Anti-inflammatory Sulfasalazine Research Articles

Combining Gut Microbiota Modulation and Enzymatic-Triggered Colonic Delivery by Prebiotic Nanoparticles Improves Mouse Colitis Therapy.

The efficacy of ulcerative colitis (UC) therapy is closely connected to the composition of gut microbiota in the gastrointestinal tract. Prebiotic-based nanoparticles (NPs) provide a more precise approach to alleviate UC via modulating gut microbiota dysbiosis. The present study develops an efficient prebiotic-based colon-targeted drug delivery system (PCDDS) by using prebiotic pectin (Pcn) and chitosan (Csn) polysaccharides as a prebiotic shell, with the anti-inflammatory drug sulfasalazine (SAS) loaded into a poly(lactic-co-glycolic acid) (PLGA) core to construct SAS@PLGA-Csn-Pcn NPs. Then, we examine its characterization, cellular uptake, and invivo therapeutic efficacy. The results of our study indicate that the Pcn/Csn shell confers efficient pH-sensitivity properties. The gut microbiota-secreted pectinase serves as the trigger agent for Pcn/Csn shell degradation, and the resulting Pcn oligosaccharides possess a substantial prebiotic property. Meanwhile, the formed PCDDSs exhibit robust biodistribution and accumulation in the colon tissue, rapid cellular uptake, efficient invivo therapeutic efficacy, and modulation of gut microbiota dysbiosis in a mouse colitis model. Collectively, our synthetic PCDDSs demonstrate a promising and synergistic strategy for UC therapy.

RTID-04. GLUGLIO - A PHASE IB/II RANDOMIZED DRUG REPURPOSING TRIAL OF GLUTAMATE SIGNALING INHIBITORS IN COMBINATION WITH CHEMORADIOTHERAPY IN PATIENTS WITH NEWLY DIAGNOSED GLIOBLASTOMA (NCT05664464)

Abstract Glioblastoma synthesizes and secretes large quantities of the excitatory neurotransmitter glutamate, driving epilepsy, neuronal death, tumor growth and invasion. Several brain-penetrating drugs that have obtained clinical approval in other pathologic conditions can inhibit glutamate synthesis, secretion and signalling, respectively, including (i) the anti-seizure drug gabapentin, which inhibits the glutamate synthesis enzyme, branched chain amino acid transaminase 1, (ii) the anti-inflammatory drug sulfasalazine, which inhibits glutamate secretion by blocking the cystine-glutamate exchanger system Xc, and (iii) the cognitive enhancer memantine, which can prevent glutamate-driven, calcium-induced neuronal death and tumor cell invasion by blocking N-methyl-D-aspartate (NMDA) type glutamate receptors. The multi-centre, open-label, parallel-group, two-arm, 1:1 randomized, phase Ib/II trial GLUGLIO explores the efficacy of a triple-combination of daily oral gabapentin, sulfasalazine and memantine in combination with standard chemoradiotherapy compared to chemoradiotherapy alone. Dosing of either drug will be sought up to the maximum approved dose and will be reevaluated in an interim safety analysis after 20 patients have been randomized into the experimental arm. The primary endpoint is progression-free survival at 6 months (PFS-6). The sample size of N = 120 patients was calculated to detect an increase in PFS-6 from 50% to 70% with a power of 80% performing exploratory hypothesis testing at a one-sided significance level of 10%. Secondary endpoints include progression-free, overall and seizure-free survival, response rate, quality of life of patients and caregivers, symptom burden, cognitive functioning, tumor glutamate levels by magnetic resonance spectroscopy as well as anti-convulsant and steroid use. Surgical tissues as well as peripheral blood and electroencephalography recordings will also be sampled longitudinally for translational analyses. Recruitment is ongoing and foreseen to be completed by mid 2026. The simultaneous targeting of glutamate synthesis, secretion and signalling will clarify whether glutamate should be further explored as a clinical target in glioblastoma patients.

