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Although achieving good activated sludge settleability is a key requirement for meeting effluent quality criteria, wastewater treatment plants often face undesired floc structure changes. Filamentous bulking has widely been studied, however, viscous sludge formation much less investigated so far. Our main goal was to find relationship between sludge floc structure and related rheological properties, moreover, to estimate pressure loss in pipe networks through hydrodynamic modelling of the non-Newtonian flows in case of well settling (ideal-like), viscous and filamentous sludge. Severe viscous and filamentous kinds of bulking were generated separately in continuous-flow lab-scale systems initially seeded with the same reference (ideal-like) biomass and the entire evolution of viscous and filamentous bulking was monitored. The results suggested correlation between the rheological properties and the floc structure transformations, and showed the most appropriate fit for the Herschel-Bulkley model (vs. Power-law and Bingham). Validated computational fluid dynamics studies estimated the pipe pressure loss in a wide Reynolds number range for the initial well settling (reference) and the final viscous and filamentous sludge as well. A practical standard modelling protocol was developed for improving energy efficiency of sludge pumping in different floc structure scenarios.
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BACKGROUND: Data suggests that tight objective monitoring may improve clinical outcomes in IBD. AIM: To assess the adherence to serial tight objective monitoring(clinical and biomarkers) and its effect on clinical outcomes. METHODS: We retrospectively reviewed the chart of 428 consecutive IBD patients started on adalimumab between January 1,2015-January 1,2019 [338 Crohn's disease(CD), 90 ulcerative colitis(UC)]. Clinical symptoms(assessed by Harvey-Bradshaw-Index,partial Mayo),C-Reactive Protein(CRP), and fecal calprotectin(FCAL) assessments were captured at treatment initiation and at 3,6,9, and12 months. Dose optimization and drug sustainability curves were plotted by Kaplan-Meier method. RESULTS: Clinical evaluation was available in nearly all patients at 3(CD-UC:95-94%), 6(90-83%), 9(86-85%) and 12(96-89%) months. CRP testing frequency decreased in CD patients over time. Compliance to serial FCAL testing was low. Clinical remission at one-year was higher in patients adherent to early assessment visit at 3 months(pâ¯=â¯0.001 for CD and UC). Adherence to early follow-up resulted in earlier dose optimization in CD and UC patients(pLogrank=0.026 for UC & pâ¯=â¯0.09 for CD). Overall drug sustainability did not differ. CONCLUSION: Clinical & CRP, but not FCAL, were frequently assessed in patients starting adalimumab. Adherence to early objective combined follow-up visits resulted in earlier dose optimization, improved one-year clinical outcomes but did not change drug sustainability.
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Adalimumab/uso terapéutico , Colitis Ulcerosa/tratamiento farmacológico , Enfermedad de Crohn/tratamiento farmacológico , Monitoreo de Drogas/estadística & datos numéricos , Cumplimiento de la Medicación/estadística & datos numéricos , Adolescente , Adulto , Biomarcadores/análisis , Proteína C-Reactiva/análisis , Colitis Ulcerosa/patología , Enfermedad de Crohn/patología , Monitoreo de Drogas/métodos , Heces/química , Femenino , Humanos , Estimación de Kaplan-Meier , Complejo de Antígeno L1 de Leucocito/análisis , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del Tratamiento , Adulto JovenRESUMEN
The tumour suppressor protein RASSF1A is phosphorylated by Aurora A kinase, thereby impairing its tumour suppressor function. Consequently, inhibiting the interaction between Aurora A and RASSF1A may be used for anti-tumour therapy. We used recombinant variants of RASSF1A to map the sites of interaction with Aurora A. The phosphorylation kinetics of three truncated RASSF1A variants has been analysed. Compared to the RASSF1A form lacking the 120 residue long N-terminal part, the Km value of the phosphorylation is increased from 10 to 45 µM upon additional deletion of the C-terminal SARAH domain. On the other hand, deletion of the flexible loop (Δ177-197) that precedes the phosphorylation site/s (T202/S203) results in a reduction of the kcat value from about 40 to 7 min-1. Direct physical interaction between the isolated SARAH domain and Aurora A was revealed by SPR. These data demonstrate that the SARAH domain of RASSF1A is involved in the binding to Aurora A kinase. Structural modelling confirms that a novel complex is feasible between the SARAH domain and the kinase domain of Aurora A. In addition, a regulatory role of the loop in the catalytic phosphorylation reaction has been demonstrated both experimentally and by structural modelling.
