Sujet(s)
Humains , Pneumopathie virale/prévention et contrôle , Infections à coronavirus/prévention et contrôle , Ventilation en pression positive continue/normes , Ventilation non effractive/normes , Pneumopathie virale/complications , Pneumopathie virale/thérapie , Insuffisance respiratoire/étiologie , Insuffisance respiratoire/thérapie , Protocoles cliniques , Infection croisée/prévention et contrôle , Infections à coronavirus/complications , Infections à coronavirus/thérapie , Pandémies/prévention et contrôle , Ventilation non effractive/méthodes , BetacoronavirusRÉSUMÉ
La fibrosis pulmonar idiopática (FPI) se caracteriza por presentar una capacidad funcional reducida, disnea e hipoxia inducida por el ejercicio, lo que disminuye su tolerancia al esfuerzo y limita su capacidad de realizar actividades diarias. Las comorbilidades son frecuentes y su presencia contribuyen al empeoramiento de la calidad de vida y aumento de la mortalidad. Por lo anterior, es que además de las terapias antifibróticas, los pacientes con FPI se benefician de un enfoque integral de la atención que puede incluir: pesquisa, diagnóstico y tratamiento de comorbilidades, ingreso a protocolos de investigación, manejo sintomático, cuidados paliativos, oxígeno suplementario, rehabilitación pulmonar, educación y apoyo por un equipo multidisciplinario.
Idiopathic pulmonary fibrosis (IPF) is characterized by reduced functional capacity, dyspnea and exercise-induced hypoxia, which decreases tolerance to exertion and limits the ability to perform daily activities. Comorbidities are frequent and their presence contribute to worsening quality of life and increased mortality. Therefore, in addition to antifibrotic therapies, patients with IPF benefit of a comprehensive approach to care that may include: screening, diagnosis and treatment of comorbidities, admission to research protocols, symptomatic management, palliative care, supplementary oxygen, pulmonary rehabilitation, education and support by a multidisciplinary team.
Sujet(s)
Humains , Fibrose pulmonaire idiopathique/thérapie , Fibrose pulmonaire idiopathique/épidémiologie , Oxygénothérapie , Équipe soignante , Comorbidité , Traitement médicamenteux adjuvant , Toux/étiologie , Dyspnée/étiologie , Fibrose pulmonaire idiopathique/complications , Fibrose pulmonaire idiopathique/traitement médicamenteuxRÉSUMÉ
Neuropathic pain (NP) is highly disabling, responds poorly to pharmacological treatment, and represents a significant cause of decreased quality of life in patients suffering from spinal cord injury (SCI). In recent years, cell therapy with autologous mesenchymal stromal cells (MSCs) has been considered as a potential therapeutic weapon in this entity. Ten patients suffering chronic SCI received 100 million MSCs into subarachnoid space by lumbar puncture (month 1 of the study) and this procedure was repeated at months 4 and 7 until reaching a total doses of 300 million MSCs. Intensity of NP was measured by standard numerical rating scale (VAS) from 0 to 10, recording scores previous to the first MSCs administration and monthly, until month 10 of follow-up. Months 1, 4, 7 and 10 of the study were selected as time points in order to a statistical analysis by the nonparametric Wilcoxon rank test. Our results showed significant and progressive improvement in NP intensity after the first administration of MSCs (p: 0.003). This study supports the benefit of intrathecal administration of autologous MSCs for the treatment of NP in patients with SCI.
Sujet(s)
Transplantation de cellules souches mésenchymateuses/méthodes , Cellules souches mésenchymateuses , Névralgie/thérapie , Traumatismes de la moelle épinière/complications , Adulte , Femelle , Humains , Mâle , Adulte d'âge moyen , Névralgie/étiologie , Résultat thérapeutiqueRÉSUMÉ
Anti-vascular endothelial growth factor (VEGF) therapy has demonstrated efficacy in treating human metastatic cancers, but therapeutic resistance is a practical limitation and most tumors eventually become unresponsive. To identify microenvironmental factors underlying the resistance of cancer to antiangiogenesis therapy, we conducted genomic analyses of intraperitoneal ovarian tumors in which adaptive resistance to anti-VEGF therapy (B20 antibody) developed. We found that expression of the microseminoprotein, prostate-associated (MSMP) gene was substantially upregulated in resistant compared with control tumors. MSMP secretion from cancer cells was induced by hypoxia, triggering MAPK signaling in endothelial cells to promote tube formation in vitro. Recruitment of the transcriptional repressor CCCTC-binding factor (CTCF) to the MSMP enhancer region was decreased by histone acetylation under hypoxic conditions in cancer cells. MSMP siRNA, delivered in vivo using the DOPC nanoliposomes, restored tumor sensitivity to anti-VEGF therapy. In ovarian cancer patients treated with bevacizumab, serum MSMP concentration increased significantly only in non-responders. These findings imply that MSMP inhibition combined with the use of antiangiogenesis drugs may be a new strategy to overcome resistance to antiangiogenesis therapy.
