Benidipine reduces ischemia reperfusion-induced systemic oxidative stress through suppression of aldosterone production in mice

Aldosterone is implicated in the pathogenesis of several cardiovascular diseases, including ischemia reperfusion (I/R) and myocardial infarction, and also causes oxidative stress and inflammation in cardiovascular systems. Benidipine, a long-acting T- and L-type calcium channel blocker, reduces infarct size following myocardial I/R in rabbits. Benidipine also inhibits the production of aldosterone in vitro. However, the precise mechanism of this phenomenon in vivo remains unknown. We therefore evaluated whether benedipine has a beneficial role through the regulation of oxidative stress in myocardial I/R. C57BL/6J mice were subjected to 30?min of left ascending coronary I/R. Benidipine was administered orally at 3?mg?kg(-1) daily for 3 weeks without any changes in hemodynamic variables. Benidipine significantly reduced infarction size (13.4±2.5%) compared with controls (25.5±3.6%). Urinary 8-hydroxy-2' deoxyguanosine (8-OHdG), a marker of oxidative DNA damage, increased significantly after I/R. I/R induced increases in 8-OHdG were significantly lower with benidipine. Local myocardial 8-OHdG was also elevated in I/R, but this augmentation was significantly suppressed with benidipine. The plasma aldosterone concentration (PAC) significantly increased 2 days after I/R and remained elevated at least 7 days after I/R. Treatment with benidipine significantly decreased I/R-induced elevation of the PAC. I/R-induced markers of fibrosis in hearts also reduced in benidipine. These results suggest that the administration of benidipine reduces myocardial infarct size as well as systemic oxidative stress after I/R. These phenomena are partially linked to reduced plasma aldosterone levels.     

Asian consensus report on functional dyspepsia

Background and Aim: Environmental factors such as food, lifestyle and prevalence of Helicobacter pylori infection are widely different in Asian countries compared with the West, and physiological functions and genetic factors of Asians may also be different from those of Westerners. Establishing an Asian consensus for functional dyspepsia is crucial in order to attract attention to such data from Asian countries, to articulate the experience and views of Asian experts, and to provide a relevant guide on management of functional dyspepsia for primary care physicians working in Asia. Methods: Consensus team members were selected from Asian experts and consensus development was carried out by using a modified Delphi method. Consensus teams collected published papers on functional dyspepsia especially from Asia and developed candidate consensus statements based on the generated clinical questions. At the first face‐to‐face meeting, each statement was reviewed and e‐mail voting was done twice. At the second face‐to‐face meeting, final voting on each statement was done using a keypad voting system. A grade of evidence and strength of recommendation were applied to each statement according to the method of the GRADE Working Group. Results: Twenty‐nine consensus statements were finalized, including seven for definition and diagnosis, five for epidemiology, nine for pathophysiology, and eight for management. Algorithms for diagnosis and management of functional dyspepsia were added. Conclusions: This consensus developed by Asian experts shows distinctive features of functional dyspepsia in Asia and will provide a guide to the diagnosis and management of functional dyspepsia for Asian primary care physicians.     

Association between ApoE phenotypes and telomere erosion in Alzheimer's disease

Although several reports suggest that Alzheimer's disease (AD) is associated with shortened telomere length, the clinical relevance of this has not yet been fully elucidated. This study was conducted to clarify the correlation of telomere length with clinical characteristics and ApoE phenotypes in 74 AD patients. Telomere length was determined from genomic DNA extracted from whole blood by quantitative real-time polymerase chain reaction. We found no significant difference in telomere length between the AD and non-dementia elderly control (n = 35) groups. Furthermore, no significant correlation was found among telomere length and the severity of cognitive decline and disease duration, age, or gender difference. However, telomere length was significantly shorter in AD patients with the ApoE4 homozygote than in those with the ApoE4 heterozygote (p < .001) and noncarriers (p < .001). These findings suggest that shortened telomere length may be associated with the ApoE4 homozygote in AD patients.     

Impulse Oscillometry; Therapeutic Impacts of Transdermal Long-Acting Beta-2 Agonist Patch in Elderly Asthma with Inhaled Corticosteroid Alone

Growing interest had been focused on the involvement of the small airways in asthma, and impulse oscillometry (IOS) has been utilized as pulmonary functions for detecting large and small airways diseases separately. IOS can measure respiratory resistance and reactance at multiple frequencies, not available by spirometry or body plethysmography, is non-invasive techniques and convenient for elderly patients with a low dependency on cooperation during tidal breathing. IOS indices were well correlated with not only predicted FEV1 but also FEF25-75, residual volume/total lung capacity, delta N2 of a single nitrogen washout test which representing air trapping and inhomogeneous ventilation in the distal lung. These parameters and QOL scores were improved by additional transdermal long-acting beta-2 agonist patch even in well-controlled elderly asthma treating with inhaled corticosteoids alone. IOS may have a complementary role of spirometry in detecting subtle airways changes in general practice. However, systemic studies are required to investigate the clinical implication of each IOS index.     

