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Motoo Kobayashi,1,2,* Yuki Okada,1,2,* Hiromichi Ueno,1 Takayuki Mizorogi,1 Kenji Ohara,1 Koh Kawasumi,1 Kohei Suruga,3 Kazunari Kadokura,3 Yasuyuki Ohnishi,2 Toshiro Arai1,2 1Laboratory of Veterinary Biochemistry, School of Veterinary Medicine, Nippon Veterinary and Life Science University, Tokyo 180-8601, Japan; 2One Health Co. Ltd, Tokyo 157-0066, Japan; 3Food Function R&D Division, International Operation Department, Kibun Foods Inc., Tokyo 206-0812, Japan*These authors contributed equally to this workCorrespondence: Toshiro AraiLaboratory of Veterinary Biochemistry, School of Veterinary Medicine, Nippon Veterinary and Life Science University, 1-7-1 Kyonancho, Musashino, Tokyo 180-8601, JapanTel +81 422 31 4151Fax +81 422 31 7841Email tarai@nvlu.ac.jpBackground: Obesity has become a serious public health problem all over the world, and prevalence of obesity has increased in cats. Obesity is characterized by continuous low-grade inflammation based on oxidative stress by excessively produced reactive oxygen species (ROS). Supplementation with anti-oxidant and anti-inflammatory compounds is very effective to relieve the obesity condition. A plant extract mixture containing Rhus verniciflua and some other herbs, Rv-PEM01-99, shows anti-oxidant and anti-inflammatory effects in animals. The aim of this study was to evaluate the effects of supplementation with Rv-PEM01-99 as an anti-inflammatory compound in healthy and obese cats.Materials and Methods: Ten healthy mix breed cats and four obesity disease cats were used. The healthy cats were randomly divided into control and test groups. Anti-inflammatory compound, Rv-PEM01-99, in which quercetin derivative is the main component, was supplemented to the healthy test group and the obesity disease cats at the dose of 100– 120 mg/kg/day (2.5– 3.0 mg/kg/day as quercetin) for 4 weeks. Metabolites, hormones and enzymes were measured before and after the compound supplementation.Results: The anti-inflammatory compound supplementation decreased serum amyloid A (SAA) concentrations as inflammatory markers in both healthy and obesity disease cats. In obesity disease cats, plasma total cholesterol concentrations and AST and ALT activities decreased significantly after the compound supplementation.Conclusion: Quercetin derivative seems to have strong anti-inflammatory activities. In the healthy cats, anti-inflammatory compound supplementation decreased plasma NEFA and SAA concentrations. In the obesity disease cats, the compound supplementation may have alleviated obesity disease by relieving inflammation and improvement of lipid metabolism in livers.Keywords: anti-inflammatory compound, cat, obesity, quercetin, SAA

Tae Murai,1 Koh Kawasumi,1 Kumi Tominaga,2 Yuki Okada,1 Motoo Kobayashi,1 Toshiro Arai1 1Laboratory of Veterinary Biochemistry, School of Veterinary Medicine, Nippon Veterinary and Life Science University, Musashino, Tokyo 180-8602, Japan; 2Research and Development Division, AstaReal Co. Ltd., Minato-ku, Tokyo 105-0011, Japan Background: Since astaxanthin (ASX) has potent anti-oxidative effects with inhibitory action of lipid peroxidation and singlet oxygen quenching activity, it is widely used as a functional food for keeping good health in human. Obesity is a risk factor for various metabolic disorders. It is characterized by low-grade chronic inflammation based on oxidative stress by excessively produced ROS. From the point of preventive medicine, natural compounds have been proposed as potential therapeutic agents in the prevention of metabolic disorder in companion animals. The purpose of this study is to evaluate the effects of ASX supplementation in healthy and obese dogs. Materials and methods: Ten healthy beagle dogs and 5 clinically obese dogs were used in this study. The healthy beagle dogs were randomly divided into 2 groups as follows: control and test groups. The test group dogs received ASX supplementation mixed with the food for 6 weeks. Five clinically obese dogs received ASX supplementation for 8 weeks. Metabolites, hormones and enzymes were measured before and after ASX supplementation. Results: In the healthy dog groups, after 6 weeks, plasma triglyceride (TG) and malondialdehyde concentrations and lactate dehydrogenase (LDH) values significantly decreased in the test group. There was no significant difference in the control group. In clinically obese dogs, plasma TG concentration decreased after 8 weeks of ASX supplementation. Plasma alanine aminotransferase and LDH values clearly decreased in all 5 dogs and 4 dogs out of 5 dogs, respectively. Conclusion: ASX supplementation (0.3 mg/kg body weight/day) for 6 weeks in healthy dogs and 8 weeks in obese dogs induced the elevation of antioxidant function and of liver function by ameliorating lipid metabolism. Keywords: astaxanthin, obese dogs, lipid metabolism, anti-oxidative activity, liver function

