- The effect of polymer and CaCl2concentrations on the sulfasalazine release from alginate-N,O-carboxymethyl chitosan beads. [Journal Article]
- PBProg Biomater 2013 Apr 04; 2(1):10
- In this study, pH-sensitive blended polymeric beads were prepared by ionic gelation of mixed alginate and N,O-carboxymethyl chitosan (NOCC) solutions in aqueous media containing calcium chloride. To ...
In this study, pH-sensitive blended polymeric beads were prepared by ionic gelation of mixed alginate and N,O-carboxymethyl chitosan (NOCC) solutions in aqueous media containing calcium chloride. To prepare drug-loaded beads, sulfasalazine (SA) as a model drug was added to the initial aqueous polymer solution. These beads were characterized and evaluated in vitro as potential carriers for colon-specific drug delivery. A 32full factorial experimental design was employed to evaluate the effect of polymer and CaCl2concentrations on swelling and drug release behavior of the beads in simulated gastrointestinal tract fluid. It was found that the rate of swelling and drug release decreased significantly with increasing polymer and CaCl2concentrations, but polymer concentration was more effective than CaCl2concentration. The beads prepared using 4.5% polymer concentration and 4% CaCl2concentration retained approximately 60% of the loaded drug before approaching the simulated colonic fluid. Based on the results, the alginate-NOCC beads prepared with high polymer concentration could be potentially suitable polymeric carriers for colon-specific delivery of SA.
- Complete resolution of erythema elevatum diutinum using oral sulfasalazine. [Journal Article]
- DODermatol Online J 2017 Oct 15; 23(10)
- Erythema elevatum diutinum (EED) is a rare, chronic small-vessel vasculitis that presents as firm, red, violaceous, or brown papules and nodules on the extensor surfaces of the limbs. Oral dapsone is...
Erythema elevatum diutinum (EED) is a rare, chronic small-vessel vasculitis that presents as firm, red, violaceous, or brown papules and nodules on the extensor surfaces of the limbs. Oral dapsone is considered first-line therapy for EED; in the current case report, a patient presenting with EED began dapsone treatment and symptoms subsided within two weeks. Seven months later, the patient became pregnant and stopped dapsone owing to her concerns with dapsone use during pregnancy, resulting in recurrence of EED symptoms. We present a novel treatment approach with oral sulfasalazine, which was given to the patient in lieu of dapsone and resulted in complete resolution of EED symptoms.
- MUC13 contributes to rewiring of glucose metabolism in pancreatic cancer. [Journal Article]
- OOncogenesis 2018 Feb 22; 7(2):19
- Pancreatic tumors are rewired for high-glucose metabolism and typically present with exceptionally poor prognosis. Recently, we have shown that MUC13, which is highly expressed in pancreatic tumors, ...
Pancreatic tumors are rewired for high-glucose metabolism and typically present with exceptionally poor prognosis. Recently, we have shown that MUC13, which is highly expressed in pancreatic tumors, promotes tumor progression via modulation of HER2 receptor tyrosine kinase activity. Herein, we investigate a novel, MUC13-mediated molecular mechanism responsible for higher glucose metabolism in pancreatic tumors. Our results demonstrate that MUC13 expression leads to the activation/nuclear translocation of NF-κB p65 and phosphorylation of IκB, which in turn upregulates the expression of important proteins (Glut-1, c-Myc, and Bcl-2) that are involved in glucose metabolism. MUC13 functionally interacts and stabilizes Glut-1 to instigate downstream events responsible for higher glucose uptake in pancreatic cancer cells. Altered MUC13 expression by overexpression and knockdown techniques effectively modulated glucose uptake, lactate secretion, and metastatic phenotypes in pancreatic cancer cells. NF-κB inhibitor, Sulfasalazine, abrogates the MUC13 and Glut-1 interaction, and attenuates events associated with MUC13-induced glucose metabolism. Pancreatic ductal adenocarcinoma (PDAC) patient tissue samples also show a positive correlation between the expression of these two proteins. These results delineate how MUC13 rewire aberrant glucose metabolism to enhance aggressiveness of pancreatic cancer and revealed a novel mechanism to develop newer therapeutic strategies for this exceptionally difficult cancer.
