in non-viable compared to viable segments (-9.47 ± 7.26% vs. -14.72 ± 7.5%), p < 0.001 and (15.67 ± 12.11% vs. 24.51 ± 16.22%), p < 0.001. Cut-off points of -9.36% for the SCS (AUC = 0.7, 95% CI = 0.63-0.77) and 19.5% for the SRS (AUC = 0.67, 95%CI = 0.61-0.73) were attained above which the segment is considered viable.SCS was able to discriminate between normokinetic, hypokinetic and akinetic segments (mean = 27.6 ± 17.13%, 18.66 ± 12.88% and 15.24 ± 10.70% respectively, p < 0.001). Circumferential and radial segmental strain analysis by FT-CMR was able to discriminate between viable and non-viable segments of the myocardium defined by LGE and between normokinetic, hypokinetic and akinetic segments, using routinely acquired cine images, and thus can provide a more objective metric for risk stratification in chronic ischemic patients.

4.
Sci Rep ; 10(1): 12369, 2020 07 23.
Artículo en Inglés | MEDLINE | ID: mdl-32703986

RESUMEN

Cranial irradiation (IR) is commonly used to treat primary brain tumors and metastatic diseases. However, cranial IR-treated patients often develop vascular abnormalities later in life that increase their risk for cerebral ischemia. Studies in rodents have demonstrated that IR impairs maintenance of the neural stem/precursor cell (NSPC) pool and depletes neurogenesis. We and others have previously shown that stroke triggers NSPC proliferation in the subventricular zone and migration towards the stroke-injured neocortex. Whether this response is sustained in the irradiated brain remains unknown. Here, we demonstrate that cranial IR in mice at an early postnatal age significantly reduced the number to neuronal progenitors responding to cortical stroke in adults. This was accompanied by a reduced number of microglia/macrophages in the peri-infarct cortex; however, the astrocytic response was not altered. Our findings indicate that IR impairs the endogenous repair capacity in the brain in response to stroke, hence pointing to another side effect of cranial radiotherapy which requires further attention.

5.
Cell Rep ; 31(9): 107699, 2020 06 02.
Artículo en Inglés | MEDLINE | ID: mdl-32492415

RESUMEN

Cranial irradiation (IR), an effective tool to treat malignant brain tumors, triggers a chronic pro-inflammatory microglial response, at least in the adult brain. Using single-cell and bulk RNA sequencing, combined with histology, we show that the microglial response in the juvenile mouse hippocampus is rapid but returns toward normal within 1 week. The response is characterized by a series of temporally distinct homeostasis-, sensome-, and inflammation-related molecular signatures. We find that a single microglial cell simultaneously upregulates transcripts associated with pro- and anti-inflammatory microglial phenotypes. Finally, we show that juvenile and adult irradiated microglia are already transcriptionally distinct in the early phase after IR. Our results indicate that microglia are involved in the initial stages but may not be responsible for driving long-term inflammation in the juvenile brain.

6.
Artículo en Inglés | MEDLINE | ID: mdl-32231082

RESUMEN

Peri-implant soft tissues play a role of paramount importance, not only on the esthetic appearance, but also on the maintenance and long-term stability of implants. The present report presents the conclusions from the Consensus Conference of the South European North African Middle Eastern Implantology & Modern Dentistry Association (SENAME) (4-6 November 2016, Cairo, Egypt). The conference focused on the topic of the soft tissue around dental implants, and in particular, on the influence of implant configurations on the marginal soft tissues, soft tissue alterations after immediate, early or delayed implant placement and immediate loading, the long-term outcomes of soft tissue stability around dental implants, and soft tissue augmentation around dental implants. Thirty world experts in this field were invited to take part in this two-day event; however, only 29 experts were in the final consensus voting process.