Gebin Li,1 Peter Lee,1 Nobuko Mori,1 Ichiro Yamamoto,1 Koh Kawasumi,1 Hisao Tanabe,2 Toshiro Arai11Department of Veterinary Science, School of Veterinary Medicine, Nippon Veterinary and Life Science University, 2Komazawa Animal Hospital, Tokyo, JapanBackground and methods: Currently, five-point body condition scoring (BCS) is widely used by veterinarians and clinicians to assess adiposity in dogs in Japan. However, BCS score assignment is subjective in nature, and most clinicians do not score with half points, instead preferring to round off values, thereby rendering less accurate assessments. Therefore, we sought to determine whether assessing body fat percentage using simple morphometric measurements and supplementing this with five-point BCS can have increased sensitivity for detecting increasing adiposity in overweight small-medium sized dog breeds via plasma metabolite validation.Results: Overall, lean body fat percentage was determined to be 15%–22% for male (non-neutered/neutered) dogs and 15%–25% for female (nonspayed/spayed). Dogs categorized as overweight by BCS had significantly higher levels of nonesterified fatty acids (P = 0.005), whereas animals categorized as overweight by BCS + body fat percentage were observed to have significantly higher levels of nonesterified fatty acids (P = 0.006), total cholesterol (P = 0.029), and triglycerides (P = 0.001) than lean animals. The increased sensitivity due to body fat percentage for gauging alterations in plasma metabolite levels may be due to increased correlation strength. Body fat percentage correlated positively with plasma insulin (r = 0.627, P = 0.002), nonesterified fatty acids (r = 0.674, P < 0.001), total cholesterol (r = 0.825, P < 0.0001), triglycerides (r = 0.5823, P < 0.005), blood urea nitrogen (r = 0.429, P < 0.05), creatinine (r = 0.490, P = 0.021), and total protein (r = 0.737, P< 0.0001) levels, which all tend to increase as a result of increasing adiposity.Conclusion: Supplementing body fat percentage with five-point BCS appears to increase the likelihood of validating overweight status in small-medium sized dog breeds by detecting changes in plasma metabolite levels, especially lipids, induced as a result of increasing adiposity.Keywords: body condition score, body fat percentage, cholesterol, dog, nonesterified fatty acid, triglycerides

Ichiro Yamamoto, Shingo Ishikawa, Li Gebin, Hiroshi Takemitsu, Megumi Fujiwara, Nobuko Mori, Yutaka Hatano, Tomoko Suzuki, Akihiro Mori, Nobuhiro Nakao, Koh Kawasumi, Toshinori Sako, Toshiro AraiLaboratory of Veterinary Biochemistry, Nippon Veterinary and Life Science University, Tokyo, JapanAbstract: The cyclin-dependent kinase 5 regulatory subunit–associated protein 1–like 1 (CDKAL1) gene encodes methylthiotransferase, and the gene contains risk variants for type 2 diabetes in humans. In this study, we performed complementary DNA cloning for Cdkal1 in the cat and dog and characterized the tissue expression profiles of its messenger RNA. Cat and dog Cdkal1 complementary DNA encoded 576 and 578 amino acids, showing very high sequence homology to mammalian CDKAL1 (>88.4%). Real-time polymerase chain reaction analyses revealed that Cdkal1 messenger RNA is highly expressed in smooth muscle and that tissue distribution of Cdkal1 is similar in cats and dogs. Genotyping analysis of single-nucleotide polymorphism for cat Cdkal1 revealed that obese cats had different tendencies from normal cats. These findings suggest that the cat and dog Cdkal1 gene is highly conserved among mammals and that cat Cdkal1 may be a candidate marker for genetic diagnosis of obesity.Keywords: cat, dog, Cdkal1, obese, cDNA cloning, Q-PCR