Sujet(s)
Bévacizumab/pharmacologie , Carcinome épithélial de l'ovaire/anatomopathologie , Résistance aux médicaments antinéoplasiques , Tumeurs de la trompe de Fallope/anatomopathologie , Protéines tumorales/métabolisme , Tumeurs du péritoine/anatomopathologie , Facteur de croissance endothéliale vasculaire de type A/antagonistes et inhibiteurs , Inhibiteurs de l'angiogenèse/pharmacologie , Animaux , Apoptose , Marqueurs biologiques tumoraux , Carcinome épithélial de l'ovaire/traitement médicamenteux , Carcinome épithélial de l'ovaire/métabolisme , Hypoxie cellulaire , Prolifération cellulaire , Tumeurs de la trompe de Fallope/traitement médicamenteux , Tumeurs de la trompe de Fallope/métabolisme , Femelle , Études de suivi , Humains , Mâle , Souris , Souris nude , Protéines tumorales/génétique , Néovascularisation pathologique , Tumeurs du péritoine/traitement médicamenteux , Tumeurs du péritoine/métabolisme , Pronostic , Cellules cancéreuses en culture , Tests d'activité antitumorale sur modèle de xénogreffeRÉSUMÉ
Resumen Las reacciones de hipersensibilidad a corticoides son raras en la población general, se dividen en dos categorías: Inmediatas, típicamente mediadas por Inmunoglobulina E (IgE), donde se incluye la anafilaxia luego de la administración de un fármaco en un corto período. Su prevalencia descrita es de 0,3-0,5%. Otra reacción es la 'no inmediata', que se manifiesta en un tiempo mayor de una hora después de la administración del fármaco. Se revisó la literatura con el objetivo de mejorar y aclarar el tratamiento en pacientes asmáticos que poseen esta condición. Se encontró que las vías posibles para generar estas reacciones son intranasal, aerosol por inhalador, oral y parenteral. Frente a esta condición se requiere una evaluación estrecha y detallada de la historia clínica, síntomas y reacciones secundarias al fármaco sospechoso. Finalmente, al momento de elegir tipo de corticoide a usar es primordial la seguridad del paciente logrando, además, el control de la enfermedad.
Hypersensitivity reactions to corticosteroids are rare in the general population, they fall into two categories: 'immediate', typically mediated by immunoglobulin E (IgE), which includes anaphylaxis after administration of a drug in a short period of time. Its reported prevalence is 0.3-0.5%. Another reaction is 'not immediate', which manifests itself in a time longer than one hour after the administration of the drug. We reviewed the literature with the aim of improving and clarifying the treatment in asthmatic patients with this condition. It was found that the possible routes to generate these reactions are intranasal, aerosol by inhaler, oral and parenteral. Facing this condition requires a close and detailed evaluation of the clinical history, symptoms and side reactions to the suspected drug. Finally, when choosing which corticosteroid to use, the patient's safety is paramount, and control of the disease is also essential.