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Aurora Quinasa A/metabolismo , Dominios y Motivos de Interacción de Proteínas , Receptores Opioides kappa/metabolismo , Aurora Quinasa A/química , Aurora Quinasa A/genética , Sitios de Unión , Cromatografía en Gel , Modelos Moleculares , Mutación , Fosforilación , Multimerización de Proteína , Receptores Opioides kappa/química , Receptores Opioides kappa/genética , Resonancia por Plasmón de SuperficieRESUMEN
The concept of a "topographical memory" in lymphocytes implies a stable expression of homing receptors mediating trafficking of lymphocytes back to the tissue of initial activation. However, a significant plasticity of the gut-homing receptor α4ß7 was found in CD8+ T cells, questioning the concept. We now demonstrate that α4ß7 expression in murine CD4+ memory T cells is, in contrast, imprinted and remains stable in the absence of the inducing factor retinoic acid (RA) or other stimuli from mucosal environments. Repetitive rounds of RA treatment enhanced the stability of de novo induced α4ß7. A novel enhancer element in the murine Itga4 locus was identified that showed, correlating to stability, selective DNA demethylation in mucosa-seeking memory cells and methylation-dependent transcriptional activity in a reporter gene assay. This implies that epigenetic mechanisms contribute to the stabilization of α4ß7 expression. Analogous DNA methylation patterns could be observed in the human ITGA4 locus, suggesting that its epigenetic regulation is conserved between mice and men. These data prove that mucosa-specific homing mediated by α4ß7 is imprinted in CD4+ memory T cells, reinstating the validity of the concept of "topographical memory" for mucosal tissues, and imply a critical role of epigenetic mechanisms.
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Linfocitos T CD4-Positivos/inmunología , Integrina alfa4/metabolismo , Intestinos/inmunología , Receptores Mensajeros de Linfocitos/metabolismo , Subgrupos de Linfocitos T/inmunología , Animales , Movimiento Celular , Células Cultivadas , Metilación de ADN , Elementos de Facilitación Genéticos/genética , Epigénesis Genética , Regulación de la Expresión Génica , Memoria Inmunológica , Integrina alfa4/genética , Cadenas beta de Integrinas/metabolismo , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Tretinoina/metabolismoRESUMEN
The factors influencing the heterogeneous clinical manifestation of hereditary angioedema due to C1-INH deficiency (C1-INH-HAE) represent one of the oldest unsolved problems of the disease. Considering that factor XII (FXII) levels may affect bradykinin production, we investigated the contribution of the functional promoter polymorphism F12-46C/T in disease phenotype. We studied 258 C1-INH-HAE patients from 113 European families, and we explored possible associations of F12-46C/T with clinical features and the SERPING1 mutational status. Given that our cohort consisted of related subjects, we implemented generalized estimating equations (GEEs), an extension of the generalized linear model accounting for the within-subject correlation. F12-46C/T carriers exhibited a significantly delayed disease onset (P < 0.001) and did not need long-term treatment (P = 0.02). In a GEE linear regression model, the presence of F12-46C/T was significantly associated with a 7-year delay in disease onset (P < 0.0001) regardless of SERPING1 mutational status. It is concluded that F12-46C/T carriage acts as an independent modifier of C1-INH-HAE severity.