Asunto(s)
Implantes Dentales , Mucosa Bucal , Consenso , Egipto , Humanos
7.
Insights Imaging ; 11(1): 38, 2020 Mar 10.
Artículo en Inglés | MEDLINE | ID: mdl-32152802

RESUMEN

BACKGROUND: The assessment of liver stiffness and the degree of fibrosis are important factors affecting the management strategy. Multiple non-invasive tools are now available to offer an adequate alternative to biopsy. In this study, we tried to compare the performance of 2D shear wave elastography (SWE) to the transient elastography/fibroscan as a non-invasive tool in the prediction of liver stiffness. This is a prospective study of 215 patients confirmed by serology to have positive virus C or B infection. 2D SWE was done followed by vibration-controlled transient elastography (VCTE) known as fibroscan at the same session. Biopsy results were collected. RESULTS: The mean age was 51.07 years ± 6.07 SD. Five cases were excluded due to insufficient data. Fibroscan failed in 30 cases out of 210 cases (failure rate of 14.3%) compared with only 12 patients (6.7% failure rate) while using SWE. Only 180 patients completed the study to the result analysis. SWE results showed significant agreement to the fibroscan results with 86.7% agreement with a tendency for overestimation of the degree of fibrosis (11.7%). The efficacy of SWE was the highest during the assessment of patients with F0 (98.9%), F1 (97.8%), and F4 (93.3%) respectively and relatively low in F2 (92.8%) and F3 (90.6%). CONCLUSION: 2D SWE is a relatively recent non-invasive tool in the assessment of liver fibrosis grading which can be used as an alternative to the fibroscan with almost similar diagnostic performance especially when fibroscan is not capable to obtain adequate results such as in obesity and ascites.

8.
Neuroscience ; 405: 92-102, 2019 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-29101080

RESUMEN

Brain injury is associated with neuroinflammation, and microglia are key players in this process. Microglia can acquire pro-inflammatory or anti-inflammatory properties, but how this affects neural stem cells (NSCs) remains controversial. Here, NSCs were grown in conditioned media collected from either non-stimulated microglia, or microglia stimulated with pro- or anti-inflammatory agents. NSC survival, proliferation, migration, and differentiation were investigated thereafter. We found that NSCs kept in conditioned medium from the anti-inflammatory microglial subtype had better survival, increased migration, and lower astrocytic differentiation compared to NSCs grown in conditioned medium collected from the pro-inflammatory subtype. Finally, we found that NSCs differentiated in microglial conditioned media generated cells expressing the pro-inflammatory chemokine CCL2, most pronounced when differentiated in medium from the pro-inflammatory microglia subtype. Our results show that microglial subtypes regulate NSCs differently and induce generation of cells with inflammatory properties.


Asunto(s)
Citocinas/metabolismo , Microglía/fisiología , Células-Madre Neurales/fisiología , Animales , Astrocitos/citología , Astrocitos/metabolismo , Astrocitos/fisiología , Diferenciación Celular/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Medios de Cultivo Condicionados , Citocinas/biosíntesis , Interleucina-4/farmacología , Lipopolisacáridos/farmacología , Ratones , Ratones Endogámicos C57BL , Microglía/citología , Microglía/efectos de los fármacos , Microglía/metabolismo , Células-Madre Neurales/citología , Células-Madre Neurales/metabolismo
9.
Trop Doct ; 48(4): 340-344, 2018 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-30153771

RESUMEN

Breaking bad news is a global challenge for all types of health providers. Our study assessed the attitude and practice from the doctors' perspective in a patriarchal society. A descriptive cross-sectional hospital-based study was conducted, involving doctors from both medical and surgical departments. Almost half of the respondents believed that Sudanese patients do not like to know their diagnosis, and a slightly higher proportion had no previous training on how to break bad news. Some 20% indicated that they would conceal the diagnosis from a patient if his or her relatives so requested. Less than one-quarter of respondents followed a standard protocol. Although most of the doctors subscribed to the notion that patients have the right to know everything about their illnesses, not all of them held this attitude towards their local patient population.