The traditional herbal medicines mixture, Banhasasim-tang, relieves the symptoms of irritable bowel syndrome via modulation of TRPA1, NaV1.5 and NaV1.7 channels

Ethnopharmacological relevance: The cause of irritable bowel syndrome (IBS), a functional gastrointestinal (GI) disorder, remains unclear. Banhasasim-tang (BHSST), a traditional herbal medicines mixture, mainly used to treat GI-related diseases, may have a potential in IBS treatment. IBS is characterized by abdominal pain as the main clinical symptom, which seriously affects the quality of life. Aim of the study: We conducted a study to evaluate the effectiveness of BHSST and its mechanisms of action in treating IBS. Materials and methods: We evaluated the efficacy of BHSST in a zymosan-induced diarrhea-predominant animal model of IBS. Electrophysiological methods were used to confirm modulation of transient receptor potential (TRP) and voltage-gated Na+ (NaV) ion channels, which are associated mechanisms of action. Results: Oral administration of BHSST decreased colon length, increased stool scores, and increased colon weight. Weight loss was also minimized without affecting food intake. In mice administered with BHSST, the mucosal thickness was suppressed, making it similar to that of normal mice, and the degree of tumor necrosis factor-α was severely reduced. These effects were similar to those of the anti-inflammatory drug—sulfasalazine—and antidepressant—amitriptyline. Moreover, pain-related behaviors were substantially reduced. Additionally, BHSST inhibited TRPA1, NaV1.5, and NaV1.7 ion channels associated with IBS-mediated visceral hypersensitivity. Conclusions: In summary, the findings suggest that BHSST has potential beneficial effects on IBS and diarrhea through the modulation of ion channels.

A mesoporous polydopamine-derived nanomedicine for targeted and synergistic treatment of inflammatory bowel disease by pH-Responsive drug release and ROS scavenging.

Repurposing clinically approved drugs to construct novel nanomedicines is currently a very attractive therapeutic approach. Selective enrichment of anti-inflammatory drugs and reactive oxygen species (ROS) scavenging at the region of inflammation by stimuli-responsive oral nanomedicine is an effective strategy for the treatment of inflammatory bowel disease (IBD). This study reports a novel nanomedicine, which is based on the excellent drug loading and free radical scavenging ability of mesoporous polydopamine nanoparticles (MPDA NPs). By initiating polyacrylic acid（PAA）polymerization on its surface, a "core-shell" structure nano-carrier with pH response is constructed. Then, under alkaline conditions, using the π-π stacking and hydrophobic interaction between the anti-inflammatory drug sulfasalazine (SAP) and MPDA, the nanomedicines (PAA@MPDA-SAP NPs) loaded efficiently (928 μ g mg-1) of SAP was successfully formed. Our results reveal that PAA@MPDA-SAP NPs can pass through the upper digestive tract smoothly and finally accumulate in the inflamed colon. Through the synergistic effect of anti-inflammation and antioxidation, it can effectively reduce the expression of pro-inflammatory factors and enhance the intestinal mucosal barrier, and finally significantly alleviate the symptoms of colitis in mice. Furthermore, we confirmed that PAA@MPDA-SAP NPs have good biocompatibility and anti-inflammatory repair ability under inflammation induction through human colonic organoids. In summary, this work provides a theoretical basis for the development of nanomedicines for IBD therapy.

Sulfasalazine for the treatment of preeclampsia in a nitric oxide synthase antagonist mouse model

IntroductionDevelopment of a therapeutic that targets the pathophysiological elements of preeclampsia would be a major advance for obstetrics, with potential to save the lives of countless mothers and babies. We recently identified anti-inflammatory drug sulfasalazine as a prospective candidate therapeutic for treatment of preeclampsia. In primary human cells and tissues in vitro, sulfasalazine potently decreased secretion of anti-angiogenic sFlt-1 and sENG, increased production of pro-angiogenic PlGF, mitigated endothelial dysfunction, and promoted whole vessel vasodilation. MethodsUsing nitric oxide synthase antagonist Nω-Nitro-l-arginine methyl ester hydrochloride, a preeclampsia-like phenotype was induced in pregnant mice, including high blood pressure, fetal growth restriction, and elevated circulating sFlt-1. Mice were treated with sulfasalazine or vehicle from gestational day (D)13.5, with blood pressure measurements across gestation, fetal measurements at D17.5, and wire myograph assessment of vasoactivity. ResultsSulfasalazine had a modest effect on blood pressure, decreasing diastolic and mean blood pressure on D13.5, but not later in gestation, or systolic blood pressure. Sulfasalazine was not able to rescue fetal growth, in male or female fetuses. There was a suggestion of improved vasoactivity with sulfasalazine, but further clarification is required. DiscussionIn this mouse model of preeclampsia, sulfasalazine did not sustain reductions in blood pressure nor affect fetal parameters of size and weight, both desirable attributes of a viable preeclampsia therapeutic. While these data suggest sulfasalazine might improve vasoactivity, murine toxicity considerations limited the dose range of sulfasalazine that could be tested in the current study.

