Pycnoporus sanguineus Polysaccharides as Reducing Agents: Self-Assembled Composite Nanoparticles for Integrative Diabetic Wound Therapy.

Purpose: Diabetic foot ulcers (DFU) are severe complications of diabetes, posing significant health and societal challenges. Elevated levels of reactive oxygen species (ROS) at the ulcer site hinder wound healing in most patients, while individuals with diabetes are also more susceptible to bacterial infections. This study aims to synthesize a comprehensive therapeutic material using polysaccharides from Pycnoporus sanguineus to promote DFU wound healing, reduce ROS levels, and minimize bacterial infections. Methods: Polysaccharides from P.sanguineus were employed as reducing and stabilizing agents to fabricate polysaccharide-based composite particles (PCPs) utilizing silver ions as templates. PCPs were characterized via UV-Vis, TEM, FTIR, XRD, and DLS. The antioxidant, antimicrobial, and cytotoxic properties of PCPs were assessed through in vitro and cellular experiments. The effects and mechanisms of PCPs on wound healing were evaluated using a diabetic ulcer mouse model. Results: PCPs exhibited spherical particles with an average size of 57.29±22.41 nm and effectively combined polysaccharides' antioxidant capacity with silver nanoparticles' antimicrobial function, showcasing synergistic therapeutic effects. In vitro and cellular experiments demonstrated that PCPs reduced cellular ROS levels by 54% at a concentration of 31.25 µg/mL and displayed potent antibacterial activity at 8 µg/mL. In vivo experiments revealed that PCPs enhanced the activities of superoxide dismutase (SOD) and catalase (CAT), promoting wound healing in DFUs and lowering the risk of bacterial infections. Conclusion: The synthesized PCPs offer a novel strategy for the comprehensive treatment of DFU. By integrating antioxidant and antimicrobial functions, PCPs effectively promote wound healing and alleviate patient suffering. The present study demonstrates a new strategy for the integrated treatment of diabetic wounds and expands the way for developing and applying the polysaccharide properties of P. sanguineus.

Effects of Acid-Reducing Agents on the Pharmacokinetics of Lazertinib in Patients with EGFR Mutation-Positive Advanced Non-Small-Cell Lung Cancer.

INTRODUCTION: Lazertinib is an irreversible, mutant-selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI). Co-administration of TKIs with acid-reducing agents (ARAs) can lead to potential drug-drug interactions, which decreases solubility and absorption of TKIs and is ultimately associated with reduced efficacy of TKIs. This retrospective analysis evaluated the effect of ARAs on the pharmacokinetics of lazertinib using data obtained from patients with advanced EGFR mutation-positive non-small-cell lung cancer. METHODS: In a total of 234 patients with lazertinib pharmacokinetics observed at steady state, dose-normalized (DN) area under the concentration-time curve (AUCss), maximum concentration (Cmax,ss), and/or trough concentration on day 15 (CD15) were compared between a group receiving ARA concomitantly for at least 4 days (ARA group) and another group not receiving ARA (non-ARA group) in a dose-proportional range. Additionally, a comparison of pharmacokinetic parameters at a therapeutic dose of 240 mg once daily was evaluated. RESULTS: Geometric mean ratios (GMRs) with 90% confidence intervals (CIs) of ARA group to non-ARA group for DNAUCss, DNCmax,ss, and DNCD15 at 40 mg to 320 mg once daily showing the dose proportionality were 0.8743 (0.7285-1.0493), 0.9035 (0.7482-1.0910), and 0.9126 (0.7364-1.1311), respectively. GMRs with 90% CIs for AUCss, Cmax,ss, and CD15 at 240 mg were 0.9136 (0.6637-1.2576), 0.9012 (0.6703-1.2116), and 0.8850 (0.6463-1.2118), respectively. CONCLUSION: All pharmacokinetic parameters were not significantly different between the two groups (p values > 0.05), indicating that co-administered ARAs did not significantly affect the steady state pharmacokinetics of lazertinib. Therefore, no dose adjustment of lazertinib is required in patients receiving concomitant ARAs. GOV IDENTIFIERS: NCT03046992, NCT04075396.

What Can Cellular Redox, Iron, and Reactive Oxygen Species Suggest About the Mechanisms and Potential Therapy of COVID-19?

