Comparison of High- and Low-Dose Rivaroxaban Regimens in Elderly East Asian Patients With Atrial Fibrillation.

BACKGROUND: In the Rivaroxaban Once-daily oral direct factor Xa inhibition Compared with vitamin K antagonism for prevention of stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) trial, rivaroxaban 20 mg was the on-label dose, and the dose-reduction criterion for rivaroxaban was a creatinine clearance of < 50 mL/min. Some Asian countries are using reduced doses label according to the J-ROCKET AF trial. The aim of this study was to assess the safety and efficacy of a high-dose rivaroxaban regimen (HDRR, 20/15 mg) and low-dose rivaroxaban regimen (LDRR, 15/10 mg) among elderly East Asian patients with atrial fibrillation (AF) in real-world practice. METHODS: This study was a multicenter, prospective, non-interventional observational study designed to evaluate the efficacy and safety of rivaroxaban in AF patients > 65 years of age with or without renal impairment. RESULTS: A total of 1,093 patients (mean age, 72.8 ± 5.8 years; 686 [62.9%] men) were included in the analysis, with 493 patients allocated to the HDRR group and 598 patients allocated to the LDRR group. A total of 765 patients received 15 mg of rivaroxaban (203 in the HDRR group and 562 in the LDRR group). There were no significant differences in the incidence rates of major bleeding (adjusted hazard ratio [HR], 0.64; 95% confidential interval [CI], 0.21-1.93), stroke (adjusted HR, 3.21; 95% CI, 0.54-19.03), and composite outcomes (adjusted HR, 1.13; 95% CI, 0.47-2.69) between the HDRR and LDRR groups. CONCLUSION: This study revealed the safety and effectiveness of either dose regimen of rivaroxaban in an Asian population for stroke prevention of AF. Considerable numbers of patients are receiving LDRR therapy in real-world practice in Asia. Both regimens were safe and effective for these patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04096547.

Oxaliplatin-based adjuvant chemotherapy rather than fluorouracil-based chemotherapy in rectal cancer is more efficient to decrease distant metastasis and increase survival after preoperative chemoradiotherapy and surgery: a meta-analysis.

PURPOSE: The standard treatment of stage II-III rectal cancer is preoperative chemoradiotherapy (CRT), followed by total mesorectal excision (TME). However, the rate of metastasis is still high following this treatment. Therefore, several adjuvant chemotherapy studies have been conducted on reducing subsequent metastases and increasing survival, although there are still no definite conclusions. METHODS: We searched for published prospective randomized controlled trials comparing adjuvant chemotherapy regimens following standard preoperative CRT and curative surgery in stage II-III rectal cancer. We systematically searched Medline, Embase, and the Cochrane Library for relevant trials done from January 2004 to January 2021. Review Manager (RevMan, version 5.3) was used to analyze the data. RESULTS: We initially searched 1955 studies. We screened and carefully selected four randomized controlled trials with 2897 patients. Compared to the 5-FU-based regimen group, the oxaliplatin-added regimen group attained a higher 3-year locoregional control rate (relative risk [RR] of 0.64, 95% confidence interval [CI], 0.48-0.86; p = 0.003) and 3-year distant metastasis control rate (RR of 0.82, 95% CI, 0.71-0.95; p = 0.007). The oxaliplatin-added regimen group had significantly increased 3-year disease-free survival with a hazard ratio (HR) of 0.85 (95% CI: 0.74-0.97, p = 0.020), but not overall survival (p = 0.740). Grade 3 or higher acute toxicity rates did not differ between the two groups (p = 0.190). CONCLUSION: The addition of oxaliplatin to adjuvant therapy for stage II-III rectal cancer following preoperative CRT and TME may increase disease-free survival without significant increases in toxicity, but not overall survival.

Anti-fibrotic effect of pycnogenol® in a polyhexamethylene guanidine-treated mouse model.

