Marmoset cytochrome P450 2B6, a propofol hydroxylase expressed in liver

1. The common marmoset (Callithrix jacchus) is a useful experimental animal to evaluate the pharmacokinetics of drug candidates. Cytochrome P450 (P450) 2B enzyme in marmoset livers has been identified; however, only limited information on the enzymatic properties and distribution has been available.

2. Marmoset P450 2B6 amino acids showed high sequence identities (>86%) with those of primates including humans and cynomolgus monkeys. Phylogenetic analysis using amino acid sequences indicated that marmoset P450 2B6 was closer to human and cynomolgus monkey P450 2B6 than to P450 2B orthologs of other species, including pigs, dogs, rabbits and rodents.

3. Quantitative polymerase chain reaction analysis using specific primers showed P450 2B6 mRNA predominantly expressed in livers among the five marmoset tissues, similar to those of humans and cynomolgus monkeys.

4. Marmoset P450 2B6 heterologously expressed in Escherichia coli membranes oxidized 7-ethoxycoumarin, pentoxyresorufin, propofol and testosterone, at roughly similar rates to those of humans and/or cynomolgus monkeys. A high capacity of marmoset P450 2B6 with propofol 4-hydroxylation (at low ionic strength conditions) with a low K_m value was relatively comparable to that for marmoset livers.

5. These results collectively indicated a high propofol 4-hydroxylation activity of P450 2B6 expressed in marmoset livers.

     

A case of diaphragmatic hernia incarceration after a heart transplant operation

We report a case of a diaphragmatic hernia after a heart transplant operation. A 43-year-old woman, who underwent orthotropic heart transplantation for hypertrophic cadiomyopathy two year earlier, presented with vomiting and epigastric pain. A computed tomography scan showed that the stomach and transverse colon were dislocated in the left thoracic cavity. We diagnosed left diaphragmatic hernia incarceration and performed laparoscopic repair of the diaphragmatic hernia. A 12 × 8 cm diaphragmatic defect was found intraoperatively on the ventrolateral aspect of the left diaphragm, and the stomach with volvulus had herniated into the thorax through the defect. The hernia was considered to be iatrogenic. The diaphragmatic defect was large, and the diaphragm was thinning. We closed the defect by mesh repair. Laparoscopic mesh repair of the diaphragmatic hernia could be performed safely and with minimal invasiveness.     

Postoperative development of sarcopenia is a strong predictor of a poor prognosis in patients with adenocarcinoma of the esophagogastric junction and upper gastric cancer

Background

There were few studies assessed the postoperative sarcopenia in patients with cancers. The objective of present study was to assess whether postoperative development of sarcopenia could predict a poor prognosis in patients with adenocarcinoma of esophagogastric junction, (AEG) and upper gastric cancer (UGC).

Screening for musculoskeletal problems in children using a questionnaire

Background

On April 1, 2016, the Ministerial ordinance was enforced, and musculoskeletal examination of the extremities was made mandatory. From 2008, the University of us started musculoskeletal direct examination. To expand the examination, from 2016, we started to use the marksheet-type questionnaire. This study aimed to report the results of a musculoskeletal examination and investigate the association between musculoskeletal examination and age/gender and reports the reliability of the collected questionnaire data.

Can muscle weakness and disability influence the relationship between pain catastrophizing and pain worsening in patients with knee osteoarthritis? A cross-sectional study

ObjectiveTo verify if the relationship between pain catastrophizing and pain worsening would be mediated by muscle weakness and disability in patients with symptomatic knee osteoarthritis.MethodsThis was a cross-sectional study in a hospital out-patient setting. Convenience sampling was used with a total of 50 participants with symptomatic knee osteoarthritis. Pain and the activities of daily livings (ADL) were assessed using the Knee Injury and Osteoarthritis Outcome Score (KOOS) subscale. Pain catastrophizing was assessed using the Coping Strategy Questionnaire (CSQ) subscale. Muscle strength of knee extension and 30-s chair stand test (30CST) were also assessed. Path analysis was performed to test the hypothetical model. Goodness of fit of models were assessed by using statistical parameters such as the chi-square value, goodness of fit index (GFI), adjusted goodness of fit index (AGFI), comparative fit index (CFI), and root mean square error of approximation (RMSEA).ResultsThe chi-square values were not significant (chi-square = 0.283, p = 0.594), and the indices of goodness of fit were high, implying a valid model (GFI = 1.000; AGFI = 0.997; CFI = 1.000; RMSEA = 0.000). Pain was influenced significantly by muscle strength and ADL; muscle strength was influenced significantly by ADL via 30CST; ADL was influenced by pain catastrophizing.ConclusionThe relationship between pain catastrophizing with pain worsening are mediated by muscle weakness and disability.     