Accumulating evidence suggests that there are important contributions to coronavirus disease (COVID-19) from redox imbalance and improperly coordinated iron, which cause cellular oxidative damage and stress. Cells have developed elaborate redox-dependent processes to handle and store iron, and their disfunction leads to several serious diseases. Cellular reductants are important as reactive oxygen species (ROS) scavengers and to power enzymatic repair mechanisms, but they also may help generate toxic ROS. These complicated interrelationships are presented in terms of a cellular redox/iron/ROS triad, including ROS generation both at improperly coordinated iron and enzymatically, ROS interconvertibility, cellular signaling and damage, and reductant and iron chelator concentration-dependent effects. This perspective provides the rational necessary to strongly suggest that COVID-19 disrupts this interdependent triad, producing a substantial contribution to the ROS load, which causes direct ROS-induced protein and phospholipid damage, taxes cellular resources and repair mechanisms, and alters cellular signaling, especially in the more critical acute respiratory distress syndrome (ARDS) phase of the infection. Specific suggestions for therapeutic interventions using reductants and chelators that may help treat COVID-19 are discussed.

Can reducing cosmetic substances help prevent chromate contact allergy?

BACKGROUND: Allergic contact dermatitis caused by Cr(VI) is often severe and difficult to treat. Therefore, primary prevention is a main goal but, secondary prevention can be valuable to ease the symptoms or prevent relapse of Cr(VI) dermatitis when sensitization has occurred. Barrier creams have been tried for many chemical substances, but until now there is no successful barrier cream against Cr(VI). OBJECTIVES: To investigate the ability of reducing agents to transform Cr(VI) into Cr(III) in an experimental situation, in order to find suitable chemicals to investigate for possible use in a barrier cream. METHODS: The capacity to reduce the amount of Cr(VI) was analyzed in water solutions of acetylcysteine, cysteine, dihydroxyacetone, glutathione, and iron sulfate heptahydrate. Thereafter the reducing capacity of acetylcysteine, dihydroxyacetone, glutathione, and iron sulfate on the amount of Cr(VI) in cement extracts was investigated. The content of Cr(VI) in the test solutions and in the cement extracts was estimated by the diphenyl carbazide spot test. RESULTS: All of the chosen chemicals reduced the amount of Cr(VI) in the test solutions and in the cement extracts to some extent. The reducing capacity was most prominent for iron sulfate. CONCLUSION: A reducing capacity was found for all chosen chemicals.

A long-term evaluation of experimental potassium oxalate concentrations on dentin hypersensitivity reduction: A triple-blind randomized clinical trial.

OBJECTIVE: The aim of this split-mouth, triple-blind, randomized clinical trial was to evaluate the long-term clinical efficacy of experimental potassium oxalate concentration (10%) in relieving dentin hypersensitivity (DH), after a four-session application protocol. METHODS: Potassium oxalate gels with different concentrations (5 and 10%) were randomly assigned to half of the 31 patients from the sample in a split-mouth design. The desensitizers were applied following a four-session protocol, one session every 48 h. The primary outcome was the assessment of pain level with the visual analog scale (VAS, 0-10), at baseline, immediately after each desensitizing session, and also after the seventh day and along 1-,3-, 6-, 9- and 12-months follow-ups. Statistical analyses were performed using Friedman repeated measures and Wilcoxon signed rank tests (α = 0.05). RESULTS: For both groups, the minimum of three sessions were required for the achievement of lower DH levels. Regardless of the concentration, the desensitizing effect was maintained all the way to the end of the 6-month follow-up. The 10%-potassium oxalate group was more effective for both 9 and 12-months follow-up periods (p < 0.001). No complications and adverse effects were observed. CONCLUSIONS: When a four-session protocol is applied, both concentrations of potassium oxalate (5 and 10%) proved to be effective on DH reduction for up to six months. However, the higher concentration promoted better long-term results. CLINICAL SIGNIFICANCE: The DH is an increasing condition in clinical practice, which affects the patient's life quality. This study provides primary clinical evidence, suggesting that multiple application sessions and higher concentrations of potassium oxalate may result in maintenance of the desensitizing effect for more extended periods. Trial registered under number: ClinicalTrials.gov NCT03083496.

The Impact of Dose and Simultaneous Use of Acid-Reducing Agents on the Effectiveness of Vemurafenib in Metastatic BRAF V600 Mutated Melanoma: a Retrospective Cohort Study.