Abstract Background Chinchillas (Chinchilla laniger) are popular as pets and are often used as laboratory animals for various studies. Pseudomonas aeruginosa is a major infectious agent that causes otitis media, pneumonia, septicaemia enteritis, and sudden death in chinchillas. This bacterium is also a leading cause of nosocomial infections in humans. To prevent propagation of P. aeruginosa infection among humans and animals, detailed characteristics of the isolates, including antibiotic susceptibility and genetic features, are needed. In this study, we surveyed P. aeruginosa distribution in chinchillas bred as pets or laboratory animals. We also characterized the isolates from these chinchillas by testing for antibiotic susceptibility and by gene analysis. Results P. aeruginosa was isolated from 41.8% of the 67 chinchillas included in the study. Slide agglutination and pulsed-field gel electrophoresis discriminated 5 serotypes and 7 unique patterns, respectively. For the antibiotic susceptibility test, 40.9% of isolates were susceptible to gentamicin, 77.3% to ciprofloxacin, 77.3% to imipenem, and 72.7% to ceftazidime. DNA analyses confirmed that none of the isolates contained the gene encoding extended-spectrum β-lactamases; however, 2 of the total 23 isolates were found to have a gene similar to the pilL gene that has been identified in the pathogenicity island of a clinical isolate of P. aeruginosa. Conclusions P. aeruginosa is widely spread in chinchillas, including strains with reduced susceptibility to the antibiotics and highly virulent strains. The periodic monitoring should be performed to help prevent the propagation of this pathogen and reduce the risk of infection from chinchillas to humans.

Introduction: In Japan, the importance of medical checkups for pet dogs is increasing. In this study, we retrospectively explored the effects of age on plasma biomarkers in healthy small dogs that underwent medical checkups., Methods: Based on the modified American Animal Hospital Association Canine Life Stage Guidelines, 52 healthy small dogs were divided into 3 groups according to their life stage: young adult (1-4 years old), mature adult (5-11 years old), senior (12-15 years old). None of the dogs were obese. Plasma was collected from animals that underwent medical checkups at Muromi Animal Hospital (Fukuoka, Japan). Plasma glucose, triglyceride (TG), total protein, blood urea nitrogen (BUN), creatinine, total cholesterol, and albumin concentrations; alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase (ALP) activities; c-reactive protein (CRP), non-esterified fatty acid, malondialdehyde (MDA), serum amyloid A (SAA), insulin, and adiponectin (ADN) concentrations; glutathione peroxidase (GPx), superoxide dismutase (SOD), malate dehydrogenase (MDH), and lactate dehydrogenase (LDH) activities; and M/L ratio (MDH/LDH) were examined. Changes in the abovementioned plasma biomarker levels were compared between canines in different life stages., Results: Plasma ADN concentrations and GPx, SOD, and MDH activities significantly decreased with age, whereas plasma ALP, BUN, TG, and MDA concentrations gradually increased. Plasma SAA levels measured by the latex agglutination method in 51 of the 52 small dogs that underwent medical checkups were below the detection limit., Conclusion: Plasma ADN concentrations, GPx, SOD activity, and BUN levels may be important biomarkers for clarifying the effect of age in healthy dogs that undergo medical checkups. However, plasma SAA values obtained by the latex agglutination method were not considered an age-related inflammation marker for healthy dogs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Kusaba, Tago, Kusaba and Kawasumi.)