Sujet(s)
Humains , Femelle , Sujet âgé , Asthme/physiopathologie , Nébuliseurs et vaporisateurs , Hypersensibilité/diagnostic , Anaphylaxie/diagnostic , Anaphylaxie/thérapie , Immunoglobuline E/immunologie , Immunoglobuline E/sang , Hormones corticosurrénaliennes/déficit , Salbutamol/administration et posologie , Anaphylaxie/étiologieRÉSUMÉ
OBJECTIVES: Shigella sonnei is a globally important diarrhoeal pathogen tracked through the surveillance network PulseNet Latin America and Caribbean (PNLA&C), which participates in PulseNet International. PNLA&C laboratories use common molecular techniques to track pathogens causing foodborne illness. We aimed to demonstrate the possibility and advantages of transitioning to whole genome sequencing (WGS) for surveillance within existing networks across a continent where S. sonnei is endemic. METHODS: We applied WGS to representative archive isolates of S. sonnei (n = 323) from laboratories in nine PNLA&C countries to generate a regional phylogenomic reference for S. sonnei and put this in the global context. We used this reference to contextualise 16 S. sonnei from three Argentinian outbreaks, using locally generated sequence data. Assembled genome sequences were used to predict antimicrobial resistance (AMR) phenotypes and identify AMR determinants. RESULTS: S. sonnei isolates clustered in five Latin American sublineages in the global phylogeny, with many (46%, 149 of 323) belonging to previously undescribed sublineages. Predicted multidrug resistance was common (77%, 249 of 323), and clinically relevant differences in AMR were found among sublineages. The regional overview showed that Argentinian outbreak isolates belonged to distinct sublineages and had different epidemiologic origins. CONCLUSIONS: Latin America contains novel genetic diversity of S. sonnei that is relevant on a global scale and commonly exhibits multidrug resistance. Retrospective passive surveillance with WGS has utility for informing treatment, identifying regionally epidemic sublineages and providing a framework for interpretation of prospective, locally sequenced outbreaks.
Sujet(s)
Dysenterie bacillaire , Maladies d'origine alimentaire , Shigella sonnei/génétique , Caraïbe/épidémiologie , ADN bactérien/analyse , ADN bactérien/génétique , Épidémies de maladies/prévention et contrôle , Épidémies de maladies/statistiques et données numériques , Résistance bactérienne aux médicaments , Dysenterie bacillaire/épidémiologie , Dysenterie bacillaire/microbiologie , Maladies d'origine alimentaire/épidémiologie , Maladies d'origine alimentaire/microbiologie , Humains , Amérique latine/épidémiologie , Surveillance de la santé publique , Études rétrospectives , Shigella sonnei/effets des médicaments et des substances chimiques , Séquençage du génome entierRÉSUMÉ
KRas is mutated in a significant number of human cancers and so there is an urgent therapeutic need to target KRas signalling. To target KRas in lung cancers we used a systems approach of integrating a genome-wide miRNA screen with patient-derived phospho-proteomic signatures of the KRas downstream pathway, and identified miR-193a-3p, which directly targets KRas. Unique aspects of miR-193a-3p biology include two functionally independent target sites in the KRas 3'UTR and clinically significant correlation between miR-193a-3p and KRas expression in patients. Rescue experiments with mutated KRas 3'UTR showed very significantly that the anti-tumour effect of miR-193a-3p is via specific direct targeting of KRas and not due to other targets. Ex vivo and in vivo studies utilizing nanoliposome packaged miR-193a-3p demonstrated significant inhibition of tumour growth, circulating tumour cell viability and decreased metastasis. These studies show the broader applicability of using miR-193a-3p as a therapeutic agent to target KRas-mutant cancer.
Sujet(s)
Régulation de l'expression des gènes tumoraux , microARN/génétique , Tumeurs/génétique , Tumeurs/anatomopathologie , Cellules tumorales circulantes/métabolisme , Protéines proto-oncogènes p21(ras)/génétique , Interférence par ARN , Régions 3' non traduites , Cycle cellulaire , Lignée cellulaire tumorale , Bases de données génétiques , Gènes rapporteurs , Humains , Métastase tumorale , Cellules tumorales circulantes/anatomopathologie , ARN messager/génétiqueRÉSUMÉ
El traqueostoma persistente es la complicación tardía más frecuente asociada al uso de traqueostomía. Se reportan tres casos de pacientes que se les realizó un cierre exitoso del traqueostoma persistente mediante técnica de cierre primario por planos con colgajo invertido. Las ventajas del método utilizado son que representa una alternativa simple, susceptible de realizar con anestesia local y de manera ambulatoria, con excelentes resultados estéticos, mejorando significativamente la calidad de vida de estos pacientes.
