bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synthesis and Antioxidant Activity of New Tetrahydro‐Naphthalene‐Indole Derivatives as Retinoid and Melatonin Analogs
Authors: Ates‐Alagoz Zeynep , Coban Tulay , Buyukbingol Erdem 
Published: March 2006

AbstractA number of retinoid‐related compounds represent classes of antioxidative and proapoptotic agents with promising potential in the treatment of neoplastic diseases. Indeed, the synthetic retinoid amide fenretinide [N‐(4‐hydroxyphenyl)retinamide] induces apoptosis of cancer cells and acts as a chemotherapeutic drug in cancer therapy. In the present work, and as a continuation of our studies on retinoid‐type compounds, the synthesis of melatonin retinamide derivatives was studied as a novel series of melatonin retinoids, using the condensation reaction sequence involving tetrahydrotetramethylnaphthalene carboxylic acid and appropriate melatonin‐type moieties. Despite of the weak DPPH inhibition activity pattern of the synthesized compounds, some of them showed a strong inhibition on lipid peroxidation (IVa–b, Va,andVIIa–c,88, 96, 90, 94, 93, and 86%, respectively at 10–4M concentration) when melatonin (85% at 10–4M concentration) was used as a reference compound.
Molecular Structure and QSAR Study on Antispasmodic Activity of some Xanthoxyline Derivatives
Authors: dos Santos Rodrigo , Kuhnen Carlos Alberto , Yunes Rosendo Augusto 
Published: March 2006

AbstractSemi‐empirical molecular orbital calculations at AM1 level were done with the aim to investigate the structure‐activity relationships of antispasmodic activities of ten 2‐(X‐benzyloxy)‐4,6‐dimethoxyacetophenones with X = H, 4′‐F, 4′‐NO2, 4′‐CH3, 4′‐Cl, 3′,4′‐(CH3)2, 4′‐OCH3, 4′‐Br, 4′‐OCH2C6H5, and 4′‐C(CH3)3, against acetylcholine‐induced contraction of the guinea pig ileum. The most significant quantum chemical descriptors for this series of compounds were the net atomic charges, nucleophilic and electrophilic frontier electron density, HOMO and LUMO orbitals, and reactivity indices. While no significant correlations were found employing molecular parameters such as heat of formation, dipole moment, molecular polarizability, and so on, good correlations were obtained using the reactivity indices of HOMO and LUMO orbitals at specific atoms of the molecules. These results indicate that the spatial distribution of HOMO and LUMO orbitals over these specific atoms play an important role for an increase of biological activity.
Synthesis of Substituted 3‐Anilino‐5‐phenyl‐1,3‐dihydro‐ 2H‐1,4‐benzodiazepine‐2‐ones and their Evaluation as Cholecystokinin‐Ligands
Authors: Offel Michael , Lattmann Pornthip , Singh Harjit , Billington D. C. , Bunprakob Yodchai , Sattayasai Jintana , Lattmann Eric 
Published: March 2006

Abstract3‐Amino‐1,4‐benzodiazepines as well as chemically related diverse amines were prepared from oxazepam and subsequently screened on the cholecystokinin receptor in a radiolabel binding assay. Oxazepam 2 was activated via its 3‐chloro‐1,4‐benzodiazepine intermediate 3 and was reacted with a large series of aliphatic and aromatic amines. The substituted 3‐anilino‐1,4‐benzodiazepine structure was identified as lead structure in a diverse series of 3‐amino‐1,4‐benzodiazepines 4‐38 and the full SAR (structure‐activity relationship) optimisation provided 3‐anilinobenzodiazepines 16–38 with CCK1 receptor selectivity to CCK2. The compounds 18, 24, 28 and 33 have shown affinities at the CCK1 receptor of 11, 10, 11 and 9 nM, respectively. These equipotent CCK1 ligands were fully evaluated in behaviour pharmacological essays. An antidepressant effect was identified in the tail suspension‐ and the Porsolt swimming‐test. The ED50 values for 24 and 28 were determined in these assays as 0.46 and 0.49 mg/kg. The mixed antagonist 37 showed in addition to the antidepressant effects anxiolytic properties.
Synthesis and Antifungal Activity of 2‐Aryl‐1,2,4‐triazolo[1,5‐a]pyridine Derivatives
Authors: Luo Yun , Hu Yongzhou 
Published: March 2006

