RESUMO
Las dilataciones en el tracto gastrointestinal se llevan a cabo para aliviar la obstrucción sintomática, ya sea funcional u orgánica, secundarias a una variedad de patologías tanto benignas como malignas. Con el advenimiento de las nuevas tecnologías, virtualmente toda estenosis digestiva puede ser manejada en forma mínimamente invasiva. Pese a su amplia difusión en la práctica actual, existen pocos estudios controlados que comparen las diferentes modalidades de dilatación. En el presente artículo realizamos una revisión de esta técnica, así como de la evidencia disponible para su aplicación en los diferentes segmentos del tracto gastrointestinal. El futuro de la dilatación incluye el desarrollo de dilatadores que permitan evaluar la dilatación durante su realización. Estos advenimientos, así como la ejecución de estudios controlados prospectivos van a mejorar las indicaciones, beneficios y riesgos para cada uno de los sistemas de dilatación existentes.
The endoscopic dilation of the gastrointestinal tract is carried out to relieve either functional or organic disorders, secondary to a variety of both benign and malignant diseases. With the advent of new technologies, virtually all digestive stenosis can be managed in a minimally invasive way. Despite its wide dissemination in actual practice, there are few controlled studies comparing the different forms of endoscopic dilation. In this article, we review this technique and the evidence available for application in different segments of the gastrointestinal tract. The future of the dilations includes the development of dilators to assess dilation during the procedure. These advents and the implementation of prospective controlled studies will improve the indications, benefits and risks for each of the existing systems of dilations.
Assuntos
Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Adulto Jovem , Fator V/genética , Hemofilia A/genética , Mutação , Autoanticorpos/biossíntese , Autoanticorpos/imunologia , Estudos de Coortes , Fator VIII/antagonistas & inibidores , Fator VIII/imunologia , Fator VIII/metabolismo , Fator VIII/uso terapêutico , Genótipo , Alemanha , Hemofilia A/tratamento farmacológico , Hemofilia A/imunologia , Hemofilia A/metabolismo , Israel , Fatores de RiscoRESUMO
La enfermedad de Von Willebrand es el desorden hemorragíparo más frecuente. Las mujeres constituyen una población particularmente sintomática debido al desafío hemostático de las menstruaciones y el parto. Nosotros revisamos las historias médicas de 54 mujeres con niveles disminuidos de factor von Willebrand (VWF) e historia de sangrado, quienes hubieran usado desmopresina durante el embarazo. No se observaron efectos adversos ni en las mujeres ni en los recién nacidos, incluso en los 5 expuestos a la medicación en el primer trimestre de gestación. No se observaron complicaciones locales asociadas a la colocación del catéter epidural. La DDAVP fue efectiva para prevenir el sangrado posparto. La desmopresina merece ser considerada como la primera elección de tratamiento; en aquellas pacientes con bajo niveles de VWF presentan complicaciones hemorrágicas, incluyendo mujeres embarazadas. Aunque el sangrado posparto aparece en una pequeña proporción de mujeres con VWD, no hay un modo apropiado de identificar quiénes van a sangrar. El uso de profilaxis con DDAVP debería ser tenido en cuenta como una alternativa segura y efectiva.
The von Willebrand disease (VWD) is the most frequent hemorrhagic disorder. Women with VWD are more symptomatic than men because the challenged of menses and delivery. We reviewed the records of 54 women with a low plasmatic VWF level and bleeding history, who had used desmopressin during pregnancy. No adverse effects were observed in mothers or newborns, incluiding those exposed to the drug during the first trimester. No local complication of epidural placement was observed. DDAVP was effective to prevent post-partum hemorrhage. DDAVP merits to be considered as the first choice of therapy, when patients with a previous or current low plasmatic VWF level present bleeding complications, including pregnant women. Although post-partum bleeding will appear in a small proportion of VWD women, there is no accurate way to identify who is going to bleed. The use of DDAVP should be regarded as a highly valuable option.
Assuntos
Humanos , Feminino , Gravidez , Adulto , Desamino Arginina Vasopressina/administração & dosagem , Desamino Arginina Vasopressina/uso terapêutico , Doenças de von Willebrand/tratamento farmacológico , Complicações Hematológicas na Gravidez/prevenção & controle , Estudos Retrospectivos , Estudos de Coortes , Avaliação de Medicamentos , Fator VIII/metabolismo , Fator de von Willebrand/genética , Fator de von Willebrand/metabolismo , Transtornos Hemorrágicos/diagnóstico , Transtornos Hemorrágicos/prevenção & controleRESUMO
Epithelioid hemangioendothelioma (EHE) is a rare tumor of vascular origin. While it can be found in any tissue, it is most often found in lung and liver and usually has an intermediate behavior. EHEs originating from pleural tissue have been less frequently described than those from other sites. Furthermore, to date, all of the cited pleural EHEs were described as highly aggressive. In the present report, we describe a rare case of pleural EHE extending to lung and bone in a 31-year-old woman. The histological diagnosis was confirmed by both conventional examination and immunohistochemistry. Her disease stabilized during the 4th course of adriamycin (45mg/m2, day 1-3), dacarbazine (300mg/m2, day 1-3) and ifosfamide (2,500mg/m2, day 1-3) with mesna, and she survived for 10 months after the diagnosis.