Thoracoscopic esophagectomy while in a prone position for esophageal cancer: a preceding anterior approach method

Background

In 2009, the rate of thoracoscopic esophagectomy for esophageal cancer was about 20 % in Japan. This low rate may be due to the difficulty in maintaining a good surgical field and the meticulous procedures that are required. The purpose of this study was to establish and evaluate a new procedure for performing a thoracoscopic esophagectomy while the patient is in a prone position using a preceding anterior approach to make the esophagectomy easier to perform.

Methods

We have performed thoracoscopic esophagectomy using our new procedure in 60 patients with esophageal cancer. Each patient was placed in a prone position and five trocars were inserted; only the left lung was ventilated and a pneumothorax was maintained. The esophagus was mobilized from the anterior structure during the first step and from the posterior structure during the second step. The lymph nodes around the esophagus were also dissected anteriorly and posteriorly. The patients were sequentially divided into two groups and their clinical outcomes were evaluated.

Results

The mean operative time for the thoracoscopic procedure for the latter 30 cases (203 min) was shorter than that for the former 30 cases (260 min) (P = 0.001). Among the 52 cases without pleural adhesion, the mean blood loss in the latter 26 cases (18 mL) was also less than that in the former 26 cases (40 mL) (P = 0.027). There were no conversions to a thoracotomy and no operative deaths in this series. Postoperative complications related to the thoracoscopic procedure occurred in 8 cases (27 %) in the former group and in 4 cases (13 %) in the latter group.

Conclusions

Thoracoscopic esophagectomy with the patient in the prone position using a preceding anterior approach is a safe and feasible procedure. As experience performing the procedure increases, the performance of the procedure stabilizes. This method seems to make the esophagectomy easier to perform.     

A case of atypical benign partial epilepsy with action myoclonus

We describe a boy, 3 years and 6 months old, who experienced a rolandic seizure accompanied by a cluster of atypical absence seizures, the EEGs for which corresponded to those of atypical benign partial epilepsy (ABPE). Of note, this patient suffered from developmental delay beginning in infancy and exhibited giant middle-latency somatosensory evoked potentials with action myoclonus. With the exceptions of ethosuximide, acetazolamide, and adrenocorticotropic hormone, which have been reported to be effective in ABPE, the atypical absence seizures were intractable despite extensive treatment with various anticonvulsants. The drugs that were effective led to a remarkable reduction in seizure frequency and EEG improvement, but the efficacy was temporary. The patient demonstrated moderate mental retardation without regression and could not walk with support or speak any meaningful words at the age of 3 years and 6 months. Based on thorough differential diagnosis, although further studies will be necessary, we propose that this boy may present a new phenotype of ABPE: ABPE with action myoclonus.     

CD133 Expression at the Metastatic Site Predicts Patients’ Outcome in Colorectal Cancer with Synchronous Liver Metastasis

Background

CD133 is a transmembrane protein that is proposed to be a stem cell marker of colorectal cancer (CRC); however, the correlation between CD133 expression and survival of CRC patients with liver metastasis has not been fully examined.

Methods

CD133 expression was evaluated immunohistochemically, both in primary tumors and synchronous liver metastases of 88 consecutive CRC patients, as well as recurrent lesions in the remnant liver of 27 of these 88 patients. The relationship between CD133 expression and clinicopathological characteristics, recurrence-free survival, and overall survival (OS) was analyzed.

Results

CD133 expression in liver metastases (mCD133) was detected in 50 of 88 patients (56.8 %), and had significant correlation with CD133 expression in primary lesions (pCD133) (p < 0.001). CD133 expression in liver recurrent lesions (recCD133) also had a significant correlation with mCD133 (p < 0.001). mCD133+ patients had significantly longer disease-free survival (p = 0.043) and OS (p = 0.014) than mCD133? patients. In addition, mCD133+ patients had a significantly lower rate of extrahepatic recurrence (p < 0.001).

Conclusions

Patients without CD133 expression in liver metastasis had significantly shorter survival, perhaps because mCD133? patients had a significantly higher rate of extrahepatic recurrence.