Persistent tracheostoma is the most common late complication associated with the use of tracheostomy. We report three cases in which patients underwent a successful closure of persistent tracheostoma using primary closure in layers with inverted flap technique. The advantages of this method are that it represents a simple alternative and is able to be performed under local anesthesia on an outpatient basis, with excellent aesthetic results, significantly improving the quality of life of these patients.
Sujet(s)
Humains , Adulte , Adulte d'âge moyen , Fistule cutanée/chirurgie , Lambeaux chirurgicaux , Maladie de la trachée/chirurgie , Trachéostomie/effets indésirables , Fistule cutanée/étiologie , Techniques de suture , Maladie de la trachée/étiologieRÉSUMÉ
Testicular germ cell tumors (TGCTs) are the most common solid tumors in young adult men. They constitute a unique pathology because of their embryonic and germ origin and their special behavior. Genetic predisposition, environmental factors involved in their development and genetic aberrations have been under study in many works throughout the last years trying to explain the susceptibility and the transformation mechanism of TGCTs. Despite the high rate of cure in this type of tumors because its particular sensitivity to cisplatin, there are tumors resistant to chemotherapy for which it is needed to find new therapies. In the present work, it has been carried out a literature review on the most important molecular aspects involved in the onset and development of such tumors, as well as a review of the major developments regarding prognostic factors, new prognostic biomarkers and the possibility of new targeted therapies (AU)
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Sujet(s)
Humains , Mâle , Jeune adulte , Tumeurs embryonnaires et germinales/diagnostic , Biologie moléculaire/méthodes , Biologie moléculaire/normes , Tumeurs du testicule/diagnostic , Cisplatine/analyse , Cisplatine/isolement et purification , Pronostic , Séminome/diagnostic , Analyse de profil d'expression de gènes/méthodes , Analyse de profil d'expression de gènes/normes , Dépistage génétique/méthodes , Prédisposition génétique à une maladie/génétique , Transformation cellulaire néoplasique/génétique , Transformation cellulaire néoplasique/anatomopathologie , Isochromosomes/génétique , Isochromosomes/physiologieRÉSUMÉ
MicroRNAs (miRNAs) are small RNA molecules that affect cellular processes by controlling gene expression. Recent studies have shown that hypoxia downregulates Drosha and Dicer, key enzymes in miRNA biogenesis, causing a decreased pool of miRNAs in cancer and resulting in increased tumor growth and metastasis. Here we demonstrate a previously unrecognized mechanism by which hypoxia downregulates Dicer. We found that miR-630, which is upregulated under hypoxic conditions, targets and downregulates Dicer expression. In an orthotopic mouse model of ovarian cancer, delivery of miR-630 using 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) nanoliposomes resulted in increased tumor growth and metastasis, and decreased Dicer expression. Treatment with the combination of anti-miR-630 and anti-vascular endothelial growth factor antibody in mice resulted in rescue of Dicer expression and significantly decreased tumor growth and metastasis. These results indicate that targeting miR-630 is a promising approach to overcome Dicer deregulation in cancer. As demonstrated in the study, use of DOPC nanoliposomes for anti-miR delivery serves as a better alternative approach to cell line-based overexpression of sense or antisense miRNAs, while avoiding potential in vitro selection effects. Findings from this study provide a new understanding of miRNA biogenesis downregulation observed under hypoxia and suggest therapeutic avenues to target this dysregulation in cancer.
Sujet(s)
Hypoxie cellulaire , DEAD-box RNA helicases/génétique , Régulation de l'expression des gènes tumoraux , microARN/physiologie , Tumeurs/étiologie , Ribonuclease III/génétique , Animaux , Lignée cellulaire tumorale , Évolution de la maladie , Femelle , Humains , Liposomes , Souris , microARN/antagonistes et inhibiteurs , Tumeurs/thérapie , Tumeurs de l'ovaire/métabolisme , Phosphatidylcholines/administration et posologie , Facteur de croissance endothéliale vasculaire de type A/antagonistes et inhibiteursRÉSUMÉ
Adrenergic stimulation adversely affects tumor growth and metastasis, but the underlying mechanisms are not well understood. Here, we uncovered a novel mechanism by which catecholamines induce inflammation by increasing prostaglandin E2 (PGE2) levels in ovarian cancer cells. Metabolic changes in tumors isolated from patients with depression and mice subjected to restraint stress showed elevated PGE2 levels. Increased metabolites, PTGS2 and PTGES protein levels were found in Skov3-ip1 and HeyA8 cells treated with norepinephrine (NE), and these changes were shown to be mediated by ADRB2 receptor signaling. Silencing PTGS2 resulted in significantly decreased migration and invasion in ovarian cancer cells in the presence of NE and decreased tumor burden and metastasis in restraint stress orthotopic models. In human ovarian cancer samples, concurrent increased ADRB2, PTGS2 and PTGES expression was associated with reduced overall and progression-free patient survival. In conclusion, increased adrenergic stimulation results in increased PGE2 synthesis via ADRB2-Nf-kB-PTGS2 axis, which drives tumor growth and metastasis.