Assuntos
Adulto , Feminino , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Diagnóstico Diferencial , Fator VIII/metabolismo , Hemangioendotelioma Epitelioide/diagnóstico , Imuno-Histoquímica , Queratinas/metabolismo , Neoplasias Pulmonares/diagnóstico , Neoplasias Pleurais/diagnóstico , Vimentina/metabolismoRESUMO
We explored the potential of fusion of hepatic locus control region 1 (HCR-1) with HCR-2 to express B-domain-deleted human factor VIII (FVIII) in four cell lines. B-domain-deleted human FVIII expression was controlled by HCR-1/HCR-2, followed by liver specific and ubiquitous promoters. Chimera enhancer HCR-1/HCR-2, followed by cytomegalovirus (CMV) promoter, gave 2-fold more FVIII expression in all cell lines (105.6 ± 2.8 for Hek-293, 68.8 ± 3.8 for HepG2, 34.8 ± 1.3 for CHO, and 27.2 ± 1.6 ng-mL-1-106 cells-1 for L.N.) when compared to the vector with CMV alone (54.8 ± 3.3 for Hek-293, 32.4 ± 1.2 for HepG2, 18.6 ± 1.1 for CHO, and 10.1 ± 1.7 ng-mL-1-106 cells-1 for L.N.). Elongation factor 1-α gene and human CMV promoters were more efficient than the promoters from the human α-1-antitrypsin gene, and fviii was less efficient in hepatic cell lines. HCR-1/HCR-2, followed by strong promoters, increases FVIII expression in vitro. Our results underscore the importance of cis sequences for enhancing in vitro FVIII expression; this may be helpful for designing new strategies to improve heterologous expression systems.
Assuntos
Humanos , Animais , Elementos Facilitadores Genéticos/genética , Fator VIII/genética , Regiões Promotoras Genéticas/genética , Vetores Genéticos/genética , Linhagem Celular , Linhagem Celular Tumoral , Células CHO , Cricetinae , Cricetulus , Citomegalovirus/genética , Fator VIII/metabolismo , Imuno-Histoquímica , Microscopia de Fluorescência , Plasmídeos , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
El objetivo del trabajo fue analizar el efecto de inmunoglobulinas (IgG) purificadas con actividad anti-factor VIII neutralizante o inhibidor lúpico, sobre el factor VIII medido por sustrato cromogénico (factor VIII SC), con el propósito de validar el método para detectar anti-factor VIII en presencia de inhibidor lúpico. Se aisló la fracción IgG (cromatografía de afinidad) a partir de plasmas normales (IgG-N), con anti-factor VIII (IgG-aFVIII) o con inhibidor lúpico (IgG-IL), preparándose un pool normal como aporte de factor VIII en los ensayos de inhibición. Se analizaron las mezclas del pool normal con IgG-N, IgG-aFVIII, IgG-IL o la combinación de IgG-aFVIII+IgG-IL, inmediatamente y luego de 2 h a 37 ºC, determinándose la actividad del factor VIII SC y el índice de inhibición inmediato (Ii) o post-incubación (Ip). La inhibición y la potenciación producida por IgG-aFVIII+IgG-IL (Ii:30%±0,7; Ip:55%±2,7), fueron similares a las observadas con IgG-aFVIII sola (Ii:30%±0,6; Ip:55%±2,7). La IgG-IL no afectó la actividad de factor VIII SC. Semejante a lo observado en plasma, la IgG-IL no interfirió en la inhibición del factor VIII SC mediada por IgG-aFVIII. Se confirmó así la especificidad del método amidolítico, que permite detectar inhibidores anti-factor VIII independientemente de la coexistencia con el inhibidor lúpico, solucionando el problema diagnóstico planteado en hemofilia A.