G protein-coupled receptor 84 (GPR84) was cloned as an orphan receptor, and medium-chain fatty acids were then revealed as endogenous ligands. GPR84 is expressed in immune cells and is believed to protect liver function from lipotoxicity caused by overeating and high-fat diet intake. This study aimed to present the molecular characterization of GPR84 in domestic cats. The deduced amino acid sequence of the feline GPR84 shows high sequence homology (83-89 %) with the orthologues from other mammalians by cDNA cloning of feline GPR84. Remarkably high mRNA expression was observed in the bone marrow by Q-PCR analysis. The inhibition of intracellular cAMP concentration was observed in cells transfected with feline GPR84 and treated with medium-chain fatty acids. Immunostaining of GPR84 and free fatty acid receptor 2 (FFAR2)/GPR43 in the bone marrow, where high mRNA expression was observed, showed reactions in macrophages and myeloid cells. To clarify whether the receptor formed homo/hetero-merization, GPR84 and FFARs were analyzed using Nano-Luc binary technology and NanoLuc bioluminescence resonance energy transfer technologies, which revealed that GPR84 formed more heteromers with FFAR2 than homomers with each other. In addition, when GPR84 and FFAR2/GPR43 were cotransfected in the cell, their localization on the cell membrane was reduced compared with that when single receptors were transfected. These results indicated that GPR84 is a functional receptor protein that is expressed in cat tissues and may have a protein-protein interaction with FFAR2/GPR43 on the cell membrane., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Thirteen dogs with intervertebral disk disease (IVDD) and 3 dogs with cervical disk herniation (CVDH) were examined to determine the effects of acupuncture on energy metabolism. Acupuncture points GV14, GV20-1, BL18, BL23, BL26, GB30, and ST36 were selected for IVDD, while GV14, GV20-1, GB20, and BL23 were selected for CVDH. All dogs except no.13 did not receive medication during acupuncture treatment. Acupuncture effects were evaluated based on the IVDD/CVDH evaluation scales in Oji 2015 and Tanaka and Nakayama 2015. Blood samples were taken before and 30 min after acupuncture treatment. Pyruvate and lactate concentrations, lactate dehydrogenase (LDH) and malate dehydrogenase (MDH) activity, the MDH/LDH ratio (M/L ratio), and LDH isozyme electrophoretic patterns served as energy metabolism markers. In IVDD/CVDH dogs that showed improvements, plasma pyruvate concentrations significantly decreased, the M/L ratio increased, and the plasma LDH isozyme pattern changed from predominantly LDH5 to predominantly LDH1. These data suggest that local redox potential is improved and energy metabolism is increased in dogs with IVDD/CVDH after acupuncture treatment. Acupuncture treatments may activate the citric acid cycle and increase ATP production, followed by improvement of the disease. Future studies with a large sample size are needed to clarify this hypothesis., (© 2022. The Author(s).)