Mycobacterium tuberculosis-Induced Upregulation of the COX-2/mPGES-1 Pathway in Human Macrophages Is Abrogated by Sulfasalazine.

Macrophages are the primary human host cells of intracellular Mycobacterium tuberculosis (M.tb) infection, where the magnitude of inflammatory reactions is crucial for determining the outcome of infection. Previously, we showed that the anti-inflammatory drug sulfasalazine (SASP) significantly reduced the M.tb bactericidal burden and histopathological inflammation in mice. Here, we asked which genes in human inflammatory macrophages are affected upon infection with M.tb and how would potential changes impact the functional state of macrophages. We used a flow cytometry sorting system which can distinguish the dead and alive states of M.tb harbored in human monocyte-derived macrophages (MDM). We found that the expression of cyclooxygenase-2 and microsomal prostaglandin E2 synthase (mPGES)-1 increased significantly in tagRFP+ MDM which were infected with alive M.tb. After exposure of polarized M1-MDM to M.tb (H37Rv strain)-conditioned medium (MTB-CM) or to the M.tb-derived 19-kD antigen, the production of PGE2 and pro-inflammatory cytokines increased 3- to 4-fold. Upon treatment of M1-MDM with SASP, the MTB-CM-induced expression of COX-2 and the release of COX products and cytokines decreased. Elevation of PGE2 in M1-MDM upon MTB-CM stimulation and modulation by SASP correlated with the activation of the NF-κB pathway. Together, infection of human macrophages by M.tb strongly induces COX-2 and mPGES-1 expression along with massive PGE2 formation which is abrogated by the anti-inflammatory drug SASP.

Identification of Target Genes Related to Sulfasalazine in Triple-Negative Breast Cancer Through Network Pharmacology.

BackgroundThe anti-inflammatory drug sulfasalazine (SAS) has been confirmed to inhibit the growth of triple-negative breast cancer (TNBC), but the mechanism is not clear. The aim of this study was to use network pharmacology to find relevant pathways of SAS in TNBC patients.Material/MethodsThrough screening of the GeneCards, CTD, and ParmMapper databases, potential genes related to SAS and TNBC were identified. In addition, gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed using the R programming language. Protein–protein interaction networks were constructed using Cytoscape. The Kaplan-Meier plotter screened genes related to TNBC prognosis. TNBC patient gene expression profiles and clinical data were downloaded from The Cancer Genome Atlas database. A heatmap was generated using the R programming language that presents the expression of potential target genes in patients with TNBC.ResultsEighty potential target genes were identified through multiple databases. The bioinformatical analyses predicted the interrelationships, potential pathways, and molecular functions of the genes from multiple aspects, which are associated with physiological processes such as the inflammatory response, metabolism of reactive oxygen species (ROS), and regulation of proteins in the matrix metalloproteinase (MMP) family. Survival analysis showed that 12 genes were correlated with TNBC prognosis. Heatmapping showed that genes such as those encoding members of the MMP family were differentially expressed in TNBC tissues and normal tissues.ConclusionsOur analysis revealed that the main reasons for the inhibitory effect of SAS on TNBC cells may be inhibition of the inflammatory response and MMP family members and activation of ROS.

Combination Immunotherapy with Passive Antibody and Sulfasalazine Accelerates Fungal Clearance and Promotes the Resolution of Pneumocystis-Associated Immunopathogenesis.

The pulmonary immune response protects healthy individuals against Pneumocystis pneumonia (PcP). However, the immune response also drives immunopathogenesis in patients who develop severe PcP, and it is generally accepted that optimal treatment requires combination strategies that promote fungal killing and also provide effective immunomodulation. The anti-inflammatory drug sulfasalazine programs macrophages for enhanced Pneumocystis phagocytosis and also suppresses PcP-related immunopathogenesis. Anti-Pneumocystis antibody opsonizes Pneumocystis organisms for greater phagocytosis and may also mask antigens that drive immunopathogenesis. Thus, we hypothesized that combining antibody and sulfasalazine would have the dual benefit of enhancing fungal clearance while dampening immunopathogenesis and allow the rescue of severe PcP. To model a clinically relevant treatment scenario in mice, therapeutic interventions were withheld until clear symptoms of pneumonia were evident. When administered individually, both passive antibody and sulfasalazine improved pulmonary function and enhanced Pneumocystis clearance to similar degrees. However, combination treatment with antibody and sulfasalazine produced a more rapid improvement, with recovery of body weight, a dramatic improvement in pulmonary function, reduced lung inflammation, and the rapid clearance of the Pneumocystis organisms. Accelerated fungal clearance in the combination treatment group was associated with a significant increase in macrophage phagocytosis of Pneumocystis Both passive antibody and sulfasalazine resulted in the suppression of Th1 cytokines and a marked increase in lung macrophages displaying an alternatively activated phenotype, which were enhanced by combination treatment. Our data support the concept that passive antibody and sulfasalazine could be an effective and specific adjunctive therapy for PcP, with the potential to accelerate fungal clearance while attenuating PcP-associated immunopathogenesis.