To analyse the effect of purified immunoglobulins (IgG) with anti-factor VIII or lupus anticoagulant activity on factor VIII measured by chromogenic substrate (factor VIIICS), in order to validate the chromogenic substrate method for detection of anti-factor VIII activity in the presence of lupus anticoagulant. IgG fractions were purified (affinity chromatography) from normal plasmas (IgG-N) and plasmas with anti-factor VIII (IgG-aFVIII) or lupus anticoagulant (IgG-LA). A normal plasma pool was prepared as source of factor VIII in the inhibition tests. Mixtures of this pool with IgG-N, IgG-aFVIII, IgG-LA or IgG-aFVIII+IgG-LA were tested immediately or after 2 h at 37 °C by factor VIIICS method; inhibition index (Ii) and post-incubation index (Ip) were calculated. The inhibitory and progressive inhibitory effects produced by IgG-aFVIII+IgG-LA (Ii:30%±0.7; Ip:55%±2.7) were similar to those observed with IgG-aFVIII (Ii:30%±0.6; Ip:55%±2.7). The IgG-LA did not inhibit the factor VIIIcs activity. As was observed in plasma samples, IgG-aFVIII and the mixture of IgG-aFVIII+IgG-LA inhibited factor VIIICS, whereas IgG-LA did not. These results confirm the specificity of the amidolytic method in detecting anti-factor VIII inhibitors independently of the presence of lupus anticoagulant, thus solving the diagnostic problem in haemophilia A.
Assuntos
Humanos , Fator VIII/antagonistas & inibidores , Fator VIII/metabolismo , Imunoglobulinas/sangue , Compostos CromogênicosRESUMO
FVIII is synthesized as a single chain precursor of approximately 280 kD with the domain structure of A1-A2-B-A3-C1-C2 and it circulates as a series of metal ion-linked heterodimers that result from cleavages at B-A3 junction as well as additional cleavages within B domain. Factor VIII is converted to its active form, factor VIIIa, upon proteolytic cleavages by thrombin and is a heterotrimer composed of the A1, A2, and A3-C1-C2 subunits. A1 subunits of factor VIIIa terminates with 36 residue segment (Met337-Arg372) rich in acidic residues. This segment is removed after cleavages at Arg336 by activated protein C, which results in inactivation of the cofactor. In the present study, site-directed mutagenesis of FVIII at Arg336 to Gln336 was performed in order to produce an inactivation resistant mutant rFVIII (rFVIIIm) with an extended physiological stability. A recombinant mutant heavy chain of FVIII (rFVIII-Hm; Arg336 to Gln336) and wild-type light chain of FVIII (rFVIII-L) were expressed in Baculovirus-insect cell (Sf9) system, and a biologically active recombinant mutant FVIII (rFVIIIm) was reconstituted from rFVIII-Hm and rFVIII-L in the FVIII-depleted human plasma containing 40 mM CaCl2. The rFVIIIm exhibited cofactor activity of FVIIIa (2.85 x 10(-2) units/mg protein) that sustained the high level activity during in vitro incubation at 37 degrees C for 24 h, while the cofactor activity of normal plasma was declined steadily for the period. These results indicate that rFVIIIm (Arg336 to Gln336) expressed in Baculovirus-insect cell system is inactivation resistant in the plasma coagulation milieu and may be useful for the treatment of hemophilia A.
Assuntos
Humanos , Animais , Baculoviridae/genética , Western Blotting , Linhagem Celular , Fator VIII/metabolismo , Fator VIII/genética , Fator VIII/química , Fator VIII/biossíntese , Vetores Genéticos , Mutagênese Sítio-Dirigida , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/genética , Proteínas Recombinantes/química , Proteínas Recombinantes/biossíntese , SpodopteraRESUMO
En una serie de 22 muestra de plasma fresco citratado (PFC) y sus correspondientes fracciones libres de globulina antihemofílica (PLGAH) recién preparadas, se determinó la concentración de antitrombina III (AT III) en mg/dl, por medio de inmunodifusión radial cuantitativa y su actividad en porcentaje mediante su capacidad de inactivar a la trombina. Ambos valores se determinaron tambiém periódicamente en alíquotas de PLGAH almacenadas a - 20-C. Los valores de AT III obtenidos en el PFC y en PLGAH recién preparado, no mostraron diferencias significativas ni en concentración ni en actividad. Durante el almacenamiento, el PLGAH mostró un decaimiento progresivo de la actividad de AT III desde la primera semana, llegando al 50% a las cuatro semanas. Durante el mismo lapso, la concentración de AT III también disminuyó significativamente desde la segunda semana sin caer a valores anormales bajos durante las 13 semans que duró el estudio. Se comentan estos hallazgos y se discute su utilidad práctica proponiéndose el empleo de PLGAH como fuente de AT III en la clínica