ABSTRACT
Las enfermedades vasculares hepáticas, a pesar de su relativamente baja prevalencia, representan un problema de salud importante en el campo de las enfermedades hepáticas. Una característica común a muchas de estas enfermedades es que pueden causar hipertensión portal, con la elevada morbimortalidad que ello conlleva. Con frecuencia estas enfermedades se diagnostican en pacientes jóvenes y el retraso en su diagnóstico y/o un tratamiento inadecuado pueden reducir de forma importante la esperanza de vida. El presente artículo revisa la evidencia actual en el síndrome de Budd-Chiari, la trombosis venosa portal en pacientes no cirróticos, la hipertensión portal idiopática, el síndrome de obstrucción sinusoidal, las malformaciones vasculares hepáticas en la telangiectasia hemorrágica hereditaria, la trombosis portal en la cirrosis, otras patologías vasculares menos frecuentes como las fístulas arterioportales, así como un apartado sobre el diagnóstico por imagen de las enfermedades vasculares hepáticas y su tratamiento desde el punto de vista hematológico (estudio de la diátesis trombótica y tratamiento anticoagulante). Las recomendaciones se han realizado de acuerdo a los estudios publicados extraídos de Pubmed. La calidad de la evidencia y la intensidad de las recomendaciones fueron graduadas de acuerdo al sistema Grading of Recommendations Assessment Development and Evaluation (GRADE). Cuando no existían evidencias suficientes, las recomendaciones se basaron en la opinión del comité que redactó la guía.
Despite their relatively low prevalence, vascular diseases of the liver represent a significant health problem in the field of liver disease. A common characteristic shared by many such diseases is their propensity to cause portal hypertension together with increased morbidity and mortality. These diseases are often diagnosed in young patients and their delayed diagnosis and/or inappropriate treatment can greatly reduce life expectancy. This article reviews the current body of evidence concerning Budd-Chiari syndrome, non-cirrhotic portal vein thrombosis, idiopathic portal hypertension, sinusoidal obstruction syndrome, hepatic vascular malformations in hereditary haemorrhagic telangiectasia, cirrhotic portal vein thrombosis and other rarer vascular diseases including arterioportal fistulas. It also includes a section on the diagnostic imaging of vascular diseases of the liver and their treatment from a haematological standpoint (study of thrombotic diathesis and anticoagulation therapy). All recommendations are based on published studies extracted from PubMed. The quality of evidence and strength of recommendations were rated in accordance with the GRADE system (Grading of Recommendations, Assessment Development and Evaluation). In the absence of sufficient evidence, recommendations were based on the opinion of the committee that produced the guide.
Subject(s)
Humans , Vascular Diseases/diagnosis , Vascular Diseases/therapy , Liver Diseases/diagnosis , Liver Diseases/therapy , Telangiectasia, Hereditary Hemorrhagic/therapy , Thrombosis/therapy , Hepatic Veno-Occlusive Disease/therapy , Arteriovenous Fistula/therapy , Budd-Chiari Syndrome/therapyABSTRACT
Centruroides tecomanus is a medically important scorpion of the state of Colima (Mexico). This communication reports the identification of venom components of this scorpion with biological activity over insects/crickets (Acheta domestica), crustaceans/fresh water shrimps (Cambarellus montezumae), and mammalians/mice (Mus musculus, strain CD1). It also describes the pharmacological effects on cell lines in culture (L5178Y cells, HeLa cells, HuTu cells and Jurkat E6-1 cells), as well as on several types of bacteria (see below). The soluble venom of this scorpion was fractionated by high-performance liquid chromatography (HPLC) and collected separately in twelve independent fractions collected over 60 min run (5 min time apart each other). The HPLC components of fraction VII were lethal to all three species used for assay. The IVth fraction had a toxic effect on freshwater shrimps. In this species, fractions VI, VII and VIII were all lethal. For crickets, fractions V and VI were toxic and fraction VII was lethal. In mouse, the lethal components were found in fraction VII, whereas fraction VIII was toxic, but not lethal, at the doses assayed. The molecular weight of peptides from the various group of fractions were identified by mass spectrometry determination. Components lethal to mice showed molecular weights from 7013 to 7487 Da. Two peptides were obtained in homogeneous form and shown to be lethal to the three species of animal used for assay. The soluble venom tested on L5178Y cell line survival was shown to be cytotoxic, at 10-100 µg/mL concentration, when compared to control murine splenocytes (p = 0.007). The soluble venom applied to Hela, Hutu and Jurkat cell lines did not show cytotoxic effects at these concentrations. On the contrary, it seems to have a proliferative effect. However the HPLC fractions I, III, VI and XII do have a cytotoxic effect on Jurkat E06-1 cells in culture at 200 µg/mL concentration. The antimicrobial activity of the venom fractions on Staphylococcus aureus (gram-positive), Escherichia coli, Pseudomonas aeruginosa y Salmonella spp (gram-negative) was measured, using the liquid inhibition growth system. The four strains of bacteria used were susceptible to fractions III and IV, affecting all four bacterial strains at concentrations below 5 µg/mL.