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Factor XII/genética , Estudios de Asociación Genética , Angioedema Hereditario Tipos I y II/genética , Polimorfismo de Nucleótido Simple , Adolescente , Adulto , Anciano , Niño , Preescolar , Proteínas Inactivadoras del Complemento 1/genética , Proteína Inhibidora del Complemento C1 , Análisis Mutacional de ADN , Femenino , Genotipo , Humanos , Lactante , Masculino , Persona de Mediana Edad , Mutación , Fenotipo , Reacción en Cadena de la Polimerasa , Polimorfismo de Longitud del Fragmento de Restricción , Adulto JovenRESUMEN
BACKGROUND: Ustekinumab is a fully human IgG1κ monoclonal antibody that blocks the biologic activity of interleukin-12/23. Ustekinumab is approved for treatment of plaque psoriasis and has been shown to be effective for induction and maintenance of clinical response in anti-TNF resistant Crohn's disease (CD). The aim of the study was to describe the real-life experience with open-label use of ustekinumab in anti-TNF resistant CD patients. METHODS: A retrospective observational open-label study. Clinical response was defined by physician's global assessment combined with decision to continue therapy. The clinical response was evaluated at 3, 6, 12months and last follow-up. RESULTS: Thirty-eight patients were included in the study. Initial clinical response was achieved in 28/38 (73.7%) of the patients. Among the initial responders, 80% with follow-up data maintained their response for 6months. At 12months of follow-up, 88.9% of patients responding at 6months maintained their response. At the last follow-up (7.9±5.2 mo) 27/38 (71%) of the patients were responding, and 73.3% were able to discontinue corticosteroids. Dose escalation was required in 47.7% of the patients and was successful in 61.1% of them. SUMMARY: In this real-life cohort of severe anti-TNF resistant CD, an initial clinical response to subcutaneous ustekinumab was observed in 73.7% of the patients. The initial response was successfully maintained in the majority of patients for up to 12months. Subcutaneous ustekinumab is an effective therapeutic option in this challenging patient cohort. The optimal dosing and injection schedule remain to be established in future studies.
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Antiinflamatorios/administración & dosificación , Anticuerpos Monoclonales Humanizados/administración & dosificación , Enfermedad de Crohn/tratamiento farmacológico , Adolescente , Adulto , Canadá , Resistencia a Medicamentos , Femenino , Estudios de Seguimiento , Humanos , Inyecciones Subcutáneas , Masculino , Persona de Mediana Edad , Retratamiento , Estudios Retrospectivos , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Ustekinumab , Adulto JovenRESUMEN
Several studies suggest that infection by Epstein-Barr virus (EBV) might be one of the environmental factors which facilitates the development of autoimmune disorders in genetically susceptible individuals. Recent data indicate that high anti-Epstein-Barr nuclear antigen 1 (EBNA)-1 immunoglobulin (Ig)G titre is a strong risk factor for multiple sclerosis (MS) in patients both with and without the main genetic predisposing trait, human leucocyte antigen (HLA)-DRB1*15:01. Because no similar studies have been published in systemic lupus erythematosus (SLE) patients, we determined the HLA-DRB1*15:01 carrier state and the serum titres against the whole EBNA-1 and its small fragments aa35-58 and aa398-404 in 301 SLE patients, 135 MS patients and in 345 healthy controls. The carrier state of the HLA-DRB1*15:01 allele was deduced from genotyping of a tagSNP (rs3135388) by applying a Taqman-based assay. The serum concentrations of antibodies to EBNA-1 and its aa35-58 or aa398-404 fragments were determined using a commercial assay (ETI-EBNA-G) and home-made enzyme-linked immunosorbent assays, respectively. The serum concentration of anti-EBNA-1 antibodies was significantly (P < 0·001) higher both in MS and SLE patients than in controls. Similar significant differences were found both in HLA-DRB1*15:01 carriers and non-carriers. Furthermore, titres of antibodies against the aa35-58 EBNA-1 fragment were elevated both in MS and SLE patients. By contrast, the levels of aa398-404 EBNA-1 antibodies were elevated significantly only in the SLE patients. These findings indicate that high anti-EBNA-1 IgG titres are HLA-DRB1*15:01-independent risk factors not only for MS, but also for SLE, while high antibody titres against the aa398-404 fragment are characteristic for SLE.