Medical fluorophore 1 (MF1), a benzoquinolizinium-based fluorescent dye, as an inflammation imaging agent.

Structure-based targeting of fluorescent dyes is essential for their use as imaging agents for disease diagnosis. Here, we describe the development of the benzoquinolizinium compound Medical fluorophore 1 (MF1) as a novel biomedical imaging agent that allows the visualization of inflammation by virtue of its unique chemical structure. Lipopolysaccharide treatment stimulated the uptake of MF1 by bone marrow-derived macrophages, with no adverse effects on cell proliferation. In vivo fluorescence lifetime imaging revealed the accumulation of MF1 in carrageenan-induced acute inflammatory lesions in mice, which peaked at 6 h. MF1-based imaging also allowed monitoring of the response to the anti-inflammatory drugs dexamethasone and sulfasalazine. Thus, MF1 can be used to diagnose diseases characterized by inflammation as well as treatment efficacy.

Sulfasalazine attenuates chronic constriction injury-induced neuroinflammation and mechanical hypersensitivity in rats

Neuropathic pain is a severe and chronic neurological disease caused by injury or disease of the somatosensory system. Currently, there are no effective treatments for neuropathic pain. Neuroinflammation, characterized by activation of spinal glial cells and increased production of pro-inflammatory cytokines (for example, IL-1β, TNF-α and IL-6), is a pathophysiological process closely related to neuropathic pain. The anti-inflammatory drug sulfasalazine (SFZ) is approved for inflammatory bowel disease and rheumatoid arthritis. Although the analgesic effect of SFZ has been reported in diabetic mice, its role in neuropathic pain caused by peripheral nerve injury has not been clarified. Here, we show that SFZ significantly alleviated mechanical hypersensitivity and attenuated neuroinflammatory response in neuropathic pain induced by chronic constriction injury (CCI) in rats. Additionally, SFZ inhibited the activation of astrocytes and abolished the CCI-induced increase of NF-κB in the spinal cord. Hence, our results show that SFZ is a potential treatment for neuropathic pain induced by peripheral nerve injury.

An in vitro and in vivo evaluation of new potential trans-sialidase inhibitors of Trypanosoma cruzi predicted by a computational drug repositioning method

Chagas disease is one of the most important neglected parasitic diseases afflicting developed and undeveloped countries. There are currently limited options for inexpensive and secure pharmacological treatment. In this study, we employed a structure-based virtual screening protocol for 3180 FDA-approved drugs for repositioning of them as potential trans-sialidase inhibitors. In vitro and in vivo evaluations were performed for the selected drugs against trypomastigotes from the INC-5 and NINOA strains of T. cruzi. Also, inhibition of sialylation by the trans-sialidase enzyme reaction was evaluated using high-performance anion-exchange chromatography with pulse amperometric detection to confirm the mechanism of action. Results from the computational study showed 38 top drugs with the best binding-energies. Four compounds with antihistaminic, anti-hypertensive, and antibiotic properties showed better trypanocidal effects (LC50 range = 4.5–25.8 μg/mL) than the reference drugs, nifurtimox and benznidazole (LC50 range = 36.1–46.8 μg/mL) in both strains in the in vitro model. The anti-inflammatory, sulfasalazine showed moderate inhibition (37.6%) of sialylation in a trans-sialidase enzyme inhibition reaction. Sulfasalazine also showed the best trypanocidal effects in short-term in vivo experiments on infected mice. This study suggests for the first time that the anti-inflammatory sulfasalazine could be used as a lead compound to develop new trans-sialidase inhibitors.