Pulmonary fibrosis (PF) is a respiratory disease that causes serious respiratory problems. The effects of French marine pine bark extract (Pycnogenol®), with antioxidant and anti-inflammatory properties, were investigated on lung fibrosis in polyhexamethylene guanidine (PHMG)-treated mice. Mice were separated into four groups (n = 6): vehicle control (VC, saline 50 µl); PHMG (1.1 mg/kg); PHMG + Pycnogenol® (0.3 mg/kg/day); and PHMG + Pycnogenol® (1 mg/kg/day). PF was induced via intratracheal instillation of PHMG. Treatment with PHMG decreased body weight and increased lung weight, both of which were improved by treatment with PHMG + Pycnogenol® (1 mg/kg). Enzyme-linked immunosorbent assay, western blotting, and PCR revealed that Pycnogenol® attenuated PHMG-induced increase in inflammatory cytokines and fibrosis-related factors in a dose-dependent manner. Finally, histopathological analysis revealed reduced inflammation/fibrosis in the PHMG + Pycnogenol® (1 mg/kg) group. Collectively, the results indicate that Pycnogenol® can be used to treat PF as it hinders fibrosis progression by inhibiting inflammatory responses in the lungs of PHMG-treated mice.

4-Hydroxycinnamic acid suppresses airway inflammation and mucus hypersecretion in allergic asthma induced by ovalbumin challenge.

In this study, we investigated whether 4-hydroxycinnamic acid (HA) has a palliative effect on asthmatic inflammatory responses using a mouse model of ovalbumin (OVA)-induced allergic asthma. The mice were divided into five groups, each consisting of seven females (normal control phosphate-buffered saline); OVA (OVA sensitization/challenge); dexamethasone (DEX, OVA sensitization/challenge + dexamethasone 3 mg/kg); HA-10 and HA-20 OVA sensitization/challenge + HA 10 and 20 mg/kg, respectively). Mice treated with HA showed a reduction in airway hyperresponsiveness and in the number of inflammatory cells in bronchoalveolar lavage fluid (BALF) compared with asthmatic control. HA treatment also reduced the levels of interleukin (IL)-5 and IL-13 in BALF and of OVA-specific immunoglobulin E in the serum compared with asthmatic control. HA treatment relieved airway inflammation and mucus overproduction caused by OVA exposure. Additionally, HA inhibited the increases in levels of nuclear factor kappa B, inducible nitric oxide synthase, and cyclooxygenase-2 that normally occur after OVA exposure. HA treatment also reduced the activity and protein level of matrix metalloproteinase-9. Taken together, HA effectively suppressed asthmatic airway inflammation and mucus production caused by OVA exposure. These findings indicate that HA has the potential to be used as a therapeutic agent for asthma.

Molecular level determination of water accommodated fraction with embryonic developmental toxicity generated by photooxidation of spilled oil.

In this study, developmental toxicity was increased as the oil was further degraded under natural sunlight. Detailed chemical composition of the degraded oils was examined by use of gas chromatography (GC) and (-) electrospray ionization ultrahigh resolution mass spectrometry (UHR-MS). Baseline toxicities were estimated based on chemical activities of polycyclic aromatic hydrocarbons, and it was obvious that the predicted chemical activities can not explain increased toxicity alone. However, the ultrahigh resolution mass spectral abundance of polar compounds including O3 and O4 class compounds was significantly increased as the photodegradation proceeded. Further examination of double bond equivalence values of the compounds showed that polar compounds with both non-aromatic and aromatic polar structures were increased. Statistical analysis indicates that the increased toxicity can be well explained by the increased polar compounds. Therefore, the oxygenated compounds identified in this study can play an important role in toxicity of degraded oils.

Characterization and Management of Arrhythmic Events in Young Patients With Brugada Syndrome.

BACKGROUND: Information on young patients with Brugada syndrome (BrS) and arrhythmic events (AEs) is limited. OBJECTIVES: The purpose of this study was to describe their characteristics and management as well as risk factors for AE recurrence. METHODS: A total of 57 patients (age ≤20 years), all with BrS and AEs, were divided into pediatric (age ≤12 years; n = 26) and adolescents (age 13 to 20 years; n = 31). RESULTS: Patients' median age at time of first AE was 14 years, with a majority of males (74%), Caucasians (70%), and probands (79%) who presented as aborted cardiac arrest (84%). A significant proportion of patients (28%) exhibited fever-related AE. Family history of sudden cardiac death (SCD), prior syncope, spontaneous type 1 Brugada electrocardiogram (ECG), inducible ventricular fibrillation at electrophysiological study, and SCN5A mutations were present in 26%, 49%, 65%, 28%, and 58% of patients, respectively. The pediatric group differed from the adolescents, with a greater proportion of females, Caucasians, fever-related AEs, and spontaneous type-1 ECG. During follow-up, 68% of pediatric and 64% of adolescents had recurrent AE, with median time of 9.9 and 27.0 months, respectively. Approximately one-third of recurrent AEs occurred on quinidine therapy, and among the pediatric group, 60% of recurrent AEs were fever-related. Risk factors for recurrent AE included sinus node dysfunction, atrial arrhythmias, intraventricular conduction delay, or large S-wave on ECG lead I in the pediatric group and the presence of SCN5A mutation among adolescents. CONCLUSIONS: Young BrS patients with AE represent a very arrhythmogenic group. Current management after first arrhythmia episode is associated with high recurrence rate. Alternative therapies, besides defibrillator implantation, should be considered.