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Antígenos Nucleares del Virus de Epstein-Barr/inmunología , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Lupus Eritematoso Sistémico/inmunología , Esclerosis Múltiple/inmunología , Fragmentos de Péptidos/sangre , Fragmentos de Péptidos/inmunología , Adulto , Alelos , Secuencia de Aminoácidos , Estudios de Casos y Controles , Femenino , Cadenas HLA-DRB1/genética , Heterocigoto , Humanos , Lupus Eritematoso Sistémico/sangre , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Esclerosis Múltiple/sangreRESUMEN
Patients with large burns suffer from anemia of critical illness. Administration of exogenous erythropoietin is ineffective, and transfusion remains the only effective treatment. We have previously shown that erythroid precursors are decreased 1 week after burn in an animal model. Therefore, we have used a two-phase liquid culture system to quantify peripheral blood mononuclear cell (PBMC) compartment-derived erythroid progenitors (EPs) in burn patients. Institutional review board approval and informed consent were obtained. Blood samples were collected at 1 to 30 days after burn, with a mean TBSA of 37.7 ± 15.8% (n = 10; 90% men; age, 46.0 ± 18 years). Four healthy volunteers served as controls. PBMCs were isolated by Ficoll-Hypaque density-gradient centrifugation and were placed in serum-free expansion medium containing cyclosporine A (1 ng/ml), granulocyte macrophage colony-stimulating factor (20 ng/ml), stem cell factor (30 ng/ml), and interleukin-3 (5 ng/ml; phase I). On day 7, cells were reseeded in serum-free expansion medium containing erythropoietin (1 U/ml), holotransferrin (0.3 mg/ml), and stem cell factor (10 ng/ml; phase II). Aliquots from the phase II culture system on day 6 were incubated with anti-CD71, CD235a, and CD36. EPs (CD71 CD36) and erythroblast subpopulations (colony-forming unit erythroids, Proerythroblasts, and intermediate erythroblasts) were identified based on the expressions of CD71 and CD235a by flow cytometry, calculated per million expanded cells, and expressed as a percentage of controls. Total EPs were significantly decreased by days 28 to 31 after the burn (19%; P < .05). Among the erythroblast subpopulations, colony-forming unit erythroids (11%; P < .004) and proerythroblasts (24%; P < .05), were decreased significantly by days 28 to 31 after the burn. PBMCs of burn patients can be used to study impaired erythropoiesis and anemia of critical illness.
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Quemaduras/sangre , Eritroblastos/metabolismo , Células Precursoras Eritroides/metabolismo , Leucocitos Mononucleares/metabolismo , Adulto , Análisis de Varianza , Estudios de Casos y Controles , Células Cultivadas , Ciclosporina/farmacología , Eritropoyetina/farmacología , Femenino , Citometría de Flujo , Factor Estimulante de Colonias de Granulocitos y Macrófagos/farmacología , Humanos , Masculino , Persona de Mediana Edad , Factor de Células Madre/farmacología , Transferrina/farmacologíaRESUMEN
The human RCCX is a common multiallelic copy number variation locus whose number of segments varies between one and four in a chromosome. The monomodular form normally comprises four functional genes, but in duplicated RCCX segments generally only the gene-encoding complement component C4 produces a protein. C4 genes can code either for a C4A or a C4B isotype protein and exhibit dichotomous size variation. Distinct RCCX variants show association with numerous diseases; however, identification of the basis of these associations is often challenging, not least because the RCCX is localized in the major histocompatibility complex (MHC) region, a genomic area characterized by exceedingly long-range linkage disequilibrium. Here we present a detailed analysis on RCCX variants and their relationship with so-called 'ancestral' or 'conserved extended' MHC haplotypes in healthy Caucasians. In addition to former investigations, precise order and size of all C4A and C4B genes were determined even in trimodular RCCX structures. Considering C4 copy numbers, length, isotype specificity and CYP21A2 copy numbers, we have identified 15 distinct RCCX variants and described the RCCX structures involved in 29 repeatedly occurring MHC haplotypes. The findings should become a useful tool for future RCCX- and MHC-related disease association studies.
