lmunotoksičnost spojeva kroma: učinak natrijevog dikromata na aktivaciju T stanica in vitro

Human T cells, isolated from peripheral blood of healthy donors, were stimulated with phytohemagglutinin and cultured in vitro in the presence of sodium dichromate (l0-3 - 10-9 M). A high (10-3 M) concentration of sodium dichromate depressed T cell proliferation whereas low levels of dichromate (10-9 M) led to a significant decrease in interleukin 2 production. The results obtained suggest a direct toxic action of sodium dichromate on the functional activity of T cells.Ljudske T stanice izolirane iz periferne krivi zdravih davalaca stimulirane su hernaglutininom i održavane u in vitro kulturi u prisustvu natrijevog dikromata (10-3 - 10-9 M). Visoka koncentracija (10-3 M) natrijevog dikromata smanjila je proliferaoiju T stanica dok su niske razine dikromata (10-9 M) izazvale značajno smanjenje proizvodnje interleukina 2. Dobiveni rezultati upućuju na direktno toksično djelovanje natrijevog dikromata na funkcionalnu aktivnost T stanica

Učinak olova na sadržaj proteina i aktivnost laktat dehidrogenaze u kulturi jetrenog tkiva

Slices of foetal and adult liver were cultured in vitro with various concentrations of Iead ions. A decrease in protein content and an increase in lactate dehydrogenase activity in the culturing medium were found. The changes were dose-dependent, and the foetal liver tissue was found to be more susceptible to the effect of lead than the tissue of adult rats.Rezovi jetre fetusa i odraslog štakora održavani su in vitro u medijima kojima su dodavane različite koncentracije dona olova. Utvrđeno je značajno smanjenje količine proteina u mediju i povećanje aktivnosti laktat dehidrogenaze. Promjene su bile ovisne o koncentraciji olova u mediju. Jetra fetusa bila je osjetljivija na učinke olova negoli jetra odraslog štakora

Kolageni elastin u jetri štakora otrovanih živinim kloridom

Intoxication of rats with mercuric chloride (0.5 mg Hg/kg of body weight, daily for 10 weeks) increased the hepatic contents of soluble and insoluble collagen and elastin. The increase was associated with elevated serum aminotransferase and alkaline phosphatase activities, and decreased total protein level in serum. Inflammatory changes were found in the liver. An increase in the fibrous protein content suggests that inflammatory reaction to mercuric chloride can result in hepatic fibrosis.Trovanje štakora živinim kloridom (0,5 mg Hg/kg tjelesne težine na dan tijekom deset tjedana) imalo je za rezultat povećan sadržaj topljivog i netopljivog kolagena i elastina u jetri. Povećanje je dovedeno u vezu s povišenim aktivnostima aminotransferaze i alkalne fosfataze u serumu, i sa smanjenim nivoom ukupnog proteina u serumu. U jetri su zamijećene upalne promjene. Povišen sadržaj vlaknastog proteina upućuje na to da upalna reakcija na živin klorid može dovesti do fibroze jetre

