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Joint Bone Spine Oct 2017To evaluate the efficacy of the triple synthetic Disease Modifying Anti-Rheumatic Drugs (sDMARD) combination methotrexate, sulfasalazine and hydroxychloroquine versus a... (Comparative Study)
Comparative Study Meta-Analysis Review
Efficacy of triple association methotrexate, sulfasalazine and hydroxychloroquine in early treatment of rheumatoid arthritis with insufficient response to methotrexate: Meta-analysis of randomized controlled trials.
OBJECTIVES
To evaluate the efficacy of the triple synthetic Disease Modifying Anti-Rheumatic Drugs (sDMARD) combination methotrexate, sulfasalazine and hydroxychloroquine versus a biologic DMARD (bDMARD) in the treatment of early rheumatoid arthritis.
METHODS
A systematic literature search was performed using the PubMed and Cochrane databases, and abstracts presented at rheumatology scientific meetings until December 2013. Randomized controlled trials comparing the efficacy and the safety of biologic DMARD with the triple combination were included. Outcome measures were Van der Heijde modified Sharp score (SHS), remission rate, ACR criteria response, adverse events.
RESULTS
A total of 1225 abstracts were screened. We extracted data from 5 trials including patients (515 in the triple combination group and 710 in the bDMARD group). We showed higher ACR70 response (OR=1.79, 95% CI [1.17, 2.72]) in patients treated with bDMARDs, whereas radiological progression was not different from patient with triple combination (OR=1.10, 95% CI [-0.04, 0.28]). At year 2, ACR70 response and remission rate, the results were similar in both groups with respectively OR=1.44 (95% CI [0.86, 2.43]) and SMD=0.45 (95% CI [0.17, 0.72]). The proportion of serious adverse events was similar in both groups OR=1.02 (95% CI [0.68, 1.52], P=0.92, I=0%). Gastro-intestinal adverse events were higher in the triple combination group (OR=1.75, 95% CI [0.73, 4.21], P=0.21, I=75%). Infectious adverse events were more frequent in the bDMARD group (OR=0.50, 95% CI [0.35, 0.70], P<0.0001, I=36%).
CONCLUSION
Biological treatment seems to be more efficient than triple combination in terms of radiological progression in RA with inadequate response to methotrexate.
Topics: Antirheumatic Agents; Arthritis, Rheumatoid; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Hydroxychloroquine; Male; Methotrexate; Pain Measurement; Randomized Controlled Trials as Topic; Risk Assessment; Severity of Illness Index; Sulfasalazine; Time Factors; Treatment Outcome
PubMed: 27989589
DOI: 10.1016/j.jbspin.2016.10.010 -
Journal of Clinical Rheumatology :... Sep 2020
Topics: Connective Tissue Diseases; Humans; Sulfasalazine
PubMed: 30896461
DOI: 10.1097/RHU.0000000000001028 -
Spectrochimica Acta. Part A, Molecular... Nov 2023The interaction of sulfasalazine (SZ) with the carrier proteins bovine serum albumin (BSA) and human serum albumin (HSA) was explored by fluorescence, absorption and...
The interaction of sulfasalazine (SZ) with the carrier proteins bovine serum albumin (BSA) and human serum albumin (HSA) was explored by fluorescence, absorption and circular dichroism (CD) spectroscopy along within silicotechniques. The spectral alteration observed in fluorescence, absorption and CD spectra upon the addition of SZ confirmed the complex formation of SZ with BSA and HSA. The inverse temperature dependence behaviour of theKvalues as well as the increase in the protein's absorption signals after the addition of SZ indicate that SZ triggered quenching of BSA/HSA fluorescence as the static quenching. The binding affinity (k) of the order of 10 M was reported towards the BSA-SZ and HSA-SZ association process. Interpretation of thermodynamic data (enthalpy change = -93.85 kJ moland entropy change = -200.81 J molKfor BSA-SZ system; enthalpy change = -74.12 kJ moland entropy change = -123.90 J molKfor HSA-SZ system) anticipated that hydrogen bond and van der Waals forces were the main intermolecular forces in the complex stabilization. Inclusion of SZ to BSA/HSA produced microenvironmental perturbations around Tyr and Trp residues. The UV, synchronous and 3D analysis confirmed the structural alteration of proteins after SZ binding, which was supported by CD results. The binding location of SZ in BSA/HSA was detected in Sudlow's site I (subdomain IIA) and the same was revealed by competitive site-marker displacement investigations. Density functional theory study was done to comprehend the feasibility of the analysis and to optimize the structure and energy gap that validated the experimental results. This study is expected to provide deep information about the pharmacology of SZ with its pharmacokinetic properties.