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Complemento C4a/genética , Complemento C4b/genética , Variaciones en el Número de Copia de ADN , Haplotipos , Complejo Mayor de Histocompatibilidad/genética , Humanos , Esteroide 21-Hidroxilasa/genética , Población Blanca/genéticaRESUMEN
BACKGROUND: The diagnostic accuracy of two indirect tests of lactose digestion, lactose breath hydrogen and lactose tolerance tests, have not been systematically reviewed for comparison with available publications on genotype. AIM: To perform a meta-analysis of available studies that compares the north-European genetic polymorphism C/T-13910 with the lactose breath hydrogen and the lactose tolerance tests, to determine their ability to predict geno/phenotype relationships. We examine the effects of lactose loading dose, inclusion of children and latitudes of study centre on comparative outcome. METHODS: An electronic database of the literature as well as individual references in articles were searched with the theme of genetics of lactase and comparisons with breath or lactose tolerance tests were carried out. Random effect and fixed effect models were used for breath and lactose tolerance tests respectively, to report summary accuracy measures with 95% confidence intervals (CI). RESULTS: The search revealed 19 studies: 17 evaluated breath hydrogen, five lactose tolerance test (3/17 overlapped). Overall sensitivity was 0.88 (CI, 0.85-0.90), specificity was 0.85 (CI, 0.82-0.87) for breath test. Heterogeneity was explored by adjusting for studies including children, high or low dose lactose and to some extent by site of study. The lactose tolerance test showed sensitivity of 0.94 (0.9-0.97) and specificity of 0.90 (0.84-0.95) with a nonsignificant heterogeneity. CONCLUSION: The diagnostic accuracy of both tests individually reflects expected geno/phenotypes when the populations are well defined.
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Hidrógeno/análisis , Lactasa/genética , Intolerancia a la Lactosa/diagnóstico , Intolerancia a la Lactosa/genética , Prueba de Tolerancia a la Lactosa , Polimorfismo de Nucleótido Simple/genética , Pruebas Respiratorias , Genotipo , Humanos , Lactasa/metabolismo , Intolerancia a la Lactosa/metabolismo , Fenotipo , Valor Predictivo de las Pruebas , Población BlancaRESUMEN
BACKGROUND: Hemolytic uremic syndrome (HUS) is a rare disease with various etiologies, making the identification of the specific forms and appropriate treatment difficult. Therefore, clinical and laboratory data from these patients need to be analyzed in national and international registries. Herein we have described 47 Hungarian HUS patients with detailed laboratory and clinical data obtained between 2008 and 2010. METHODS: Blood samples and clinical data of 47 patients with HUS diagnosed according to characteristic clinical signs were submitted for diagnostic evaluation, including complement protein and genetic analysis, measurement of ADAMTS13 activity and antibody analysis against O157LPS and factor H. RESULTS: There were 8 patients with typical diarrhea-positive HUS; 13 with atypical HUS (aHUS) and 26 with secondary HUS/thrombotic thrombocytopenic purpura group characterized by signs of complement consumption and decreased ADAMTS13 activity. Thus, decreased total alternative pathway activity is a promising diagnostic parameter with good sensitivity for aHUS. CONCLUSIONS: These observations highlight the requirement for multiple diagnostic tests together with clinical data to identify the specific cause of HUS. Because the long-term prognosis of aHUS, eg, graft survival after renal transplantation, may vary according to the molecular etiology, it is important for all affected patients to undergo a detailed molecular diagnosis of the disease. There is a clear clinical need for the development and application of novel assay in this field to allow more rapid efficient diagnosis of patients who undergo a first episode of HUS.