Modificated Mahuang-Tang, a traditional herbal medicine suppresses inflammatory responses induced by cigarette smoke in human airway epithelial cell and mice.

BACKGROUND: Cigarette smoke (CS) is a major contributor to the high incidence of chronic obstructive pulmonary disease (COPD) featured as chronic inflammation and airway obstruction. Mahuang-Tang is a traditional polyherbal mixture composed of four different herbs. It is widely used in Asia as a remedy for allergic reaction and inflammation. PURPOSE: We investigated the effects of a modificated Mahuang-Tang water extract (MTWE) against airway inflammation caused by CS and lipopolysaccharide (LPS) in mice and cigarette smoke condensate (CSC)-stimulated NCI-H292 cells. METHODS: CS exposed to animals for 1 h per day from day 1 to day 7 and treated with LPS intranasally on day 4. One hour before CS exposure, animals were received MTWE (50 or 100 mg/kg) by oral gavage. Inflammatory cell count and cytokines levels were measured in the bronchoalveolar lavage fluid. Expression levels of matrix metalloprotease-9 (MMP-9) and extracellular signal-regulated kinase (Erk) were analyzed by western blotting. RESULTS: MTWE markedly decreased the neutrophil and other inflammatory cell counts in the bronchoalveolar lavage fluid and reduced proinflammatory mediators as evidenced by the decreases in inflammatory cell recruitment in lung tissue. Furthermore, MTWE meaningfully declined MMP-9 expression and reduced the Erk phosphorylation, caused by the CS and LPS exposure. In in vitro experiments, MTWE suppressed the elevated expression of proinflammatory cytokines induced by CSC treatment. MTWE reduced Erk phosphorylation and MMP-9 expression in CSC-stimulated H292 cells. CONCLUSION: Overall, MTWE effectively inhibited the pulmonary inflammation and MMP-9 expression caused by the CS and LPS exposure, which was closely involved in suppression of Erk phosphorylation. These results suggest that MTWE possesses a potential for the treatment of COPD.

S-Allyl cysteine reduces eosinophilic airway inflammation and mucus overproduction on ovalbumin-induced allergic asthma model.

S-Allyl cysteine (SAC) is an active component in garlic and has various pharmacological effects, such as anti-inflammatory, anti-oxidant, and anti-cancer activities. In this study, we explored the suppressive effects of SAC on allergic airway inflammation induced in an ovalbumin (OVA)-induced asthma mouse model. To induce asthma, BALB/c mice were sensitized to OVA on days 0 and 14 by intraperitoneal injection and exposed to OVA from days 21 to 23 using a nebulizer. SAC was administered to mice by oral gavage at a dose of 10 or 20 mg/kg from days 18 to 23. SAC significantly reduced airway hyperresponsiveness, inflammatory cell counts, and Th2 type cytokines in bronchoalveolar lavage fluid induced by OVA exposure, which was accompanied by reduced serum OVA-specific immunoglobulin E. In histological analysis of the lung tissue, administration of SAC reduced inflammatory cell accumulation into lung tissue and mucus production in airway goblet cells induced by OVA exposure. Additionally, SAC significantly decreased MUC5AC expression and nuclear factor-κB phosphorylation induced by OVA exposure. In summary, SAC effectively suppressed allergic airway inflammation and mucus production in OVA-challenged asthmatic mice. Therefore, SAC shows potential for use in treating allergic asthma.

Adjuvant Chemotherapy in Rectal Cancer Patients Treated With Preoperative Chemoradiation and Total Mesorectal Excision: A Multicenter and Retrospective Propensity-Score Matching Study.

