Portal hypertension associated angiogenesis assay in experimental studies (literature review)

The review presents literature data on portal hypertension associated angiogenesis assay in experimental studies. The information was collected from the PubMed database, the Google Scholar retrieval system, and the reference lists from relevant publications for 1981 – 2017 using the keywords: “portal hypertension,” “µCT,” “angiogenesis,” “immunohistochemistry,” “intravital microscopy,” “microspheres.” Analysis of the literature showed that intra- and extrahepatic angiogenesis assays, such as micro-computed tomography in vivo and ex vivo, intravital microscopy, and computer image processing allow us to establish its important role in portal hypertension pathogenesis. The development of anti-angiogenic therapy, which would be focused on newly formed vessels, may be a perspective direction in the treatment of portal hypertension and its complications.В обзоре представлены литературные данные о современных методах изучения ангиогенеза, ассоциированного с портальной гипертензией, в эксперименте. для поиска научных статей применялись база данных PubMed, поисковая система Google Scholar, а также пристатейные списки литературы. Соответствующие цели обзора публикации отбирались за период с 1981 по 2017 год по терминам: «портальная гипертензия», «микрокт», «ангиогенез», «иммуногистохимия», «интравитальная микроскопия», «микросферы». анализ литературы показал, что современные методы изучения внутри- и внепечёночного ангиогенеза, такие как микрокомпьютерная томография in vivo и ex vivo, интравитальная микроскопия, а также эффективные средства компьютерной обработки изображений, позволяют установить его важную роль в патогенезе портальной гипертензии. разработка способов антиангиогенной терапии, избирательно направленной на новообразованные сосуды, может быть перспективным направлением в лечении портальной гипертензии и связанных с ней осложнений

Fabrication Principles and Their Contribution to the Superior In Vivo Therapeutic Efficacy of Nano-Liposomes Remote Loaded with Glucocorticoids

We report here the design, development and performance of a novel formulation of liposome- encapsulated glucocorticoids (GCs). A highly efficient (>90%) and stable GC encapsulation was obtained based on a transmembrane calcium acetate gradient driving the active accumulation of an amphipathic weak acid GC pro-drug into the intraliposome aqueous compartment, where it forms a GC-calcium precipitate. We demonstrate fabrication principles that derive from the physicochemical properties of the GC and the liposomal lipids, which play a crucial role in GC release rate and kinetics. These principles allow fabrication of formulations that exhibit either a fast, second-order (t1/2 ∼1 h), or a slow, zero-order release rate (t1/2 ∼ 50 h) kinetics. A high therapeutic efficacy was found in murine models of experimental autoimmune encephalomyelitis (EAE) and hematological malignancies

Activated MCTC mast cells infiltrate diseased lung areas in cystic fibrosis and idiopathic pulmonary fibrosis

<p>Abstract</p> <p>Background</p> <p>Although mast cells are regarded as important regulators of inflammation and tissue remodelling, their role in cystic fibrosis (CF) and idiopathic pulmonary fibrosis (IPF) has remained less studied. This study investigates the densities and phenotypes of mast cell populations in multiple lung compartments from patients with CF, IPF and never smoking controls.</p> <p>Methods</p> <p>Small airways, pulmonary vessels, and lung parenchyma were subjected to detailed immunohistochemical analyses using lungs from patients with CF (20 lung regions; 5 patients), IPF (21 regions; 7 patients) and controls (16 regions; 8 subjects). In each compartment the densities and distribution of MC_Tand MC_TCmast cell populations were studied as well as the mast cell expression of IL-6 and TGF-β.</p> <p>Results</p> <p>In the alveolar parenchyma in lungs from patients with CF, MC_TCnumbers increased in areas showing cellular inflammation or fibrosis compared to controls. Apart from an altered balance between MC_TCand MC_Tcells, mast cell in CF lungs showed elevated expression of IL-6. In CF, a decrease in total mast cell numbers was observed in small airways and pulmonary vessels. In patients with IPF, a significantly elevated MC_TCdensity was present in fibrotic areas of the alveolar parenchyma with increased mast cell expression of TGF-β. The total mast cell density was unchanged in small airways and decreased in pulmonary vessels in IPF. Both the density, as well as the percentage, of MC_TCcorrelated positively with the degree of fibrosis. The increased density of MC_TC, as well as MC_TCexpression of TGF-β, correlated negatively with patient lung function.</p> <p>Conclusions</p> <p>The present study reveals that altered mast cell populations, with increased numbers of MC_TCin diseased alveolar parenchyma, represents a significant component of the histopathology in CF and IPF. The mast cell alterations correlated to the degree of tissue remodelling and to lung function parameters. Further investigations of mast cells in these diseases may open for new therapeutic strategies.</p

Association of mast cells with lung function in chronic obstructive pulmonary disease

BACKGROUND: In asthma, higher chymase positive mast cell (MC-C) numbers are associated with less airway obstruction. In COPD, the distribution of MC-C and tryptase positive mast cells (MC-T) in central and peripheral airways, and their relation with lung function, is unknown. We compared MC-T and MC-C distributions in COPD and controls without airflow limitation, and determined their relation with lung function. METHODS: Lung tissue sections from 19 COPD patients (median [interquartile range] FEV(1)% predicted 56 [23–75]) and 10 controls were stained for tryptase and chymase. Numbers of MC-T and MC-C were determined in different regions of central and peripheral airways and percentage of degranulation was determined. RESULTS: COPD patients had lower MC-T numbers in the subepithelial area of central airways than controls. In COPD, MC-T numbers in the airway wall and more specifically in the epithelium and subepithelial area of peripheral airways correlated positively with FEV(1)/VC (Spearman's rho (r(s)) 0.47, p = 0.05 and r(s )0.48, p = 0.05, respectively); MC-C numbers in airway smooth muscle of peripheral airways correlated positively with FEV(1)% predicted (r(s )0.57, p = 0.02). Both in COPD patients and controls the percentage of degranulated MC-T and MC-C mast cells was higher in peripheral than in central airways (all p < 0.05), but this was not different between the groups. CONCLUSION: More MC-T and MC-C in peripheral airways correlate with better lung function in COPD patients. It is yet to determine whether this reflects a protective association of mast cells with COPD pathogenesis, or that other explanations are to be considered

Mast cells induce activation of human lung fibroblasts in vitro

Mast cells are able to induce proliferation of skin fibroblasts; however, their effect on lung fibroblasts has not been clearly established. Using in vitro cocultures of rat or human mast cells with lung fibroblasts, the authors determined whether mast cells alter proliferation, collagen synthesis, and metalloproteinase production from lung fibroblasts. Mast cells enhanced the proliferation of human fibroblasts (mean +/- SEM: 90% +/- 4.7% increase, P 0.05), respectively. Rat mast cell sonicate added to lung fibroblasts induced the activation of metalloproteinase-9 while inhibiting that of metaloproteinase-2. The addition of lipopolysaccharide (LPS)-stimulated lung macrophage supernatant further enhanced the poliferative effect of mast cells on fibroblasts (by 60% +/- 7.8%, P < .001) and induced synthesis of collagen from these cells (190% +/- 28% increase versus control, P < .05). This study demonstrates that mast cells influence several aspects of lung fibroblast function in vitro