Therapeutic effects of phlorotannins in the treatment of neurodegenerative disorders

Phlorotannins are natural polyphenolic compounds produced by brown marine algae and are currently found in nutritional supplements. Although they are known to cross the blood–brain barrier, their neuropharmacological actions remain unclear. Here we review the potential therapeutic benefits of phlorotannins in the treatment of neurodegenerative diseases. In mouse models of Alzheimer’s disease, ethanol intoxication and fear stress, the phlorotannin monomer phloroglucinol and the compounds eckol, dieckol and phlorofucofuroeckol A have been shown to improve cognitive function. In a mouse model of Parkinson’s disease, phloroglucinol treatment led to improved motor performance. Additional neurological benefits associated with phlorotannin intake have been demonstrated in stroke, sleep disorders, and pain response. These effects may stem from the inhibition of disease-inducing plaque synthesis and aggregation, suppression of microglial activation, modulation of pro-inflammatory signaling, reduction of glutamate-induced excitotoxicity, and scavenging of reactive oxygen species. Clinical trials of phlorotannins have not reported significant adverse effects, suggesting these compounds to be promising bioactive agents in the treatment of neurological diseases. We therefore propose a putative biophysical mechanism of phlorotannin action in addition to future directions for phlorotannin research

bending resistance and cyclic fatigue resistance of waveone gold reciproc blue and hyflex edm instruments

Abstract Background/purpose Several single-file systems manufactured using different heat treatment and operated by different kinematics have been released. This study compared the bending resistance and cyclic fatigue resistance of three NiTi files, and examined their phase-transformation behavior. Materials and methods WaveOne Gold Primary (WOG), Reciproc Blue R25 (RPB), and HyFlex EDM OneFile (HDM) were tested (N = 40/instrument). A vertical load was applied to a point 3 mm from the tip, and the stress was measured until a displacement of 3 mm. Tests were conducted at either room temperature (RT: 22 °C) or body temperature (BT: 37 °C) (n = 10). Cyclic fatigue resistance tests were performed in an artificial canal, which had a curvature angle of 40° and a 5-mm radius. Tests were conducted at either RT or BT (n = 10). Instruments were operated according to the manufacturers' instructions. Test results were analyzed using the Kruskal–Wallis and the Mann–Whitney tests. Additional three instruments of each brand were subjected to differential scanning calorimetry (DSC). Results At RT the bending resistance of three files were not significantly different. However, at BT the bending resistance of RPB was highest, followed by WOG, and HDM (P  Conclusion HDM presented superior flexibility and cyclic fatigue resistance at BT

Compositional assessment of carotenoid-biofortified rice using substantial equivalence

One important aspect in assessing the safety of genetically modified (GM) crops for human consumption is characterizing their nutrient composition. A β-carotene-biofortified rice was generated by inserting phytoene synthase (Psy) and carotene desaturase (Crtl) genes isolated from Capsicum and Pantoea into the genome of a conventional variety of rice (Nakdongbyeo). Nutrients (proximates, amino acids, fatty acids, minerals, and vitamins), anti-nutritive components (trypsin inhibitors and phytic acid), and ferulic acid in GM rice were compared with those in the parent line Nakdongbyeo. Statistical comparisons to test for equivalence showed that all of the analyzed components in the GM plants were equivalent to those in its non-transgenic counterpart, and most nutritional components fell within the range of values reported for other commercial lines, indicating the safety of the GM plant.Key words: Genetically modified crop, β-Carotene, Transgenic rice, Nutrient, Substantial equivalence

Palliative radiotherapy in patients with a symptomatic pelvic mass of metastatic colorectal cancer

<p>Abstract</p> <p>Background</p> <p>To evaluate the palliative role of radiotherapy (RT) and define the effectiveness of chemotherapy combined with palliative RT (CCRT) in patients with a symptomatic pelvic mass of metastatic colorectal cancer.</p> <p>Methods</p> <p>From August 1995 to December 2007, 80 patients with a symptomatic pelvic mass of metastatic colorectal cancer were treated with palliative RT at Samsung Medical Center. Initial presenting symptoms were pain (68 cases), bleeding (18 cases), and obstruction (nine cases). The pelvic mass originated from rectal cancer in 58 patients (73%) and from colon cancer in 22 patients (27%). Initially 72 patients (90%) were treated with surgery, including 64 complete local excisions; 77% in colon cancer and 81% in rectal cancer. The total RT dose ranged 8-60 Gy (median: 36 Gy) with 1.8-8 Gy per fraction. When the <b>α/β </b>for the tumor was assumed to be 10 Gy for the biologically equivalent dose (BED), the median RT dose was 46.8 Gy₁₀(14.4-78). Twenty one patients (26%) were treated with CCRT. Symptom palliation was assessed one month after the completion of RT.</p> <p>Results</p> <p>Symptom palliation was achieved in 80% of the cases. During the median follow-up period of five months (1-44 months), 45% of the cases experienced reappearance of symptoms; the median symptom control duration was five months. Median survival after RT was six months. On univariate analysis, the only significant prognostic factor for symptom control duration was BED ≥40 Gy₁₀(p < 0.05), and CCRT was a marginally significant factor (p = 0.0644). On multivariate analysis, BED and CCRT were significant prognostic factors for symptom control duration (p < 0.05).</p> <p>Conclusions</p> <p>RT was an effective palliation method in patients with a symptomatic pelvic mass of metastatic colorectal cancer. For improvement of symptom control rate and duration, a BED ≥ 40 Gy₁₀is recommended when possible. Considering the low morbidity and improved symptom palliation, CCRT might be considered in patients with good performance status.</p