PURPOSE: The role of adjuvant chemotherapy after preoperative chemoradiation therapy (CRT) and curative surgery in rectal cancer has yet to be definitely determined. We performed a retrospective and multicenter study to evaluate whether adjuvant chemotherapy (AC) could reduce recurrence and improve survival in locally advanced rectal cancer. METHODS AND MATERIALS: We analyzed data from 8 tertiary institutions for 1442 patients with rectal cancer who underwent preoperative CRT and total mesorectal excision. Patients were classified into 2 groups: the AC group (patients who received chemotherapy after surgery) and the observation group (those who did not receive chemotherapy after surgery). Propensity-score matching was used to assess the exact role of AC. The AC group was then subdivided to investigate the impact of adding oxaliplatin to 5-fluorouracil (5-FU). Group 1 was treated with 5-FU/folinic acid or capecitabine without oxaliplatin, and group 2 received 5-FU/folinic acid or capecitabine with oxaliplatin. RESULTS: The 3-year relapse-free survival rates in the AC and observation groups were 85.9% and 84.3%, respectively (P = .532). The 3-year overall survival rates in the AC and observation groups were 94.9% and 89.9%, respectively (P = .123). The rates of locoregional recurrence (2.2% vs 3.2%, P = .294) and distant metastasis (12.4% vs 12.9%, P = .927) at 3 years were not significantly different between the two groups. The 3-year relapse-free survival rates of group 1 and group 2 were 71.5% and 74.8%, respectively (P = .426). The 3-year overall survival rates of group 1 and group 2 were 89.9% and 96.5%, respectively (P = .102). CONCLUSIONS: This multicenter study found insufficient evidence to support the use of 5-FU-based AC after preoperative CRT and curative surgery in rectal cancer.

Characteristics of early repolarization parameters and prognostic implications in the general ambulatory Korean population.

BACKGROUND: We tested a hypothesis that the 2 fundamental components of early repolarization (ER), J wave and ST elevation (STE) might have different prevalence and prognostic implications. METHODS: The study population comprised 26,345 general ambulatory Korean subjects (mean 48.0±10.2years old, 53.2% male) who underwent medical checkups from January 2002 to December 2002. ER was found in 2950 subjects (11.2%), who were divided into 3 groups (J [J wave only, n=1874, 7.1%], JST [both J wave and STE, n=489, 1.8%], and ST [STE only, n=587, 2.3%]). RESULTS: The prevalence of STE decreased with age, whereas J waves remained at a constant level in all age groups. The most common pattern of ER was the J pattern, with a horizontal/descending ST segment in the inferior leads; in lateral precordial leads, ST or JST patterns with ascending ST segments were more common. During the mean follow-up of 126.0±11.1months, a total of 710 subjects died (2.7%). Subjects in the J group were at higher risk (Hazard ratio 1.60, 95% confidence interval 1.27-2.01, p<0.001), while those in the JST and ST groups showed similar survival outcomes compared to controls without J waves or STE. CONCLUSIONS: J waves and STE showed different age and lead distributions and prognostic implications. The presence of the J wave itself was associated with a higher relative risk of mortality. However, due to the low event rate, its clinical significance appears to be limited.

Analysis of Geometric Shifts and Proper Setup-Margin in Prostate Cancer Patients Treated With Pelvic Intensity-Modulated Radiotherapy Using Endorectal Ballooning and Daily Enema for Prostate Immobilization.

We evaluate geometric shifts of daily setup for evaluating the appropriateness of treatment and determining proper margins for the planning target volume (PTV) in prostate cancer patients.We analyzed 1200 sets of pretreatment megavoltage-CT scans that were acquired from 40 patients with intermediate to high-risk prostate cancer. They received whole pelvic intensity-modulated radiotherapy (IMRT). They underwent daily endorectal ballooning and enema to limit intrapelvic organ movement. The mean and standard deviation (SD) of daily translational shifts in right-to-left (X), anterior-to-posterior (Y), and superior-to-inferior (Z) were evaluated for systemic and random error.The mean ±â€ŠSD of systemic error (Σ) in X, Y, Z, and roll was 2.21 ±â€Š3.42 mm, -0.67 ±â€Š2.27 mm, 1.05 ±â€Š2.87 mm, and -0.43 ±â€Š0.89°, respectively. The mean ±â€ŠSD of random error (δ) was 1.95 ±â€Š1.60 mm in X, 1.02 ±â€Š0.50 mm in Y, 1.01 ±â€Š0.48 mm in Z, and 0.37 ±â€Š0.15° in roll. The calculated proper PTV margins that cover >95% of the target on average were 8.20 (X), 5.25 (Y), and 6.45 (Z) mm. Mean systemic geometrical shifts of IMRT were not statistically different in all transitional and three-dimensional shifts from early to late weeks. There was no grade 3 or higher gastrointestinal or genitourianry toxicity.The whole pelvic IMRT technique is a feasible and effective modality that limits intrapelvic organ motion and reduces setup uncertainties. Proper margins for the PTV can be determined by using geometric shifts data.