Background/aim: Recently, the number of patients with cancer receiving outpatient chemotherapy using oral anticancer drugs has increased, but the currently available outpatient cancer chemotherapy is not safer than that available before. The present study aimed to identify risk factors associated with unplanned acute care (UAC) requiring outpatient chemotherapy-related consultation and hospitalisation., Patients and Methods: We conducted a case- control study among 1,674 patients who received oral anticancer drug treatment either alone or in combination with injectable anticancer drugs at National Cancer Center Hospital East, Japan, between December 1, 2014, and November 30, 2015., Results: Body mass index (BMI) was identified as a risk factor for UAC during chemotherapy. Patients with a BMI of <18.5 kg/m 2 , classified as underweight according to the World Health Organization classification of nutritional status, had a significantly higher risk of UAC., Conclusion: A low BMI immediately before the occurrence of chemotherapy-related UAC is a risk factor for adverse effects; therefore, underweight patients need more careful monitoring and supportive care., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: It has recently been suggested that concomitant medication may affect the clinical outcome of patients treated with immune checkpoint inhibitors (ICIs). However, only a few studies on the impact of concomitant medication on immune-related adverse events (irAEs) have previously been reported. Here, we aimed to determine the impact of concomitant medication on the efficacy and safety of ICIs., Methods: We retrospectively analyzed the data of 300 patients treated with nivolumab or pembrolizumab for advanced non-small cell lung cancer (NSCLC) between January 2016 and July 2018. Multivariate logistic regression analysis was used to assess the effect of concomitant medication on treatment response or irAEs. A multivariate Cox proportional hazards model was used to evaluate concomitant medication-related factors associated with time-to-treatment failure or overall survival (OS)., Results: A total of 70 patients responded to treatment and 137 experienced irAEs. The response rate and incidence of irAEs in patients treated with ICIs were not significantly associated with concomitant medication. Multivariate analysis showed that the use of opioids was an independent factor (time-to-treatment failure: hazard ratio 1.39, p = 0.021, OS: hazard ratio 1.54, p = 0.007)., Conclusions: The efficacy and safety of nivolumab or pembrolizumab in the treatment of patients with advanced NSCLC were not significantly influenced by concomitant medication. However, opioid usage might be associated with shorter OS in patients treated with these ICIs. Further mechanistic investigations should explore whether these associations are purely prognostic or contribute to ICI resistance., (© 2021 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

G protein-coupled receptors 41 and 43 were identified and characterized as free fatty acid receptors (FFAR) 3 and 2, respectively. FFAR2 and FFAR3 mediate short-chain fatty acids (SCFAs) as signalling molecules. The present study aimed to give molecular characterization of FFAR2 and FFAR3 in the domestic cat. High homology with that in other mammals was revealed by cDNA cloning of cat FFAR2 FFAR3. We analyzed the tissue distribution of cat FFAR2 and FFAR3 mRNA using quantitative polymerase chain reaction. The inhibition of intracellular cAMP concentrations was observed in cells transfected with cat FFAR2 or FFAR3 and treated with SCFAs. The activation of nuclear factor of activated T cells-luciferase reporter was only observed in cat FFAR2 transfected cells but not in FFAR3. Split luciferase assay (NanoLuc Binary Technology; NanoBiT) for FFAR2 or FFAR3 and Arrestin-3/β-arrestin-2 revealed acetate-/propionate-induced recruitment to cat FFAR2 or FFAR3 in CHO-K1 cells. Our results indicate that FFAR2 and FFAR3 are functional receptor proteins that are expressed in cat tissues and show differential distribution patterns., (© 2020 The Authors. Veterinary Medicine and Science published by John Wiley & Sons Ltd.)

The present study assessed the safety of outpatient oral anticancer chemotherapeutic drugs by investigating the type and frequency of serious adverse effects (SAEs). Emergency hospitalization, unplanned consultations and telephone calls were investigated in 1,832 patients who received oral anticancer drug treatment at the National Cancer Center Hospital East between December 1, 2014 and November 30, 2015. Oral cytotoxic anticancer and molecular targeted drugs were administrated to 1,140 (62.2%) and 692 (37.8%) patients, respectively. A total of 52 (2.8%) SAEs were reported, with 32 (2.8%) occurring following cytotoxic anticancer drug administration and 20 (2.9%) occurring after molecular targeted drug treatment. The most common SAE was gastrointestinal toxicity. The median time to SAE occurrence was 32 days (range, 5-1,705 days). The rate of unplanned consultations and telephone calls were 5.5 and 37.9% among all patients, respectively, with skin reactions being the most common reason for unplanned consultations. SAEs often occurred early after treatment initiation. It was concluded that measures against gastrointestinal toxicity are particularly important were administering chemotherapeutic agents., (Copyright © 2020, Spandidos Publications.)