AbstractA series of novel antifungal triazole derivatives 2‐aryl‐1,2,4‐triazolo[1,5‐a]pyridine 9a–m were synthesized and tested in vitro for their growth inhibitory activities against C. albicans and T. rubrum. The MIC values indicate that the activities of three compounds were superior or comparable to fluconazole against both tested fungi, worthy of further investigation of its antifungal activities.
Comparison of etanercept and methotrexate, alone and combined, in the treatment of rheumatoid arthritis: Two‐year clinical and radiographic results from the TEMPO study, a double‐blind, randomized trial
Authors: van der Heijde Désirée , Klareskog Lars , Rodriguez‐Valverde Vicente , Codreanu Catalin , Bolosiu Horatiu , Melo‐Gomes Jose , Tornero‐Molina Jesus , Wajdula Joseph , Pedersen Ronald , Fatenejad Saeed ,   TEMPO Study Investigators
Published: March 2006

AbstractObjectiveTo evaluate the efficacy, including radiographic changes, and safety of etanercept and methotrexate (MTX), used in combination and alone, in patients with rheumatoid arthritis (RA) in whom previous treatment with a disease‐modifying antirheumatic drug other than MTX had failed.MethodsPatients with RA were treated with etanercept (25 mg subcutaneously twice weekly), oral MTX (up to 20 mg weekly), or combination therapy with etanercept plus MTX through a second year, in a double‐blinded manner. Clinical response was assessed using American College of Rheumatology (ACR) criteria and the Disease Activity Score (DAS), in a modified intent‐to‐treat analysis with the last observation carried forward (LOCF) and in a population of completers. Radiographs of the hands, wrists, and forefeet were scored for erosions and joint space narrowing at annual intervals.ResultsA total of 503 of 686 patients continued into year 2 of the study. During the 2 years, significantly fewer patients receiving combination therapy withdrew from the study (29% of the combination therapy group, 39% of the etanercept group, and 48% of the MTX group). Both the LOCF and the completer analyses yielded similar results. The ACR 20% improvement (ACR20), ACR50, and ACR70 responses and the remission rates (based on a DAS of <1.6) were significantly higher with combination therapy than with either monotherapy (P < 0.01). Similarly, improvement in disability (based on the Health Assessment Questionnaire) was greater with combination therapy (P < 0.01). The combination therapy group showed significantly less radiographic progression than did either group receiving monotherapy (P < 0.05); moreover, radiographic progression was significantly lower in the etanercept group compared with the MTX group (P < 0.05). For the second consecutive year, overall disease progression in the combination therapy group was negative, with the 95% confidence interval less than zero. Adverse events were similar in the 3 treatment groups.ConclusionEtanercept in combination with MTX reduced disease activity, slowed radiographic progression, and improved function more effectively than did either monotherapy over a 2‐year period. No increase in toxicity was associated with combination treatment with etanercept plus MTX.
Targeting of angiogenic endothelial cells at sites of inflammation by dexamethasone phosphate–containing RGD peptide liposomes inhibits experimental arthritis
Authors: Koning Gerben A. , Schiffelers Raymond M. , Wauben Marca H. M. , Kok Robbert J. , Mastrobattista Enrico , Molema Grietje , ten Hagen Timo L. M. , Storm Gert 
Published: March 2006

AbstractObjectiveTo investigate whether RGD peptide–exposing long circulating polyethylene glycol (PEG) liposomes (RGD‐PEG–L) targeted to αvβ3 integrins expressed on angiogenic vascular endothelial cells (VECs) are able to bind VECs at sites of inflammation and whether such liposomes containing dexamethasone phosphate (DEXP) can be used as carriers to interfere with the development of experimental arthritis.MethodsBinding and internalization of RGD‐PEG–L were studied by fluorescence‐activated cell sorting and confocal microscopy using fluorescently labeled liposomes. Radiolabeled liposomes were used to test in vivo pharmacokinetics and inflammation site targeting in lipopolysaccharide (LPS)–induced inflammation and adjuvant‐induced arthritis (AIA) in rats. In vivo inflammation targeting was visualized by intravital microscopy using fluorescently labeled RGD‐PEG–L. Therapeutic efficacy of DEXP‐encapsulating RGD‐PEG–L compared with nontargeted liposomes was evaluated in rats with AIA.ResultsRGD‐PEG–L bound to and were taken up by proliferating human VECs in vitro. In vivo, increased targeting of radiolabeled RGD‐PEG–L to areas of LPS‐induced inflammation in rats was observed. Specific association with the blood vessel wall at the site of inflammation was confirmed by intravital microscopy. One single intravenous injection of DEXP encapsulated in RGD‐PEG–L resulted in a strong and long‐lasting antiarthritic effect in rat AIA.ConclusionRGD‐targeted PEG liposomes represent an endothelial cell–specific drug delivery system that targets VECs at sites of inflammation. Use of these liposomes to deliver DEXP to VECs at arthritis‐affected sites proved efficacious in rat adjuvant arthritis. These data indicate that VECs have an essential role in the inflammation process and suggest the possibility of using VEC targeting for therapeutic intervention in inflammatory processes such as arthritis.
Inhibition of systemic sclerosis dermal fibroblast type I collagen production and gene expression by simvastatin
Authors: Louneva Natalia , Huaman Gonzalo , Fertala Joanna , Jiménez Sergio A. 
Published: March 2006