Application of the adverse outcome pathway framework to genotoxic modes of action

In May 2017, the Health and Environmental Sciences Institute's Genetic Toxicology Technical Committee hosted a workshop to discuss whether mode of action (MOA) investigation is enhanced through the application of the adverse outcome pathway (AOP) framework. As AOPs are a relatively new approach in genetic toxicology, this report describes how AOPs could be harnessed to advance MOA analysis of genotoxicity pathways using five example case studies. Each of these genetic toxicology AOPs proposed for further development includes the relevant molecular initiating events, key events, and adverse outcomes (AOs), identification and/or further development of the appropriate assays to link an agent to these events, and discussion regarding the biological plausibility of the proposed AOP. A key difference between these proposed genetic toxicology AOPs versus traditional AOPs is that the AO is a genetic toxicology endpoint of potential significance in risk characterization, in contrast to an adverse state of an organism or a population. The first two detailed case studies describe provisional AOPs for aurora kinase inhibition and tubulin binding, leading to the common AO of aneuploidy. The remaining three case studies highlight provisional AOPs that lead to chromosome breakage or mutation via indirect DNA interaction (inhibition of topoisomerase II, production of cellular reactive oxygen species, and inhibition of DNA synthesis). These case studies serve as starting points for genotoxicity AOPs that could ultimately be published and utilized by the broader toxicology community and illustrate the practical considerations and evidence required to formalize such AOPs so that they may be applied to genetic toxicity evaluation schemes. Environ. Mol. Mutagen. 61:114–134, 2020. © 2019 Wiley Periodicals, Inc.     

Potassium excretion in healthy Japanese women was increased by a dietary intervention utilizing home-parcel delivery of Okinawan vegetables.

Potassium, which is abundant in vegetables, is inversely related to blood pressure. Although the situation has changed somewhat in recent years, the Okinawan diet has generally included a large amount of vegetables, and until recently Okinawans had the lowest rates of mortality due to stroke and coronary heart disease in Japan. Based on the hypothesis that these low mortality rates are partly attributable to increased potassium intake resulting from the high vegetable consumption, this study examined whether increasing the consumption of typical yellow-green Okinawan vegetables increases potassium intake. The purpose of this investigation was to determine whether increased consumption of these vegetables should be one of the dietary modifications recommended in public health promotion programs for Okinawans. The study employed 56 healthy, normotensive, free-living Japanese women aged 18-38 years living in Okinawa. They were randomized to a dietary intervention group (n=27) or a control group (n=29). Members of the dietary intervention group received an average weight of 371.4 g/day of a combination of the following vegetables twice weekly through an express home parcel deliver service for a period of 14 days: Goya (Momordica charantia), green papaya (Carica papaya), Handama (Gynura bicolor), Karashina (Brassica juncea), Njana (Crepidiastrum lanceolatium), Fuchiba (Artemisia vulgaris) and Fudanso (Beta vulgaris); and they consumed an average of 144.9 g/day, resulting in a 20.5% increase in their urinary potassium excretion over the baseline (p=0.045). The members of the control group were asked to avoid these vegetables, and the change in potassium excretion in this group was not significant (p=0.595). Urinary sodium and magnesium excretions, systolic and diastolic blood pressures, folic acid, triglycerides and serum high density lipoprotein cholesterol, low density lipoprotein cholesterol and total cholesterols changed non-significantly in both groups. Also, post-intervention urinary potassium excretion correlated positively with vegetable consumption in both the dietary intervention (p<0.0001) and control (p=0.008) groups and with Okinawan vegetable intake in the dietary intervention group (p=0.0004).