Sujet(s)
Dinoprostone/biosynthèse , Norépinéphrine/métabolisme , Tumeurs de l'ovaire/métabolisme , Tumeurs de l'ovaire/anatomopathologie , Transduction du signal , Animaux , Lignée cellulaire tumorale , Cyclooxygenase 2/déficit , Cyclooxygenase 2/génétique , Femelle , Extinction de l'expression des gènes , Humains , Souris , Métastase tumorale , Prostaglandin-E synthases/métabolismeRÉSUMÉ
The myc oncogene is overexpressed in almost half of all breast and ovarian cancers, but attempts at therapeutic interventions against myc have proven to be challenging. Myc regulates multiple biological processes, including the cell cycle, and as such is associated with cell proliferation and tumor progression. We identified a protein signature of high myc, low p27 and high phospho-Rb significantly correlated with poor patient survival in breast and ovarian cancers. Screening of a miRNA library by functional proteomics in multiple cell lines and integration of data from patient tumors revealed a panel of five microRNAs (miRNAs) (miR-124, miR-365, miR-34b*, miR-18a and miR-506) as potential tumor suppressors capable of reversing the p27/myc/phospho-Rb protein signature. Mechanistic studies revealed an RNA-activation function of miR-124 resulting in direct induction of p27 protein levels by binding to and inducing transcription on the p27 promoter region leading to a subsequent G1 arrest. Additionally, in vivo studies utilizing a xenograft model demonstrated that nanoparticle-mediated delivery of miR-124 could reduce tumor growth and sensitize cells to etoposide, suggesting a clinical application of miRNAs as therapeutics to target the functional effect of myc on tumor growth.
Sujet(s)
Tumeurs du sein/génétique , Inhibiteur p27 de kinase cycline-dépendante/génétique , Régulation de l'expression des gènes tumoraux , Gènes myc , microARN/physiologie , Tumeurs de l'ovaire/génétique , Protéine du rétinoblastome/génétique , Tumeurs du sein/métabolisme , Tumeurs du sein/mortalité , Tumeurs du sein/anatomopathologie , Inhibiteur p27 de kinase cycline-dépendante/métabolisme , Femelle , Humains , Tumeurs de l'ovaire/métabolisme , Tumeurs de l'ovaire/mortalité , Tumeurs de l'ovaire/anatomopathologie , Phosphoprotéines/métabolisme , Protéomique/méthodes , Protéine du rétinoblastome/métabolisme , Transcriptome , Cellules cancéreuses en cultureRÉSUMÉ
Zika virus (ZIKV) is an emerging mosquito-borne flavivirus circulating in Asia and Africa. In 2013, a large outbreak was reported on the archipelago of French Polynesia. In this study, we report the detection and molecular characterization of Zika virus for the first time in Chile from an outbreak among the inhabitants of Easter Island. A total of 89 samples from patients suspected of having ZIKV infection were collected between the period from January to May, 2014. Molecular diagnosis of the virus was performed by RT-PCR followed by the sequencing of the region containing the NS5 gene. A comparison of the viral nucleic acid sequence with those of other strains of ZIKA virus was performed using the MEGA software. Fifty-one samples were found positive for ZIKV by RT-PCR analysis. Further analysis of the NS5 gene revealed that the ZIKV strains identified in Easter Island were most closely related to those found in French Polynesia (99.8 to 99.9% nt and 100% aa sequence identity). These results strongly suggest that the transmission pathway leading to the introduction of Zika virus on Easter Island has its origin in French Polynesia.
