1,721,057 research outputs found
S100A12 as diagnostic tool in the differential diagnosis of sJIA associated MAS vs. hereditary or acquired HLH
Full text linkReaching the threshold: a multilayer pathogenesis of macrophage activation syndrome.
No full textMacrophage activation syndrome (MAS) is a potentially fatal complication of rheumatic diseases. The condition is considered part of secondary hemophagocytic lymphohistiocytoses (HLH). There are similarities in genetic background, pathogenesis, and clinical and laboratory features with primary HLH (p-HLH). We describe findings in mouse models of secondary HLH, comparing them with models of p-HLH and the cellular and molecular mechanisms involved, and relate them to recent findings in patients with secondary HLH. A multilayer model is presented in which background inflammation, infections, and genetics all contribute in different proportions and in several ways. Once the "threshold" has been reached, inflammatory cytokines are the final effectors, independent of the interplay between different upstream pathogenic factors
Medicament for preventing peritoneal fibrosis due to long term peritoneal dialysis, comprises MEK 1 or 2 activity modulating agent
No full textAbstract: NOVELTY - Peritoneal fibrosis is prevented using an agent for modulating MEK 1 and/or MEK 2 activity.
USE - For preventing or treating fibrosis of the peritoneal membrane, including peritoneal opacification, tanned peritoneal syndrome, mural fibrosis and sclerosing peritonitis syndrome, which results from long-term peritoneal dialysis.
ADVANTAGE - An effective treatment for preventing progressive loss of peritoneal dialytic capacity in patients undergoing peritoneal dialysis.
DETAILED DESCRIPTION - A composition comprising an agent for modulating MEK 1 and/or MEK 2 activity is used to prepare a medicament for preventing or treating peritoneal fibrosis. INDEPENDENT CLAIMS are also included for the following:
(1) Method for identifying therapeutic agents suitable for treating peritoneal fibrosis, comprising contacting the compound to be analyzed with the polynucleotide and/or polypeptide MEK 1 and/or MEK 2 and then detecting the bond between the compound and polynucleotide and/or polypeptide;
(2) Method for identifying therapeutic agents suitable for treating peritoneal fibrosis, comprising measuring the activity of MEK 1 and/or MEK 2 at a given concentration of the compound to be analyzed or in the absence of this compound, and measuring the same activity at different concentration of this compound;
(3) Method for identifying therapeutic agents suitable for treating peritoneal fibrosis, comprising measuring the activity of MEK 1 and/or MEK 2 at a given concentration of the compound to be analyzed, and measuring the same activity in the presence of a compound which is known to modulate MEK 1 or MEK 2 activity; and
(4) Method for obtaining useful data for the diagnosis and/or prognosis of peritoneal fibrosis, by determining the expression of MEK 1 and/or MEK 2 in a sample taken from a mammal and the comparing these MEK 1 and/or MEK 2 expression values with those in a healthy or ill mammal
In vitro activity of propyl gallate-azole drug combination against fluconazole- and itraconazole-resistant Candida albicans strains
No full textAims: The influence of an antioxidant, propyl gallate (PG), on the In vitro antifungal activity of itraconazole and fluconazole, was investigated to determine whether PG could increase the antifungal activity and reduce strain resistance. Methods and Results: Susceptibility tests were performed against azole-resistant isolates of Candida albicans by the microbroth dilution method in the presence of PG at 400 mug ml(-1). PG-triazole combination brought about a marked reduction of inhibitory azole concentration. In particular, the MIC90 for itraconazole and fluconazole dropped from 1 mug ml(-1) to 0.125 mug ml(-1) and from >64 mug ml(-1)-8 mug ml(-1), respectively. Conclusions: It is likely that more than one mechanism is involved in the above synergistic interaction, including effects of PG on ATP synthesis, thus reducing the ABC transporters activity, or an effect on the target of azole, i.e. the P-450 cytochrome. Significance and Impact of the Study: The PG-triazole combination may have a role in future topical antifungal strategies but other studies are warranted