- Age-Dependent Oxidation of Extracellular Cysteine/Cystine Redox State (Eh(Cys/CySS)) in Mouse Lung Fibroblasts is Mediated by a Decline in Slc7a11 Expression. [Journal Article]
- FRFree Radic Biol Med 2018 Feb 16
- Aging is associated with progressive oxidation of the extracellular environment. The redox state of human plasma, defined by the concentrations of cysteine (Cys) and cystine (CySS), becomes more oxid...
Aging is associated with progressive oxidation of the extracellular environment. The redox state of human plasma, defined by the concentrations of cysteine (Cys) and cystine (CySS), becomes more oxidized as we age. Recently, we showed that fibroblasts isolated from the lungs of young and old mice retain this differential phenotype; old cells produce and maintain a more oxidizing extracellular redox potential (Eh(Cys/CySS)) than young cells. Microarray analysis identified down-regulation of Slc7a11, the light subunit of the CySS/glutamate transporter, as a potential mediator of age-related oxidation in these cells. The purpose of the present study was to investigate the mechanistic link between Slc7a11 expression and extracellular Eh(Cys/CySS). Sulforaphane treatment or overexpression of Slc7a11 was used to increase Slc7a11 in lung fibroblasts from old mice, and sulfasalazine treatment or siRNA-mediated knock down was used to decrease Slc7a11 in young fibroblasts. Slc7a11 mRNA levels were measured by real-time PCR, Slc7a11 activity was determined by measuring the rate of glutamate release, Cys, CySS, glutathione (GSH) and its disulfide (GSSG) were measured by HPLC, and Eh(Cys/CySS) was calculated from the Nernst equation. The results showed that both Eh(Cys/CySS) and Eh(GSH/GSSG) were more oxidized in the conditioned media of old cells than in young cells. Up-regulation of Slc7a11 via overexpression or sulforaphane treatment restored extracellular Eh(Cys/CySS) in cultures of old cells, whereas down-regulation reproduced the oxidizing Eh(Cys/CySS) in young cells. Only sulforaphane treatment was able to increase total GSH and restore Eh(GSH/GSSG), whereas overexpression, knock down and sulfasalazine had no effect on these parameters. In addition, inhibition of GSH synthesis with buthionine sulfoximine had no effect on the ability of cells to restore their extracellular redox potential in response to an oxidative challenge. In conclusion, our study reveals Slc7a11 is the key regulator of age-dependent changes in extracellular Eh(Cys/CySS) in primary mouse lung fibroblasts, and its effects are not dependent on GSH synthesis.
- Therapeutic efficacy of osthole against dinitrobenzene sulphonic acid induced-colitis in rats. [Journal Article]
- BPBiomed Pharmacother 2018 Feb 05; 100:42-51
- Several mediators were associated with the pathogenesis of inflammatory bowel disease such as oxidative stress through the production of reactive oxygen metabolites, neutrophils infiltration and rele...
Several mediators were associated with the pathogenesis of inflammatory bowel disease such as oxidative stress through the production of reactive oxygen metabolites, neutrophils infiltration and release of pro-inflammatory cytokines. This study was designed to investigate the therapeutic efficacy of osthole against dinitrobenzene sulfonic acid (DNBS) induced-colitis in rats through its anti-oxidant and anti-inflammatory properties. Colitis was induced in rats by single intracolonic instillation of (250 μl DNBS-25 mg/rat). Then 4 days later, rats were received oral administration of either (osthole 50 mg/kg), (sulfasalazine 500 mg/kg) or both in combination for 7 consecutive days. Body weight, some hematological parameters, colonic malondialdehyde (MDA) and myeloperoxidase activity (MPO), antioxidant parameters, colon injury and mucosa architectures were assessed. T helper (Th1)-related cytokines [Tumor necrosis factor alpha (TNF-α) and interferon-gamma (INF-γ)], Th2-relarted cytokines (interleukin-4 [IL-4 and IL-10], and Th-17 related cytokines [IL-17] were determined by ELISA. Osthole significantly improved the loss in body weight. That was accompanied with a remarkable amelioration of the disruption of the colonic architecture as well as a significant improvement in the antioxidant defense system. A reduction in MPO and MDA was observed in flamed colon. Treatment with either osthole or combination therapy showed suppressive activities on pro-inflammatory Th2-related cytokines and upregulation of anti-inflammatory Th2-related cytokines The results of this study suggest that osthole exert beneficial therapeutic effect in experimental colitis and improved the efficacy of the synthetized drugs such as sulfasalazine. Therefore, osthole may have a valuable sound in the treatment of inflammatory bowel disease.