Update of EULAR recommendations for the treatment of systemic sclerosis

The aim was to update the 2009 European League against Rheumatism (EULAR) recommendations for the treatment of systemic sclerosis (SSc), with attention to new therapeutic questions. Update of the previous treatment recommendations was performed according to EULAR standard operating procedures. The task force consisted of 32 SSc clinical experts from Europe and the USA, 2 patients nominated by the pan-European patient association for SSc (Federation of European Scleroderma Associations (FESCA)), a clinical epidemiologist and 2 research fellows. All centres from the EULAR Scleroderma Trials and Research group were invited to submit and select clinical questions concerning SSc treatment using a Delphi approach. Accordingly, 46 clinical questions addressing 26 different interventions were selected for systematic literature review. The new recommendations were based on the available evidence and developed in a consensus meeting with clinical experts and patients. The procedure resulted in 16 recommendations being developed (instead of 14 in 2009) that address treatment of several SSc-related organ complications: Raynaud's phenomenon (RP), digital ulcers (DUs), pulmonary arterial hypertension (PAH), skin and lung disease, scleroderma renal crisis and gastrointestinal involvement. Compared with the 2009 recommendations, the 2016 recommendations include phosphodiesterase type 5 (PDE-5) inhibitors for the treatment of SSc-related RP and DUs, riociguat, new aspects for endothelin receptor antagonists, prostacyclin analogues and PDE-5 inhibitors for SSc-related PAH. New recommendations regarding the use of fluoxetine for SSc-related RP and haematopoietic stem cell transplantation for selected patients with rapidly progressive SSc were also added. In addition, several comments regarding other treatments addressed in clinical questions and suggestions for the SSc research agenda were formulated. These updated data-derived and consensus-derived recommendations will help rheumatologists to manage patients with SSc in an evidence-based way. These recommendations also give directions for future clinical research in SSc

Učinak olova na sadržaj proteina i aktivnost laktat dehidrogenaze u kulturi jetrenog tkiva

Slices of foetal and adult liver were cultured in vitro with various concentrations of Iead ions. A decrease in protein content and an increase in lactate dehydrogenase activity in the culturing medium were found. The changes were dose-dependent, and the foetal liver tissue was found to be more susceptible to the effect of lead than the tissue of adult rats.Rezovi jetre fetusa i odraslog štakora održavani su in vitro u medijima kojima su dodavane različite koncentracije dona olova. Utvrđeno je značajno smanjenje količine proteina u mediju i povećanje aktivnosti laktat dehidrogenaze. Promjene su bile ovisne o koncentraciji olova u mediju. Jetra fetusa bila je osjetljivija na učinke olova negoli jetra odraslog štakora

Kolageni elastin u jetri štakora otrovanih živinim kloridom

Intoxication of rats with mercuric chloride (0.5 mg Hg/kg of body weight, daily for 10 weeks) increased the hepatic contents of soluble and insoluble collagen and elastin. The increase was associated with elevated serum aminotransferase and alkaline phosphatase activities, and decreased total protein level in serum. Inflammatory changes were found in the liver. An increase in the fibrous protein content suggests that inflammatory reaction to mercuric chloride can result in hepatic fibrosis.Trovanje štakora živinim kloridom (0,5 mg Hg/kg tjelesne težine na dan tijekom deset tjedana) imalo je za rezultat povećan sadržaj topljivog i netopljivog kolagena i elastina u jetri. Povećanje je dovedeno u vezu s povišenim aktivnostima aminotransferaze i alkalne fosfataze u serumu, i sa smanjenim nivoom ukupnog proteina u serumu. U jetri su zamijećene upalne promjene. Povišen sadržaj vlaknastog proteina upućuje na to da upalna reakcija na živin klorid može dovesti do fibroze jetre

A review of glucosamine for knee osteoarthritis: why patented crystalline glucosamine sulfate should be differentiated from other glucosamines to maximize clinical outcomes

The European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) treatment algorithm for knee osteoarthritis (OA) recommends symptomatic slow-acting drugs for osteoarthritis (SYSADOAs) first line for the medium to long term management of OA, due to their ability to control pain, improve function, and delay joint structural changes. Among SYSADOAs, glucosamine is probably the most widely used intervention. In the present review of glucosamine for knee OA, we have investigated whether the evidence is greater for the patented crystalline glucosamine sulfate (pCGS) preparation (Rottapharm/Meda) than for other glucosamine formulations. Glucosamine is actually widely available in many forms, as the prescription-grade pCGS preparation, generic and over-the-counter formulations of glucosamine sulfate (GS) and food supplements containing glucosamine hydrochloride (GH), which vary substantially in molecular form, pharmaceutical formulation and dose regimens. Only pCGS is given as a highly bioavailable once daily dose (1500mg) with a proven pharmacological effect. pCGS consistently reaches the plasma levels of around 10 lM required to inhibit interleukin-1 induced expression of genes involved in the pathophysiology of joint inflammation and tissue destruction, compared with sub-therapeutic levels achieved with GH. It is evident, from careful consideration of the evidence base, that only the pCGS formulation of glucosamine reliably provides an effect size on pain that is higher than that of paracetamol and equivalent to that provided by non-steroidal antiinflammatory drugs. In comparison, the effect size on pain of non-crystalline GS preparations and GH from randomized controlled trials is repeatedly demonstrated to be zero. In addition, there is evidence that chronic administration of pCGS has disease-modifying effects, with a reduction in the need for total joint replacement surgery lasting for at least 5 years after treatment cessation. Consequently, the pCGS preparation (Rottapharm/Meda) is the logical choice, with demonstrated medium-term control of pain and lasting impact on disease progression