Cell-based assays to study ERK pathway/caveolin1 interactions
Full text linkCaveolin1, the main component of caveolae, plays a major role in regulating cell motility, gene expression, and cytoskeleton remodeling downstream of many membrane receptors. Here, we summarize different techniques set up to study changes in cell morphology and cell motility regulated by ERK/caveolin1 interactions during induction of epithelial mesenchymal transition (EMT) in mesothelial cells (MCs)
Targeting the ERK/NF-κB/Snail1 pathway as a potential therapeutic strategy to prevent the failure of peritoneal dialysis
No full textPeritoneal dialysis is frequently used as an alternative to haemodialysis for the treatment of end-stage renal disease. The peritoneum acts in dialysis as a semipermeable membrane across which ultrafiltration and diffusion take place. Continual exposure to bio-incompatible solutions and episodes of peritonitis or haemoperitoneum damage the peritoneal membrane, which progressively undergoes fibrosis and angiogenesis, leading ultimately to ultrafiltration failure. Changes induced by prolonged inflammatory stimuli in peritoneal mesothelial cells are reminiscent of those occurring during epithelial-to-mesenchymal transition (EMT). Thus, the mechanistic regulation of EMT genesis in the peritoneal membrane is relevant from both basic and clinical perspectives.
In our study, we reproduced EMT in vitro by treating primary mesothelial cells with effluent from patients undergoing peritoneal dialysis or by co-stimulation with transforming growth factor (TGF)-β1 and interleukin (IL)-1β. All of the aforementioned stimuli induced a genuine EMT, characterised by reduced E-cadherin and cytokeratin expression, cell scattering, and spindle-like morphology. We tried to identify the molecular mechanisms underlying this phenomenon and concluded that Snail1, induced by both ERK and NF-κB, is a master molecule that induces EMT in this experimental system. Interestingly, the blockage of ERK/NF-κB/Snail1 signalling in ex vivo cultured mesothelial cells from patients undergoing peritoneal dialysis reverted morphological and biochemical EMT in these cells. Modulation of the ERK/NF-κB/Snail1 activation pathway may thus provide a means of counteracting the progressive alteration of the peritoneal membrane and prolong the viability of peritoneal dialysis for the treatment of uremic patients
Use of composition for inhibiting activity of TAK1 and for manufacturing medicament for treating peritoneal fibrosis, and used in kit as biomarker for determining peritoneal fibrosis and determining progression of peritoneal fibrosis
No full textAbstract: NOVELTY - Use of a composition is claimed for inhibiting activity of TAK1 and for manufacturing a medicament for treating peritoneal fibrosis, where the composition comprises an agent.
USE - Used for inhibiting activity of TAK1 and for manufacturing a medicament for treating peritoneal fibrosis, and used in a kit as a biomarker for determining peritoneal fibrosis and determining progression of peritoneal fibrosis in a biological sample of mammal (all claimed).
ADVANTAGE - The composition prevents and reverses mesenchymal-epithelial transition of peritoneum during peritoneal dialysis treatment.
DETAILED DESCRIPTION - INDEPENDENT CLAIMS are also included for:
(1) a method for diagnosis and prognosis of peritoneal fibrosis, which involves obtaining a biological sample from mammal; and detecting and quantifying product of expression of TAK1 or its fragment or active molecule; and
(2) a method for determining progression of peritoneal fibrosis, which involves determining concentration or activity of expression product of TAK1 or its fragment in a biological sample, which is isolated from mammal;
(3) determining another concentration or activity of expression product of previously obtained product in a biological sample; and
(4) comparing difference between both concentrations of the product to find a significant deviation
Nerve Growth Factor, Acting Through TrkA, Down-Regulates the Inflammatory Response in Human Monocytes After Toll-Like Receptor Stimulation.
No full text- …