- Photodegradation of sulfasalazine and its human metabolites in water by UV and UV/peroxydisulfate processes. [Journal Article]
- WRWater Res 2018 Apr 15; 133:299-309
- The widespread occurrence of pharmaceuticals and their metabolites in natural waters has raised great concerns about their potential risks on human health and ecological systems. This study systemati...
The widespread occurrence of pharmaceuticals and their metabolites in natural waters has raised great concerns about their potential risks on human health and ecological systems. This study systematically investigates the degradation of sulfasalazine (SSZ) and its two human metabolites, sulfapyridine (SPD) and 5-aminosalicylic acid (5-ASA), by UV and UV/peroxydisulfate (UV/PDS) processes. Experimental results show that SPD and 5-ASA were readily degraded upon UV 254 nm direct photolysis, with quantum yields measured to be (8.6 ± 0.8) × 10-3and (2.4 ± 0.1) × 10-2 mol Einstein-1, respectively. Although SSZ was resistant to direct UV photolysis, it could be effectively removed by both UV/H2O2and UV/PDS processes, with fluence-based pseudo-first-order rate constants determined to be 0.0030 and 0.0038 cm2 mJ-1, respectively. Second-order rate constant between SO4•-and SSZ was measured as (1.33 ± 0.01) × 109 M-1s-1by competition kinetic method. A kinetic model was established for predicting the degradation rate of SSZ in the UV/PDS process. Increasing the dosage of PDS significantly enhanced the degradation of SSZ in the UV/PDS process, which can be well predicted by the developed kinetic model. Natural water constituents, such as natural organic matter (NOM) and bicarbonate (HCO3-), influenced the degradation of SSZ differently. The azo functional group of SSZ molecule was predicted as the reactive site susceptible to electrophilic attack by SO4•-by frontier electron densities (FEDs) calculations. Four intermediate products arising from azo bond cleavage and SO2extrusion were identified by solid phase extraction-liquid chromatography-triple quadrupole mass spectrometry (SPE-LC-MS/MS). Based on the products identified, detailed transformation pathways for SSZ degradation in the UV/PDS system were proposed. Results reveal that UV/PDS could be an efficient approach for remediation of water contaminated by SSZ and its metabolites.
- Glutamate Excitotoxicity Linked to Spermine Oxidase Overexpression. [Journal Article]
- MNMol Neurobiol 2018 Feb 03
- Excitotoxic stress has been associated with several different neurological disorders, and it is one of the main causes of neuronal degeneration and death. To identify new potential proteins that coul...