Sensitive approach for voltammetric determination of anti-inflammatory drug sulfasalazine using liquid mercury free silver solid amalgam electrode

Voltammetric study of the anti-inflammatory drug sulfasalazine was investigated employing polished silver solid amalgam electrode. One reduction and appropriate oxidation peak were recorded in a wide range of pH. The reduction peak was well developed and easily evaluable, and thus, it was chosen for further examination. The highest reduction response was observed in citrate buffer of pH 5 about the potential E p = −0.1 V vs. Ag|AgCl. Parameters of adsorptive stripping square wave voltammetry were optimized, and it was reached excellent repeatability of measurements (RSD = 2.79 %) and determinations (RSD ≤5.33 %) as well, low limit of detection (LOD = 2.5 × 10−9 mol dm−3) and quantification (LOQ = 8.3 × 10−9 mol dm−3). Developed method was applied to the analysis of pharmaceutical preparation with excellent recovery (96.99–102.52 %). The designed method provides “environmental friendly” tool for sulfasalazine analysis and brings simple and sensitive tool for its determination.

Anti-inflammatory Actions of (+)-3'α-Angeloxy-4'-keto-3',4'-dihydroseselin (Pd-Ib) against Dextran Sulfate Sodium-Induced Colitis in C57BL/6 Mice.

The immunoregulatory protective properties of (+)-3'α-angeloxy-4'-keto-3',4'-dihydroseselin (Pd-Ib) isolated from Bupleurum malconense has not been reported. In the present study, the therapeutic effect of Pd-Ib (30, 60, and 120 mg/kg/day) was examined in a mouse model of dextran sulfate sodium (DSS)-induced acute colitis. Administration of Pd-Ib significantly reduced the disease activity index, inhibited the shortening of colon length, reduced colonic tissue damage, and suppressed colonic myeloperoxidase activity and nitric oxide levels in mice with DSS-induced colitis. Moreover, Pd-Ib greatly suppressed the secretion of pro-inflammatory cytokines TNF-α, IFN-γ, IL-6, and IL-17A while enhancing the level of anti-inflammatory cytokine IL-4. The protein levels of phosphorylated STAT3 (p-STAT3) and phosphorylated p38 (p-p38) were down-regulated in the colonic tissues of DSS-treated mice. Importantly, the anti-inflammatory effect of Pd-Ib against acute colitis was comparable to the anti-inflammatory sulfa drug sulfasalazine (300 mg/kg). Furthermore, the in vitro study showed that the inhibitory effect of Pd-Ib on p-STAT3 and IL-6 protein levels was accompanied by the reduction of MAPKs (JNK and p38). In conclusion, this study suggested that Pd-Ib attenuated DSS-induced acute colitis via the regulation of interleukins principally through the STAT3 and MAPK pathways.

Ets-1 regulates intracellular glutathione levels: key target for resistant ovarian cancer

BackgroundOvarian cancer is characterized by high rates of metastasis and therapeutic resistance. Many chemotherapeutic agents rely on the induction of oxidative stress to cause cancer cell death, thus targeting redox regulation is a promising strategy to overcome drug resistance.MethodsWe have used a tetracycline-inducible Ets-1 overexpression model derived from 2008 ovarian cancer cells in the present study. To examine the role of Ets-1 in glutathione regulation we have measured intracellular reactive oxygen species and glutathione levels, as well as glutathione peroxidase enzyme activity. Glutathione synthesis was limited using transsulfuration or Sxc- pathway blocking agents, and glutamate release was measured to confirm Sxc- blockade. Cell viability following drug treatment was assessed via crystal violet assay. Oxidative stress was induced through glucose oxidase treatment, which produces hydrogen peroxide by glucose oxidation. The protein expressions of redox-related factors were measured through western blotting.ResultsOverexpression of Ets-1 was associated with decreased intracellular ROS, concomitantly with increased intracellular GSH, GPX antioxidant activity, and Sxc- transporter activity. Under basal conditions, inhibition of the transsulfuration pathway resulted in decreased GSH levels and GPX activity in all cell lines, whereas inhibition of Sxc- by sulfasalazine decreased GPX activity in Ets-1-expressing cells only. However, under oxidative stress the intracellular GSH levels decreased significantly in correlation with increased Ets-1 expression following sulfasalazine treatment.ConclusionsIn this study we have identified a role for proto-oncogene Ets-1 in the regulation of intracellular glutathione levels, and examined the effects of the anti-inflammatory drug sulfasalazine on glutathione depletion using an ovarian cancer cell model. The findings from this study show that Ets-1 mediates enhanced Sxc- activity to increase glutathione levels under oxidative stress, suggesting that Ets-1 could be a promising putative target to enhance conventional therapeutic strategies.