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Síndrome Hemolítico-Urémico/clasificación , Síndrome Hemolítico-Urémico/diagnóstico , Proteínas ADAM/sangre , Proteína ADAMTS13 , Adolescente , Adulto , Anticuerpos Antibacterianos/sangre , Autoanticuerpos/sangre , Biomarcadores/sangre , Proteínas Sanguíneas/genética , Niño , Preescolar , Complemento C3/análisis , Proteínas Inactivadoras del Complemento C3b/genética , Factor B del Complemento/análisis , Factor H de Complemento/análisis , Factor H de Complemento/inmunología , Factor I de Complemento/análisis , Escherichia coli O157/inmunología , Femenino , Predisposición Genética a la Enfermedad , Síndrome Hemolítico-Urémico/sangre , Síndrome Hemolítico-Urémico/epidemiología , Síndrome Hemolítico-Urémico/genética , Humanos , Hungría/epidemiología , Lactante , Lipopolisacáridos/inmunología , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Pronóstico , Adulto JovenRESUMEN
The serum levels of interleukin 6 (IL6) are known to be elevated in two diseases of the elderly age, myelodysplastic syndrome (MDS) and multiple myeloma (MM). Authors suppose that one of the possible causes of this elevation could be a difference between these patients and healthy subjects in the frequency of polymorphic variants of the genes regulating IL6 levels. Scarce and contradictory comparative data are available for MM and to our best knowledge this is the first study on IL6 promoter and IL6 receptor (IL6R) polymorphism in MDS. Therefore we determined the Asp358Ala polymorphism of the IL6 receptor gene and the -174 G>C promoter polymorphism of the IL6 gene in blood samples of 102 MDS and 100 MM patients and 99 age- and sex-matched hospitalized controls had been tested for this purpose as well. There was no significant difference between patients with either disease and controls regarding IL6 promoter/L-6R. Authors therefore assume other mechanisms causing high IL6 levels are not related to either of these polymorphisms. Moreover authors consider important to propose a hypothesis how elements of signal transduction in iron metabolism might be involved in the development of MM and MDS in elderly age.
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Interleucina-6/genética , Mieloma Múltiple/genética , Síndromes Mielodisplásicos/genética , Regiones Promotoras Genéticas , Adulto , Anciano , Anciano de 80 o más Años , Secuencia de Bases , Estudios de Casos y Controles , Cartilla de ADN , Humanos , Persona de Mediana Edad , Reacción en Cadena de la PolimerasaRESUMEN
The amino acid composition of intrinsically disordered proteins and protein segments characteristically differs from that of ordered proteins. This observation forms the basis of several disorder prediction methods. These, however, usually perform worse for smaller proteins (or segments) than for larger ones. We show that the regions of amino acid composition space corresponding to ordered and disordered proteins overlap with each other, and the extent of the overlap (the "twilight zone") is larger for short than for long chains. To explain this finding, we used two-dimensional lattice model proteins containing hydrophobic, polar, and charged monomers and revealed the relation among chain length, amino acid composition, and disorder. Because the number of chain configurations exponentially grows with chain length, a larger fraction of longer chains can reach a low-energy, ordered state than do shorter chains. The amount of information carried by the amino acid composition about whether a protein or segment is (dis)ordered grows with increasing chain length. Smaller proteins rely more on specific interactions for stability, which limits the possible accuracy of disorder prediction methods. For proteins in the "twilight zone", size can determine order, as illustrated by the example of two-state homodimers.
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Modelos Químicos , Modelos Moleculares , Análisis de Secuencia de Proteína/métodos , Secuencia de Aminoácidos , Simulación por Computador , Datos de Secuencia Molecular , Conformación Proteica , Relación Estructura-ActividadRESUMEN
In this review article, earlier and recent work of the research group on the copy number polymorphism of the C4B gene are summarized. In a study performed in 1991 a sharp decrease was found among healthy elderly (>60 years old) people as compared to healthy young (<45 years old) people in the frequency of the individuals with a low copy number of the C4B gene (one of the two genes (C4A and C4B) encoding the C4 complement protein). This observation indicated that subjects with a low C4B copy number are selected out from the population of healthy individuals due to their increased morbidity/mortality of some disease(s). In accordance with this assumption a marked accumulation of low C4B copy number carriers was found in patients with acute myocardial infarction (AMI) and stroke as compared to age-matched healthy subjects. In addition it was demonstrated that AMI patients who carry a low copy number of the C4B gene have a highly significantly increased risk for short-term (1 year) post-AMI mortality as compared to non-carriers. These relationships, which were first revealed more than 15 years ago by our group, have been recently supported by new data obtained using up-to-date genotyping methods worked out by our group in two Caucasian populations, Hungarian and Icelandic. In addition, we proved that this relationship concerns only recent smokers. These findings indicate that there is strong connection between low copy number of the C4B gene on one hand and cardiovascular disease morbidity and mortality on the other. Hypotheses and the results of recent studies aiming to elucidate the mechanism of this association as well as other diseases connected with the low C4B copy number are discussed.