Is There A Role For Tnf-α Antagonists In The Treatment Of Ssc? Eustar Expert Consensus Development Using The Delphi Technique

Objective: To obtain experiences and expert opinion on treatment of SSc patients with TNF-α antagonists. Methods: An investigation was carried out among the EUSTAR centres into their expertise on use of TNF-α antagonists. Assessment forms on the frequency of TNF-α inhibitor use were distributed to EULAR Scleroderma Trials and Research Group (EUSTAR) centres. Afterwards, a three round Delphi exercise was performed to obtain expert consensus on the use of TNF-α inhibitors in SSc. Results: Seventy-nine centres returned information on use of TNF-α antagonists in SSc patients. A total of 65 patients were treated with TNF-a inhibitors in 14 different centres. Forty-eight of the 65 patients treated with TNF-α inhibitors improved. Improvement was mainly seen in patients with arthritis, whereas the effects on fibrosis varied. In the first round of the subsequent Delphi approach, 71 out of 79 experts stated that they would use TNF-α antagonists in SSc. Arthritis was suggested as an indication for TNFa antagonists by 75% of the experts. However, after the third stage of the Delphi exercise, the acceptance for the off-label use of TNF-a antagonists decreased and 59% recommended that TNF-α antagonists should not be used or only used in clinical trials in SSc patients, while 38% of the experts suggested the use of TNF-a antagonists for arthritis associated with SSc. Conclusions: Most of the experts do not recommend the routine use of TNF-a antagonists in systemic sclerosis. Arthritis might be a potential indication in SSc, although controlled clinical trials with TNF-α antagonists are needed before general recommendations can be given. © Copyright Clinical and Experimental Rheumatology 2011.292 SUPPL. 65S40S45Keyser, F.D., Mielants, H., Veys, E.M., Current use of biologicals for the treatment of spondyloarthropathies (2001) Expert Opin Pharmacother, 2, pp. 85-93Olsen, N.J., Stein, C.M., New drugs for rheumatoid arthritis (2004) N Engl J Med, 350, pp. 2167-2179Chua, C.C., Chua, B.H., Tumor necrosis factor-alpha induces mRNA for collagenase and TIMP in human skin fibroblasts (1990) Connect Tissue Res, 25, pp. 161-170Mauviel, A., Daireaux, M., Redini, F., Galera, P., Loyau, G., Pujol, J.P., Tumor necrosis factor inhibits collagen and fibronectin synthesis in human dermal fibroblasts (1988) FEBS Lett, 236, pp. 47-52Liu, J.Y., Brass, D.M., Hoyle, G.W., Brody, A.R., TNF-alpha receptor knockout mice are protected from the fibroproliferative effects of inhaled asbestos fibers (1998) Am J Pathol, 153, pp. 1839-1847Piguet, P.F., Vesin, C., Treatment by human recombinant soluble TNF receptor of pulmonary fibrosis induced by bleomycin or silica in mice (1994) Eur Respir J, 7, pp. 515-518Khan, S.B., Cook, H.T., Bhangal, G., Smith, J., Tam, F.W., Pusey, C.D., Antibody blockade of TNF-alpha reduces inflammation and scarring in experimental crescentic glomerulonephritis (2005) Kidney Int, 67, pp. 1812-1820Distler, J.H., Schett, G., Gay, S., Distler, O., The controversial role of tumor necrosis factor alpha in fibrotic diseases (2008) Arthritis Rheum, 58, pp. 2228-2235Varga, J., Abraham, D., Systemic sclerosis: A prototypic multisystem fibrotic disorder (2007) J Clin Invest, 117, pp. 557-567Gabrielli, A., Avvedimento, E.V., Krieg, T., Scleroderma (2009) N Engl J Med, 360, pp. 1989-2003Bosello, S., De Santis, M., Tolusso, B., Zoli, A., Ferraccioli, G., Tumor necrosis factor-alpha inhibitor therapy in erosive polyarthritis secondary to systemic sclerosis (2005) Ann Intern Med, 143, pp. 918-920Antoniou, K.M., Mamoulaki, M., Malagari, K., Infliximab therapy in pulmonary fibrosis associated with collagen vascular disease (2007) Clin Exp Rheumatol, 25, pp. 23-28Bargagli, E., Galeazzi, M., Bellisai, F., Volterrani, L., Rottoli, P., Infliximab treatment in a patient with systemic sclerosis associated with