Asunto(s)
Actitud del Personal de Salud , Relaciones Médico-Paciente , Revelación de la Verdad , Adulto , Estudios Transversales , Ética Profesional , Femenino , Humanos , Masculino , Derechos del Paciente/ética , Relaciones Médico-Paciente/ética , Sudán , Revelación de la Verdad/ética
10.
Arch Virol ; 163(9): 2433-2442, 2018 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-29860675

RESUMEN

Toll-like receptors (TLRs) give the innate immune system a considerable specificity for a large range of pathogens. TLR3 detects dsRNA of viruses while TLR9 recognizes bacterial and viral unmethylated CpG motifs. This study examined whether there is a potential association between single-nucleotide polymorphisms (SNPs) in the TLR3.rs3775290 (c.1377C/T), TLR9.rs5743836 (-1237T→C) and TLR9.rs352140 (G2848A) genes and HCV infection among Egyptian patients and healthcare workers (HCWs). We enrolled 546 subjects (409 HCWs and 137 patients) divided into four groups: group 1 included 265 seronegative, aviremic subjects; group 2 included 25 seronegative, viremic subjects; group 3 included 87 subjects with spontaneously resolved HCV infection; and group 4 included 169 chronic HCV patients. All subjects were genotyped for TLR3.rs3775290, TLR9.rs5743836 and TLR9.rs352140 SNPs by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) analysis. TLR3.rs3775290 "CC" genotype was associated with chronic HCV infection, where there was a significantly greater frequency of this genotype among chronic patients when compared to subjects with spontaneously resolved infection (63.9% vs. 51.9%; p = 0.033; OR = 1.639 and 95% CI = 0.94-2.84). However, this SNP did not correlate with the HCV RNA load among the chronic subjects (p > 0.05). There was no significant difference in TLR9.rs5743836 and TLR9.rs352140 genotype distribution between groups (p > 0.05). Lack of association between the three SNPs was found, as the three SNPs are located on two different chromosomes. In conclusion, the TLR3.rs3775290 "CC" genotype was associated with HCV chronicity, while the TLR9 gene may not play a major role in HCV infection.


Asunto(s)
Hepacivirus/inmunología , Hepatitis C Crónica/genética , Linfocitos/metabolismo , Polimorfismo de Nucleótido Simple , Receptor Toll-Like 3/genética , Receptor Toll-Like 9/genética , Adulto , Estudios de Casos y Controles , Egipto , Femenino , Expresión Génica , Predisposición Genética a la Enfermedad , Personal de Salud , Hepatitis C Crónica/inmunología , Hepatitis C Crónica/virología , Humanos , Inmunidad Innata , Linfocitos/inmunología , Linfocitos/virología , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Pacientes Ambulatorios , ARN Viral/genética , Remisión Espontánea , Receptor Toll-Like 3/inmunología , Receptor Toll-Like 9/inmunología , Carga Viral
11.
Int J Cardiovasc Imaging ; 34(6): 975-983, 2018 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-29349525

RESUMEN

To evaluate the role of CT pulmonary angiography (CTPA) in the assessment of pulmonary embolism (PE) severity and the related CT cardiac changes, reflecting the clinical status of the patients and predicting the outcome. A prospective study of 184 patients presented with suspicious acute PE. All patients underwent CTPA followed by ECHO. Pulmonary artery obstructive index (PAOI) using Qanadli Score was calculated and cardiac changes recorded. The patients' outcome was followed up for 30 days. Only 150 patients completed the study; 26.7% needed ICU admission while 13.3% died during follow-up. There was a significant relationship between the PAOI and the risk classification, right ventricular dysfunction (RVD) diagnosed by ECHO and the patients' short outcome. We found PAOI cut off value 45% for mortality and 35% for ICU admission and 27.5% for RVD with 60, 75 and 90% sensitivity and 80, 73.3 and 68.6% specificity respectively. CT RV/LV ratio was the most sensitive parameter to predict RV dysfunction followed by pulmonary artery diameter. CTPA is not only used for diagnosis but also to assess the severity of PE, the effect on the right ventricular function and subsequently the need for ICU admission and prediction of the outcome.


