Assessment of long-term cultivated human precision-cut lung slices as an ex vivo system for evaluation of chronic cytotoxicity and functionality.

BACKGROUND: Investigation of basic chronic inflammatory mechanisms and development of new therapeutics targeting the respiratory tract requires appropriate testing systems, including those to monitor long- persistence. Human precision-cut lung slices (PCLS) have been demonstrated to mimic the human respiratory tract and have potential of an alternative, ex-vivo system to replace or augment in-vitro testing and animal models. So far, most research on PCLS has been conducted for short cultivation periods (≤72 h), while analyses of slowly metabolized therapeutics require long-term survival of PCLS in culture. In the present study, we evaluated viability, physiology and structural integrity of PCLS cultured for up to 15 days. METHODS: PCLS were cultured for 15 days and various parameters were assessed at different time points. RESULTS: Structural integrity and viability of cultured PCLS remained constant for 15 days. Moreover, bronchoconstriction was inducible over the whole period of cultivation, though with decreased sensitivity (EC501d = 4 × 10-8 M vs. EC5015d = 4 × 10-6 M) and reduced maximum of initial airway area (1d = 0.5% vs. 15d = 18.7%). In contrast, even though still clearly inducible compared to medium control, LPS-induced TNF-α secretion decreased significantly from day 1 to day 15 of culture. CONCLUSIONS: Overall, though long-term cultivation of PCLS need further investigation for cytokine secretion, possibly on a cellular level, PCLS are feasible for bronchoconstriction studies and toxicity assays.

Complement activation correlates with liver necrosis and fibrosis in chronic hepatitis C.

Chronic hepatitis C viral infection modulates complement. The aim of this study was to determine whether complement analysis predicts liver inflammation and fibrosis in patients with chronic hepatitis C. 50 chronic hepatitis C patients who underwent a liver biopsy were compared to 50 healthy controls and 35 patients with various liver diseases. Total plasma complement activity (CH50) in plasma was diminished in hepatitis C patients suggesting complement activation. This decrease correlated with increased necrosis (r = -0.24, p < 0.05), and patients with levels below the normal range had a higher METAVIR activity score reflecting enhanced inflammation. SC5b-9, a marker of complement activation, correlated with inflammation (r = 0.40, p < 0.05), activity (r = 0.42, p < 0.05), and fibrosis scores (r = 0.49, p < 0.05). Finally, the prevalence of C1q auto-antibodies was higher in hepatitis C patients, and their presence was associated with increased inflammation and seemed to affect fibrosis. We conclude that complement-induced liver inflammation contributes to fibrosis in patients with chronic hepatitis C.

Circulating fibronectin isoforms predict the degree of fibrosis in chronic hepatitis C.

OBJECTIVE: Hepatic stellate cells only produce fibronectin isoforms in disease states. The isoform-defining domains can be detected in the blood circulation. This study examines whether circulating levels of fibronectin isoforms show a relationship with liver fibrosis on histology in patients with chronic hepatitis C. MATERIAL AND METHODS: In a prospective study, 50 patients with chronic hepatitis C who underwent a liver biopsy were compared to 50 matched controls and 35 patients with other liver conditions. RESULTS: Circulating levels of the fibronectin isoforms were significantly higher in patients with chronic hepatitis C compared to healthy controls [oncofetal fibronectin (oFN) 2.45 +/- 0.17 versus 1.76 +/- 0.16 mg/l, P < 0.005; extra domain-A (EDA) 1.05 +/- 0.06 versus 0.86 +/- 0.06 mg/l, P < 0.05; and extra domain-B (EDB) 14.55 +/- 0.74 versus 9.31 +/- 0.58 mg/l, P < 0.001], even though total fibronectin was lower (198.9 +/- 3.5 versus 343.6 +/- 14.5 mg/l, P < 0.001). A correlation with the fibrosis score was found for both oFN (r = 0.46, P < 0.005) and EDA (r = 0.51, P < 0.001). The combination of an elevation in both markers (oFN and EDA) in the upper quartile was associated with a specificity of > 99% for predicting significant fibrosis (stages 2-4) and 95% for predicting advanced fibrosis (stages 3-4). A combination of decreased values in the lowest tertile for both markers had a specificity of 94% for excluding significant fibrosis. Based on these findings, 30% of the patients scheduled for a liver biopsy could be correctly classified as having or not having significant fibrosis. The remainder would have to proceed with a biopsy. CONCLUSION: Circulating fibronectin isoforms produced by activated stellate cells represent a viable marker for the presence of significant fibrosis or a lack thereof.

Rhinophyma: diagnosis and treatment options for a disfiguring tumor of the nose.

Rhinophyma is a benign dermatologic disease of the nose affecting primarily Caucasian men in their fifth to seventh decades of life. It is characterized by a slowly progressive enlargement with irregular thickening of the nasal skin and nodular deformation. It is assumed to be the end stage of chronic acne rosacea. Main reasons that urge the patients to seek help are plastic cosmetic and functional impairments such as nasal obstruction. Surgical removal of the hyperplastic tumor mass is the treatment of choice for rhinophyma. In a retrospective review, the authors describe the pros and cons of the main treatment modalities that have been described in literature and present their own clinical experience.

Chondrosarcoma of the larynx and review of the literature.

Chondrosarcoma (CS) of the larynx was first described in 1935. Cartilaginous tumours of the larynx are largely rare and there is little literature concerning them. Laryngeal CS manifest with a different pathological behaviour to other malignancies of the larynx and as such the treatment of these neoplasias are different. The purpose of this review is to present a detailed report of the laryngeal CS in recent literature. We present a case of laryngeal CS of the cricoid cartilage and a case of a sarcomatous neoplasm of the vocal cord as a potential differential diagnosis. Although representing a rare malignancy, the last decade has brought new insights in surgical treatment of laryngeal CS and subsequent reduction in recurrence rates, whereas progress in tumour biology and etiological agents is still scarce. We concentrate on new insights in classification, radiologic and pathologic features, and treatment modalities in the last two decades. Based on the literary evidence the authors recommend a conservative laryngeal function-preserving surgery. Total laryngectomy should be reserved to recurrent CS and rare cases of voluminous high-grade CS of the larynx.

Acute recurrent pancreatitis curtaining an intraductal papillary mucinous tumor of the pancreas.

Intraductal papillary mucinous tumor (IPMN) of the pancreas is a rare pancreatic tumor characterized by intraductal proliferation of mucin producing cells with hypersecretion of mucin that leads to cystic dilatation of the involved ducts. The usual clinical presentation is recurrent episodes of pancreatitis due to hypersecretion of mucin and temporary obstruction of the main pancreatic duct.