Protective effects of cathelicidin‐encoding Lactococcus lactis in murine ulcerative colitis

Intrarectal administration of mouse cathelin-related antimicrobial peptide (mCRAMP) reduced intestinal inflammation in mice. In the current study, we examined whether mCRAMP-transformed Lactococcus lactis given orally attained similar protective effects. mCRAMP was produced and secreted from the transformed L. lactis. Murine colitis was induced by ingestion of 3% dextran sulfate sodium (DSS) for 7 days. Eight or 10 log colony forming unit (cfu) L. lactis or the transformed strains with or without nisin induction were given orally as a parallel treatment with DSS. The body weight, fecal microbiota populations, clinical symptoms and histological examinations of colonic tissues were determined. Myeloperoxidase (MPO) activity and malondialdehyde (MDA) level were also evaluated to reflect the degree of inflammation. A prototype anti-inflammatory drug sulfasalazine was used as a reference drug to compare the efficacy and mechanisms of action for ulcerative colitis (UC). Compared with the control group with colitis, cathelicidin-transformed L. lactis could improve the clinical symptoms, maintain crypt integrity and preserve mucus content (P < 0.01). The number of apoptotic cells, MPO activity and MDA level were also significantly reduced (P < 0.05). The increases of fecal microbiota in colitis animals were markedly prevented (P < 0.001). Unlike mCRAMP-encoding L. lactis, effective doses of sulfasalazine only alleviated the clinical symptoms (P < 0.01) but not the mucosal damage in the colon. mCRAMP-transformed L. lactis has been shown to produce mCRAMP, effectively preventing murine UC. Oral administration of this biological preparation is better than sulfasalazine for the treatment of UC.

A yeast-based screen reveals that sulfasalazine inhibits tetrahydrobiopterin biosynthesis

We introduce an approach for detection of drug-protein interactions that combines a new yeast three-hybrid screening for identification of interactions with affinity chromatography for their unambiguous validation. We applied the methodology to the profiling of clinically approved drugs, resulting in the identification of previously known and unknown drug-protein interactions. In particular, we were able to identify off-targets for erlotinib and atorvastatin, as well as an enzyme target for the anti-inflammatory drug sulfasalazine. We demonstrate that sulfasalazine and its metabolites, sulfapyridine and mesalamine, are inhibitors of the enzyme catalyzing the final step in the biosynthesis of the cofactor tetrahydrobiopterin. The interference with tetrahydrobiopterin metabolism provides an explanation for some of the beneficial and deleterious properties of sulfasalazine and furthermore suggests new and improved therapies for the drug. This work thus establishes a powerful approach for drug profiling and provides new insights in the mechanism of action of clinically approved drugs.

Anti-inflammatory therapy in an ovine model of fetal hypoxia induced by single umbilical artery ligation

Perinatal morbidity and mortality are significantly higher in pregnancies complicated by chronic hypoxia and intrauterine growth restriction (IUGR). Clinically, placental insufficiency and IUGR are strongly associated with a fetoplacental inflammatory response. To explore this further, hypoxia was induced in one fetus in twin-bearing pregnant sheep (n=9) by performing single umbilical artery ligation (SUAL) at 110 days gestation. Five ewes were administered the anti-inflammatory drug sulfasalazine (SSZ) daily, beginning 24h before surgery. Fetal blood gases and inflammatory markers were examined. In both SSZ- and placebo-treated ewes, SUAL fetuses were hypoxic and growth-restricted at 1 week (P<0.05). A fetoplacental inflammatory response was observed in SUAL pregnancies, with elevated pro-inflammatory cytokines, activin A and prostaglandin E(2). SSZ did not mitigate this inflammatory response. It is concluded that SUAL induces fetal hypoxia and a fetoplacental inflammatory response and that SSZ does not improve oxygenation or reduce inflammation. Further studies to explore whether alternative anti-inflammatory treatments may improve IUGR outcomes are warranted.