Background: Animals tend to increase in body weight and body condition score (BCS) with aging. Serum diagnostic markers related to energy metabolism may show changes even in healthy cats with aging., Materials and Methods: Seventy domestic cats were recruited for this study. Based upon the modified AAFP-AAHA Feline Life Stage Guidelines, animals were divided into six groups: Junior (7 months-2 years), Prime (3 -6 years), Mature (7-10 years), Senior (11-14 years), Geriatric-obese (15 years ≤) and Geriatric-thin (15 years ≤). Their body condition scores (BCS) ranged from 3/9 to 9/9. Changes in metabolites, inflammatory markers, hormone concentrations and enzyme activities related to energy metabolism were investigated in serum of 70 domestic cats of various ages., Results: Serum glucose (GLU) concentrations in the Mature, Senior, and Geriatric-obese groups were significantly higher than those in the Junior group. Serum amyloid A (SAA) concentrations in the Geriatric-thin group were significantly increased compared with the Junior group. SAA concentrations in the Geriatric-obese group tended to increase although there were no statistically significant differences. In the Mature, Senior, Geriatric-obese and Geriatric-thin groups, malate dehydrogenase/lactate dehydrogenase (M/L) ratio, an energy metabolic indicator, tended to decrease compared with the Junior group. In the Senior group, triglyceride (TG) concentrations were significantly increased compared with the Junior group. In the Geriatric-obese and Geriatric-thin groups, blood urea nitrogen (BUN) concentrations were significantly increased compared with the Junior group. In the Geriatric-obese group, albumin (ALB) concentrations were decreased compared with the Junior group., Conclusion: Aged domestic cats tend to increase in body weight and BCS. In addition, serum GLU, TG, SAA, and BUN concentrations increased and serum ALB concentrations and M/L ratio decreased. These diagnostic markers may be useful to detect small changes related to energy metabolism with aging that may cause obesity with light inflammation in healthy cats., Competing Interests: The authors report no conflicts of interest and declare that this study was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2020 Mizorogi et al.)

The objective of this study was to evaluate blood levels of various hormones and compounds related to energy metabolism in cows with subacute ruminal acidosis (SARA). We investigated 11 lactating cows presumed to have SARA based on duration of ruminal pH <5.6 and reticulum pH <6.3 in 2015-2016. Kraft pulp (KP) was used to supplement feed of 7 of the cows studied in an effort to reduce SARA. We continuously monitored ruminal pH and measured blood concentrations of hormones and metabolites related to energy metabolism. Blood measurements included glucose (GLU), total cholesterol (TC), free fatty acid (FFA), insulin, adiponectin (ADN), malate dehydrogenase (MDH), and lactate dehydrogenase (LDH). Additionally, we analyzed milk data (milk yield, milk fat percentage, milk protein percentage, milk urea nitrogen, and protein fat ratio) and reproduction data. The results demonstrated that ADN levels at 4 weeks post-parturition correlated with the total amount of time that the ruminal or reticulum fluid pH was under the threshold during 1 week post-parturition, as well as the numbers of days the cows were diagnosed with SARA (SARA-positive days) up to 30 days post-parturition. SARA-positive days in 2016 were higher than those in 2015. In both years, numbers of SARA-positive days for cows supplemented with KP were lower than those for cows without KP. Increased ADN levels may be a compensatory reaction to frequent SARA which modulates the inflammatory response against high LPS levels and improves insulin resistance caused by LPS. ADN may serve as an estimative index for SARA.

Accumulated visceral and subcutaneous fat masses were measured with computed tomography (CT) in cats with various body condition scores (BCS) from 5/9 to 9/9. BCS does not always reflect visceral fat accumulation which induces pro-inflammatory reactions. Obese cats with accumulated visceral fat showed low plasma adiponectin and high serum amyloid A (SAA) concentrations, an inflammatory marker. Based on the above results, new diagnostic criteria for obesity disease were established as follows. For overweight cats with high BCS of >7/9, showing two or more of the following three symptoms, low adiponectin concentrations, hyperlipidemia, and high SAA concentrations, categorizes them as having obesity disease. Cats with BCS 6/9-9/9, without inflammatory reactions, were classified as simple obesity, which is similar to metabolically healthy obesity (MHO) defined in human medicine. Simple obesity group showed significantly higher adiponectin concentrations than those in control group. The obesity disease group showed significantly higher plasma triglyceride (TG) and SAA concentrations and lower concentrations of adiponectin than the control group. Moreover, plasma glucose and malondialdehyde (MDA) concentrations in the obesity disease group were higher than those in healthy control group, although the differences were not statistically significant. Establishing criteria for obesity disease based on visceral fat accumulation and inflammation markers levels contributes to early and correct diagnosis of obesity in cats.