Asunto(s)
Angiografía por Tomografía Computarizada/métodos , Embolia Pulmonar/diagnóstico por imagen , Disfunción Ventricular Derecha/diagnóstico por imagen , Enfermedad Aguda , Adulto , Anciano , Ecocardiografía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Evaluación de Resultado en la Atención de Salud , Pronóstico , Estudios Prospectivos , Medición de Riesgo , Índice de Severidad de la Enfermedad , Factores de Tiempo
12.
Oncoimmunology ; 7(2): e1382790, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29308302

RESUMEN

High-grade gliomas are malignant aggressive primary brain tumors with limited therapeutic options, and dismal prognosis for patients. Microglia, the resident immune cells of the brain, are recruited and reprogrammed into tumor-supporting cells by glioma cells, which in turn positively influence tumor expansion and infiltration into surrounding brain tissues. Here, we report that glioma-induced microglia conversion is coupled to an increase of histone H4 lysine 16 (H4K16) acetylation level in microglia, through increased nuclear localization of the deacetylase SIRT1, which in turn results in deacetylation of the H4K16 acetyltransferase hMOF and its recruitment to the chromatin at promoter regions of microglial target genes. Furthermore, we demonstrate that manipulation of the microglial H4K16 acetylation level, taking advantage of the intrinsic H4K16 deacetylase or acetyltransferase activities of SIRT1 and hMOF, respectively, modulated the tumor-supporting function of microglia. This study provides evidence that post-translational modifications of histones and the histone-modifying enzymes controlling them, such as H4K16 acetylation regulated by hMOF and SIRT1, are part of the microglial pro-tumoral activation pathway initiated by glioma cancer cells and represent potentially novel therapeutic targets.

13.
Nat Immunol ; 17(11): 1282-1290, 2016 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-27618552

RESUMEN

Glioma cells recruit and exploit microglia (the resident immune cells of the brain) for their proliferation and invasion ability. The underlying molecular mechanism used by glioma cells to transform microglia into a tumor-supporting phenotype has remained elusive. We found that glioma-induced microglia conversion was coupled to a reduction in the basal activity of microglial caspase-3 and increased S-nitrosylation of mitochondria-associated caspase-3 through inhibition of thioredoxin-2 activity, and that inhibition of caspase-3 regulated microglial tumor-supporting function. Furthermore, we identified the activity of nitric oxide synthase 2 (NOS2, also known as iNOS) originating from the glioma cells as a driving stimulus in the control of microglial caspase-3 activity. Repression of glioma NOS2 expression in vivo led to a reduction in both microglia recruitment and tumor expansion, whereas depletion of microglial caspase-3 gene promoted tumor growth. Our results provide evidence that inhibition of the denitrosylation of S-nitrosylated procaspase-3 mediated by the redox protein Trx2 is a part of the microglial pro-tumoral activation pathway initiated by glioma cancer cells.


Asunto(s)
Caspasa 3/metabolismo , Glioma/metabolismo , Glioma/patología , Microglía/metabolismo , Fenotipo , Animales , Línea Celular Tumoral , Movimiento Celular , Modelos Animales de Enfermedad , Activación Enzimática , Técnicas de Silenciamiento del Gen , Glioma/inmunología , Xenoinjertos , Humanos , Masculino , Ratones , Microglía/inmunología , Mitocondrias/metabolismo , Proteínas Mitocondriales/metabolismo , Óxido Nítrico Sintasa de Tipo II/genética , Óxido Nítrico Sintasa de Tipo II/metabolismo , Tiorredoxinas/metabolismo , Carga Tumoral
14.
Oncotarget ; 7(3): 2239-48, 2016 Jan 19.
Artículo en Inglés | MEDLINE | ID: mdl-26734998

RESUMEN

Cortical ischemia induces proliferation of neural stem/progenitor cells (NSPCs) in the subventricular zone (SVZ) and provokes migration of these cells toward the injured area. Despite sustained migration of NSPCs for an extended period of time after injury, they do not appear to survive. Here, we hypothesized that the anti-apoptotic broad-spectrum caspase inhibitor Q-VD-OPh would increase NSPC survival in the injured cortex. However, contrary to our expectations, caspase inhibition did not promote NSPC survival and cortical neurogenesis. On the contrary, it abolished ischemia-induced proliferation and decreased the number of migrating neuroblasts in the injured cortex. Moreover, caspase inhibition decreased the levels of the chemoattractant chemokine CCL2 (MCP-1) and the pro-inflammatory cytokine IL-1ß. We hence for the first time show that caspase inhibition abrogates the response of NSPCs to an ischemic injury, presumably by inhibiting the production of pro-inflammatory factors. Thus, caution is warranted if anti-apoptotic strategies are applied for neuroprotection.


