Inhibition of amyloid-induced toxicity by ergothioneine in a transgenic Caenorhabditis elegans model.

The abnormal accumulation of ß-amyloid peptide (Aß) is recognized as a central component in the pathogenesis of Alzheimer disease. While many aspects of Aß-mediated neurotoxicity remain elusive, Aß has been associated with numerous underlying pathologies, including oxidative and nitrosative stress, inflammation, metal ion imbalance, mitochondrial dysfunction, and even tau pathology. Ergothioneine (ET), a naturally occurring thiol/thione-derivative of histidine, has demonstrated antioxidant and neuroprotective properties against various oxidative and neurotoxic stressors. This study investigates ET's potential to counteract Aß-toxicity in transgenic Caenorhabditis elegans overexpressing a human Aß peptide. The accumulation of Aß in this model leads to paralysis and premature death. We show that ET dose-dependently reduces Aß-oligomerization and extends the lifespan and healthspan of the nematodes.

Nationwide multi-institutional retrospective analysis of high-dose-rate brachytherapy combined with external beam radiotherapy for localized prostate cancer: An Asian Prostate HDR-BT Consortium.

PURPOSE: To report outcomes and risk factors of high-dose-rate (HDR) brachytherapy combined with external beam radiotherapy with or without androgen deprivation therapy (ADT) in prostate cancer patients. MATERIALS AND METHODS: This multi-institutional retrospective analysis comprised 3424 patients with localized prostate cancer at 16 Asian hospitals. One-thirds (27.7%) of patients received only neoadjuvant ADT, whereas almost half (49.5%) of patients received both neoadjuvant and adjuvant ADT. Mean duration of neoadjuvant and adjuvant ADT were 8.6 months and 27.9 months, respectively. Biochemical failure was defined by Phoenix ASTRO consensus. Biochemical control rate, clinical disease-free survival (cDFS), cause-specific survival, and overall survival (OS) were calculated. RESULTS: Median followup was 66 months. Ten-year biochemical control, cDFS, cause-specific survival, and OS rate were 81.4%, 81.0%, 97.2%, and 85.6%, respectively. Receiving both neoadjuvant and adjuvant ADT was detected as a favorable factor for biochemical control, cDFS, and OS, but pelvic irradiation was detected as an adverse factor for cause-specific survival, and OS. Ten-year cumulative rates of late Grade ≥2 genitourinary and gastrointestinal toxicities were 26.8% and 4.1%, respectively; receiving both neoadjuvant and adjuvant ADT was detected as a favorable factor for preventing both toxicities. CONCLUSIONS: HDR combined with external beam radiotherapy was an effective and safe treatment for localized prostate cancer. Combination of long-term ADT was suggested to be necessary, even for HDR brachytherapy, and was useful in suppressing late toxicities. Meanwhile, pelvic irradiation was suggested to have an adverse effect on OS of our study population.

Administration of Pure Ergothioneine to Healthy Human Subjects: Uptake, Metabolism, and Effects on Biomarkers of Oxidative Damage and Inflammation.

AIM: We investigated the uptake and pharmacokinetics of l-ergothioneine (ET), a dietary thione with free radical scavenging and cytoprotective capabilities, after oral administration to humans, and its effect on biomarkers of oxidative damage and inflammation. RESULTS: After oral administration, ET is avidly absorbed and retained by the body with significant elevations in plasma and whole blood concentrations, and relatively low urinary excretion (<4% of administered ET). ET levels in whole blood were highly correlated to levels of hercynine and S-methyl-ergothioneine, suggesting that they may be metabolites. After ET administration, some decreasing trends were seen in biomarkers of oxidative damage and inflammation, including allantoin (urate oxidation), 8-hydroxy-2'-deoxyguanosine (DNA damage), 8-iso-PGF2α (lipid peroxidation), protein carbonylation, and C-reactive protein. However, most of the changes were non-significant. INNOVATION: This is the first study investigating the administration of pure ET to healthy human volunteers and monitoring its uptake and pharmacokinetics. This compound is rapidly gaining attention due to its unique properties, and this study lays the foundation for future human studies. CONCLUSION: The uptake and retention of ET by the body suggests an important physiological function. The decreasing trend of oxidative damage biomarkers is consistent with animal studies suggesting that ET may function as a major antioxidant but perhaps only under conditions of oxidative stress. Antioxid. Redox Signal. 26, 193-206.

Ergothioneine levels in an elderly population decrease with age and incidence of cognitive decline; a risk factor for neurodegeneration?

Ergothioneine (ET), a naturally occurring thione, can accumulate in the human body at high concentrations from diet. Following absorption via a specific transporter, OCTN1, ET may accumulate preferentially in tissues predisposed to higher levels of oxidative stress and inflammation. Given its potential cytoprotective effects, we examined how ET levels change with age. We found that whole blood ET levels in elderly individuals decline significantly beyond 60 years of age. Additionally, a subset of these subjects with mild cognitive impairment had significantly lower plasma ET levels compared with age-matched subjects. This decline suggests that deficiency in ET may be a risk factor, predisposing individuals to neurodegenerative diseases.

Does radiotherapy increase oxidative stress? A study with nasopharyngeal cancer patients revealing anomalies in isoprostanes measurements.

This study aimed to examine if exposure to ionizing radiation during clinical radiotherapy (RT) causes increased oxidative damage. Seven patients with nasopharyngeal cancer (NPC) who underwent RT took part in this controlled-trial study. Blood and urine samples were obtained for F(2)-isoprostanes (F(2)-IsoPs) measurement. Urinary F(2)-IsoPs levels were elevated pre-treatment and remained high (but did not increase) during treatment, but decreased to the normal range after treatment. Plasma F(2)-IsoPs decreased significantly after the start of treatment before rising midway through treatment. Levels decreased significantly to below baseline following treatment. However, the patients were observed to have substantially lower levels of plasma esterified arachidonic acid (AA) residues than controls. The data shows that NPC is associated with elevated F(2)-isoprostanes in urine and in plasma after correction for decreased AA levels. RT did not increase these levels and, indeed, was associated with falls in F(2)-IsoPs. The validity and usefulness of correction of plasma F(2)-IsoPs for lowered AA levels is discussed.

A study of complications arising from different methods of anesthesia used in high-dose-rate brachytherapy for cervical cancer.

The purpose of this report is to review the complications related to different methods of anesthesia for high-dose-rate (HDR) brachytherapy for cervical carcinoma. All patients diagnosed with cervical cancer between 1999 and 2002 treated with 3-channel HDR brachytherapy were entered. Complications due to anesthesia for each fraction of brachytherapy were graded using the Common Toxicity Criteria. Eighty-four fractions of brachytherapy were delivered to 18 patients: 19 fractions with patients under general anesthesia (GA), 41 with patients under topical anesthesia and sedation, 5 with patients under paracervical nerve block, and 19 with patients under conscious sedation. Thirteen complications were reported: 12 related to GA and 1 due to paracervical nerve block. Of complications due to GA, 7 were grade 1 and 5 were grade 2. The complication due to paracervical nerve block (seizure) was grade 3. GA had significantly more complications than topical anesthesia or conscious sedation (both P < 0.001). HDR brachytherapy for cervical cancer under GA has significantly more complications than other methods. Given the increasing use of fractionated 3-channel brachytherapy, further investigation of risks and benefits of anesthetic techniques is required.