AbstractObjectiveTo examine whether statins are capable of modulating collagen gene expression in cultured systemic sclerosis dermal fibroblasts.MethodsCultured dermal fibroblasts from 3 patients with diffuse systemic sclerosis of recent onset were treated with 5 μM and 10 μM of simvastatin for 3 or 4 days. Morphologic features, cytotoxicity, and type I collagen production and messenger RNA (mRNA) levels in the fibroblasts were examined. The effects of mevalonate, geranylgeranyl pyrophosphate (GGPP), and farnesyl pyrophosphate (FPP), which are lipids downstream from the hydroxymethylglutaryl–coenzyme A block, were also examined. Transient transfections with COL1A1 promoter‐reporter constructs and electrophoretic gel mobility shift assays were utilized to examine COL1A1 transcription and Sp1 and CCAAT‐box binding factor (CBF) binding.ResultsSimvastatin did not cause morphologic changes or cytotoxicity in the fibroblasts, even after 4 days of treatment. Type I collagen production and mRNA levels showed a potent and dose‐related inhibition following 3 and 4 days of treatment. The inhibition of collagen gene expression by simvastatin was completely reversed by mevalonate and GGPP, but not by FPP. The statin effects occurred at the transcriptional level and involved the proximal COL1A1 promoter region encompassing −174 bp. A significant reduction in Sp1 and CBF binding activity was also found in simvastatin‐treated cells.ConclusionSimvastatin is a powerful inhibitor of type I collagen gene expression in normal and systemic sclerosis fibroblasts. The pleiotropic protective effects of statins on various endothelial and immune cell functions in conjunction with their potent inhibitory effects on type I collagen gene expression suggest that statins may be effective therapeutic agents in systemic sclerosis.
Ectopic calcification among families in the Azores: Clinical and radiologic manifestations in families with diffuse idiopathic skeletal hyperostosis and chondrocalcinosis
Authors: Bruges‐Armas Jácome , Couto Ana Rita , Timms Andrew , Santos Margarida R. , Bettencourt Bruno Filipe , Peixoto Maria José , Colquhoun Katherine , McNally Eugene G. , Carneiro Victor , Herrero‐Beaumont Gabriel , Brown Matthew A. 
Published: March 2006

AbstractObjectiveTwelve families that were multiply affected with diffuse idiopathic skeletal hyperostosis (DISH) and/or chondrocalcinosis, were identified on the island of Terceira, The Azores, potentially supporting the hypothesis that the 2 disorders share common etiopathogenic factors. The present study was undertaken to investigate this hypothesis.MethodsOne hundred three individuals from 12 unrelated families were assessed. Probands were identified from patients attending the Rheumatic Diseases Clinic, Hospital de Santo Espírito, in The Azores. Family members were assessed by rheumatologists and radiologists. Radiographs of all family members were obtained, including radiographs of the dorsolumbar spine, pelvis, knees, elbows, and wrists, and all cases were screened for known features of chondrocalcinosis.ResultsEctopic calcifications were identified in 70 patients. The most frequent symptoms or findings were as follows: axial pain, elbow, knee and metacarpophalangeal (MCP) joint pain, swelling, and/or deformity, and radiographic enthesopathic changes. Elbow and MCP joint periarticular calcifications were observed in 35 and 5 patients, respectively, and chondrocalcinosis was identified in 12 patients. Fifteen patients had sacroiliac disease (ankylosis or sclerosis) on computed tomography scans. Fifty‐two patients could be classified as having definite (17%), probable (26%), or possible (31%) DISH. Concomitant DISH and chondrocalcinosis was diagnosed in 12 patients. Pyrophosphate crystals were identified from knee effusions in 13 patients. The pattern of disease transmission was compatible with an autosomal‐dominant monogenic disease. The mean age at which symptoms developed was 38 years.ConclusionThese families may represent a familial type of pyrophosphate arthropathy with a phenotype that includes peripheral and axial enthesopathic calcifications. The concurrence of DISH and chondrocalcinosis suggests a shared pathogenic mechanism in the 2 conditions.
Evaluation of classical complement pathway activation in rheumatoid arthritis: Measurement of C1q–C4 complexes as novel activation products
Authors: Wouters Diana , Voskuyl Alexandre E. , Molenaar Esmeralda T. H. , Dijkmans Ben A. C. , Hack C. Erik 
Published: March 2006