Asunto(s)
Inhibidores de Caspasas/farmacología , Caspasas/metabolismo , Corteza Cerebral/patología , Hipoxia-Isquemia Encefálica/patología , Ventrículos Laterales/citología , Células-Madre Neurales/metabolismo , Clorometilcetonas de Aminoácidos/farmacología , Animales , Movimiento Celular , Proliferación Celular , Supervivencia Celular/efectos de los fármacos , Quimiocina CCL2/metabolismo , Femenino , Interleucina-1beta/metabolismo , Ratones , Ratones Endogámicos C57BL , Neurogénesis/efectos de los fármacos , Quinolinas/farmacología
15.
Glia ; 63(12): 2220-30, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26179283

RESUMEN

The mechanisms of neuronal injury after hypoxia-ischemia (HI) are different in the immature and the adult brain, but microglia activation has not been compared. The purpose of this study was to phenotype resident microglia and blood-derived macrophages in the hippocampus after HI in neonatal (postnatal day 9, P9) or adult (3 months of age, 3mo) mice. Unilateral brain injury after HI was induced in Cx3cr1(GFP/+) Ccr2(RFP/+) male mice on P9 (n = 34) or at 3mo (n = 53) using the Vannucci model. Resident microglia (Cx3cr1-GFP+) proliferated and were activated earlier after HI in the P9 (1-3 days) than that in the 3mo hippocampus, but remained longer in the adult brain (3-7 days). Blood-derived macrophages (Ccr2-RFP+) peaked 3 days after HI in both immature (P9) and adult (3mo) hippocampi but were twice as frequent in adult brains, 41% vs. 21% of all microglia/macrophages. CCL2 expression was three times higher in the P9 hippocampi, indicating that the proinflammatory response was more pronounced in the immature brain after HI. This corresponded well with the higher numbers of galectin-3-positive resident microglia in the P9 hippocampi, but did not correlate with CD16/32- or CD206-positive resident microglia or blood-derived macrophages. In conclusion, resident microglia, rather than infiltrating blood-derived macrophages, proliferate and are activated earlier in the immature than in the adult brain, but remain increased longer in the adult brain. The inflammatory response is more pronounced in the immature brain, and this correlate well with galectin-3 expression in resident microglia.


Asunto(s)
Hipocampo/inmunología , Hipoxia-Isquemia Encefálica/inmunología , Macrófagos/fisiología , Microglía/inmunología , Animales , Animales Recién Nacidos , Receptor 1 de Quimiocinas CX3C , Proteínas de Unión al Calcio/metabolismo , Recuento de Células , Modelos Animales de Enfermedad , Hipocampo/crecimiento & desarrollo , Hipocampo/patología , Hipoxia-Isquemia Encefálica/patología , Antígeno Ki-67/metabolismo , Lectinas Tipo C/metabolismo , Macrófagos/patología , Masculino , Lectinas de Unión a Manosa/metabolismo , Ratones Transgénicos , Proteínas de Microfilamentos/metabolismo , Microglía/patología , Receptores CCR2/genética , Receptores CCR2/metabolismo , Receptores de Superficie Celular/metabolismo , Receptores de Quimiocina/genética , Receptores de Quimiocina/metabolismo , Receptores de IgG/metabolismo , Factores de Tiempo
16.
Biochimie ; 101: 208-14, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-24491357

