Abstract：
OBJECTIVE:To determine the effects of a glycinamide ribonucleotide formyltransferase (GARFT) inhibitor on macrophage inflammatory processes and in vivo in rat adjuvant arthritis. METHODS:GARFT inhibitors, LY309886 (6S-2',5'-thienyl-5, 10-dideazatetrahydrofolic acid) and LY329201 (R)-N-[[5-[2-(2-amino-1,4,5,6,7,8-hexahydro-4-oxopyrido[2,3-d]pyrimidin-6-yl)ethyl]-2-thienyl]carbonyl]-L-glutamatic acid disodium salt, were investigated in vitro and ex vivo on primary murine peritoneal macrophages and in the RAW macrophage cell line for both purine depletion and inhibition of LPS induced monokine secretion. In vivo efficacy following GARFT inhibition was evaluated in modified rat adjuvant arthritis. RESULTS:LY309886 inhibited purine biosynthesis in the RAW cell line with an EC50 of 90 nM, an effect readily reversible with exogenous hypoxanthine. LY309886 and LY329201 also inhibited LPS induced TNF alpha and MIP1 alpha in these cells and in primary macrophages. A similar effect could be demonstrated ex vivo with mice dosed for two days with 3 mg/kg of LY329201. LY329201 as well as methotrexate demonstrated a dose dependent reduction in both paw and spleen weight and improved joint histology following 2 weeks of dosing in a rat adjuvant arthritis study. CONCLUSION:These results suggest that GARFT inhibitors should be tested in the treatment of rheumatoid arthritis by considering their mechanism of action, here successfully tested on activated macrophages.
journal_name
Clin Exp Rheumatoljournal_title
Clinical and experimental rheumatologyauthors
Chintalacharuvu S,Evans GF,Shih C,Bryant HU,Sandusky GE,Zuckerman SHkeywords:
subject
Has Abstractpub_date
2005-07-01 00:00:00pages
438-46issue
4eissn
0392-856Xissn
1593-098Xjournal_volume
23pub_type
杂志文章abstract：OBJECTIVE:To evaluate the prevalence and clinical correlations of antibodies against Saccharomyces cerevisiae (ASCA) among patients with BD. METHODS:Twenty-seven BD patients were studied. Data from medical files and from patients' interviews was collected, regarding the entire spectrum of disease manifestations, and a...
journal_title：Clinical and experimental rheumatology
pub_type： 杂志文章
doi：
更新日期：2002-07-01 00:00:00
abstract：:The antiperinuclear factor (APF) test is as sensitive and specific for rheumatoid arthritis as the classical rheumatoid factor tests. Five European laboratories decided to perform a consensus study on the interlaboratory variability of the APF test. They used different donor cells, different conjugates and different c...
journal_title：Clinical and experimental rheumatology
pub_type： 杂志文章
doi：
更新日期：1993-01-01 00:00:00
abstract：:We report herein the results of the cross-cultural adaptation and validation into the Korean language of the parent's version of two health related quality of life instruments. The Childhood Health Assessment Questionnaire (CHAQ) is a disease specific health instrument that measures functional ability in daily living ...
journal_title：Clinical and experimental rheumatology
pub_type： 杂志文章
doi：
更新日期：2001-07-01 00:00:00
abstract：:There is general agreement that the hepatitis C virus is efficiently transmitted parenterally, while data on viral transmission from mothers to babies or by sexual or non-sexual household contact are conflicting. In Italy, hepatitis C accounts for approximately 20% of all cases of acute viral hepatitis. It is more fre...
journal_title：Clinical and experimental rheumatology
pub_type： 杂志文章,评审
doi：
更新日期：1995-11-01 00:00:00
abstract：OBJECTIVES:To analyse clinical severity/activity of rheumatoid arthritis (RA) according to smoking status. METHODS:The QUEST-RA multinational database reviews patients for Core Data Set measures including 28 swollen and tender joint count, physician global estimate, erythrocyte sedimentation rate (ESR), HAQ-function, ...
journal_title：Clinical and experimental rheumatology
pub_type： 杂志文章
doi：
更新日期：2010-11-01 00:00:00
abstract：:Podagra is a term used to describe acute monoarthritis of the first metatarsophalangeal (1st MTP) joint. The most common diagnoses of arthritis in this joint are: crystal-induced synovitis, septic arthritis, traumatic conditions and reactive arthritis. When etiologies other than gout are involved this is frequently re...
journal_title：Clinical and experimental rheumatology
pub_type： 杂志文章
doi：
更新日期：2005-03-01 00:00:00
abstract：OBJECTIVES:This paper aims to identify clinical and serological differences, damage accrual and mortality, in juvenile, adult and late-onset SLE. METHODS:We conducted our study with patients fulfilling SLE classification criteria taken from the Hospital Gregorio Marañon Autoimmune Systemic Rheumatic Diseases' Registry...