The aim of this study is to discuss the effect of anti-oxidant supplement (Rv-PEM01-99, Kibun Foods, Inc., Tokyo, Japan) on changes in energy metabolism in obese dogs. 200 mg/kg/day of Rv-PEM01-99 (equivalent to 5 mg kg/day of quercetin derivative) were applied for 6 weeks to the Beagle dogs fed high fat diet (HFD) or control diet (CD). In the present study, body weight (BW) decreasing effect of Rv-PEM 01-99 in obese dogs was not clear. However, plasma alkaline phosphatase (ALP) activities at the end of experiment were significantly decreased compared to those at the start of experiment in obese dogs supplemented with Rv-PEM 01-99 (paired- t test, p < 0.05). In control dogs supplemented with Rv-PEM 01-99, Plasma malondialdehyde (MDA), and triglycerides (TG) levels and lactate dehydrogenase (LDH) activities were significantly decreased compared to those at the start of experiment (paired- t test, p < 0.05). From these findings, Rv-PEM 01-99 seems to be not harmful for dogs. Anti-lipid peroxide effect and liver function improvement are expected in the dogs supplemented with Rv-PEM 01-99.

Melanocortin 4 receptor (MC4R), which is a member of the G protein-coupled receptor (GPCR) family, mediates regulation of energy homeostasis upon the binding of α-melanocyte-stimulating hormone (α-MSH) in the central nervous system (CNS). Melanocortin 2 receptor accessory protein 2 (MRAP2) modulates the function of MC4R. We performed cDNA cloning of cat MC4R and MRAP2 and characterized their amino acid sequences, mRNA expression patterns in cat tissues, protein-protein interactions, and functions. We found high sequence homology (>88%) with other mammalian MC4R and MRAP2 encoding 332 and 206 amino acid residues, respectively. Reverse transcription-polymerase chain reaction analysis revealed that cat MC4R and MRAP2 mRNA were expressed highly in the CNS. In CHO-K1 cells transfected with cat MC4R, stimulation with α-MSH increased intracellular cyclic adenosine monophosphate (cAMP) concentration in a dose-dependent manner. Furthermore, the presence of MRAP2 enhanced the cat MC4R-mediated cAMP production. These results suggested that cat MC4R acts as a neuronal mediator in the CNS and that its function is modulated by MRAP2. In addition, our NanoBiT study showed the dynamics of their interactions in living cells; stimulation with α-MSH slightly affected the interaction between MC4R and MRAP2, and did not affect MC4R homodimerization, suggesting that they interact in the basal state and that structural change of MC4R by activation may affect the interaction between MC4R and MRAP2., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objectives: A recent study of community pharmacists in Canada reported that they required additional education. We conducted a survey of community pharmacists to evaluate the adequacy of education and training in oral anticancer agents in Japan., Methods: Between May and June 2014, community pharmacists were asked to complete a questionnaire by using two different survey strategies, one online and one via postal mail., Results: Three hundred community pharmacists responded to an online survey and 283 community pharmacists responded to a mailed survey. Only 6-10% of respondents felt that they had received adequate education in oncology or oral chemotherapy. Although 81% of Japanese pharmacists had attended at least one continuing education event related to oncology in the past 2 years, only 54% felt comfortable dispensing oral anticancer agents and only 40% felt comfortable educating patients about oral chemotherapy. In a multivariate analysis, confidence in educating patients about oral chemotherapy was associated with an understanding of chemotherapy cycles and doses (odds ratio = 4.89, 95% confidence interval [2.53-9.45]) and the number of continuing education events they had attended (odds ratio = 1.67, 95% confidence interval [1.35-2.08])., Conclusions: This is the first report to evaluate whether community pharmacists are equipped to ensure the safe use of oral anticancer agents in Japan. The results are similar to those previously reported for Canadian pharmacists, namely a low rate of positive responses for education in oncology and oral chemotherapy, demonstrating a similar need for additional education and training in oral chemotherapy., (© The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Eradication of schistosomiasis japonica in Yamanashi Prefecture was officially declared in 1996, and all surveillance and health campaign were finished by the end of 2001. Schistosomiasis control had been carried out by strong collaboration among local Government, local people and academia, thought which knowledge and experiences of the disease control were accumulated among the local people. It is 20 th anniversary of the disease eradication in Yamanashi. We planned to analyze the current situation whether the local people still keep the knowledge of schistosomiasis or not. There was no more knowledge kept in the middle school students, to whom the local Government did not educate about schistosomiasis. Among adult individuals, elderly people who have experienced endemic condition still know about it at almost comparable level as in the past. However, younger people who learned it in the primary school but no experience of the disease transmission started losing the knowledge. Those situations of the adult local people were compared with the veterinarian group. It was confirmed that the veterinarian group had correct and proper knowledge of schistosomiasis japonica not only in elderly groups, but also in younger age group. Considering that methods for control and prevention of infectious diseases are common to some extent, their knowledge and experiences would be applicable for other infectious diseases in future. Therefore, the knowledge would be worth keeping in the local people. Taken together, individuals with specialty, such as veterinarians, are expected to play roles in public health for promotion of health and welfare.