Efficacy of sulfasalazine in the treatment of generalized lichen planus: randomized double‐blinded clinical trial on 52 patients

Oral sulfasalazine has been reported to be effective in patients with idiopathic cutaneous lichen planus (LP). Our purpose was to evaluate the efficacy of this drug in the treatment of generalized cutaneous lichen planus (GLP). In this study, we evaluated the effectiveness of the anti-inflammatory drug sulfasalazine for the treatment of GLP. A total of 52 patients with GLP presenting at the outpatient clinic were enrolled in this double-blind, randomized, placebo-controlled, prospective study. Of these patients, 44 completed the period of study. The patients were randomly divided into two groups. One group received placebo and the other was given sulfasalazine maximum 2.5 g/day. The patients were evaluated at the third and sixth weeks of treatment for improvement rate and occurrence of complications. After 6 weeks of treatment, the rate of cutaneous lesions improvement was 9.6% (two patients) in the placebo group and 82.6% (19 patients) in the sulfasalazine group. The improvement rate of pruritus was 14.3% in the placebo group and 91.3% in the sulfasalazine group. Side-effects which were mild and tolerable were detected in 30.7% of patients, but three patients left the study because of side effects. Most of the reported side-effects included gastrointestinal upset and headache. Statistically, sulfasalazine was more effective than placebo in reducing cutaneous lesions and improving pruritus after 6 weeks of treatment. According to our study, sulfasalazine is a relatively safe and effective treatment option and may be an alternative therapy for the treatment of generalized lichen planus.

Cross-Reactivity in Drug Hypersensitivity Reactions to Sulfasalazine and Sulfamethoxazole

Background: Sulfonamides are generally classified into 2 groups: antibiotics and non-antibiotics. Recent studies showed that patients allergic to sulfonamide antibiotics do not have a specific risk for an allergy to sulfonamide non-antibiotic. However, the anti-inflammatory drug sulfasalazine represents an important exception. Used in rheumatic diseases, it is classified as a non-antibiotic sulfonamide, but is structurally related to antibiotic sulfonamides. Therefore, we aimed to analyze in vitro the cross-reactivity between the antimicrobial sulfamethoxazole and the anti-inflammatory drug sulfasalazine. Methods: PBMC from 2 patients with severe hypersensitivity syndrome to sulfasalazine, 3 patients with sulfamethoxazole allergy and 5 healthy donors were isolated and incubated with medium only (negative control), 2 concentrations (10, 100 µg/ml) of sulfapyridine, 2 concentrations (100, 200 µg/ml) of sulfamethoxazole, and tetanus toxoid (10 µg/ml) as a positive control. After 6 days of culture, ³H-thymidine was added and cell proliferation was measured. Results: In all patients tested, the lymphocyte transformation tests were positive for both sulfapyridine and sulfamethoxazole, suggesting a strong cross-reactivity to these drugs. None of the healthy donors reacted to any of the drugs tested. We refrained from provoking our patients with either sulfasalazine or sulfamethoxazole, as they had a clear, typical history, severe symptoms and were positive on in vitro tests to both compounds. Conclusions: We demonstrate that in the case of sulfamethoxazole and sulfasalazine, cross-reactivity is dependent on chemical features rather than the indication of the drugs. Therefore, patients with hypersensitivity to sulfasalazine or sulfamethoxazole should be specifically advised to avoid both drugs.

Accurate quantitation of glutathione in cell lysates through surface-assisted laser desorption/ionization mass spectrometry using gold nanoparticles

We developed a method for the determination of three aminothiols—cysteine, glutathione (GSH), and homocysteine—using surface-assisted laser desorption/ionization mass spectrometry (SALDI-MS). The analytes were first captured using the unmodified 14-nm gold nanoparticles; N-2-mercaptopropionylglycine–modified gold nanoparticles serving as internal standard were sequentially added, and then the sample was analyzed using SALDI-MS. This approach provided good quantitative linearity of the three analytes ( R 2 = ∼0.99), with good reproducibility (relative standard deviations: <10%), in the analyses of GSH in the lysates of human red blood cells and MCF-7 cancer breast cells in the presence and absence of the anti-inflammatory drug sulfasalazine. The internal-standard SALDI-MS approach provides simplicity, accuracy, and precision to the determination of GSH in cells under drug invasion, to open an avenue for SALDI-MS to be used for the precise quantitative determination of a variety of analytes. From the Clinical Editor This paper reports the development of a surface assisted laser desorption/ionization mass spectrometry method to precisely determine aminothiols-cysteine (Cys), glutathione (GSH), and homocysteine (HCys)