Triglyceride-Lowering Effects of Two Probiotics, Lactobacillus plantarum KY1032 and Lactobacillus curvatus HY7601, in a Rat Model of High-Fat Diet-Induced Hypertriglyceridemia.

The triglyceride-lowering effect of probiotics Lactobacillus plantarum KY1032 and Lactobacillus curvatus HY7601 were investigated. Male SD Wistar rats were randomly divided into three groups and fed high-fat diet (HFD), HFD and probiotics (5 X 10(9) CFU/day of L. plantarum KY1032 and 5 X 10(9) CFU/day of L. curvatus HY7601), or normal diet for 6 weeks. Probiotic treatment significantly lowered the elevated plasma triglyceride and increased plasma free fatty acid, glycerol, and plasma apolipoprotein A-V (ApoA-V) levels. The probiotic-treated group showed elevated hepatic mRNA expression of PPARα, bile acid receptor (FXR), and ApoA-V. These results demonstrate that L. plantarum KY1032 and L. curvatus HY7601 lower triglycerides in hypertriglyceridemic rats by upregulating ApoA-V, PPARα, and FXR.

Apple Pomace Extract Improves Endurance in Exercise Performance by Increasing Strength and Weight of Skeletal Muscle.

Ursolic acid is a lipophilic pentacyclic triterpenoid found in many fruits and herbs and is used in several herbal folk medicines for diabetes. In this study, we evaluated the effects of apple pomace extract (APE; ursolic acid content, 183 mg/g) on skeletal muscle atrophy. To examine APE therapeutic potential in muscle atrophy, we investigated APE effects on the expression of biomarkers associated with muscle atrophy and hypertrophy. We found that APE inhibited atrophy, while inducing hypertrophy in C2C12 myotubes by decreasing the expression of atrophy-related genes and increasing the expression of hypertrophy-associated genes. The in vivo experiments using mice fed a diet with or without APE showed that APE intake increased skeletal muscle mass, as well as grip strength and exercise capacity. In addition, APE significantly improved endurance in the mice, as evidenced by increased exhaustive running time and muscle weight, and reduced the expression of the genes involved in the development of muscle atrophy. APE also decreased the concentration of serum lactate and lactate dehydrogenase, inorganic phosphate, and creatinine, the indicators of accumulated fatigue and exercise-induced stress. These results suggest that APE may be useful as an ergogenic functional food or dietary supplement.

GRP78 Protein Expression as Prognostic Values in Neoadjuvant Chemoradiotherapy and Laparoscopic Surgery for Locally Advanced Rectal Cancer.

PURPOSE: We investigated the relationships between biomarkers related to endoplasmic reticulum stress proteins (glucose-regulated protein of molecular mass 78 [GRP78] and Cripto-1 [teratocarcinoma-derived growth factor 1 protein]), pathologic response, and prognosis in locally advanced rectal cancer. MATERIALS AND METHODS: All clinical stage II and III rectal cancer patients received 50.4 Gy over 5.5 weeks, plus 5-fluorouracil (400 mg/m(2)/day) and leucovorin (20 mg/m(2)/day) bolus on days 1 to 5 and 29 to 33, and surgery was performed at 7 to 10 weeks after completion of all therapies. Expression of GRP78 and Cripto-1 proteins was determined by immunohistochemistry and was assessed in 101 patients with rectal cancer treated with neoadjuvant chemoradiotherapy (CRT). RESULTS: High expression of GRP78 and Cripto-1 proteins was observed in 86 patients (85.1%) and 49 patients (48.5%), respectively. Low expression of GRP78 protein was associated with a significantly high rate of down staging (80.0% vs. 52.3%, respectively; p=0.046) and a significantly low rate of recurrence (0% vs. 33.7%, respectively; p=0.008) compared with high expression of GRP78 protein. Mean recurrence-free survival according to GRP78 expression could not be estimated because the low expression group did not develop recurrence events but showed a significant correlation with time to recurrence, based on the log rank method (p=0.007). GRP78 also showed correlation with overall survival, based on the log rank method (p=0.045). CONCLUSION: GRP78 expression is a predictive and prognostic factor for down staging, recurrence, and survival in rectal cancer patients treated with 5-fluorouracil and leucovorin neoadjuvant CRT.

