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Clinical Rheumatology Dec 2023We sought to investigate the reasons why spondyloarthritis (SpA) patients failed to respond to non-steroidal anti-inflammatory drugs (NSAIDs) and conventional synthetic...
OBJECTIVE
We sought to investigate the reasons why spondyloarthritis (SpA) patients failed to respond to non-steroidal anti-inflammatory drugs (NSAIDs) and conventional synthetic disease-modifying antirheumatic drugs (cDMARDs) and the influences of different initial cDMARDs on the likelihood of a switch to biologics.
METHODS
SpA patients were divided into a conventional drug maintenance group and a biologics conversion group to determine the causes of conversion to biologics. Then, we divided all patients into three groups according to different initial cDMARDs, NSAID monotherapy, NSAID + (sulfasalazine or thalidomide) double combination, and NSAID + sulfasalazine + thalidomide triple combination therapy groups, to clarify the influence of initial treatment on later conversion to biologics.
RESULTS
This study includes 202 patients, including 97 patients in the conventional drug maintenance group and 105 patients in the biologics conversion group. The mean age of the conventional drug maintenance group was higher than that of the biologics conversion group (40.8 ± 14.3 vs. 33.8 ± 12.3 years, P < 0.05). Uveitis (OR 5.356, P < 0.05) is positively correlated with conversion to biological therapy, while age (OR 0.940, P < 0.05) is negatively correlated. The proportion of NSAID monotherapy, double combination, and triple combination groups converted to biological agents was 80%, 51.1%, and 23.2%, respectively (P < 0.05).
CONCLUSION
Age and uveitis are related to conversion to biologics therapy. The early combination of sulfasalazine and thalidomide with NSAIDs may lower the probability of conversion to biologics therapy in the later stage and offer a new option for patients with limited use of biologics in SpA patients. Key Points • Patients' move to biologics may be caused mostly by inadequate disease control by conventional oral medications. • Regardless of axial vs. peripheral joint involvement, combination drug therapy was superior to single drug therapy in controlling SpA and decreasing the probability of conversion to a biological agent. • For SpA patients who are not candidates for biologics due to contraindications or other reasons, early combination application of NSAIDs, sulfasalazine, and thalidomide may be a new choice.
Topics: Humans; Biological Products; Sulfasalazine; Thalidomide; Spondylarthritis; Antirheumatic Agents; Anti-Inflammatory Agents, Non-Steroidal; Biological Factors; Analgesics; Uveitis
PubMed: 37740841
DOI: 10.1007/s10067-023-06724-3 -
Clinical and Experimental Pharmacology... Jul 2022A thorough understanding of the pathological process underlying hypertension-induced cardiac remodelling may help in prevention and treatment of heart failure....
A thorough understanding of the pathological process underlying hypertension-induced cardiac remodelling may help in prevention and treatment of heart failure. Angiotensin II (AngII) results in cardiac fibrosis and hypertrophy partly through activation of inflammation, which increases the fibroblasts and promotes extracellular matrix production. Sulfasalazine (SASP) has evident anti-inflammatory effects and pharmacological functions on autoimmune disease. The roles of SASP in the cardiac remodelling remain unknown. In this study, we established AngII-induced cardiac remodelling mice model and then treated with SASP. Blood pressure, cardiac pump function and pathological changes of cardiac remodelling were analysed in these mice. To explore the mechanism, phosphorylated Akt was detected in vivo and vitro. In this study, we found that SASP aggravated cardiac dysfunction, hypertrophy and fibrosis after AngII infusion. In addition, SASP activated Akt in AngII-remodelled mouse hearts and cardiac cells. Our findings indicate that independent of anti-inflammatory property, SASP exacerbates AngII-induced cardiac remodelling by activation of Akt signalling pathway.
Topics: Angiotensin II; Animals; Cardiomegaly; Fibrosis; Hypertrophy; Mice; Mice, Inbred C57BL; Myocardium; Myocytes, Cardiac; Proto-Oncogene Proteins c-akt; Signal Transduction; Sulfasalazine; Ventricular Remodeling
PubMed: 35538895
DOI: 10.1111/1440-1681.13653 -
Journal of Ethnopharmacology Dec 2023Origanum majorana L. is a member of the Lamiaceae family and is commonly used in Egyptian cuisine as a seasoning and flavor enhancer. It is also recognized as a...