Excitotoxic stress has been associated with several different neurological disorders, and it is one of the main causes of neuronal degeneration and death. To identify new potential proteins that could represent key factors in excitotoxic stress and to study the relationship between polyamine catabolism and excitotoxic damage, a novel transgenic mouse line overexpressing spermine oxidase enzyme in the neocortex (Dach-SMOX) has been engineered. These transgenic mice are more susceptible to excitotoxic injury and display a higher oxidative stress, highlighted by 8-Oxo-2'-deoxyguanosine increase and activation of defense mechanisms, as demonstrated by the increase of nuclear factor erythroid 2-related factor 2 (Nrf-2) in the nucleus. In Dach-SMOX astrocytes and neurons, an alteration of the phosphorylated and non-phosphorylated subunits of glutamate receptors increases the kainic acid response in these mice. Moreover, a decrease in excitatory amino acid transporters and an increase in the system xc-transporter, a Nrf-2 target, was observed. Sulfasalazine, a system xc-transporter inhibitor, was shown to revert the increased susceptibility of Dach-SMOX mice treated with kainic acid. We demonstrated that astrocytes play a crucial role in this process: neuronal spermine oxidase overexpression resulted in an alteration of glutamate excitability, in glutamate uptake and efflux in astrocytes involved in the synapse. Considering the involvement of oxidative stress in many neurodegenerative diseases, Dach-SMOX transgenic mouse can be considered as a suitable in vivo genetic model to study the involvement of spermine oxidase in excitotoxicity, which can be considered as a possible therapeutic target.
- Safety of live vaccines on immunosuppressive or immunomodulatory therapy-a retrospective study in three Swiss Travel Clinics. [Journal Article]
- JTJ Travel Med 2018 Jan 01; 25(1)
- CONCLUSIONS: Safety of live vaccines given to immunosuppressed patients cannot be concluded. However, it is re-assuring that in the examined patient groups no serious side effects or infections by the attenuated vaccine strain occurred.
- Piperlongumine rapidly induces the death of human pancreatic cancer cells mainly through the induction of ferroptosis. [Journal Article]
- IJInt J Oncol 2018; 52(3):1011-1022
- Pancreatic cancer is one of the most lethal types of cancer with a mortality rate of almost 95%. Treatment with current chemotherapeutic drugs has limited success due to poor responses. Therefore, th...
Pancreatic cancer is one of the most lethal types of cancer with a mortality rate of almost 95%. Treatment with current chemotherapeutic drugs has limited success due to poor responses. Therefore, the development of novel drugs or effective combination therapies is urgently required. Piperlongumine (PL) is a natural product with cytotoxic properties restricted to cancer cells by significantly increasing intracellular reactive oxygen species (ROS) levels. In the present study, we demonstrated that PL induced cancer cell death through, at least in part, the induction of ferroptosis, as the cancer cell-killing activity was inhibited by the antioxidant, N‑acetylcysteine, ferroptosis inhibitors (ferrostatin‑1 and liproxstatin‑1) and the iron chelator, deferoxamine (DFO), but not by the apoptosis inhibitor, Z-VAD-FMK, or the necrosis inhibitor, necrostatin‑1. Cotylenin A (CN‑A; a plant growth regulator) exhibits potent antitumor activities in several cancer cell lines, including pancreatic cancer cell lines. We found that CN‑A and PL synergistically induced the death of pancreatic cancer MIAPaCa‑2 and PANC‑1 cells for 16 h. CN‑A enhanced the induction of ROS by PL for 4 h. The synergistic induction of cell death was also abrogated by the ferroptosis inhibitors and DFO. The present results revealed that clinically approved sulfasalazine (SSZ), a ferroptosis inducer, enhanced the death of pancreatic cancer cells induced by PL and the combined effects were abrogated by the ferroptosis inhibitors and DFO. SSZ further enhanced the cancer cell-killing activities induced by combined treatment with PL plus CN‑A. On the other hand, the synergistic induction of cell death by PL and CN‑A was not observed in mouse embryonic fibroblasts (MEFs), and SSZ did not enhance the death of MEFs induced by PL plus CN‑A. These results suggest that the triple combined treatment with PL, CN‑A and SSZ is highly effective against pancreatic cancer.
New Search Next
- Mesalazine as a cause of fetal anemia and hydrops fetalis: A case report. [Case Reports]
- MMedicine (Baltimore) 2017; 96(50):e9277
- CONCLUSIONS: A causal relationship must be suspected between the fetal anemia and the maternal use of mesalazine. This fetal side-effect should be considered in pregnant women on mesalazine (and its prodrug sulfasalazine).