lung fibrosis and pulmonary hypertension (2008) Respiration, 75, pp. 346-349Denton, C.P., Engelhart, M., Tvede, N., An open-label pilot study of infliximab therapy in diffuse cutaneous systemic sclerosis (2009) Ann Rheum Dis, 68, pp. 1433-1439Ellman, M.H., Macdonald, P.A., Katz, R.S., Open label use of etanercept in eight scleroderma patients (2003) Ann Rheum Dis, 62 (SUPPL. I), p. 229Lam, G.K., Hummers, L.K., Woods, A., Wigley, F.M., Efficacy and safety of etanercept in the treatment of scleroderma-associated joint disease (2007) J Rheumatol, 34, pp. 1636-1637. , JulAlexis, A.F., Strober, B.E., Off-label dermatologic uses of anti-TNF-α therapies (2005) J Cutan Med Surg, 9, pp. 296-302Avouac, J., Walker, U., Tyndall, A., Characteristics of joint involvement and relationships with systemic inflammation in systemic sclerosis: Results from the EULAR Scleroderma Trial and Research Group (EUSTAR) database (2010) J Rheumatol, 37, pp. 1488-1501Khanna, D., Agrawal, H., Clements, P.J., Infliximab may be effective in the treatment of steroid-resistant eosinophilic fasciitis: Report of three cases (2010) Rheumatology, 49, pp. 1184-1188. , OxfordTzaribachev, N., Holzer, U., Schedel, J., Maier, V., Klein, R., Kuemmerle-Deschner, J., Infliximab effective in steroid-dependent juvenile eosinophilic fasciitis (2008) Rheumatology, 47, pp. 930-932. , OxfordAllanore, Y., Devos-Francois, G., Caramella, C., Boumler, P., Jounieaux, V., Kahan, A., Fatal exacerbation of fibrosing alveolitis associated with systemic sclerosis in a patient treated with adalimumab (2006) Ann Rheum Dis, 65, pp. 834-835Marie, I., Lahaxe, L., Levesque, H., Hellot, P., Pulmonary actinomycosis in a patient with diffuse systemic sclerosis treated with infliximab (2008) QJM, 101, pp. 419-421Ostor, A.J., Crisp, A.J., Somerville, M.F., Scott, D.G., Fatal exacerbation of rheumatoid arthritis associated fibrosing alveolitis in patients given infliximab (2004) BMJ, 329, p. 1266Amjadi, S., Maranian, P., Furst, D.E., Course of the modified Rodnan skin thickness score in systemic sclerosis clinical trials: Analysis of three large multicentre, double-blind, randomized controlled trials (2009) Arthritis Rheum, 60, pp. 2490-2498Denton, C.P., Merkel, P.A., Furst, D.E., Recombinant human anti-transforming growth factor beta1 antibody therapy in systemic sclerosis: A multicenter, randomized, placebo-controlled phase I/II trial of CAT-192 (2007) Arthritis Rheum, 56, pp. 323-333Kaldas, M., Khanna, P.P., Furst, D.E., Sensitivity to change of the modified Rodnan skin score in diffuse systemic sclerosis-assessment of individual body sites in two large randomized controlled trials (2009) Rheumatology, 48, pp. 1143-1146. , OxfordPostlethwaite, A.E., Wong, W.K., Clements, P., A multicenter, randomized, double-blind, placebo-controlled trial of oral type I collagen treatment in patients with diffuse cutaneous systemic sclerosis: I. Oral type I collagen does not improve skin in all patients, but may improve skin in late-phase disease (2008) Arthritis Rheum, 58, pp. 1810-1822Walker, U.A., Tyndall, A., Czirjak, L., Clinical risk assessment of organ manifestations in systemic sclerosis: A report from the EULAR Scleroderma Trials and Research group database (2007) Ann Rheum Dis, 66, pp. 754-763Linstone, H., Turoff, M., (2002) The Delphi Method. Techniques and Applications, , New Jersey Institute of Technology, California, USAJones, J., Hunter, D., Consensus methods for medical and health services research (1995) BMJ, 311, pp. 376-380Generini, S., Steiner, G., Miniati, I., Anti-hnRNP and other autoantibodies in systemic sclerosis with joint involvement (2009) Rheumatology, 48, pp. 920-925. , OxfordMatucci-Cerinic, M., Allanore, Y., Czirjak, L., The challenge of early systemic sclerosis for the EULAR Scleroderma Trial and Research group (EUSTAR) community. It is time to cut the Gordian knot and develop a prevention or rescue strategy (2009) Ann Rheum Dis, 68, pp. 1377-138