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Complemento C4/genética , Enfermedad/genética , Dosificación de Gen/genética , Complemento C4/metabolismo , Humanos , Fenotipo , Polimorfismo Genético/genética , Factores de RiesgoRESUMEN
Esophageal replacement using artificial material is not a new concept. Prior experiences with prostheses, allografts and composite grafts have not proved particularly successful. The aim of this study is to investigate whether cryopreserved animal trachea is suitable for the replacement of the esophagus. In 12 beagle dogs a 6-cm-long segment of the cervical esophagus was removed, and was replaced with cryopreserved trachea, which had been stored for 21 days on -86 degrees C. The proximal and distal ends of the esophagus were joined together with the graft by simple continuous suture (Biosyn 3/0) and covered with the sternohyoid flap. Postoperatively 16 hematological parameters were measured. The dogs were planned to be euthanized at random on days 28, 42 and 56 after the operation. Tests for air leak were performed and the inner diameter of the graft was measured to detect shrinkage. The microscopic structure of the graft was analyzed using haematoxylin and eosin staining. There was no indication of insufficiency. Based on the air leak test the sutures withheld properly. The inner diameter of the graft narrowed from an average 19 mm (+/- 1 mm) to 15.8 mm (+/- 0.6 mm). In length, the graft shortened from an average 60 mm to 47 mm (+/- 3 mm). No feeding difficulty was observed. In two cases wound suppuration was found involving only the cutaneous and subcutaneous layers. Concerning the laboratory parameters, only the fibrinogen level and white blood cell count showed temporary although significant changes. Histology findings on the 56th day showed absolute integration of the trachea with the esophagus, with disintegration of the tracheal cartilages. Cryopreserved trachea seems to be suitable for the replacement of a 5-6-cm-long esophageal segment.
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Criopreservación/métodos , Esofagectomía/métodos , Trasplante de Tejidos/métodos , Tráquea , Anastomosis Quirúrgica/métodos , Animales , Biopsia con Aguja , Modelos Animales de Enfermedad , Perros , Inmunohistoquímica , Masculino , Procedimientos de Cirugía Plástica/métodos , Factores de Riesgo , Sensibilidad y Especificidad , Inmunología del Trasplante , Trasplante HomólogoRESUMEN
We investigated the clinical characteristics and immunoserological alterations in patients with mixed connective tissue disease (MCTD) associated with pulmonary arterial hypertension (PAH). Anti-U1RNP autoantibodies, anti-endothelial cell antibodies (AECA) and serum thrombomodulin (TM) as well as von Willebrand factor antigen (vWFAg) concentrations were measured in 25 patients with MCTD associated with PAH and in 154 MCTD patients without PAH. The results showed that the probability of survival was lower in MCTD patients with PAH than in the 154 MCTD-non-PAH patients (5-year survival rate in MCTD with PAH: 73%, versus 96% in MCTD-non-PAH; P < 0.01). AECA were more frequently present in the sera of MCTD patients with PAH than in MCTD-non-PAH (P < 0.001). Serum TM and vWFAg levels were higher in MCTD-PAH patients than in MCTD-non-PAH patients (TM: P < 0.001; vWFAg: P < 0.001). Significant correlation was noticed between the quantity of AECA and TM level (r = 0.466) as well as the quantity of AECA and vWFAg level (r = 0.550). In conclusion, our results suggest that in MCTD the presence of AECA and endothelial cell activation may play a role in the development of PAH and in the maintenance of obliterative vascular processes.