BACKGROUND: The impact of dose and simultaneous use of acid-reducing agents (ARAs) on the effectiveness of vemurafenib is unknown. OBJECTIVES: To determine the association between progression of metastatic BRAF V600 mutated melanoma and (1) dose reductions of vemurafenib and (2) simultaneous use of vemurafenib and ARAs. PATIENT AND METHODS: A retrospective cohort study of 112 first-line vemurafenib users for melanoma was conducted (March 2012-March 2016), using electronic patient records and pharmacy dispensing records of a Dutch academic hospital. Cox regression analysis was used to estimate the risk of progression with full-dose (n = 64) versus reduced-dose vemurafenib (n = 48) and with simultaneous use of vemurafenib and ARAs (n = 35) versus vemurafenib alone (n = 77). Analyses were adjusted for age and sex. RESULTS: In total, disease progression occurred in 55% of treated patients on vemurafenib, with a median progression-free survival of 6.0 (95% confidence interval [CI] 5.0-6.9) months. Compared to patients on vemurafenib alone, there was no increased risk of progression among patients requiring vemurafenib at a reduced dose or among patients receiving simultaneous therapy with vemurafenib and ARAs. In addition, there was no increased risk of progression among patients who used reduced-dose vemurafenib and ARAs versus those receiving full-dose vemurafenib as sole therapy. However, a tendency for progression was observed among patients who used full-dose vemurafenib and ARAs versus full-dose vemurafenib alone (adjusted hazard ratio [HRa] 2.37; 95% CI 0.97-5.76), which became statistically significant in a sensitivity analysis (HRa 4.56; 95% CI 1.51-13.75). CONCLUSIONS: There was no association between the use of vemurafenib in a reduced dose or the simultaneous use of vemurafenib and ARAs and the risk of progression. In addition, there was no association between the simultaneous use of vemurafenib in a reduced dose and ARAs and the risk of progression. However, patients tolerating  full-dose vemurafenib simultaneously with ARAs might have an increased risk of progression. This finding requires prospective validation.

Predictive factors for the effect of acid-reducing agents on drug exposure.

OBJECTIVES: Acid-reducing agents (ARAs) may affect drug exposure for orally-administered drugs exhibiting pH-dependent solubility. The aim of this research was to investigate factors predicting the effect of ARAs on drug exposure. Dose (mg)/250 mL/solubility at neutral pH and ratio of solubility at acidic pH to that at neutral pH were investigated as potential factors. MATERIALS AND METHODS: Drug-drug interaction (DDI) study results with ARAs were selected based on PubMed search from 2007 to 2016 and novel drug approvals at the US Food and Drug Administration (FDA) from 2014 to 2016. For the selected drugs, solubility data at acidic and neutral pH were obtained from publications, FDA and European Medicines Agency (EMA) review report, and Japanese interview form. RESULTS: 32 DDI study results with ARAs from 27 drugs having solubility data were obtained. The effect of ARAs on the Cmax or AUC ratio% (with/without ARAs) decreased with the increasing values of both factors, but the ratio of solubility showed higher values of squared correlation coefficient R2 (0.75 - 0.78) than the dose (mg)/250 mL/solubility at neutral pH (0.48 - 0.59). CONCLUSION: Ratio of solubility at acidic pH to that at neutral pH was a good predictor to estimate the effect of ARAs on drug exposure. Prediction of the effect of ARAs on drug exposure using solubility data would help to consider the necessity and timing for conducting a dedicated DDI study with ARAs and contribute to efficient drug development.
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Clinical and instrumental evaluation of the efficacy of a new depigmenting agent containing a combination of a retinoid, a phenolic agent and an antioxidant for the treatment of solar lentigines.

BACKGROUND: Solar lentigines are common benign macular hyperpigmented lesions localized on sun-exposed areas. OBJECTIVE: To evaluate the efficacy and safety of a new depigmenting agent containing a retinoid (retinaldehyde), a new phenolic agent (4-(1-phenylethyl)-resorcinol) and a reducing agent (δ-tocopheryl-ß-D-glucopyranoside) in the topical treatment of solar lentigines. PATIENTS AND METHODS: Twenty patients with solar lentigines of the face and hands applied the depigmenting agent on each lentigo once daily for 12 weeks. The outcome was evaluated at 45 days (T1) and 3 months (T2) after the end of treatment compared to baseline (T0) by means of clinical evaluation, Mexameter® and Visioface devices for digital and ultraviolet computerized image analysis of skin color as well as in vivo reflectance confocal microscopy. RESULTS: Image analysis and confocal laser reflectance microscopy showed that hyperpigmentation was significantly reduced at T2 compared to baseline and to controls. CONCLUSION: The study treatment was well tolerated and showed significant improvement in the depigmentation of solar lentigines.