Topics: Humans; Serum Albumin, Bovine; Serum Albumin, Human; Binding Sites; Sulfasalazine; Protein Binding; Molecular Docking Simulation; Spectrometry, Fluorescence; Thermodynamics; Circular Dichroism
PubMed: 37269654
DOI: 10.1016/j.saa.2023.122865 -
Experimental Biology and Medicine... Apr 2022The pathogenesis of sulfasalazine (SFZ)-induced nephrotoxicity is unclear. Moreover, there are no reports on the protective effects of β-caryophyllene (BCP) against...
The pathogenesis of sulfasalazine (SFZ)-induced nephrotoxicity is unclear. Moreover, there are no reports on the protective effects of β-caryophyllene (BCP) against SFZ-induced renal injury. Hence, in this study, we measured several oxidative stress and inflammatory regulatory molecules alongside the effects of BCP in SFZ-intoxicated rats. Male rats ( = 48) were distributed to six equal groups as follows: negative control (NC), normal rats treated with low (N-LD; 200 mg/kg/day) and high (N-HD; 400 mg/kg/day) BCP doses, and animals treated with SFZ individually (PC; 600 mg/kg/day) or combined with BCP low (P-LD) and high (P-HD) doses. All drugs were administrated for 14 consecutive days. The NC, N-LD, and N-HD groups showed comparable renal histology and biochemistry. In contrast, abnormal histology, and increased creatinine and urea alongside oliguria and proteinuria were detected in the PC group. Renal specimens from the PC group revealed increased levels of nuclear factor-kappa B (NF-κB), transforming growth factor (TGF)-β with kidney injury molecule (KIM)-1, while the levels of nuclear factor erythroid 2-related factor 2 (Nrf2), AMP-activated protein kinase (AMPK), and protein kinase B (AKT) declined, relative to controls. The PC renal tissue also had markedly higher levels of inflammatory cytokines (tumor necrosis factor [TNF]-α/interleukin [IL]-1β/IL-6) and pro-oxidants (malondialdehyde [MDA]/HO/protein carbonyls), whereas those of antioxidants (glutathione [GSH]/glutathione peroxidase [GPx]/superoxide dismutase-1 [SOD1]/catalase [CAT]) and IL-10 decreased and were associated with marked apoptosis. Both BCP regimens ameliorated renal functions and histology, and reduced NF-κB, TGF-β, and KIM-1 levels in addition to those of oxidative stress and inflammation markers. Both protocols also augmented Nrf2, AMPK, AKT, antioxidants, and IL-10. However, P-HD showed better alleviating effects than the N-HD group. In conclusion, this study is the first to link NF-κB, TGF-β, Nrf2, AMPK, and AKT with SFZ-induced nephrotoxicity. In addition, this is the first report to reveal antioxidative and anti-inflammatory effects for BCP against SFZ-associated nephropathy.
Topics: AMP-Activated Protein Kinases; Animals; Anti-Inflammatory Agents; Antioxidants; Glutathione; Hydrogen Peroxide; Interleukin-10; Kidney; Male; NF-E2-Related Factor 2; NF-kappa B; Oxidative Stress; Polycyclic Sesquiterpenes; Proto-Oncogene Proteins c-akt; Rats; Sulfasalazine; Transforming Growth Factor beta
PubMed: 35068213
DOI: 10.1177/15353702211073804 -
Journal of Pharmaceutical and... Oct 2023Sulfasalazine has been identified as a candidate molecule to be investigated as an intervention to treat preterm pre-eclampsia during pregnancy. However, placental...