Sujet(s)
Épidémies de maladies , Infection par le virus Zika/épidémiologie , Virus Zika/isolement et purification , Analyse de regroupements , Humains , Épidémiologie moléculaire , Phylogenèse , Polynésie/épidémiologie , ARN viral/génétique , RT-PCR , Analyse de séquence d'ADN , Similitude de séquences , Virus Zika/classification , Virus Zika/génétiqueRÉSUMÉ
Testicular germ cell tumors (TGCTs) are the most common solid tumors in young adult men. They constitute a unique pathology because of their embryonic and germ origin and their special behavior. Genetic predisposition, environmental factors involved in their development and genetic aberrations have been under study in many works throughout the last years trying to explain the susceptibility and the transformation mechanism of TGCTs. Despite the high rate of cure in this type of tumors because its particular sensitivity to cisplatin, there are tumors resistant to chemotherapy for which it is needed to find new therapies. In the present work, it has been carried out a literature review on the most important molecular aspects involved in the onset and development of such tumors, as well as a review of the major developments regarding prognostic factors, new prognostic biomarkers and the possibility of new targeted therapies.
Sujet(s)
Tumeurs embryonnaires et germinales/génétique , Tumeurs du testicule/génétique , Humains , Mâle , Biologie moléculaire/méthodes , Biologie moléculaire/tendances , Tumeurs embryonnaires et germinales/thérapie , Tumeurs du testicule/thérapieRÉSUMÉ
Clostridium difficile infection has gained importance in recent years as a result of the rapid spread of epidemic strains, including hypervirulent strains. This study reports the molecular epidemiology of C. difficile obtained from hospitalized patients in Chile. Seven hundred and nineteen isolates of toxigenic C. difficile from 45 hospitals across the country were characterized through toxin profile, pulsed-field gel electrophoresis (PFGE), and sequencing of the tcdC gene. In addition, polymerase chain reaction (PCR) ribotyping and multilocus sequence typing (MLST) were performed on a subset of selected strains. PFGE typing of 719 isolates of C. difficile produced 60 PFGE patterns (subtypes). Subtype 1 was predominant (79% of isolates) and related to the hypervirulent strain (NAP1). Subtype 1 showed 73% relatedness with nine other subtypes, which had a similar tcdC deletion. Subtype 1 corresponded to ribotype 027 and ST1. This report shows the wide dissemination of the hypervirulent strain NAP1/027/ST1 in Chile.
Sujet(s)
Clostridioides difficile/isolement et purification , Infections à Clostridium/épidémiologie , Infections à Clostridium/microbiologie , Épidémies , Adolescent , Adulte , Sujet âgé , Sujet âgé de 80 ans ou plus , Toxines bactériennes/génétique , Enfant , Enfant d'âge préscolaire , Chili/épidémiologie , Clostridioides difficile/classification , Clostridioides difficile/génétique , Analyse de regroupements , Électrophorèse en champ pulsé , Femelle , Génotype , Hôpitaux , Humains , Nourrisson , Nouveau-né , Mâle , Adulte d'âge moyen , Épidémiologie moléculaire , Typage par séquençage multilocus , Ribotypage , Jeune adulteRÉSUMÉ
Objetivo: Analizar la morfología medular en pacientes con paraplejia traumática crónica a nivel dorsal, en vistas a su posible inclusión en ensayos de terapia celular. Material y método: Se han valorado los estudios de Resonancia Magnética (RM) en 100 pacientes con paraplejia traumática a nivel dorsal (ASIA A) que han solicitado ser incluidos en un ensayo clínico de terapia celular. Resultados: En el 14% de los casos, la presencia de artefactos impidió el estudio. Un 30% mostró grandes deformidades cifóticas vertebrales, con ocupación del canal raquídeo. Entre los pacientes con un correcto estudio morfológico, el 16% mostró una sección medular completa y el 12% interrupción prácticamente total, persistiendo solo algunos tractos de tejido entre los bordes de sección medular. En el 83% de los casos se observaron quistes intramedulares, con un volumen medio de 0,95 ± 0,89 cc. Una cavitación extensa, identificable como siringomielia postraumática, se vio solo en tres pacientes. Un grado variable de atrofia medular, generalmente segmentaria, se apreció en más del 60% de los pacientes estudiados. Conclusión: Si se considera, de acuerdo con experiencias preclínicas, que una continuidad anatómica de la médula y lesiones intramedulares limitadas son criterios de posible eficacia de la terapia celular, estos datos sugieren que solo aproximadamente el 30% de los pacientes con una paraplejia traumática crónicamente establecida, a nivel dorsal, podrían ser razonablemente válidos para entrar en estos ensayos (AU)
