Search results for "Fibrosis"
showing 10 items of 901 documents
Extraction socket healing in rats treated with bisphosphonate: Animal model for bisphosphonate related osteonecrosis of jaws in multiple myeloma pati…
2010
Aim: The aim of this study is to replicate both clinical and histological presentation of bisphosphonate induced osteonecrosis of the jaws (BONJ) in an animal model of the disease state. Successful recapitulation of a BONJlike indication in an animal model will be useful for studying pathogenesis, as well as prevention and treatment strategies for BONJ. Materials and Methods: Eighty (80) rats were prospectively and randomly divided into two groups; control group(40) and study group(40). All animals in study group, injected with a dose of 1 mg/kg dexamethasone (DX) subcutaneously on day 7, 14, or 21; and 1, 2, or 3 doses of 7.5 ?g/kg zoledronic acid (ZA) subcutaneously administered to coinci…
Phase ia/ii, two-arm, open-label, dose-escalation study of oral panobinostat administered via two dosing schedules in patients with advanced hematolo…
2013
Panobinostat is a potent oral pandeacetylase inhibitor that leads to acetylation of intracellular proteins, inhibits cellular proliferation and induces apoptosis in leukemic cell lines. A phase Ia/II study was designed to determine the maximum-tolerated dose (MTD) of daily panobinostat, administered on two schedules: three times a week every week or every other week on a 28-day treatment cycle in patients with advanced hematologic malignancies. The criteria for hematologic dose-limiting toxicities differed between patients with indications associated with severe cytopenias at baseline (leukemia and myeloid disorders) and those less commonly associated with baseline cytopenias (lymphoma and …
Disseminated tuberculosis in a patient treated with a JAK2 selective inhibitor: a case report
2012
Abstract Background Primary myelofibrosis is a myeloproliferative disorder characterized by bone marrow fibrosis, abnormal cytokine expression, splenomegaly and anemia. The activation of JAK2 and the increased levels of circulating proinflammatory cytokines seem to play an important role in the pathogenesis of myelofibrosis. Novel therapeutic agents targeting JAKs have been developed for the treatment of myeloproliferative disorders. Ruxolitinib (INCB018424) is the most recent among them. Case presentation To our knowledge, there is no evidence from clinical trials of an increased risk of tuberculosis during treatment with JAK inhibitors. Here we describe the first case of tuberculosis in a…
Upregulation of activin-B and follistatin in pulmonary fibrosis: a translational study using human biopsies and a specific inhibitor in mouse fibrosi…
2014
Background: Activins are members of the TGF-ß superfamily of growth factors. First, we identified by expression array screening that activin-B and follistatin are upregulated in human idiopathic pulmonary fibrosis (IPF). Next, we wanted to clarify their specific role in lung fibrosis formation. Methods: We used specific antibodies for activin-A and -B subunits and follistatin to measure and localize their levels in idiopathic pulmonary fibrosis and control lung biopsies. To inhibit activin signaling, we used soluble activin type IIB receptor fused to the Fc portion of human IgG1 (sActRIIB-Fc) in two different mouse models of pulmonary fibrosis. Results: Activin-B and follistatin mRNA levels…
Expanding the clinical spectrum of hereditary fibrosing poikiloderma with tendon contractures, myopathy and pulmonary fibrosis due to FAM111B mutatio…
2015
Background Hereditary Fibrosing Poikiloderma (HFP) with tendon contractures, myopathy and pulmonary fibrosis (POIKTMP [MIM 615704]) is a very recently described entity of syndromic inherited poikiloderma. Previously by using whole exome sequencing in five families, we identified the causative gene, FAM111B (NM_198947.3), the function of which is still unknown. Our objective in this study was to better define the specific features of POIKTMP through a larger series of patients. Methods Clinical and molecular data of two families and eight independent sporadic cases, including six new cases, were collected. Results Key features consist of: (i) early-onset poikiloderma, hypotrichosis and hypoh…
Vascular damage and lack of angiogenesis in systemic sclerosis skin
2003
The aim of this study was to analyse microvascular damage and compensatory angiogenesis in skin from patients with systemic sclerosis (SSc) compared with systemic lupus erythematosus (SLE), Raynaud's phenomenon (RP) and healthy controls. Immunohistochemistry was used for skin biopsies (9 SSc, 10 SLE, 9 RP and 12 healthy controls) using von Willebrand factor and beta3 integrin subunit specific antibodies, TechMate immunostaining robot and biotin-streptavidin protocol. In the early stages of SSc, vWF was found in the perivascular space and interstitial matrix in papillary but not in the reticular dermis, in particular around small oedematous blood vessels infiltrated by mononuclear cells. The…
Expression of LFA-1 (CD11a/CD18) and ICAM-1 (CD54) in an animal model of renal interstitial fibrosis induced by unilateral ureteral obstruction
2000
Unilateral ureteral obstruction (UUO) has been used as an experimental model to induce tubulointerstitial damage and interstitial fibrosis. UUO is characterized by cellular proliferation, accumulation of inflammatory cells, and subsequent replacement of renal parenchyma by fibrous tissue. The influx of inflammatory cells into the renal interstitium is mediated by adhesion molecules. In this study, the development of fibrosis in the UUO model of the rat was examined and its relation to the time course of LFA-1 and ICAM-1 expression was assessed by immunohistochemistry. An increase in interstitial connective tissue was detected on day 10 after UUO, with a maximum on day 35. After unilateral u…
Neutral pH and low–glucose degradation product dialysis fluids induce major early alterations of the peritoneal membrane in children on peritoneal di…
2018
WOS: 000439138700024 PubMed ID: 29776755 The effect of peritoneal dialysates with low-glucose degradation products on peritoneal membrane morphology is largely unknown, with functional relevancy predominantly derived from experimental studies. To investigate this, we performed automated quantitative histomorphometry and molecular analyses on 256 standardized peritoneal and 172 omental specimens from 56 children with normal renal function, 90 children with end-stage kidney disease at time of catheter insertion, and 82 children undergoing peritoneal dialysis using dialysates with low-glucose degradation products. Follow-up biopsies were obtained from 24 children after a median peritoneal dial…
TIMP expression in toxic and cholestatic liver injury in rat.
1997
Abstract Background/Aims: Hepatic fibrosis is a dynamic pathological process with a net accumulation of extracellular matrix proteins. Recent evidence suggests that besides their increased synthesis, inhibition of matrix degradation plays a significant role. ECM degradation occurs via metalloproteinases which are inhibited in situ by specific tissue inhibitors of metalloproteinases (TIMPs). The aim of our studies was to determine the expression of TIMPs during toxic liver injury and cholestatic liver injury leading to fibrosis. Methods: We examined the expression of TIMP-1, -2 and -3 in two different rat models for liver injury (intraperitoneal CCl 4 injection and bile duct ligation) by Nor…
M2 Polarized Macrophages and Giant Cells Contribute to Myofibrosis in Neuromuscular Sarcoidosis
2011
The etiopathogenesis of sarcoidosis, a systemic granulomatous disease, still remains obscure. A multitude of organs have been described to be affected in systemic sarcoidosis. Skeletal muscles may also be affected, leading to myalgia and weakness. A workup of the specific immune response with emphasis on the macrophage response is provided herein. Affected muscle tissue from seven patients with systemic sarcoidosis was analyzed and compared with that from seven patients with other myopathies containing macrophagocytic infiltration. Monocytes/macrophages and giant cells in granulomas of muscle tissue from patients with sarcoidosis show a status of alternative activation (M2) based on their e…