RESUMEN

Here, we report evidence that matrin 3 (MATR3), a highly conserved inner nuclear matrix phosphoprotein, whose function is largely unknown, interacts specifically with the heat shock proteins glucose-regulated protein 78 (GRP78), GRP75 and glutathione S-transferase π isoform 2 (GSTπ2). Using immunoprecipitation experiments of lysates obtained from control and tributyltin oxide (TBTO)-treated thymoma cell line (EL4), we identified MATR3 and its partners by MS/MS analysis and confirmed by immunoblot. We also show that MATR3 undergoes degradation as reported before and that this cleavage process, which is inhibited by the broad-spectrum caspase inhibitor, z-VAD-FMK, is more marked in TBTO-treated cells. Further, we found that the heat shock protein glucose-regulated protein 78 was downregulated in the TBTO-treated cells. The GRP78 protein is known to protect cells from apoptosis by complexing with procaspase 7 thereby preventing caspase activation cascade. By immunoblot analysis, we found that the levels of procaspases-3 and -7 were lower in TBTO-treated cells; in contrast, the level of p20, the active form of caspase 3, was relatively higher in the treated cells compared to that of control cells. We propose that the TBTO-mediated downregulation of GRP78 triggers the caspase cascade pathway leading to MATR3 degradation.


Asunto(s)
Gutatión-S-Transferasa pi/metabolismo , Proteínas HSP70 de Choque Térmico/metabolismo , Proteínas de Choque Térmico/metabolismo , Proteínas de la Membrana/metabolismo , Proteínas Asociadas a Matriz Nuclear/metabolismo , Proteínas de Unión al ARN/metabolismo , Secuencia de Aminoácidos , Animales , Antineoplásicos/farmacología , Caspasa 3/metabolismo , Caspasa 7/metabolismo , Línea Celular Tumoral , Regulación hacia Abajo , Inmunoprecipitación , Inmunosupresores/farmacología , Ratones , Datos de Secuencia Molecular , Unión Proteica , Timoma , Compuestos de Trialquiltina/farmacología
17.
Cell Transplant ; 23(12): 1657-71, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24152680

RESUMEN

Radiotherapy is an effective treatment for brain tumors but often results in cognitive deficits in survivors. Transplantation of embryonic or brain-derived neural stem/progenitor cells (BNSPCs) ameliorated cognitive impairment after irradiation (IR) in animal models. However, such an approach in patients requires a clinically relevant source of cells. We show for the first time the utilization of enteric neural stem/progenitor cells (ENSPCs) from the postnatal intestinal wall as a source of autologous cells for brain repair after injury caused by IR. Cells were isolated from the intestinal wall and propagated in vitro for 1 week. Differentiation assays showed that ENSPCs are multipotent and generated neurons, astrocytes, and myofibroblasts. To investigate whether ENSPCs can be used in vivo, postnatal day 9 mice were subjected to a single moderate irradiation dose (6 or 8 Gy). Twelve days later, mice received an intrahippocampal injection of syngeneic ENSPCs. Four weeks after transplantation, 0.5% and 1% of grafted ENSPCs were detected in the dentate gyrus of sham and irradiated animals, respectively, and only 0.1% was detected after 16 weeks. Grafted ENSPCs remained undifferentiated but failed to restore IR-induced loss of BNSPCs and the subsequent impaired growth of the dentate gyrus. We observed microglia activation, astrogliosis, and loss of granule neurons associated with grafted ENSPC clusters. Transplantation of ENSPCs did not ameliorate IR-induced impaired learning and memory. In summary, while autologous ENSPC grafting to the brain worked technically, even in the absence of immunosuppression, the protocols need to be modified to improve survival and integration.


Asunto(s)
Envejecimiento/fisiología , Sistema Nervioso Entérico/citología , Hipocampo/citología , Hipocampo/efectos de la radiación , Rayos Infrarrojos , Células-Madre Neurales/citología , Células-Madre Neurales/trasplante , Animales , Diferenciación Celular/efectos de la radiación , Femenino , Inflamación/patología , Aprendizaje , Ratones Endogámicos C57BL , Microglía/metabolismo , Microglía/efectos de la radiación , Neurogénesis/efectos de la radiación
18.
J Appl Toxicol ; 34(12): 1361-7, 2014 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-24375594