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Hipertensión Pulmonar/etiología , Enfermedad Mixta del Tejido Conjuntivo/complicaciones , Arteria Pulmonar/fisiopatología , Adulto , Anticuerpos Anticardiolipina/sangre , Anticuerpos Anticardiolipina/inmunología , Anticuerpos Antinucleares/sangre , Anticuerpos Antinucleares/inmunología , Autoanticuerpos/sangre , Autoanticuerpos/inmunología , Ecocardiografía Doppler , Femenino , Humanos , Hipertensión Pulmonar/inmunología , Hipertensión Pulmonar/fisiopatología , Masculino , Persona de Mediana Edad , Enfermedad Mixta del Tejido Conjuntivo/inmunología , Enfermedad Mixta del Tejido Conjuntivo/fisiopatología , Ribonucleoproteína Nuclear Pequeña U1/inmunología , Análisis de SupervivenciaRESUMEN
Inherited thrombophilias are associated with an increased risk of maternal thromboembolism and certain adverse pregnancy outcomes, including second- and third-trimester fetal loss, placental abruption, severe intrauterine growth restriction, and early-onset, severe preeclampsia. Pregnant patients with severe thrombophilias, especially antithrombinopathies are at very high risk for both thromboembolism and adverse pregnancy outcomes. A case of a patient with antithrombin deficiency is reported, who had two successful pregnancies after eight miscarriages. Our case shows that a combined treatment with antithrombin substitution and a prophylactic, body-weight-adjusted dose of low-molecular-weight heparin may be successful in preventing pregnancy loss and thromboembolism in antithrombin deficiency during pregnancy, although other complications, such as preeclampsia and intrauterine growth restriction cannot always be prevented.
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Aborto Habitual/prevención & control , Anticoagulantes/uso terapéutico , Fibrina/deficiencia , Heparina/uso terapéutico , Complicaciones Hematológicas del Embarazo/genética , Adulto , Femenino , Humanos , Infertilidad Femenina/etiología , Infertilidad Femenina/terapia , Embarazo , Tromboembolia/genética , Trombofilia/genética , Resultado del TratamientoRESUMEN
Nepsilon-Monomethyllysine was identified in the serum, urine, brain, and liver samples of rats treated per os with L-deprenyl. The identification procedure included reaction with Fmoc chloride, clean-up, and analysis using HPLC-UV-MS. Oral administration of (-)-N-14C-methyl-N-propynyl(2-phenyl-1-methyl)ethylammonium hydrochloride L-deprenyl) to rats resulted in transfer of the radiolabelled methyl group to the Nepsilon-amino group of the endogenous lysine. The radiolabelled Nepsilon-monomethyllysine was urinary eliminated together with the other radiolabelled deprenyl metabolites, such as deprenyl-N-oxide and methamphetamine. The presence of Nepsilon-monomethyllysine has also been traced, and its concentrations were compared in the serum, liver and brain of rats subjected to L-deprenyl treatment. Methyl group transfer from the L-deprenyl to endogenous compounds; and the urinary elimination of their products may offer a vital way to eliminate or to decrease the degree of drug transmethylation to the lysine constituents of blood vessels' proteins.
Asunto(s)
Cromatografía Líquida de Alta Presión/métodos , Lisina/análogos & derivados , Espectrometría de Masas/métodos , Animales , Lisina/análisis , Masculino , Ratas , Ratas WistarRESUMEN
SUMMARY: Although 41% of patients with spontaneous rupture of the esophagus also suffer from gastro duodenal ulcer disease, cases of synchronous spontaneous esophageal and duodenal ulcer perforation have thus far not been reported in the literature. We report on the case of a 61-year-old man who presented with a 72-hour history of esophageal rupture and duodenal ulcer perforation. Following appropriate circulatory resuscitation we performed double resection; involving the esophagus, cardia and the distal part of the stomach, followed by substitution by means of gastro-jejunal transposition as a one-stage procedure. With reference to this case with a favorable outcome, we are presenting an analysis of indications for resectional surgery in advanced spontaneous esophageal perforation.
Asunto(s)
Procedimientos Quirúrgicos del Sistema Digestivo/métodos , Úlcera Duodenal/complicaciones , Perforación del Esófago/cirugía , Úlcera Péptica Perforada/cirugía , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Administration of (14)C-labelled L-deprenyl to rats results in the urinary elimination of a 14C-labelled compound. The 9-fluorenylmethoxycarbonyl chloride-reacted urine sample is fractionated by high-performance liquid chromatography (HPLC) on an octadecyl silica stationary phase. N(epsilon)-Monomethyl-lysine is identified in the fraction containing the majority of the radioactivity. Structural elucidation is carried out using HPLC-mass spectrometry in atmospheric pressure chemical ionization mode. Identification of the 14C-labelled fragment in Ne-monomethyl-lysine is an experimental proof that an N-methylated amino acid is generated by transmethylation from a well-known drug. This type of transmethylation may have basic importance in the positive side effects of certain drugs.