Phytochemical analysis of Origanum majorana L. extract and investigation of its antioxidant, anti-inflammatory and immunomodulatory effects against experimentally induced colitis downregulating Th17 cells.
ETHNOPHARMACOLOGICAL RELEVANCE
Origanum majorana L. is a member of the Lamiaceae family and is commonly used in Egyptian cuisine as a seasoning and flavor enhancer. It is also recognized as a well-known traditional medicine in Egypt and is widely used for treating abdominal colic due to its antispasmodic properties. However, the protective effects of Origanum majorana L. against ulcerative colitis and its underlying mechanisms remain unclear.
AIM OF THE STUDY
This study aimed to identify the biologically active components present in methanol extracts of Origanum majorana L. using gas chromatography/mass spectrometry (GC/MS). Additionally, it aimed to investigate the therapeutic effects of these extracts on acetic acid-induced ulcerative colitis and elucidate the potential mechanisms involved.
MATERIALS AND METHODS
We conducted a GC-MS analysis of the methanolic extract obtained from Origanum majorana L. Thirty-two male rats were included in the study and divided into four experimental groups, with eight rats in each group: sham, UC, UC + O. majorana, and UC sulfasalazine. After euthanizing the rats, colon tissue samples were collected for gross and microscopic examinations, assessment of oxidative stress, and molecular evaluation. GC-MS analysis identified 15 components in the extracts. Pretreatment with O. majorana L. extract and sulfasalazine significantly improved the disease activity index (DAI) and resulted in notable improvements in macroscopic and microscopic colon findings. Additionally, both treatments demonstrated preventive effects against colonic oxidative damage by reducing the levels of malondialdehyde (MDA) and increasing the levels of the antioxidant systems superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH), which operate through the Nrf2/HO-1 signaling pathway. Moreover, these treatments downregulated the colonic inflammatory cascade by inhibiting NFκB, TNFα, IL-1β, IL6, IL23, IL17, COX-2, and iNOS, subsequently leading to downregulation of the JAK2/STAT3 signaling pathway and a decrease in the Th17 cell response. Furthermore, a reduction in the number of apoptotic epithelial cells that expressed caspase-3 was observed.
CONCLUSION
pretreatment with O. majorana L. extract significantly ameliorated acetic acid-induced ulcerative colitis. This effect could be attributed to the protective, antioxidant, anti-inflammatory, and anti-apoptotic properties of the extract.
Topics: Rats; Male; Animals; Antioxidants; Colitis, Ulcerative; Sulfasalazine; Origanum; Th17 Cells; Colitis; Anti-Inflammatory Agents; Colon; Oils, Volatile; Phytochemicals; Plant Extracts; Glutathione
PubMed: 37348796
DOI: 10.1016/j.jep.2023.116826 -
BMC Oral Health Nov 2022Studies have shown that excessive iron can lead to an increased incidence of cancer. The role of adipocyte enhancer-binding protein 1 (AEBP1) on ferroptosis is unknown....
BACKGROUND
Studies have shown that excessive iron can lead to an increased incidence of cancer. The role of adipocyte enhancer-binding protein 1 (AEBP1) on ferroptosis is unknown. Thus, we explored the effect of AEBP1 silencing in regulation of ferroptosis in cisplatin-resistant oral cancer cells.
METHODS
The functions of AEBP1 silencing and sulfasalazine (SSZ) treatment were determined on oral cancer cell lines and tumor xenograft mouse models. Then we evaluated the functions of AEBP1 on cell proliferation, migration, invasion, lipid reactive oxygen species (ROS), labile iron pool (LIP) and free iron, lipid peroxidation, and expression levels of ferroptosis-related genes.
RESULTS
AEBP1 was highly expressed in oral cancer cells and tissues. AEBP1 silencing inhibited oral cancer cell proliferation, migration, and invasion after SSZ treatment. SSZ-induced ferroptosis is due to enhanced ROS level, free iron, and lipid peroxidation, which were distinctly increased by AEBP1 silencing. Meanwhile, AEBP1 silencing enhanced the effects of SSZ on levels of LIP and Fe, lipid peroxidation, as well as the expression levels of ferroptosis-related genes in the tumor xenograft mouse models. Importantly, AEBP1 silencing suppressed tumor growth in vivo. Furthermore, silencing of AEBP1 might activate the JNK/ P38 /ERK pathway.
CONCLUSION
This research suggested that silencing of AEBP1 predisposes cisplatin-resistant oral cancer cells to ferroptosis via the JNK/p38 /ERK pathway.