journal_title：Clinical and experimental rheumatology
pub_type： 杂志文章
doi：
更新日期：2015-11-01 00:00:00
abstract：:To evaluate the extent of food allergy/intolerance in rheumatoid arthritis, an elemental (hypoallergenic) diet was studied in a controlled, double-blind pilot study. Ten patients were allocated to an experimental group and 7 to a control group. The patients in the experimental group received an elemental diet for 3 we...
journal_title：Clinical and experimental rheumatology
pub_type： 临床试验,杂志文章,随机对照试验
doi：
更新日期：1994-05-01 00:00:00
abstract：:Leg ulcers are associated with antiphospholipid antibodies in patients with systemic lupus erythematosus. They may also occur in patients with primary antiphospholipid syndrome(PAPS). Histopathologic findings at the edges of the ulcers may give insight into their pathogenesis. In a patient with PAPS and a leg ulcer, a...
journal_title：Clinical and experimental rheumatology
pub_type： 杂志文章
doi：
更新日期：1991-01-01 00:00:00
abstract：OBJECTIVE:Fibromyalgia (FMS) is a chronic syndrome characterized by widespread pain, troubled sleep, disturbed mood, and fatigue. Several analgesic strategies have been evaluated but the results are moderate and inconsistent. Antidepressant agents are now considered the treatment of choice in most patients. It has been...
journal_title：Clinical and experimental rheumatology
pub_type： 杂志文章,多中心研究,随机对照试验
doi：
更新日期：2007-03-01 00:00:00
abstract：:The introduction of tumor necrosis factor (TNF) inhibitors for the treatment of rheumatoid arthritis (RA) represented a significant advance in the treatment of this debilitating disease, and led to dramatic changes in overall treatment goals and guidelines. Despite these advances, best practice use of TNF inhibitors i...
journal_title：Clinical and experimental rheumatology
pub_type： 杂志文章,评审
doi：
更新日期：2010-05-01 00:00:00
abstract：OBJECTIVES:Limited data exist regarding the incidence rate and relative risks of major adverse cardiovascular events in women with lupus who have successfully delivered compared to those who have not been pregnant. METHODS:A retrospective, population-based matched cohort study was performed on women with lupus from 20...
journal_title：Clinical and experimental rheumatology
pub_type： 杂志文章
doi：
更新日期：2014-01-01 00:00:00
abstract：OBJECTIVE:To investigate the composition and expression of sialic acid in the labial salivary glands (LSG) in Sjögren's syndrome (SS). METHODS:LSG of 19 patients with primary SS (n = 11) or secondary SS (n = 8) were studied. Specimens from 7 healthy women served as controls. Computer-assisted microscopy was employed t...
journal_title：Clinical and experimental rheumatology
pub_type： 杂志文章
doi：
更新日期：1999-11-01 00:00:00
abstract：OBJECTIVE:To investigate the prevalence of antibodies to neuroblastoma cells in patients with rheumatoid arthritis (RA) complicated by peripheral neuropathy (PN), and to determine whether there is any relationship of these antibodies with the severity of neuropathy. METHODS:The study was carried out on 28 patients wit...
journal_title：Clinical and experimental rheumatology
pub_type： 杂志文章
doi：
更新日期：2000-01-01 00:00:00
abstract：:Relationships between clinical features of psoriatic arthritis and HLA antigens were examined in 60 patients. HLA-B locus antigens, Bw38, B17, B27 and possibly Bw39 were significantly increased, while HLA-D and DR specificities were not. Cw6 was not studied. The relative risk for disease was doubled in patients having...
journal_title：Clinical and experimental rheumatology
pub_type： 杂志文章
doi：
更新日期：1984-04-01 00:00:00
abstract：OBJECTIVES:Since the 1980 ACR classification criteria for systemic sclerosis (SSc) do not identify 20% with SSc, revised criteria are necessary. METHODS:Suggested new criteria from the literature were sent in random order to 96 SSc experts. A 3-round Delphi Consensus eliminated criteria. Then cluster analysis reduced ...
journal_title：Clinical and experimental rheumatology
pub_type： 杂志文章
doi：
更新日期：2013-03-01 00:00:00
abstract：BACKGROUND AND OBJECTIVES:Vitamin D is a steroid hormone with important skeletal and non-skeletal biologic functions. Vitamin D deficiency is common and manifests with musculoskeletal symptoms. In rheumatoid arthritis (RA), vitamin D deficiency may be associated with increased disease activity and disability. We aimed ...
journal_title：Clinical and experimental rheumatology
pub_type： 杂志文章
doi：
更新日期：2010-09-01 00:00:00
abstract：:The clinical relevance of the concept of bioavailability rests on two main principles. First, that measurement of the active component at the site of action is generally not possible and, secondly, that a relationship exists between on the one hand efficacy and/or safety and on the other hand concentration of the acti...
journal_title：Clinical and experimental rheumatology
pub_type： 杂志文章,评审
doi：
更新日期：2010-09-01 00:00:00
abstract：:The immunological function of patients with inactive systemic lupus erythematosus (SLE) receiving chronically administered, low-dose cyclophosphamide (CY) together with prednisolone (PSL) was compared with that of inactive patients receiving PSL alone. A striking selective suppression of "genuine" resting, but not "pa...