RESUMEN

We treated the thymoma cell line (EL4) with two model immunosuppressants, rapamycin and tributyltin oxide (TBTO), and compared their effects on the expression levels of proteins that are downstream targets of mTOR kinase 1 (mammalian target of rapamycin, known also as mechanistic target of rapamycin): p70 ribosomal S6 kinase1 and 4E-binding protein 1, a repressor of the cap-binding protein eIF4E. In addition, we evaluated the levels of ribosomal protein S6, p-eIF4B, substrates of p70S6 kinase1, matrin 3 and ribonucleotide reductase, subunit RRM2. The levels of these proteins were evaluated in cell lysates by immunoblot. We found that both compounds inhibited the phosphorylation state of p70S6 kinase 1 and its substrates; however, TBTO, in contrast to rapamycin, reduced the level of the total p70S6k1. Besides, we detected a band with a molecular weight of c. 32 kDa only in the TBTO-treated lysates. This band was detected with a monoclonal antibody specific for S6k1, suggesting that this band might be a degradation product of the kinase. Further, TBTO and rapamycin differentially affected 4E-binding protein 1; the former compound stimulated its phosphorylation state whereas the latter inhibited it. The two immunosuppressants did not affect the level of ribonucleotide reductase, but TBTO downregulated matrin3, in agreement with a previous report, whereas rapamycin had no effect on the expression level of this latter protein. We conclude that TBTO inhibits, like rapamycin, the p70 S6 kinase 1 pathway, but with a different mechanism. However, in contrast to rapamycin, which inhibits the cap-dependent translation, TBTO increases the phosphorylation of 4E-binding protein1.


Asunto(s)
Inmunosupresores/toxicidad , Transducción de Señal/efectos de los fármacos , Sirolimus/farmacología , Serina-Treonina Quinasas TOR/antagonistas & inhibidores , Timo/efectos de los fármacos , Compuestos de Trialquiltina/toxicidad , Animales , Western Blotting , Línea Celular Tumoral , Electroforesis en Gel de Poliacrilamida , Ratones , Fosforilación , Proteínas Quinasas S6 Ribosómicas 70-kDa/metabolismo , Timo/inmunología , Timo/metabolismo
19.
Brain Res ; 1503: 62-77, 2013 Mar 29.
Artículo en Inglés | MEDLINE | ID: mdl-23391595

RESUMEN

Hyaluronan is a large glycosaminoglycan, which is abundant in the extracellular matrix of the developing rodent brain. In the adult brain however, levels of hyaluronan are significantly reduced. In this study, we used neurocan-GFP as a histochemical probe to analyze the distribution of hyaluronan in the adult mouse subventricular zone (SVZ), as well as in the rostral migratory stream (RMS). Interestingly, we observed that hyaluronan is generally downregulated in the adult brain, but notably remains at high levels in the SVZ and RMS; areas in which neural stem/progenitor cells (NSPCs) persist, proliferate and migrate throughout life. In addition, we found that the receptor for hyaluronan-mediated motility (Rhamm) was expressed in migrating neuroblasts in these areas, indicating that Rhamm could be involved in regulating hyaluronan-mediated cell migration. Hyaluronan levels are balanced by synthesis through hyaluronan synthases (Has) and degradation by hyaluronidases (Hyal). We found that Has1 and Has2, as well as Hyal1 and Hyal2 were expressed in GFAP positive cells in the adult rodent SVZ and RMS, indicating that astrocytes could be regulating hyaluronan-mediated functions in these areas. We also demonstrate that hyaluronan levels are substantially increased at six weeks following a photothrombotic stroke lesion to the adult mouse cortex. Furthermore, GFAP positive cells in the peri-infarct area express Rhamm. Thus, hyaluronan may be involved in regulating cell migration in the normal SVZ and RMS and could also be responsible for priming the peri-infarct area following an ischemic lesion for cell migration.