Subject(s)
Anti-Bacterial Agents/isolation & purification , Antineoplastic Agents/isolation & purification , Apoptosis/drug effects , Drug Discovery , Insecticides/isolation & purification , Scorpion Venoms/chemistry , Amino Acid Sequence , Animals , Anti-Bacterial Agents/adverse effects , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Antineoplastic Agents/adverse effects , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Arthropod Proteins/chemistry , Arthropod Proteins/isolation & purification , Arthropod Proteins/pharmacology , Arthropod Proteins/toxicity , Astacoidea/drug effects , Astacoidea/growth & development , Cell Line, Tumor , Cells, Cultured , Gram-Negative Bacteria/drug effects , Gram-Negative Bacteria/growth & development , Gryllidae , Humans , Injections, Intraperitoneal , Insecticides/chemistry , Insecticides/pharmacology , Insecticides/toxicity , Mexico , Mice , Microbial Sensitivity Tests , Scorpion Venoms/administration & dosage , Scorpion Venoms/toxicity , Scorpions/growth & development , Spleen/cytology , Spleen/drug effects , Staphylococcus aureus/drug effects , Staphylococcus aureus/growth & developmentSubject(s)
Humans , Male , Middle Aged , Carcinoma, Hepatocellular/complications , Carcinoma, Hepatocellular/diagnosis , Liver Cirrhosis/complications , Liver Cirrhosis/diagnosis , Heparin/therapeutic use , Ethanol/adverse effects , Thrombosis/complications , Thrombosis , Carcinoma, Hepatocellular/physiopathology , Carcinoma, HepatocellularABSTRACT
OBJECTIVES: Theprognostic value of p53 expression in epithelial ovarian cancer remains unresolved. We hypothesized that prognosis may relate more to expression of p21(waf1/cip1), the major downstream effector of p53, which can also be induced through p53-independent mechanisms. We therefore studied the relationship of p53 and p21(waf1/cip1) expression in epithelial ovarian cancers to clinicopathological variables and prognosis. METHODS: Fixed, embedded tumors from 85 patients with untreated, primary epithelial ovarian cancer were immunostained with antibodies to p53 and p21(waf1/cip1). Expression was correlated with clinicopathological features and prognosis. Survival curves were calculated by the Kaplan-Meier method and compared using the log-rank test for p53, p21(waf1/cip1), and all combinations of expression of the two markers. RESULTS: Sixty-two percent of tumors expressed p53, and 42% expressed p21(waf1/cip1). There was no correlation between p53 and p21(waf1/cip1) expression. Advanced stage, grade, age >/=50, and p53 expression were associated with worse disease-free survival. Patients whose tumors were p53(+)/waf1(-), however, had a particularly strong association with poorer disease-free survival when compared with other combinations of p53 and p21(waf1/cip1) expression (P = 0.003). Neither p53, nor p21(waf1/cip1), nor combinations of expression were independently related to survival when histology, age, stage, and differentiation were considered. CONCLUSIONS: p53 expression in the absence of p21(waf1/cip1) expression is a better marker of poor prognosis than either p53 or p21(waf1/cip1) expression status alone in univariate analysis. Absence of independent prognostic significance may be related to the paucity of early stage cases in the current study.