Objective: To analyze the spinal cord morphology in patients with chronic traumatic paraplegia at the thoracic level, for a possible inclusion in trials of cell therapy. Material and method: We reviewed Magnetic Resonance (MR) studies in 100 patients with a traumatic thoracic paraplegia (ASIA A). Results: In 14% of cases, the presence of artifacts prevented the study. 30% showed large vertebral kyphotic deformities, with occupation of the vertebral canal. Among patients with a correct morphological study, 16% showed complete spinal cord transection and 12% showed only some tracts of tissue between the edges of the sectioned spinal cord. In 83% of cases intramedullary cysts were observed, with a mean volume of 0.95 ± 0.89 cc. Extensive cavitation, identified as post-traumatic syringomyelia was seen only in three patients. Varying degree of spinal cord atrophy, being generally segmental, was observed in over 60% of the patients. Conclusion: If according to preclinical studies, anatomical continuity of the spinal cord and limited intramedullary lesions are criteria for possible efficacy of cell therapy, these data suggest that only about 30% of patients with traumatic paraplegia chronically established, at dorsal level, could be reasonably valid for entry in first clinical trials (AU)
Sujet(s)
Humains , Mâle , Femelle , Jeune adulte , Adulte , Adulte d'âge moyen , Rachis/anatomopathologie , Rachis/chirurgie , Rachis , Paraplégie/complications , Paraplégie/chirurgie , Paraplégie , Moelle spinale/anatomopathologie , Moelle spinale , Thérapie cellulaire et tissulaire/méthodes , Thérapie cellulaire et tissulaire , Ostéosynthese intramedullaire/tendances , Imagerie par résonance magnétiqueRÉSUMÉ
INTRODUCTION: Placentas from both early-onset (EOPE) and late-onset pre-eclampsia (LOPE) exhibit signs of underperfusion, which in turn, may be associated with altered angiogenesis. Tyrosine 951 (Y951) and Y1175 phosphorylation of the vascular endothelial growth factor receptor 2 (VEGFR2) induced by VEGF triggers the angiogenesis process. Endothelial markers such as CD31 and CD34 have been used for estimating angiogenic processes in several tissues, including placenta. We asked whether vascular density in placental villi was related to Y951/Y1175 phosphorylation of VEGFR2 in LOPE or EOPE. METHODS: We obtained placental samples from women with normal pregnancies (n = 22), LOPE (n = 13), EOPE (n = 15) and preterm deliveries (n = 10). Slices from placental tissue were used for CD31 immunostaining. We estimated the expression of CD31, CD34, VEGF, and VEGFR2 by western blot and quantitative PCR. Y951 phosphorylation of VEGFR2 was estimated by western blot, whereas Y1175 phosphorylation was analyzed by ELISA. RESULTS: Vessel density in terminal villi and CD31 and CD34 protein abundance were increased in LOPE and EOPE compared to normal pregnancy. However, mRNA levels for CD31 and CD34 were lower in LOPE than in normal pregnancy and VEGF mRNA was higher in EOPE. VEGFR2 protein concentration was not different among the studied groups. Y951 and Y1175 phosphorylation of VEGFR2 was higher in LOPE than in the normotensive group, but only Y951 exhibited greater phosphorylation in EOPE compared to normal pregnancy. DISCUSSION: Changes in vessel formation in the pre-eclamptic placenta are controversial. Our study suggests a pro-angiogenic state in both LOPE and EOPE. These changes are however, associated with differential expression of endothelial markers and VEGFR2 activation. CONCLUSION: There is evidence of increased placental angiogenesis in LOPE and EOPE that is associated with differential activation of VEGFR2.