Asunto(s)
Isquemia Encefálica/patología , Movimiento Celular/fisiología , Corteza Cerebral/metabolismo , Ventrículos Cerebrales/patología , Proteínas de la Matriz Extracelular/metabolismo , Receptores de Hialuranos/metabolismo , Ácido Hialurónico/metabolismo , Células Madre Adultas/fisiología , Animales , Línea Celular Transformada , Proliferación Celular , Modelos Animales de Enfermedad , Lateralidad Funcional , Regulación de la Expresión Génica/fisiología , Proteína Ácida Fibrilar de la Glía/metabolismo , Glucuronosiltransferasa/genética , Glucuronosiltransferasa/metabolismo , Proteínas Fluorescentes Verdes/genética , Proteínas Fluorescentes Verdes/metabolismo , Humanos , Ácido Hialurónico/clasificación , Ratones , Ratones Endogámicos C57BL , Proteínas Asociadas a Microtúbulos/metabolismo , Molécula L1 de Adhesión de Célula Nerviosa/metabolismo , Neurocano/genética , Neurocano/metabolismo , Neuropéptidos/metabolismo , Ácidos Siálicos/metabolismo , Transfección
20.
Toxicol Sci ; 126(1): 84-100, 2012 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-22174045

RESUMEN

We report the results of phosphoproteomic analysis of mouse thymoma cells treated with tributyltin oxide (TBTO), an immunotoxic compound. After cell lysis, phosphoproteins were isolated using Phosphoprotein Purification Kit, separated by SDS-PAGE and subsequently digested with trypsin. Phosphopeptides were enriched employing titanium dioxide, and the obtained fractions were analyzed by nano-LC-MS/MS. A total of 160 phosphoproteins and 328 phosphorylation sites were identified in thymoma cells. Among the differentially phosphorylated proteins identified in TBTO-treated cells were key enzymes, which catalyze rate-limiting steps in pathways that are sensitive to cellular energy status. These proteins included acetyl-CoA carboxylase isoform 1, which catalyzes the rate-limiting step of fatty acid synthesis. Another enzyme was glutamine: fructose-6-phosphate amidotransferase, GFAT1, the first and rate-limiting enzyme for the hexoamine synthesis pathway. Pyruvate dehydrogenase (PDH), a multicomplex enzyme that catalyzes the rate-limiting step of aerobic oxidation of fuel carbohydrates, was identified in both TBTO-treated and control cells; however, phosphorylation at residue S293, known to inhibit PDH activity, was identified only in control cells. A lower expression level of ribosomal protein S6 kinase 1, a downstream kinase of the mammalian target of rapamycin signaling pathway implicated in protein synthesis through phosphorylation of 40 ribosomal S6, was observed in the treated cells. Giant kinases like AMP-activated protein kinase (AMPK) and cAMP-dependent protein kinase (PKAR1A), which are known to mediate the phosphorylation of these enzymes, were identified in TBTO-treated cells. Downregulation of proteins, such as MAPK, matrin-3 and ribonucleotide reductase, subunit RRM2, which are implicated in cell proliferation, was also observed in TBTO-treated cells. Together, the results show that TBTO affects proliferation and energy sensor pathways.


Asunto(s)
Proliferación Celular/efectos de los fármacos , Metabolismo Energético/efectos de los fármacos , Contaminantes Ambientales/toxicidad , Fosfoproteínas/metabolismo , Timo/efectos de los fármacos , Compuestos de Trialquiltina/toxicidad , Acetil-CoA Carboxilasa/química , Acetil-CoA Carboxilasa/metabolismo , Animales , Línea Celular Tumoral , Cromatografía Líquida de Alta Presión , Glutamina-Fructosa-6-Fosfato Transaminasa (Isomerizadora) , Isoenzimas/química , Isoenzimas/metabolismo , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Ratones , Microtecnología , Transferasas de Grupos Nitrogenados/química , Transferasas de Grupos Nitrogenados/metabolismo , Proteínas Asociadas a Matriz Nuclear/química , Proteínas Asociadas a Matriz Nuclear/metabolismo , Fosfoproteínas/química , Fosfoproteínas/aislamiento & purificación , Fosforilación/efectos de los fármacos , Procesamiento Proteico-Postraduccional/efectos de los fármacos , Proteómica/métodos , Complejo Piruvato Deshidrogenasa/química , Complejo Piruvato Deshidrogenasa/metabolismo , Proteínas de Unión al ARN/química , Proteínas de Unión al ARN/metabolismo , Espectrometría de Masas en Tándem , Timo/metabolismo
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...