AbstractObjectiveNovel activation products that are stable and minimally susceptible to in vitro artefacts have recently been described in the classical complement pathway. The present study assessed circulating levels of these products, i.e., covalent complexes between the recognition molecule of the classical pathway (C1q) and activated C4, in plasma samples from patients with rheumatoid arthritis (RA) to establish the relationship between these levels and the clinical and immunologic parameters in these patients.MethodsC1q–C4 levels were measured in plasma samples from 41 patients with active RA and 43 patients with inactive RA. These levels were related to other complement activation products and to disease activity according to the Disease Activity Score in 28 joints (DAS28), using Spearman's rank correlations.ResultsC1q–C4 plasma levels were significantly higher in patients with active RA as compared with patients with RA in clinical remission (median 3.3 arbitrary units [AU], range 0.4–13.4 versus 1.7 AU, range 0.2–5.5; P = 0.0001), suggesting that activation of the classical complement pathway reflects disease activity. This was supported by a significant correlation between C1q–C4 levels and the DAS28 (r = 0.398, P = 0.0002). Levels of other complement activation products, such as activated C4 (C4b/c), were also significantly elevated in patients with active disease compared with patients with inactive disease (P = 0.03), and were correlated with C1q–C4 levels (r = 0.329, P = 0.002). Levels of C1q–C4 complexes were higher in synovial fluid samples than in plasma samples from the 4 patients tested.ConclusionSystemic complement activation via the classical pathway in patients with RA correlates with disease activity. These results indicate that C1q–C4 complexes may be used as a biomarker for RA.
Peripheral blood T lymphocytes from patients with early rheumatoid arthritis express RANKL and interleukin‐15 on the cell surface and promote osteoclastogenesis in autologous monocytes
Authors: Miranda‐Carús María‐Eugenia , Benito‐Miguel Marta , Balsa Alejandro , Cobo‐Ibáñez Tatiana , Pérez De Ayala Carlos , Pascual‐Salcedo Dora , Martín‐Mola Emilio 
Published: March 2006

AbstractObjectiveTo investigate the osteoclastogenic potential of T cells from the peripheral blood (PB) and synovial fluid (SF) of patients with rheumatoid arthritis (RA) on autologous monocytes, and to study the cytokines implicated in this process.MethodsT cells and monocytes were isolated from the PB of 20 healthy subjects and 20 patients with early RA, and from the SF of 20 patients with established RA. Autologous T cell/monocyte cocultures were established in the absence of exogenous cytokines or growth factors in order to examine spontaneous ex vivo osteoclast differentiation by tartrate‐resistant acid phosphatase staining and calcified matrix resorption activity.ResultsSurface RANKL was expressed on freshly isolated T cells from the PB of patients with early RA and the SF of patients with established RA. In addition, surface interleukin‐15 (IL‐15) was detected on freshly isolated T cells and monocytes from the PB of patients with early RA and the SF of patients with established RA. Autologous T cell/monocyte cocultures derived from the SF of patients with established RA and from the PB of patients with early RA, but not from the PB of healthy controls, resulted in osteoclast differentiation that was significantly inhibited by osteoprotegerin (OPG) and by neutralizing monoclonal antibodies to IL‐15, IL‐17, tumor necrosis factor α (TNFα), and IL‐1β. OPG, anti‐TNFα, and anti–IL‐1β demonstrated a cooperative inhibitory effect. At 1‐year followup, surface RANKL and IL‐15 and ex vivo osteoclastogenesis were no longer observed on PB T cells or monocytes from patients with early RA in whom clinical remission had been achieved with treatment.ConclusionT cells are important contributors to the pathogenesis of bone erosions in RA through interaction with osteoclast precursors of the monocyte/macrophage lineage.
The safety of infliximab, combined with background treatments, among patients with rheumatoid arthritis and various comorbidities: A large, randomized, placebo‐controlled trial
Authors: Westhovens Rene , Yocum David , Han John , Berman Alberto , Strusberg Ingrid , Geusens Piet , Rahman Mahboob U. ,   START Study Group
Published: March 2006