Sulfasalazine has been identified as a candidate molecule to be investigated as an intervention to treat preterm pre-eclampsia during pregnancy. However, placental exposure of sulfasalazine and its systemically absorbed metabolite, sulfapyridine, is unknown. A robust liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated to simultaneously quantitate these analytes in human placenta with an application to a pilot clinical trial. The placental tissue was homogenised using a water:methanol (1:1, v/v) mixture, followed by sample extraction using both protein precipitation and solid phase extraction. Sulfasalazine-d4 and sulfapyridine-d4 were used as internal standards. An Agilent Poroshell EC-C18 (3.0 ×100 mm, 2.7 µm) column was used for chromatographic separation, with gradient elution employed at a flow rate of 0.450 mL/min over a total run time of seven minutes. The mobile phases consisted of water with 0.1% formic acid (mobile phase A) and acetonitrile:methanol (90:10, v/v) with 0.1% formic acid (mobile phase B). A Shimadzu-8040 mass spectrometer was operated in multiple reaction monitoring (MRM) mode using positive electrospray ionisation (ESI). For both analytes, the assay was validated over the range 30-30,000 ng/mL, or 150-150,000 ng/g. During inter-day validations (n = 18), the average accuracies of quality controls ranged from 101.6% to 112.7% with corresponding precisions of 4.4-6.7% for sulfasalazine, and from 97.4% to 108.4%, with corresponding precisions of 3.7-10.0% for sulfapyridine. No significant matrix effects were observed, and the method proved to be sensitive and specific for both analytes. This study presents the first validated analytical method for quantifying sulfasalazine and sulfapyridine in human placenta as part of a pilot clinical trial to generate preliminary data on its pharmacokinetics and efficacy as in intervention for preterm pre-eclampsia.
Topics: Pregnancy; Infant, Newborn; Humans; Female; Chromatography, Liquid; Sulfapyridine; Sulfasalazine; Methanol; Pre-Eclampsia; Tandem Mass Spectrometry; Placenta
PubMed: 37597383
DOI: 10.1016/j.jpba.2023.115633 -
Biomedical Chromatography : BMC Apr 2020Green TLC-densitometric and RP-HPLC methods were developed and validated for the determination of the active prodrug sulfasalazine (SZ), its active metabolite mesalazine...
Green TLC-densitometric and RP-HPLC methods were developed and validated for the determination of the active prodrug sulfasalazine (SZ), its active metabolite mesalazine (MZ) and the major active metabolite of mesalazine, N-acetyl-5-aminosalicylic acid (AS). In the developed TLC-densitometric method, chromatographic separation was carried out on TLC silica gel plates 60 F using a developing system consisting of ethyl acetate-methanol-ammonia solution 33% (8:2.5:0.3, by volume) and then scanning the separated bands at 215 nm using hydrochlorothiazide as an internal standard with linearity ranges of 0.4-3, 0.4-2.4 and 0.3-2 for SZ, MZ and AS, respectively. The developed RP-HPLC method depended on chromatographic separation using a C column with a solvent mixture of methanol-aqueous acetic acid solution (pH 5) as a mobile phase with gradient elution mode and UV scanning at 243 nm using pyrazinamide as internal standard with linearity ranges of 5-50, 5-40, and 3-20 for SZ, MZ and AS, respectively. US Food and Drug Administration guidelines were followed during validation of the methods. The greenness of the developed methods was estimated using the greenness profile and the Eco-Scale approach. Both methods passed the four quadrants of the greenness profile and had Eco-Scale score ˃75, thus they were considered to be green according to these approaches.
Topics: Chromatography, High Pressure Liquid; Chromatography, Thin Layer; Densitometry; Drug Stability; Green Chemistry Technology; Humans; Linear Models; Reproducibility of Results; Sensitivity and Specificity; Sulfasalazine
PubMed: 32012304
DOI: 10.1002/bmc.4804 -
Scandinavian Journal of Gastroenterology Oct 2022Abdominal pain (AP) is a common feature in the general population. However, in patients with juvenile idiopathic arthritis (JIA) AP has scantily been studied. Among...