journal_title：Clinical and experimental rheumatology
pub_type： 杂志文章
doi：
更新日期：1993-05-01 00:00:00
abstract：OBJECTIVE:To characterize the systemic manifestations and joint disease in patents with recurrent aphthous stomatitis (RAS). METHODS:The presence and features of extra-oral manifestations were determined by a rheumatologist, who examined and interviewed 64 patients, referred during 1993 to the oral medicine clinic for...
journal_title：Clinical and experimental rheumatology
pub_type： 杂志文章
doi：
更新日期：1996-07-01 00:00:00
abstract：OBJECTIVE:In patients with rheumatoid arthritis (RA) of longer duration, glucocorticoid receptor (GR) down-regulation has been reported without any change in cortisol levels. This phenomenon might play a role in the aetio-pathogenesis of RA. Therefore we studied GR expression, as well as the serum cortisol levels, in p...
journal_title：Clinical and experimental rheumatology
pub_type： 杂志文章
doi：
更新日期：2002-07-01 00:00:00
abstract：OBJECTIVES:Epidemiological studies of rheumatoid arthritis in Asia are rare. The aim of this research was to study the epidemiology and associated medical expenses of rheumatoid arthritis in Taiwan. METHODS:Cases of rheumatoid arthritis, based on the 1987 American College of Rheumatology criteria, were retrieved from ...
journal_title：Clinical and experimental rheumatology
pub_type： 杂志文章
doi：
更新日期：2012-05-01 00:00:00
abstract：OBJECTIVES:The anti-inflammatory effect of adenosine is partially mediated via the A3 adenosine receptor (A3AR), a Gi protein associated cell surface receptor. The highly selective A3AR agonist, IB-MECA was earlier shown to prevent the clinical and pathological manifestations of arthritis in experimental animal models ...
journal_title：Clinical and experimental rheumatology
pub_type： 杂志文章
doi：
更新日期：2006-07-01 00:00:00
abstract：OBJECTIVES:The purpose of this study was to have an overview of the current approach to psoriatic arthritis (PsA) by a group of Italian rheumatologists. METHODS:Rheumatologists from all around Italy were asked to participate in a survey to give their opinion on a number of statements made by a panel of rheumatologists...
journal_title：Clinical and experimental rheumatology
pub_type： 杂志文章
doi：
更新日期：2016-11-01 00:00:00
abstract：OBJECTIVE:To investigate autoantibody induction in rheumatoid arthritis (RA) and ankylosing spondylitis (AS) in a cohort of French patients treated with TNF-alpha blockers. METHODS:We tested the serum of patients for antinuclear antibodies (ANA), anti-DNA antibodies and C4 complement at baseline, and for each infusion...
journal_title：Clinical and experimental rheumatology
pub_type： 临床试验,杂志文章
doi：
更新日期：2008-05-01 00:00:00
abstract：:A young female patient who had documented seropositive rheumatoid arthritis and was treated consecutively with aspirin, diclofenac, and gold salts was admitted years later for severe neutropenia. On examination she had, in addition, fever, positive rheumatoid factor, reversible swan-neck deformity of the fingers but o...
journal_title：Clinical and experimental rheumatology
pub_type： 杂志文章
doi：
更新日期：1989-05-01 00:00:00
abstract：OBJECTIVES:To test the hypothesis that classical phagocytic functions are constitutively stimulated in patients with Behçet's disease (BD). METHODS:Four study groups were analysed: active BD (aBD; n=30), inactive BD (iBD; n=31); septic patients (SP; n=25); healthy controls (HC; n=30). Microbicide activity against Stre...
journal_title：Clinical and experimental rheumatology
pub_type： 杂志文章
doi：
更新日期：2015-11-01 00:00:00
abstract：OBJECTIVES:The purpose of this study was to evaluate homocysteine (Hcy) serum levels in women with systemic sclerosis (SSc) compared with healthy controls and to examine possible associations between Hcy and markers of arterial stiffness. METHODS:A cross-sectional study was performed at a single hospital between Novem...
journal_title：Clinical and experimental rheumatology
pub_type： 杂志文章
doi：
更新日期：2020-05-01 00:00:00
abstract：OBJECTIVE:To evaluate serum soluble CD30 levels (sCD30) in an early arthritis series and assess their ability to predict the outcome in patients with rheumatoid arthritis (RA) and undifferentiated arthritis (UA) at one year follow-up. METHODS:Serum sCD30 levels were measured by ELISA from 92 adult patients with RA and...
journal_title：Clinical and experimental rheumatology
pub_type： 杂志文章
doi：
更新日期：2008-09-01 00:00:00
abstract：:Monoclonal antibodies have been produced that recognise conventionally defined cross-reactive idiotopes (CRI) expressed on rheumatoid factors. However, it is now evident that these "CRI" are markers for variable region sequences encoded by germline V gene segments and, therefore, that most of these reagents recognise ...
journal_title：Clinical and experimental rheumatology
pub_type： 杂志文章,评审
doi：
更新日期：1994-11-01 00:00:00