Update of EULAR recommendations for the treatment of systemic sclerosis

The aim was to update the 2009 European League against Rheumatism (EULAR) recommendations for the treatment of systemic sclerosis (SSc), with attention to new therapeutic questions. Update of the previous treatment recommendations was performed according to EULAR standard operating procedures. The task force consisted of 32 SSc clinical experts from Europe and the USA, 2 patients nominated by the pan-European patient association for SSc (Federation of European Scleroderma Associations (FESCA)), a clinical epidemiologist and 2 research fellows. All centres from the EULAR Scleroderma Trials and Research group were invited to submit and select clinical questions concerning SSc treatment using a Delphi approach. Accordingly, 46 clinical questions addressing 26 different interventions were selected for systematic literature review. The new recommendations were based on the available evidence and developed in a consensus meeting with clinical experts and patients. The procedure resulted in 16 recommendations being developed (instead of 14 in 2009) that address treatment of several SSc-related organ complications: Raynaud's phenomenon (RP), digital ulcers (DUs), pulmonary arterial hypertension (PAH), skin and lung disease, scleroderma renal crisis and gastrointestinal involvement. Compared with the 2009 recommendations, the 2016 recommendations include phosphodiesterase type 5 (PDE-5) inhibitors for the treatment of SSc-related RP and DUs, riociguat, new aspects for endothelin receptor antagonists, prostacyclin analogues and PDE-5 inhibitors for SSc-related PAH. New recommendations regarding the use of fluoxetine for SSc-related RP and haematopoietic stem cell transplantation for selected patients with rapidly progressive SSc were also added. In addition, several comments regarding other treatments addressed in clinical questions and suggestions for the SSc research agenda were formulated. These updated data-derived and consensus-derived recommendations will help rheumatologists to manage patients with SSc in an evidence-based way. These recommendations also give directions for future clinical research in SSc. © Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/