OBJECTIVES
Abdominal pain (AP) is a common feature in the general population. However, in patients with juvenile idiopathic arthritis (JIA) AP has scantily been studied. Among other reasons, gastrointestinal symptoms may present as side effects due to the medical treatment of JIA. The aim of the study was to explore the frequency of AP and its relationship to disease components and health-related quality of life (HRQoL) among young adults with JIA.
METHODS
This study included a cohort of 97 Finnish patients belonging to the population-based Nordic JIA cohort at their 17-year follow-up study visit. Mean age of the patients was 23 years. AP, functional status, fatigue, HRQoL, disease characteristics of JIA, and comorbidities were evaluated. AP was classified into three categories according to frequency: (1) never, (2) seldom (one to three times a month) and (3) frequent (at least once a week).
RESULTS
About 48 (50%) young adults with JIA reported AP. Seldom AP was reported by 37 (38%), and frequent AP by 11 (11%) patients. AP was significantly associated with fatigue, female gender, functional status and arthritis-related pain. Patients having frequent AP reported lower HRQoL. AP was associated with the use of methotrexate and sulfasalazine, but not with nonsteroidal anti-inflammatory drugs (NSAIDs).
CONCLUSION
AP is an important complaint in young adults with JIA and is associated with fatigue, female gender, methotrexate and sulfasalazine use. Patients with JIA reporting frequent AP with lower functional status and higher arthritis-related pain values have lower HRQoL.
Topics: Abdominal Pain; Adult; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Antirheumatic Agents; Arthritis, Juvenile; Fatigue; Female; Finland; Follow-Up Studies; Humans; Methotrexate; Quality of Life; Sulfasalazine; Young Adult
PubMed: 35546660
DOI: 10.1080/00365521.2022.2072691 -
Scientific Reports Oct 2021Gliomas are primary brain tumors with still poor prognosis for the patients despite a combination of cytoreduction via surgery followed by a radio-chemotherapy. One...
Gliomas are primary brain tumors with still poor prognosis for the patients despite a combination of cytoreduction via surgery followed by a radio-chemotherapy. One strategy to find effective treatment is to combine two different compounds in one hybrid molecule via linker to add to or at best potentiate their impact on malignant cells. Here, we report on the effects of a newly synthesized hybrid of sulfasalazine (SAS) and dihydroartemisinin (DHA), called AC254. In previous studies, both SAS and DHA have already proved to have anti-tumor properties themselves and to have sensitizing respectively potentiating effects on other treatments against malignant tumors. We investigated the impact of individual drugs SAS and DHA, their 1:1 combination and a novel SAS-DHA hybrid compound (AC254) on rodent and human glioma cells. In our study SAS alone showed no or only a mild effect on glioma, whereas DHA led to a significant reduction of cell viability in a dose-dependent manner. Next we compared the efficacy of the hybrid AC254 to the combinational treatment of its parent compounds SAS and DHA. The hybrid was highly efficient in combating glioma cells compared to single treatment strategies regarding cell viability and cell death. Interestingly, AC254 showed a remarkable advantage over the combinational treatment with both parent compounds in most used concentrations. In addition to its reduction of tumor cell viability and induction of cell death, the hybrid AC254 displayed changes in cell cycle and reduction of cell migration. Taken together, these results demonstrate that clinically established compounds such as SAS and DHA can be potentiated in their anti-cancer effects by chemical hybridization. Thus, this concept provides the opportunity to devise new effective chemotherapeutic agents.
Topics: Antineoplastic Agents; Artemisinins; Brain Neoplasms; Cell Cycle; Cell Death; Cell Line, Tumor; Glioma; Humans; Sulfasalazine
PubMed: 34675351
DOI: 10.1038/s41598-021-99960-z -
Sulfasalazine and its metabolites inhibit platelet function in patients with inflammatory arthritis.Clinical Rheumatology Feb 2016The purpose of this study is to assess the effect of sulfasalazine and its metabolites on platelet function in patients with inflammatory arthritis (IA). One hundred...
