Fibroblasts: modulating the rhythm of the heart

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65742/1/jphysiol.2008.153387.pd

Learning about View of Life and Death, Especially from Children’s Death Caused by Natural Disasters in the City of Manado, Province of North Sulawesi,Indonesa

This is a study conducted by our research group about the psychological background of local people in Manado,Indonesia. Interviews were made to a group of locals concerning their approach to death and consequent state of mind focused on their religious beliefs on Obon festival,conversation with spirits,reincarnation and the influence of holy men. We recognized the fantasy they believed that spirit comes back from afterworld in the ceremony. In addition,we understood the event that spirit returns from afterworld once a year and“offering” is common sense. However,these custom had difference depended on regions and their social rank. As a result,these local people were difficult to share the common sense about the event. Reporting to spirit and conversation to spirit were common events in whole regions in Indonesia,but the quality might be different. Especially,idea about reincarnation was modified among young and old generations.調査・事例等報

Effect of Charge Substitutions at Residue His-142 on Voltage Gating of Connexin43 Channels

AbstractPrevious studies indicate that the carboxyl terminal of connexin43 (Cx43CT) is involved in fast transjunctional voltage gating. Separate studies support the notion of an intramolecular association between Cx43CT and a region of the cytoplasmic loop (amino acids 119–144; referred to as “L2”). Structural analysis of L2 shows two α-helical domains, each with a histidine residue in its sequence (H126 and H142). Here, we determined the effect of H142 replacement by lysine, alanine, and glutamate on the voltage gating of Cx43 channels. Mutation H142E led to a significant reduction in the frequency of occurrence of the residual state and a prolongation of dwell open time. Macroscopically, there was a large reduction in the fast component of voltage gating. These results resembled those observed for a mutant lacking the carboxyl terminal (CT) domain. NMR experiments showed that mutation H142E significantly decreased the Cx43CT-L2 interaction and disrupted the secondary structure of L2. Overall, our data support the hypothesis that fast voltage gating involves an intramolecular particle-receptor interaction between CT and L2. Some of the structural constrains of fast voltage gating may be shared with those involved in the chemical gating of Cx43

Deterioration of high-resolution computed tomography findings predicts disease progression after initial decline in forced vital capacity in idiopathic pulmonary fibrosis patients treated with pirfenidone

Background Pirfenidone suppresses the decline of forced vital capacity (FVC) in patients with idiopathic pulmonary fibrosis (IPF). However, IPF progresses in some patients despite treatment. We analyzed patients with meaningful FVC declines during pirfenidone treatment and explored the factors predictive of disease progression after FVC decline. Methods This study was a retrospective, multicenter, observational study conducted by the Okayama Respiratory Disease Study Group. We defined initial decline in %FVC as 5% or greater per 6-month period during pirfenidone treatment. IPF patients who were treated with pirfenidone and experienced an initial decline from December 2008 to September 2017 were enrolled. Results We analyzed 21 patients with IPF. After the initial decline, 4 (19.0%) patients showed improvement in disease, 11 (52.4%) showed stable disease, and 6 (28.6%) showed progressive disease. There was no significant correlation between %FVC reduction on initial decline and subsequent %FVC change (p = 0.475). Deterioration of high-resolution computed tomography (HRCT) findings on initial decline was observed significantly more often in the progressive versus improved/stable disease groups (100% vs 20.0%, p = 0.009). Conclusions We revealed that deterioration of HRCT findings may predict disease progression after the initial decline in %FVC in IPF patients treated with pirfenidone

Nintedanib can be used safely and effectively for idiopathic pulmonary fibrosis with predicted forced vital capacity <= 50%: A multi-center retrospective analysis

Background Nintedanib is a multi-kinase inhibitor approved for idiopathic pulmonary fibrosis (IPF); however, its efficacy and safety for patients with IPF and restricted pulmonary function remain unclear. Therefore, the objective of this study was to determine the efficacy and safety of nintedanib for patients with IPF and forced vital capacity (FVC) ≤ 50%. Methods This was a multi-center retrospective study performed by the Okayama Respiratory Disease Study Group. Patients were allocated into FVC ≤ 50% and FVC > 50% groups based on their predicted FVC. The primary endpoints were FVC changes from baseline after 6 and 12 months. Results 45 patients were eligible for the study. 18 patients had FVC ≤ 50%, and 27 patients had FVC > 50%. Overall, 31 and 19 patients underwent pulmonary function tests at 6 and 12 months after initiating nintedanib, respectively. FVC changes from baseline at 6 and 12 months after initiating nintedanib were comparable between the two groups. Adverse events were seen in all patients, and the rates of patients who discontinued nintedanib were also comparable (38.9% vs. 37.0%, p = 1.000). Multiple regression analysis showed that age and forced expiratory volume in 1 second (FEV1)/FVC were negatively correlated with changes in FVC at 6 months after initiating nintedanib. Conclusions Our data suggest that nintedanib can be a useful agent for IPF patients, including those with a low FVC, and that age and FEV1/FVC are predictive markers for changes in FVC following nintedanib treatment

Effects of air temperature and humidity on sleeping women by the ventilation and air-conditioner, Japan

The effect of ventilation system on the sleeping persons has not been well studied. This is because mechanical ventilation systems had not previously been widely used in residential buildings in Japan. However, 24-hour mechanical ventilation is now mandatory in highly airtight and insulated houses. This study compared the temperature and humidity in bedrooms using either regular mechanical ventilation or desiccant ventilation when the air conditioner was switched off by a timer. The experiments investigated the sleep quality, thermoregulatory responses, and thermal comfort of young woman participants during the sleeping period at night. The desiccant ventilation reduces the air temperature and humidity by 1 °C and 20% Rh, respectively. While the air conditioner was turned off, the women’s skin temperatures increased by about 0.5 °C, but did not increase awakenings, as a result, the sleep efficiency was maintained at 96%. Thermal and comfort sensations were obtained significantly on the cooler and more comfortable side with the desiccant ventilation system than without desiccant system

Complex structure of electrophysiological gradients emerging during long-duration ventricular fibrillation in the canine heart

Long-duration ventricular fibrillation (LDVF) in the globally ischemic heart is a common setting of cardiac arrest. Electrical heterogeneities during LDVF may affect outcomes of defibrillation and resuscitation. Previous studies in large mammalian hearts have investigated the role of Purkinje fibers and electrophysiological gradients between the endocardium (Endo) and epicardium (Epi). Much less is known about gradients between the right ventricle (RV) and left ventricle (LV) and within each chamber during LDVF. We studied the transmural distribution of the VF activation rate (VFR) in the RV and LV and at the junction of RV, LV, and septum (Sep) during LDVF using plunge needle electrodes in opened-chest dogs. We also used optical mapping to analyze the Epi distribution of VFR, action potential duration (APD), and diastolic interval (DI) during LDVF in the RV and LV of isolated hearts. Transmural VFR gradients developed in both the RV and LV, with a faster VFR in Endo. Concurrently, large VFR gradients developed in Epi, with the fastest VFR in the RV-Sep junction, intermediate in the RV, and slowest in the LV. Optical mapping revealed a progressively increasing VFR dispersion within both the LV and RV, with a mosaic presence of fully inexcitable areas after 4–8 min of LDVF. The transmural, interchamber, and intrachamber VFR heterogeneities were of similar magnitude. In both chambers, the inverse of VFR was highly correlated with DI, but not APD, at all time points of LDVF. We conclude that the complex VFR gradients during LDVF in the canine heart cannot be explained solely by the distribution of Purkinje fibers and are related to regional differences in the electrical depression secondary to LDVF