Cytotoxicity of the Ascidian Cystodytes dellechiajei Against Tumor Cells and Study of the Involvement of Associated Microbiota in the Production of Cytotoxic Compounds

Many cytotoxic compounds of therapeutic interest have been isolated from marine invertebrates, and some of them have been reported to be of microbial origin. Pyridoacridine alkaloids are the main compounds extracted from the ascidian Cystodytes dellechiajei. Here we describe the in vitro antiproliferative activity against different tumor cell lines of the ascidian extracts and provide some insights on the role of the microbial community associated with the tunicate in the production of these compounds. C. dellechiajei extracts showed remarkably high antiproliferative activity (IC50 ≤5 μg/mL) in human lung carcinoma A-549, colon adenocarcinoma H-116, pancreatic adenocarcinoma PSN-1 and breast carcinoma SKBR3 cell lines. Moreover, we found that the maximum activity was located in the tunic tissue of the colony, which harbours a microbial community. In order to ascertain the involvement of this community in the synthesis of the bioactive compounds different approachs that included culture and culture independent methods were carried out. We undertook a screening for antiproliferative activities of the bacterial isolates from the ascidian, as well as a comprative analysis of the cytotoxic activities and the microbial communities from two color morphs of the ascidian, green and blue. In addition, the changes of the antiproliferative activities and the composition of the microbial communities were studied from ascidians kept in aquaria and treated with antibiotics for one month. Our data obtained from the different experiments did not point out to bacteria as the source of the cytotoxic compounds, suggesting thus an ascidian origin

日本人女性の食事からのカルシウム摂取量

This study was initiated 1. to examine if there was any secular changes in dietary calcium (Ca) intake among Japanese women in past 15 years, and 2. to identify the food groups insufficient intake of which may induce Ca insufficiency. 24-Hour food duplicate samples were collected from 433 and 760 adult women in the first (1977-1981) and the second survey (1991-1998), respectively, from various parts of Japan. Daily Ca intakes were estimated from weights of food items in the duplicate samples, taking advantages of food composition tables (FCT-based estimates). Possible difference in means was examined by Student's t-test and multiple comparison test (Scheffe), and that in distribution by chi-square test. The average dietary intake of Ca was 607 and 605 mg/day in the first and the second survey, respectively, with no significant difference. The subjects, separately for the two surveys, were classified by the Ca intake into 5 groups, i.e., those with intake of 419 or less, 420 to 539,540 to 659,660 to 999 and 1,000 or more mg Ca/day, and also by decade of ages. Reduced Ca intake from fish (including shellfish) and vegetables coupled with increased intake from milk (including milk products) were noted among the three low Ca intake groups when the intakes were compared between the two surveys, whereas no food group-specific changes were noted among the two high intake groups. Ca intake from milk was high in the latter two groups. Further analysis showed that low intakes of pulse, fish, milk, vegetables and algae were associated with insufficiency in Ca intakes. Classification by ages showed that Ca insufficiency among those at the ages of 20's was attributable to low intakes of pulse, fish and algae. When compared between the two surveys, reduced intakes of fish and vegetables and increased intake of milk were commonly observed in most age groups, and milk intake was substantially increased at advanced ages. FCT-based estimates and ICP-MS measurements gave 581 and 542 mg/day as averages for the former and the latter, respectively. The observation that the latter is 93% of the former suggests that Ca insufficiency should be taken more seriously than the estimates would suggest

QUALITY OF LIFE AND HEART RATE VARIABILITY FOLLOWING ACUTE MYOCARDIAL INFARCTION

Objective : The aim of this study was to investigate whether cardiac autonomic function measuredby heart rate variability (HRV) indices are related to quality of life (QOL) improvements inpatients with acute myocardial infarction (AMI) treated by percutaneous coronary intervention.Methods : We enrolled 20 consecutive patients with AMI. Measures of HRV, obtained fromboth frequency and time domain analyses using 24-h Holter monitoring before discharge, were asfollows : low and high frequency (HF) domain measures, the square root of the mean squared differencesof successive R-R intervals (rMSSD), and the percentage of differences between adjacentnormal R-R intervals >50 ms for the whole analysis (pNN50). QOL was determined byphysical and mental component summary (PCS and MCS, respectively) scores derived from theJapanese Medical Outcomes Study 36-item Short Form Health Survey before and 6 months afterdischarge.Results : The subjects showed significant improvement in the MCS, but not the PCS score.　There were also positive correlations between the parasympathetic parameters of HF, rMSSD,and pNN50 and the change in MCS score. In a multivariate analysis, rMSSD was found to beindependently associated with the change in MCS score.Conclusions : Parasympathetic tone, as measured by HRV, is independently associated withQOL, which emphasizes the role of cardiac autonomic function on QOL in patients with AMI

Efficacy and Safety of Remote Cardiac Rehabilitation in the Recovery Phase of Cardiovascular Diseases: Protocol for a Multicenter, Nonrandomized, Single-Arm, Interventional Trial

BackgroundConventional group-based outpatient cardiac rehabilitation through monitoring and center-based approaches for patients in the recovery phase has shown strong evidence for the prevention of cardiovascular diseases. However, there are some cases in which maintaining attendance of center-based cardiac rehabilitation is difficult. ObjectiveThis study aims to ascertain the safety and efficacy of remote cardiac rehabilitation (RCR) in the recovery phase in patients with cardiovascular disease. MethodsPatients satisfying the study criteria will be recruited from multiple institutions (approximately 30) across Japan. In total, 75 patients (approximately 2 or 3 patients from each institution) are proposed to be recruited. Patients enrolled in the RCR group will be lent devices necessary for RCR (including calibrated ergometers and tablets). Patients will perform anaerobic exercise at home using ergometer for 30-40 minutes at least 3 times weekly. During exercise, an instructor will monitor the patient in real time (using interactive video tools and monitoring tools for various vital data). Moreover, educational instructions will be given 3 times weekly using e-learning methods. ResultsThe primary endpoint is the peak oxygen uptake 2-3 months from the start of exercise or 6-min walk test. The extracted data will be compared between RCR patients and controls without RCR. ConclusionsThe establishment of the system of RCR proposed in this study will lead to the development of more extensive applications, which have been insufficient through conventional interventions. Trial RegistrationUniversity Hospital Medical Information Network—Clinical Trials Registry UMIN–CTR UMIN000042942; https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000048983 International Registered Report Identifier (IRRID)DERR1-10.2196/3072

Renal replacement therapy as a therapeutic option for right heart failure in severe pulmonary arterial hypertension

Abstract Pulmonary arterial hypertension (PAH) is a progressively life‐threatening disease that causes right heart failure (RHF). Renal dysfunction frequently complicates PAH with RHF and is associated with a worse prognosis. Renal replacement therapy (RRT) may be a therapeutic option, although its efficacy and safety are unclear. We describe a 30‐year‐old male with severe PAH who developed renal insufficiency and diuretic‐refractory volume overload complicated with RHF but was successfully managed with intermittent RRT via a subcutaneously fixed superficial artery for 4 years. RRT led to haemodynamic stability, which enabled us to carefully de‐titrate parenteral PAH drugs without worsening RHF. This case highlights that RRT may be a potential alternative for haemodynamic and volume control of refractory fluid retention complicated with RHF in severe PAH cases. Further studies are warranted to gain more insight into patient selection and the optimal timing of RRT in PAH patients with deteriorating RHF