The purpose of this study is to assess the effect of sulfasalazine and its metabolites on platelet function in patients with inflammatory arthritis (IA). One hundred thirty-five consecutive patients with an established diagnosis of IA were screened. Those with a history of cardiovascular disease (CVD), taking anti-platelet agents or non-steroidal anti-inflammatory drugs (NSAIDs) were excluded. A total of 32 patients were investigated, 15 taking sulfasalazine and 17 taking other disease-modifying anti-rheumatic drugs (DMARDs) and no sulfasalazine. These two cohorts were compared to 15 patients with stable CVD on long-term aspirin. The effect of sulfasalazine and its metabolites on arachidonic acid (AA)-induced platelet aggregation was also tested in vitro in samples from healthy donors (n = 18). Demographics, CVD risk factors and disease activity indices were similar in the sulfasalazine and other DMARD groups. AA-induced platelet aggregation was significantly inhibited in the sulfasalazine group (9 ± 7 %) and comparable to that in the aspirin group (10 ± 6 %). In contrast, there was no effect on AA-induced platelet aggregation in the other DMARDs group (77 ± 12 %) (p < 0.001). Furthermore, sulfasalazine therapy had no effect on platelet aggregation in response to multiple other agonists. Sulfasalazine and its metabolites (5-aminosalicylic acid and sulfapyridine) exerted an additive and dose-dependent inhibitory effect on AA-induced platelet aggregation in vitro (p < 0.001). The inhibition of AA-induced platelet aggregation by sulfasalazine is comparable to that achieved by aspirin and is dependent on both sulfasalazine and its metabolites. This represents a potential mechanism that may contribute to the known cardioprotective effect of sulfasalazine in patients with IA.
Topics: Adult; Antirheumatic Agents; Arthritis, Rheumatoid; Blood Platelets; Cohort Studies; Female; Humans; Male; Middle Aged; Platelet Function Tests; Spondylarthropathies; Sulfasalazine
PubMed: 25253538
DOI: 10.1007/s10067-014-2769-x -
Journal of Cellular and Molecular... Jun 2021The aim of this study was to explore the role of sulfasalazine on proliferation and metastasis in gastric cancer by inhibition of xCT. The relationships between clinical...
The aim of this study was to explore the role of sulfasalazine on proliferation and metastasis in gastric cancer by inhibition of xCT. The relationships between clinical characteristics and xCT expression were analysed. An immunohistochemical staining assay and Western blot were performed among gastric cancers and normal gastric tissues. qPCR and Western blot were also used to evaluate the mRNA and protein expression in the normal gastric cell and eight gastric cancer cells, respectively. CCK-8 and colony formation assays were used to evaluate the effect of sulfasalazine on the proliferation and colony formation ability of three gastric cancers. The effect of sulfasalazine on the migration and invasion abilities of three cancer cells was assessed by the Transwell assay. xCT protein is up-regulated in gastric cancer specimens and cells. Three gastric cancer cells with high, medium and low expression of xCT were selected for the following analyses. CCK-8 assays revealed that sulfasalazine could attenuate the proliferation of HGC-27 and AGS. Also, the colony formation assay revealed that sulfasalazine might attenuate the colony formation ability in HGC-27 and AGS cells. Plus, the Transwell assays demonstrated that sulfasalazine might attenuate the migration and invasion abilities in HGC-27 and AGS cells. In conclusion, higher expression of xCT is associated with advanced tumour stage and poor overall survival of gastric cancer. Sulfasalazine can attenuate the proliferation, colony formation, metastasis and invasion of gastric cancer in vitro. Further study is required to validate our findings.
Topics: Amino Acid Transport System y+; Anti-Inflammatory Agents, Non-Steroidal; Apoptosis; Biomarkers, Tumor; Cell Proliferation; Gene Expression Regulation, Neoplastic; Humans; Prognosis; Stomach Neoplasms; Sulfasalazine; Survival Rate; Tumor Cells, Cultured
PubMed: 33988296
DOI: 10.1111/jcmm.16548