Paricalcitol Pretreatment Attenuates Renal Ischemia-Reperfusion Injury via Prostaglandin E 2

The protective mechanism of paricalcitol remains unclear in renal ischemia-reperfusion (IR) injury. We investigated the renoprotective effects of paricalcitol in IR injury through the prostaglandin E2 (PGE2) receptor EP4. Paricalcitol was injected into IR-exposed HK-2 cells and mice subjected to bilateral kidney ischemia for 23 min and reperfusion for 24 hr. Paricalcitol prevented IR-induced cell death and EP4 antagonist cotreatment offset these protective effects. Paricalcitol increased phosphorylation of Akt and cyclic AMP responsive element binding protein (CREB) and suppressed nuclear factor-κB (NF-κB) in IR-exposed cells and cotreatment of EP4 antagonist or EP4 small interfering RNA blunted these signals. In vivo studies showed that paricalcitol improved renal dysfunction and tubular necrosis after IR injury and cotreatment with EP4 antagonist inhibited the protective effects of paricalcitol. Phosphorylation of Akt was increased and nuclear translocation of p65 NF-κB was decreased in paricalcitol-treated mice with IR injury, which was reversed by EP4 blockade. Paricalcitol decreased oxidative stress and apoptosis in renal IR injury. Paricalcitol also attenuated the infiltration of inflammatory cells and production of proinflammatory cytokines after IR injury. EP4 antagonist abolished these antioxidant, anti-inflammatory, and antiapoptotic effects. The EP4 plays a pivotal role in the protective effects of paricalcitol in renal IR injury

Impact of multivessel versus single-vessel disease on the association between low diastolic blood pressure and mortality after acute myocardial infarction with revascularization

Background: Previous studies demonstrated a J-shaped relationship between low diastolic blood pressure (DBP) and adverse clinical outcomes in patients with acute myocardial infarction (AMI) that was sensitive to revascularization. Hypothesized herein, was that this relationship differs between patients with multivessel disease (MVD) and those with single-vessel disease due to differing degrees of myocardial ischemic burden. Methods: Among 9,983 AMI patients from the Korea Acute Myocardial Infarction Registry database who underwent percutaneous coronary intervention and were followed up for a median duration of 3.2 years, average on-treatment DBP was calculated at admission, discharge, and every scheduled visit and divided into these parameters: &lt; 70 mmHg, 70–74 mmHg, 75–79 mmHg, and ≥ 80 mmHg. The relationship between average on-treatment DBP and clinical outcomes including all-cause death, cardiovascular (CV) death, non-CV death, and hospitalization for heart failure was analyzed using the Cox regression models adjusted for clinical covariates. Results: In patients with MVD, all-cause death (hazard ratio [HR]: 1.47; 95% confidence interval [CI]: 1.06–2.04, p = 0.012) and CV death (HR: 1.59; 95% CI: 1.02–2.46, p = 0.027) were significantly increased in patients with a DBP &lt; 70 mmHg, showing a J-shaped relationship. However, these findings were not significant for single-vessel disease. On a sensitivity analysis excluding subjects with a baseline SBP &lt; 120 mmHg, an increased risk of a low DBP &lt; 70 mmHg remained in MVD. Conclusions: The J-shaped relationship between low DBP and adverse clinical outcomes in AMI patients who underwent revascularization persisted in MVD, which has a high ischemic burden. These high-risk patients require cautious treatment

The effect of periodontitis on recipient outcomes after kidney transplantation

Background Recent several reports have demonstrated that periodontitis is prevalent and adversely affects the survival in patients with chronic kidney disease (CKD) or end-stage kidney disease. However, its impact on transplant outcomes remains uncertain. Methods This retrospective cohort study included 136 and 167 patients, respectively, who underwent living donor kidney transplantation (KT) at Seoul National University Hospital from July 2012 to August 2016 and Korea University Hospital from April 2008 to October 2018. We divided patients into three groups according to stages of periodontitis based on a new classification system. Results Patients with severe periodontitis were older, had a higher prevalence of diabetes, a higher body mass index and C-reactive protein level, a lower cardiac output, and were more likely to be smokers, indicating its association with chronic systemic inflammation. After KT, stage IV periodontitis was independently associated with a lower incidence of acute T cell-mediated rejection, suggesting the possible effect of periodontitis on immune function. However, 1-year and 3-year estimated glomerular filtration rates were not different. Among the KT recipients followed up more than 3 years, new-onset cardiovascular disease occurred in nine patients, and coronary artery disease occurred more frequently in patients with stage IV periodontitis. However, diabetes was the independent predictor of new-onset coronary artery disease in multivariate logistic regression analysis. Conclusion Our findings showed that periodontitis might be an important player in determining posttransplant outcomes in recipients. Further interventional trials to test whether treating periodontitis could modify transplant outcome are needed