Topics: Humans; Mice; Animals; Cisplatin; Ferroptosis; Reactive Oxygen Species; Cell Line, Tumor; Mouth Neoplasms; Sulfasalazine; Iron; Carboxypeptidases; Repressor Proteins
PubMed: 36352396
DOI: 10.1186/s12903-022-02503-9 -
RMD Open Mar 2024Sulfasalazine-induced cytopenia, nephrotoxicity and hepatotoxicity is uncommon during long-term treatment. Some guidelines recommend 3 monthly monitoring blood tests...
BACKGROUND
Sulfasalazine-induced cytopenia, nephrotoxicity and hepatotoxicity is uncommon during long-term treatment. Some guidelines recommend 3 monthly monitoring blood tests indefinitely during long-term treatment while others recommend stopping monitoring after 1 year. To rationalise monitoring, we developed and validated a prognostic model for clinically significant blood, liver or kidney toxicity during established sulfasalazine treatment.
DESIGN
Retrospective cohort study.
SETTING
UK primary care. Data from Clinical Practice Research Datalink Gold and Aurum formed independent development and validation cohorts.
PARTICIPANTS
Age ≥18 years, new diagnosis of an inflammatory condition and sulfasalazine prescription.
STUDY PERIOD
1 January 2007 to 31 December 2019.
OUTCOME
Sulfasalazine discontinuation with abnormal monitoring blood-test result.
ANALYSIS
Patients were followed up from 6 months after first primary care prescription to the earliest of outcome, drug discontinuation, death, 5 years or 31 December 2019. Penalised Cox regression was performed to develop the risk equation. Multiple imputation handled missing predictor data. Model performance was assessed in terms of calibration and discrimination.
RESULTS
8936 participants were included in the development cohort (473 events, 23 299 person-years) and 5203 participants were included in the validation cohort (280 events, 12 867 person-years). Nine candidate predictors were included. The optimism adjusted R and Royston D statistic in the development data were 0.13 and 0.79, respectively. The calibration slope (95% CI) and Royston D statistic (95% CI) in validation cohort was 1.19 (0.96 to 1.43) and 0.87 (0.67 to 1.07), respectively.
CONCLUSION
This prognostic model for sulfasalazine toxicity uses readily available data and should be used to risk-stratify blood-test monitoring during established sulfasalazine treatment.
Topics: Humans; Adolescent; Sulfasalazine; Prognosis; Retrospective Studies
PubMed: 38453215
DOI: 10.1136/rmdopen-2023-003980 -
Journal of Infection and Chemotherapy :... Feb 2023Pneumocystis pneumonia (PCP) is an opportunistic lung infection and has been reported among patients with rheumatoid arthritis (RA). An animal study revealed that...
INTRODUCTION
Pneumocystis pneumonia (PCP) is an opportunistic lung infection and has been reported among patients with rheumatoid arthritis (RA). An animal study revealed that sulfasalazine enhances Pneumocystis clearance from the lung by accelerating macrophage activity.
METHODS
The self-controlled case series (SCCS) method was used to investigate the association between sulfasalazine use and PCP development in patients with RA without the effect of time-invariant, interpatient confounders. PCP episodes which developed in patients with RA at five hospitals between 2003 and 2019 were identified. PCP was defined by the following criteria: 1) detection of Pneumocystis jirovecii in respiratory specimens by polymerase chain reaction; 2) clinical symptoms (pyrexia, dry cough, dyspnea or hypoxia); 3) diffuse interstitial infiltrate on chest imaging; and 4) absence of PCP prophylaxis. The PCP incidence rate ratio (IRR) was compared between periods with and without sulfasalazine use by conditional Poisson regression.
RESULTS
Fifty episodes of PCP were identified in 49 patients. Thirty patients received sulfasalazine at some point during their observation. While 49 episodes of PCP developed in 170.3 person-years without sulfasalazine use, only one episode of PCP developed in 103.7 person-years with sulfasalazine use. Sulfasalazine use was associated with a decreased PCP risk (adjusted IRR <0.01; 95% confidence interval <0.01-0.03) after adjusting for age and glucocorticoid, methotrexate, and tumor necrosis factor inhibitor administration.
CONCLUSION
Our study demonstrated a preventive effect of sulfasalazine against PCP in patients with RA.