The effect of ozone on progression or regression of artificial caries-like enamel lesions in vitro.

OBJECTIVE: This study investigated the effect of ozone on the progression or regression of artificial caries-like lesions on enamel following pH cycling conditions in vitro. METHODS: A randomized, single blind, four legs design was used. 20 full thickness enamel slabs were allocated to each of the four groups which were: Fluoride free toothpaste (control); ozone alone; Reductant/Patient Kit alone and a combination of both ozone/Reductant/Patient Kit. Artificial lesions were created and subjected to the pH cycling regime for a 14 days period. Assessments were carried out before and after the pH cycling on the slabs using the microhardness testing and Quantitative Light-induced Fluorescence (QLF). RESULTS: Statistical significant difference were found in the percentage change of enamel microhardness before and after pH cycling between ozone/Reductant/Patient Kit group and all the other three groups of the study, as well as between Reductant/Patient Kit group and control. There was a statistical significant difference in the change of size and severity of the lesion (ΔQ) between all the three regimes tested and the control with a trend favouring ozone/Reductant/Patient Kit group. CONCLUSIONS: In our model, it appeared that ozone treatment alone is not effective in protecting the enamel against demineralisation or promoting remineralisation, unless combined with the Reductant/Patient Kit, which contain high levels of fluoride.

Reducing agents decrease the oxidative burst and improve clinical outcomes in COPD patients: a randomised controlled trial on the effects of sulphurous thermal water inhalation.

BACKGROUND: Inhalation of thermal water with antioxidant properties is empirically used for COPD. AIMS: To evaluate the effects of sulphurous thermal water (reducing agents) on airway oxidant stress and clinical outcomes in COPD. METHODS: Forty moderate-to-severe COPD patients were randomly assigned to receive 12-day inhalation with sulphurous thermal water or isotonic saline. Patients were assessed for superoxide anion (O2 (-)) production in the exhaled breath condensate and clinical outcomes at recruitment, the day after the conclusion of the 12-day inhalation treatment, and one month after the end of the inhalation treatment. RESULTS: Inhalation of reducing agents resulted in a significant reduction of O2 (-) production in exhaled breath condensate of COPD patients at the end of the inhalatory treatment and at followup compared to baseline. A significant improvement in the COPD assessment test (CAT) questionnaire was shown one month after the end of the inhalatory treatment only in patients receiving sulphurous water. CONCLUSION: Thermal water inhalation produced an in vivo antioxidant effect and improvement in health status in COPD patients. Larger studies are required in order to evaluate whether inhalation of thermal water is able to modify relevant clinical outcomes of the disease (the study was registered at clinicaltrial.gov-identifier: NCT01664767).

Protective effects of thymol on altered plasma lipid peroxidation and nonenzymic antioxidants in isoproterenol-induced myocardial infarcted rats.

This study evaluates the protective effects of thymol on altered plasma lipid peroxidation products and nonenzymic antioxidants in isoproterenol (ISO)-induced myocardial infarcted rats. Male albino Wistar rats were pre and cotreated with thymol (7.5 mg/kg body weight) daily for 7 days. ISO (100 mg/kg body weight) was subcutaneously injected into rats on 6th and 7th day to induce myocardial infarction (MI). Increased activity/levels of serum creatine kinase-MB (CK-MB), plasma thiobarbituric acid reactive substances, lipid hydroperoxides, and conjugated dienes with decreased levels of plasma reduced glutathione (GSH), vitamin C, and vitamin E were observed in ISO-induced myocardial infarcted rats. Pre and cotreatment with thymol (7.5 mg/kg body weight) showed normalized activity of serum CK-MB and near normalized levels of plasma lipid peroxidation products, reduced GSH, vitamin C, and vitamin E in myocardial infarcted rats. Furthermore, the in vitro study on reducing power of thymol confirmed its potent antioxidant action. Thus, thymol protects ISO-induced MI in rats by its antilipid peroxidation and antioxidant properties.