Sujet(s)
Néovascularisation pathologique/physiopathologie , Placenta/vascularisation , Pré-éclampsie/métabolisme , Récepteur-2 au facteur croissance endothéliale vasculaire/métabolisme , Adulte , Antigènes CD34/métabolisme , Femelle , Humains , Phosphorylation , Placenta/métabolisme , Antigènes CD31/métabolisme , Grossesse , Naissance prématurée , ARN messager/métabolisme , Récepteur-2 au facteur croissance endothéliale vasculaire/génétiqueRÉSUMÉ
The aromatic herb Cymbopogon citratus Stapf is widely used in tropical and subtropical countries in cooking, as a herbal tea, and in traditional medicine for hypertension and diabetes. Some of its properties have been associated with the in vitro antioxidant effect of polyphenols isolated from their aerial parts. However, little is known about C. citratus effects on endothelial cells oxidative injury. Using chromatographic procedures, a polyphenol-rich fraction was obtained from C. citratus (CCF) and their antioxidant properties were assessed by cooper-induced LDL oxidation assay. The main constituents of the active CCF, identified by high-performance liquid chromatography with diode-array detection and mass spectrometry (HPLC-DAD-MS), were chlorogenic acid, isoorientin and swertiajaponin. CCF 10 and 100 µg/ml diminishes reactive oxidative species (ROS) production in human umbilical vein endothelial cell (HUVECs), challenged with high D-glucose (60% inhibition), hydrogen peroxide (80% inhibition) or oxidised low-density lipoprotein (55% inhibition). CCF 10 or 100 µg/ml did not change nitric oxide (NO) production. However, CCF was able to inhibit vasoconstriction induced by the thromboxane A2 receptor agonist U46619, which suggest a NO-independent vasodilatador effect on blood vessels. Our results suggest that lemon grass antioxidant properties might prevent endothelial dysfunction associated to an oxidative imbalance promoted by different oxidative stimuli.
Sujet(s)
Cymbopogon/composition chimique , Glucose/effets indésirables , Cellules endothéliales de la veine ombilicale humaine/métabolisme , Peroxyde d'hydrogène/effets indésirables , Lipoprotéines LDL/effets indésirables , Polyphénols/composition chimique , Glucose/pharmacologie , Humains , Peroxyde d'hydrogène/pharmacologie , Oxydoréduction , Extraits de plantes/pharmacologie , Espèces réactives de l'oxygèneRÉSUMÉ
La trombosis del seno lateral es una complicación potencialmente mortal de la otitis media aguda, aunque infrecuente en la actualidad debido al amplio uso de antibióticos. Sus manifestaciones clínicas son habitualmente fiebre, cefalea y otalgia, agregándose vómitos, edema de papila y compromiso del estado general. El examen diagnóstico de elección es la resonancia magnética en fase venosa y el manejo incluye terapia antibiótica endovenosa, miringotomía con instalación de tubo de ventilación y mastoidectomía, asociado o no a anticoagulación. Se reporta el caso de un escolar de 9 años derivado al Hospital Carlos Van Buren con un hidrocéfalo ótico secundario a una trombosis del seno lateral, manejado con terapia antibiótica endovenosa, mastoidectomía simple, miringotomía con instalación de tubos de ventilación y anticoagulación, evolucionando favorablemente con regresión de la sintomatología y recanalización del seno en el control imagenológico. Se realiza una revisión bibliográfica sobre la presentación clínica, diagnóstico y manejo de la trombosis del seno lateral en niños como complicación de la otitis media aguda.
Lateral sinus thrombosis (LST) is a potentially life threatening complication of acute otitis media. However, report rates have been decreasing since the spreaded use of antibiotic prescription. Patient developing LST usually complain about fever, headache and ear pain. Consequently, they may develop vomiting, papilledema and unhealthy-ness. Magnetic resonance venography (MRV) is considered the gold standard for LST diagnosis. Management procedures include parenteral antibiotics, myringotomy with tympanostomy tube and mastoidectomy, associated or not with anticoagulant therapy. The present study reports the case of a 9-year-old male referred to the Hospital Carlos Van Buren diagnosed with an otitic hydrocephalus secondary to lateral sinus thrombosis, managed with intravenous antibiotic therapy, simple mastoidectomy, myringotomy with tympanostomy tube placement and anticoagulation. Favorable clinical and imagenologic outcomes were obtained. We provide a brief summary about clinical features, diagnosis and management of the LST in children as a complication of acute otitis media.