Topics: Arthritis, Rheumatoid; Methotrexate; Opportunistic Infections; Pneumocystis carinii; Pneumonia, Pneumocystis; Retrospective Studies; Sulfasalazine; Humans
PubMed: 36334836
DOI: 10.1016/j.jiac.2022.10.019 -
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 -
The Journal of Dermatology Dec 2023Interleukin 17A (IL-17A) inhibitors, such as secukinumab, have been widely used as the mainstream treatment for chronic plaque psoriasis; however, cutaneous adverse...
Interleukin 17A (IL-17A) inhibitors, such as secukinumab, have been widely used as the mainstream treatment for chronic plaque psoriasis; however, cutaneous adverse events have been reported. Here, we report a 43-year-old Chinese man who developed herpetiform pemphigus (HP) during secukinumab treatment for his psoriasis. He presented with (1) clinical features of HP, which resembled bullous pemphigoid; histopathological features of intraepidermal blisters, eosinophilic/neutrophilic spongiosis, and liquefactive degeneration of the basal cell layer; (3) positive anti-desmoglein 1 antibody by enzyme-linked immunosorbent assay and cell surface IgG reactivity within the epidermis by indirect immunofluorescence assay; and (4) a satisfactory response to salicylazosulfapyridine (sulfasalazine). To the best of our knowledge, this is the first report of the development of HP after the use of secukinumab for psoriasis.
Topics: Adult; Humans; Male; Pemphigoid, Bullous; Pemphigus; Psoriasis; Sulfasalazine
PubMed: 37641883
DOI: 10.1111/1346-8138.16936 -
Annals of the Rheumatic Diseases Nov 2023
Topics: Humans; Sulfasalazine; Antirheumatic Agents; Arthritis, Rheumatoid
PubMed: 37586761
DOI: 10.1136/ard-2023-224660 -
Journal of Ethnopharmacology Jun 2021Ginseng is a valuable medicinal herb used in China for the prevention and treatment of cancer, diabetes, cardiovascular diseases and other diseases. As the main active...
ETHNOPHARMACOLOGICAL RELEVANCE
Ginseng is a valuable medicinal herb used in China for the prevention and treatment of cancer, diabetes, cardiovascular diseases and other diseases. As the main active ingredient of ginseng, ginsenoside has a wide range of pharmacological effects. Ginsenoside Rh2, a protopanaxadiol saponin from ginseng, exhibits anti-inflammatory and anticancer effects.
AIM OF THE STUDY
The potential biological mechanism of Rh2 in the treatment of ulcerative colitis (UC) has not been clarified clearly. In our research, we aimed to explore the therapeutic effects of Rh2 on dextran sodium sulfate (DSS)-induced colitis and elucidate the mechanism of Rh2 in treating UC.
METHODS
DSS-induced UC mice were established and randomly divided into the following four groups: control group, DSS group, Rh2 (50 mg/kg) group and sulfasalazine (SASP, 200 mg/kg) group. Except for the control group, 3% DSS drinking water was given to each group for 7 days, and the other two groups were intragastrically administered with Rh2 and SASP for 10 days. At the end of the experiment, colon samples were collected, and phenotypic and pathological analyses were performed in UC mice. Then, Western blot, immunohistochemistry and quantitative real-time PCR analyses were performed to determine the expression of signaling pathway-related factors.
RESULTS
Rh2 markedly alleviated DSS-induced body weight loss, intestinal damage, colon length shortening and disease activity index (DAI) scores. Furthermore, proinflammatory cytokines, such as TNF-α, IL-6 and IL-1β, were reduced by Rh2. Additionally, STAT3/miR-214 activation was also suppressed by Rh2 administration. In vitro, we demonstrated that Rh2 effectively inhibited IL-6-induced STAT3 phosphorylation and miR-214 expression in cultured normal colonic epithelial cells.
CONCLUSION
Our results suggested that Rh2 exhibits potential application value in the treatment of UC, and its mechanism is related to the downregulation of STAT3/miR-214 levels, which is expected to be applicable in the treatment of clinical UC.
Topics: Animals; Anti-Inflammatory Agents; Cell Line; Colitis, Ulcerative; Cytokines; Dextran Sulfate; Disease Models, Animal; Ginsenosides; Humans; Inflammation; Male; Mice, Inbred C57BL; MicroRNAs; STAT3 Transcription Factor; Signal Transduction; Sulfasalazine; Mice
PubMed: 33705918
DOI: 10.1016/j.jep.2021.113997