Evaluation of natural reductants protecting red blood cell membranes against oxidative damage in psoriatic patients.

OBJECTIVE: Psoriasis is a chronic skin disease and one of its main causes could be the oxidative stress. The use of natural reductants, in the treatment of several diseases, is well known but the effects of such treatments on the chronic psoriasis are not clear. The aim of this study is to evaluate the efficacy of the treatment with organic matrix, deriving from micro-flora, grown in shallow hyper thermal water tubs at Guardia Piemontese-Acquappesa (CS) Italy, in patients affected by moderate psoriasis. MATERIALS AND METHODS: The study has been performed on 10 subjects with plaque psoriasis and on 10 healthy control subjects. Clinical severity of psoriasis was determined according to Psoriasis and Severity Index (PASI). The treatment efficacy was observed trough the evaluation of membrane fluidity, by fluorescence polarization, lipid peroxidation, anion permeability and haemolysis in red blood cells. RESULTS: After 12 days of patients' treatment, a significant reduction of PASI score was observed, this result is supported by a significant improvement of all studied parameters. CONCLUSIONS: The results, obtained by the evaluation of all studied parameters in patients treated with the organic matrix, are evidence of the efficacy of this treatment, according to PASI evaluation. Thus our results, suggest that this therapeutic line may be useful in the treatment of moderate psoriatic lesions and also in improving the life quality of psoriatic patients.

Oxalic acid under adhesive restorations as a means to reduce dentin sensitivity: a four-month clinical trial.

The aim of this double-blind randomized controlled clinical trial was to evaluate the reduction of dentin sensitivity using an oxalate-based compound, placed under adhesive restorations, during a four-month period. One hundred three preoperatively sensitive teeth, on 36 patients aged 25-66 years (mean, 40.3±7), were included in the study. Group A (experimental) was treated with oxalic acid (BisBlock) before resin-based composite (RBC) restorations (n=52), and group B (control) was treated with distilled water before RBC restorations (n=51). The first tooth in each patient was randomly assigned to group A, and the second tooth received group B. Clinical evaluation as made by a thermal/evaporation test with an air syringe and measurement by visual analog scale (VAS) at baseline and four months after treatment. The results showed sensitivity reduction during the evaluation period (expressed in VAS values): group A, 7.6 to 0.8; group B, 7.3 to 2.6. We concluded from this study that both treatments reduced dentin sensitivity during the evaluation period, with group A showing significantly less dentin sensitivity after four months (p<0.05).

[The frequency of risk factors associated with obesity and being overweight in university students from Colima, Mexico]. / Frecuencia y factores de riesgo asociados a sobrepeso y obesidad en universitarios de Colima, México.

OBJECTIVE: Determining risk factor frequency regarding obesity and being overweight in university students. METHODS: A cross-sectional analytic study was carried out on 821 students from the University of Colima. Some variables analysed were age, gender, alcoholism, smoking and weight-control drug use. RESULTS: 821 students were included (380 male, 441 female), 20.9±2.5 average age. 27.8 % of males were overweight and 14.7 % suffered from obesity; this was 17 % and 5.2 % in females, respectively. Smoking (2.1 OR; 1.4-3.8 95 % CI; p=0.01) and alcoholism (2.1 OR; 1.2-3.6 95 % CI; p=0.003) were associated with being overweight and being obese. Weight-control drug use was a protective factor in both genders (0.4 OR; 0.2-0.8 95 % CI; p=0.01); diet control was only a protective factor in women (2.2. OR; 1.1-3.4 95 % CI; p=0.01). CONCLUSIONS: 31.6 % of university students were overweight and suffered from obesity. Smoking and alcoholism in males were associated with being overweight and suffering from obesity. Weight-control and diet-control drug use were protective factors.