AbstractObjectiveTo assess the risk of serious infections following 22 weeks of infliximab therapy, and to further characterize the safety profile of infliximab in combination with background treatments during 1 year in patients with rheumatoid arthritis (RA) with various comorbidities.MethodsPatients with active RA despite receiving methotrexate (MTX) were randomly assigned to receive infusions of placebo (group 1, n = 363), 3 mg/kg infliximab (group 2, n = 360), or 10 mg/kg infliximab (group 3, n = 361) at weeks 0, 2, 6, and 14. At week 22, patients in placebo group 1 began receiving 3 mg/kg infliximab, and patients in group 3 continued to receive an infliximab dose of 10 mg/kg. Patients in group 2 who failed to meet predefined response criteria received increasing doses of infliximab in increments of 1.5 mg/kg.ResultsAt week 22, the relative risk of developing serious infections in groups 2 and 3, compared with group 1, was 1.0 (95% confidence interval [95% CI] 0.3–3.1, P = 0.995) and 3.1 (95% CI 1.2–7.9, P = 0.013), respectively. The incidence of serious adverse events was 7.8% in groups 2 and 3 compared with 7.5% in group 1. From week 22 to week 54, 11.8%, 9.9%, and 10.3% of patients in groups 1, 2, and 3, respectively, reported occurrences of serious adverse events. Through week 54, 1 patient in group 1, 2 patients in group 2, and 4 patients in group 3 developed active tuberculosis.ConclusionThe risk of serious infections in patients receiving the approved infliximab dose of 3 mg/kg plus MTX was similar to that in patients receiving MTX alone. Patients receiving the unapproved induction regimen of 10 mg/kg infliximab plus MTX followed by a 10 mg/kg maintenance regimen had an increased risk of serious infections through week 22.
Disc space narrowing as a new risk factor for vertebral fracture: The OFELY study
Authors: Sornay‐Rendu Elisabeth , Allard Chloé , Munoz Françoise , Duboeuf François , Delmas Pierre D. 
Published: March 2006

AbstractObjectiveIn a previous cross‐sectional analysis, we found a positive association between disc space narrowing (DSN) and vertebral fracture. The aim of the present study was to analyze prospectively the risk of vertebral and nonvertebral fractures in women with spine osteoarthritis (OA).MethodsUsing radiographs, spine OA was evaluated in 634 postmenopausal women from the OFELY (Os des Femmes de Lyon) cohort (mean ± SD age 61.2 ± 9 years). Prevalence and severity of spine OA were assessed by scoring osteophytes and DSN. Incidental clinical fractures were prospectively registered during annual followup, and vertebral fractures were evaluated by radiography every 4 years.ResultsDuring an 11‐year followup, fractures occurred in 121 women, including 42 with vertebral fractures. No association was found between osteophytes and the risk of fracture. In contrast, DSN was associated with an increased risk of vertebral fractures but not of nonvertebral fractures. After adjusting for confounding variables, the presence of DSN was associated with a marked increased risk of vertebral fractures, with an odds ratio of 6.59 (95% confidence interval 1.36–31.9). In addition, 95% of incident vertebral fractures were located above the disc with the most severe narrowing.ConclusionThis longitudinal study shows that, despite a higher bone mineral density (BMD), women with spine OA do not have a reduced risk of fracture and that DSN is significantly associated with vertebral fracture risk. The location of DSN and of incident vertebral fractures suggests that disc degeneration impairs the biomechanics of the above spine, which leads to the increased risk of vertebral fractures, independent of BMD. We suggest that DSN is a newly identified risk factor for vertebral fracture that should be taken into consideration when assessing vertebral fracture risk in postmenopausal women.