Approach to diagnosis and pathological examination in bronchial Dieulafoy disease: a case series

<p>Abstract</p> <p>Background</p> <p>There are limited series concerning Dieulafoy disease of the bronchus. We describe the clinical presentation of a series of 7 patients diagnosed with Dieulafoy disease of the bronchus and provide information about the pathological diagnosis approach.</p> <p>Patients and methods</p> <p>A retrospective review of patients who underwent surgery for massive and unexplained recurrent hemoptysis in a referral center during a 11-year period.</p> <p>Results</p> <p>Seven heavy smoker (49 pack years) patients (5 males) mean aged 54 years experienced a massive hemoptysis (350–1000 ml) unrelated to a known lung disease and frequently recurrent. Bronchial contrast extravasation was observed in 3 patients, combining both CT scan and bronchial arteriography. Efficacy of bronchial artery embolization was achieved in 40% of cases before surgery. Pathological examination demonstrated a minute defect in 3 cases and a large and dysplasic superficial bronchial artery in the submucosa in all cases.</p> <p>Conclusion</p> <p>Dieulafoy disease should be suspected in patients with massive and unexplained episodes of recurrent hemoptysis, in order to avoid hazardous endoscopic biopsies and to alert the pathologist if surgery is performed.</p

Treatment of mouse liver slices with cholestatic hepatotoxicants results in down-regulation of Fxr and its target genes

Background Unexpected cholestasis substantially contributes to drug failure in clinical trials. Current models used for safety assessment in drug development do not accurately predict cholestasis in humans. Therefore, it is of relevance to develop new screening models that allow identifying drugs with cholestatic properties. Methods We employed mouse precision cut liver slices (PCLS), which were incubated 24 h with two model cholestatic compounds: cyclosporin A (CsA) and chlorpromazine (CPZ). Subsequently, transcriptome analysis using DNA microarrays and q-PCR were performed to identify relevant biological processes and biomarkers. Additionally, histology was carried out and levels of triglycerides (TG) and bile acids (BA) were measured. To verify the ex vivo mouse data, these were compared with publically available human data relevant for cholestasis. Results Whole genome gene expression analysis showed that CsA up-regulated pathways related to NF-¿B, ER stress and inflammation. Both CsA and CPZ down-regulated processes related to extracellular matrix (ECM) remodelling, BA homeostasis, Fxr signalling, and energy metabolism. The differential expression of a number of characteristic genes (e.g. Abcg5, Abcg8, Klf15, and Baat) could be confirmed by q-PCR. Histology revealed that CsA but not CPZ induced “ballooning” of hepatocytes. No effects on TG and BA levels were observed after incubation of PCLS with CsA and CPZ. A substantial number of processes altered in CsA- and CPZ-treated mouse PCLS ex vivo was also found to be affected in liver biopsies of cholestatic patients. Conclusion The present study demonstrated that mouse PCLS can be used as a tool to identify mechanisms of action of cholestatic model compounds. The induction of general stress responses and down-regulated Fxr signalling could play a role in the development of drug induced cholestasis. Importantly, comparative data analysis showed that the ex vivo mouse findings are also relevant for human pathology. Moreover, this work provides a set of genes that are potentially useful to assess drugs for cholestatic properties

Effect of oxygen concentration and selected protocol factors on viability and gene expression of mouse liver slices

Precision cut liver slices (PCLSs) are widely used as a model to study hepatotoxicity. For culturing of PCLS diverse protocols are used which could affect slices viability and results. We aimed to identify the most optimal culture protocol for mouse PCLS. Slices were cultured for 24 h under different concentrations of serum, glucose, insulin, and oxygen. Thereafter, slices viability was assessed by biochemical methods. Transcriptome analysis was performed to identify changes introduced by culture at different oxygen concentrations (20%, 40%, 60%, and 80% of oxygen). Medium composition did not affect the slices viability. Although metabolic competence was unaffected by oxygen concentrations, culturing at 80% of oxygen yielded slices with the best biochemical characteristics. The comparison of uncultured vs. cultured slices revealed 2524 genes to be differentially expressed. Genes involved in drug metabolism, peroxisomal and mitochondrial functions were down-regulated while several adaptive/stress response processes were up-regulated. Moreover, 80% of oxygen was the most favorable condition with respect to maintenance of expression of genes involved in drug and energy metabolism. The outcome of this study indicates that mouse PCLS are a valuable tool in research on hepatic functions and toxicity, particularly if they are cultured under a controlled oxygen concentration of 80%

Delayed senescence in cauliflower transformed with an autoregulated isopentenyl transferase gene

Cauliflower (Brassica oleracea var. botrytis) was transformed, using Agrobacterium tumefaciens, with an autoregulated isopentenyl transferase (ipt) gene under the control of a senescence-associated gene promoter, pSAG12, isolated from Arabidopsis thaliana. The effect of introducing this chimeric construct on cytokinin (CK) content, chlorophyll retention, and plant morphology and development were investigated. A range of CK and chlorophyll contents was found among the individual primary transformants. Progeny were studied from one of the primary transformed lines that did not have elevated cytokinin content and was phenotypically similar to the parent line but displayed delayed leaf senescence. The pSAG12:ipt gene was inherited in a Mendelian manner, and the effect of this gene on senescence-related parameters was observed in a number of the progeny. While the pSAG12:ipt progeny did exhibit delayed leaf senescence, it was accompanied by undesirable agronomic traits, including less synchronous curd initiation, smaller curd size, and greater susceptibility to fungal infection

Resonancia magnética con ácido gadoxético —contraste hepatoespecífico— para la evaluación de lesiones focales

La resonancia magnética con gadolinio para la evaluación de lesiones hepáticas es un método cada vez más utilizado en la práctica clínica, particularmente para pacientes con lesiones focales sospechosas, ya sean benignas o malignas. En el caso del carcinoma hepatocelular, el rendimiento diagnóstico de la resonancia magnética a través de protocolos «convencionales» y mediante la tomografía computarizada multidetector, que consiste en la evaluación de múltiples fases con contraste intravenoso, depende en gran medida del tamaño de la lesión, considerándose más certero en lesiones > 2 cm. Sin embargo, para aquellas lesiones de 1-2 cm, el establecimiento de un diagnóstico definitivo es un verdadero reto, con valores de sensibilidad del 45-65%, aunque por lo general con una excelente especificidad (> 95%). Además, si la lesión tiene un diámetro < 1 cm, el diagnóstico es generalmente poco fiable. En estos 2 últimos escenarios, el uso complementario de medios de contraste hepatoespecíficos puede ser útil. El objetivo de este artículo es revisar la evidencia actual de la utilidad de este nuevo método de diagnóstico no invasivo en las lesiones hepáticas