Frecuencia y factores de riesgo asociados a sobrepeso y obesidad en universitarios de Colima, México / The frequency of risk factors associated with obesity and being overweight in university students from Colima, Mexico

Objetivo Determinar la frecuencia y factores de riesgo para sobrepeso y obesidad en jóvenes universitarios. Métodos Se realizó un estudio transversal analítico en 821 alumnos inscritos de la Universidad de Colima. Entre las variables analizadas se encuentran: edad, género, alcoholismo, tabaquismo y utilización de medicamentos o sustancias para control de peso. Resultados Se estudiaron 821 alumnos (380 hombres y 441 mujeres) con una edad promedio de 20,9±2,5 años. Las frecuencias de sobrepeso y obesidad en hombres fueron de 27,8 por ciento y 14,7 por ciento y en mujeres de 17 por ciento y 5,2 por ciento. En hombres el tabaquismo (OR 2,1, IC 95 por ciento 1,4-3,8;p=0,01) y etilismo (OR 2,1, IC 95 por ciento 1,2-3,6;p=0,003), estuvieron asociados a sobrepeso y obesidad. Fueron factores protectores en ambos géneros el uso de sustancias para control de peso (OR 0,4, IC 95 por ciento 0,2-0,8;p=0,01); mientras que el control dietético fue un factor protector sólo en las mujeres (OR 2,2, IC 95 por ciento 1,1- 3,4;p=0,01). Conclusiones En estudiantes universitarios, el 31,6 por ciento presentó sobrepeso y obesidad. En hombres, el tabaquismo y etilismo se asociaron a sobrepeso y obesidad. El uso de sustancias para bajar de peso y control dietético fueron factores protectores.

Objective Determining risk factor frequency regarding obesity and being overweight in university students. Methods A cross-sectional analytic study was carried out on 821 students from the University of Colima. Some variables analysed were age, gender, alcoholism, smoking and weight-control drug use. Results 821 students were included (380 male, 441 female), 20.9±2.5 average age. 27.8 percent of males were overweight and 14.7 percent suffered from obesity; this was 17 percent and 5.2 percent in females, respectively. Smoking (2.1 OR; 1.4-3.8 95 percent CI; p=0.01) and alcoholism (2.1 OR; 1.2-3.6 95 percent CI; p=0.003) were associated with being overweight and being obese. Weight-control drug use was a protective factor in both genders (0.4 OR; 0.2-0.8 95 percent CI; p=0.01); diet control was only a protective factor in women (2.2. OR; 1.1-3.4 95 percent CI; p=0.01). Conclusions 31.6 percent of university students were overweight and suffered from obesity. Smoking and alcoholism in males were associated with being overweight and suffering from obesity. Weight-control and diet-control drug use were protective factors.

[Recent advances in the study of bioreductive drugs targeted tumor hypoxia].

Tumor hypoxia is the necessary process in the development of solid tumors, which is the key factor for drug resistance, recurrence, attack and shift of tumor. Hypoxic tumor cells have a certain extent of tolerance to radiation and chemotherapy. Tumor hypoxia is an important target for medication therapy. In the recent years, the bioreductive drugs targeted tumor hypoxia has made great process in the treatment of tumors. The latest advances of bioreductive drugs targeted hypoxia were reviewed in this paper.

Reduction of prion infectivity and levels of scrapie prion protein by lithium aluminum hydride: implications for RNA in prion diseases.

Previous studies indicate that RNA may be required for proteinase-resistant prion protein (PrP) amplification and for infectious prion formation in vitro, suggesting that RNA molecules may function as cellular cofactors for abnormal PrP (PrPSc) formation and become part of the structure of the infectious agent. To address this question, we used chemicals that can cleave phosphodiester bonds of RNA and assessed their effects on the infectious agent. Lithium aluminum hydride, a reducing agent that can induce reductive cleavage of oxidized molecules such as carbonyls, carboxyl acids, esters, and phosphodiester bonds, did not affect cellular PrP degradation; however, it destroyed PrPSc, extended the scrapie incubation period, and markedly reduced total RNA concentrations. These results prompted us to investigate whether RNA molecules are cofactors for PrPSc propagation. RNase A treatment of partially purified PrP and of 263K scrapie brain homogenates was sufficient to increase the sensitivity of PrPSc to proteinase K degradation. This is the first evidence that suggests that RNA molecules are a component of PrPSc. Treatment with RNase A alone and PrP degradation by RNase A plus proteinase K in vitro, however, did not result in loss of scrapie infectivity compared with the effects of lithium aluminum hydride. Together, these data suggest that RNA molecules may be important for maintaining the structure of PrPSc and that oxidized molecules can be important in scrapie agent replication and prion infectivity.