Cynandione A attenuates lipopolysaccharide-induced production of inflammatory mediators via MAPK inhibition and NF-κB inactivation in RAW264.7 macrophages and protects mice against endotoxin shock.

Cynanchum wilfordii has been traditionally used in eastern Asia for the treatment of various diseases such as gastrointestinal diseases and arteriosclerosis. Cynandione A (CA), an acetophenone, is one of major constituents from roots of C. wilfordii. In the present study, the anti-inflammatory activities of CA were investigated in lipopolysaccharide (LPS)-treated RAW264.7 macrophages and LPS-administered C57BL/6 N mice. CA significantly decreased LPS-induced production of nitric oxide and prostaglandin E2 in a dose-dependent manner, while CA up to 200 µM did not exhibit cytotoxic activity. Our data also showed that CA significantly attenuated expression of iNOS and COX-2 in LPS-stimulated macrophages. CA inhibited phosphorylation of IκB-α and MAP kinases such as ERK and p38. Furthermore, we demonstrated that CA inhibited translocation of NF-κB to the nucleus, transcription of the NF-κB minimal promoter and NF-κB DNA binding activity. Administration of CA significantly decreased the plasma levels of pro-inflammatory cytokines such as TNF-α, IL-6, and IL-1ß in LPS-injected mice and improved survival of septic mice with lethal endotoxemia. These results demonstrate that CA has effective inhibitory effects on production of inflammatory mediators via suppressing activation of NF-κB and MAPK signaling pathways, suggesting that CA may be used as a potential anti-inflammatory agent for the prevention and treatment of inflammatory diseases.

Paced QRS axis as a predictor of pacing-induced left ventricular dysfunction.

PURPOSE: The selection of the optimal right ventricular (RV) pacing site remains unclear. We hypothesized that a normal paced QRS axis would provide a physiological ventricular activation and lead to a better long-term outcome. METHODS: We evaluated 187 patients who underwent a permanent pacemaker implantation and were dependent on RV pacing. The pacing sites were classified as the apex and non-apex according to the chest radiography. A paced QRS axis was defined as that between -30° and 90°. Preservation of the left ventricular (LV) systolic function was defined as that with a <10 % decrease in the ejection fraction after the pacemaker implantation. RESULTS: The median follow-up period was 5.8 years (interquartile 3.9-9.0). Radiographically, the RV leads were located in the apex (n = 148, 79 %) or non-apex (n = 39, 21 %). In the electrocardiogram, normal paced and abnormal paced QRS axes were observed in 28 patients (15 %) and 159 patients (85 %), respectively. The LV ejection fraction was decreased in the patients with an abnormal paced QRS axis (-10 ± 10 %, P < 0.001), but not in those with a normal axis (0 ± 6 %, P = 0.80). The electrocardiographic determinant differentiated a preserved LV function (95 % vs. 35 %, log-rank P = 0.04). Among the patients with radiographically non-apical pacing, a normal paced QRS axis was an additional meaningful predictor of a preserved LV function after the pacemaker implantation (95 % vs. 24 %, log-rank P = 0.002). CONCLUSION: Compared with the radiographic method, a normal paced QRS axis was associated with a preserved LV function.

Ameliorative effects of pine bark extract on spermatotoxicity by α-chlorohydrin in rats.

We investigated the protective effects of pine bark extract (Pycnogenol®, PYC, Horphag Research Ltd., Route de Belis, France) against α-chlorohydrin (ACH)-induced spermatotoxicity in rats. Rats were orally administered ACH (30 mg/kg/day) with or without PYC (20 mg/kg/day) for 7 days. Administration of ACH significantly decreased sperm motility. α-Chlorohydrin also caused histopathological alterations and apoptotic changes in caput epididymides. An increased malondialdehyde concentration and decreased glutathione content, as well as catalase and glutathione peroxidase activities were also found. In contrast, PYC treatment significantly prevented ACH-induced spermatotoxicity, including decreased sperm motility, histopathological lesions, and apoptotic changes in the caput epididymis. Pycnogenol® also had an antioxidant benefit by decreasing malondialdehyde and increasing levels of the antioxidant glutathione and the activities of the antioxidant enzymes catalase and peroxidase in epididymal tissues. These results indicate that PYC treatment attenuated ACH-induced spermatotoxicity through antioxidant and antiapoptotic effects.

Non-oliguric hyperkalemia in extremely low birth weight infants.

PURPOSE: It is to examine clinical manifestations, early biochemical indicators, and risk factors for non-oliguric hyperkalemia (NOHK) in extremely low birth weight infants (ELBWI). MATERIALS AND METHODS: We collected clinical and biochemical data from 75 ELBWI admitted to Ajou University Hospital between Jan. 2008 and Jun. 2011 by reviewing medical records retrospectively. NOHK was defined as serum potassium≥7 mmol/L during the first 72 hours of life with urine output≥1 mL/kg/h. RESULTS: NOHK developed in 26.7% (20/75) of ELBWI. Among NOHK developed in ELBWI, 85% (17/20) developed within postnatal (PN) 48 hours, 5% (1/20) experienced cardiac arrhythmia and 20% (4/20) of NOHK infants expired within PN 72 hours. There were statistically significant differences in gestational age, use of antenatal steroid, and serum phosphorous level at PN 24 hours, and serum sodium, calcium, and urea levels at PN 72 hours between NOHK and non-NOHK groups (p-value<0.050). However, there were no statistical differences in the rate of intraventricular hemorrhage, arrhythmia, mortality occurred, methods of fluid therapy, supplementation of amino acid and calcium, frequencies of umbilical artery catheterization and urine output between the two groups. CONCLUSION: NOHK is not a rare complication in ELBWI. It occurs more frequently in ELBWI with younger gestational age and who didn't use antenatal steroid. Furthermore, electrolyte imbalance such as hypernatremia, hypocalcemia and hyperphosphatemia occurred more often in NOHK group within PN 72 hours. Therefore, more use of antenatal steroid and careful control by monitoring electrolyte imbalance should be considered in order to prevent NOHK in ELBWI.

Effect of substrate modification in catheter ablation of paroxysmal atrial fibrillation: pulmonary vein isolation alone or with complex fractionated electrogram ablation.

Catheter ablation of atrial fibrillation that targets complex fractionated electrogram sites has been widely applied in the management of persistent atrial fibrillation. The clinical outcomes of pulmonary vein isolation alone and pulmonary vein isolation plus the use of complex fractionated electrogram-guided ablation (CFEA) have not been fully compared in patients with paroxysmal atrial fibrillation.This prospective study included 70 patients with symptomatic paroxysmal atrial fibrillation that remained inducible after pulmonary vein isolation. For radio-frequency catheter ablation, patients were nonrandomly assigned to a control group (pulmonary vein isolation alone, Group 1, n=35) or a CFEA group (pulmonary vein isolation plus additional CFEA, Group 2, n=35). The times to first recurrence of atrial tachyarrhythmias were compared between the 2 groups.In Group 2, CFEA rendered atrial fibrillation noninducible in 16 patients (45.7%) and converted inducible atrial fibrillation into inducible atrial flutters in 12 patients (34.3%). Atrial fibrillation remained inducible in 7 patients (20%) after the combined ablation procedures. After a mean follow-up of 23 months, freedom from recurrence of atrial tachyarrhythmias was significantly higher in Group 2 than in Group 1 (P=0.037). In Group 1, all of the recurrent tachyarrhythmias were atrial fibrillation, whereas regular tachycardia was the major mechanism of recurrent arrhythmias in Group 2 (atrial tachycardia or atrial flutter in 5 of 6 patients and atrial fibrillation in 1 patient).We found that CFEA after pulmonary vein isolation significantly reduced recurrent atrial tachyarrhythmia and might modify the pattern of arrhythmia recurrence in patients with paroxysmal atrial fibrillation.