Reliable and short synthetic routes to polycyclic aromatic hydrocarbons and nanographenes are important in materials science. Herein, we report an efficient one-step annulative π-extension reaction of alkynes that provides access to diarylphenanthrenes and related nanographene precursors. In the presence of a cationic palladium/o-chloranil catalyst system and dibenzosiloles or dibenzogermoles as π-extending agents, a variety of diarylacetylenes are transformed successfully into 9,10-diarylphenanthrenes in a single step with good functional-group tolerance. Furthermore, double π-extension reactions of 1,4-bis(phenylethynyl)benzene and diphenyl-1,3-butadiyne are demonstrated, affording oligoarylene products, which show potential for application in the synthesis of larger polycyclic aromatic hydrocarbons and nanographenes., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background In the Japanese healthcare system, board certification not only maintains the quality of daily practice but is also required for hospitals to receive healthcare reimbursement. To date, no data on the effects of the board certification system in Japanese hospitals have been reported. Objective We performed a survey to clarify the impact of pharmacist certification on the quality of chemotherapy. Setting A nationwide mailing survey was conducted in Japan. Method We surveyed oncology pharmacists from 388 cancer designated hospitals (DHs) and 984 randomly selected general hospitals (GHs). Main outcome measure Multivariate analysis of factors for compliance with standard cancer chemotherapy to clarify the impact of pharmacist certification on the quality of chemotherapy. Results The response rate was 70.6 % (274/388) at the DHs and 43.4 % (428/984) at the GHs. Of the 13 different regimens, 66.1 % (181/274) of DHs and 64.7 % (277/428) of GHs reported having experienced either improper doses or intervals of drug administration. The median number of improper regimens was 1 at both the DHs (range 0-15) and GHs (range 0-22). We identified two groups of hospitals, those with two or more improper regimens and those with one improper regimen or less. Univariate analysis showed significant differences in the number of DHs (p < 0.01), performance of more than 10 chemotherapies per day (p < 0.05), presence of more than 400 beds (p < 0.01) and the professional qualifications of oncology pharmacists or medical oncologists. From multivariate analysis, significant differences were observed in certifications from the Japanese Society of Pharmacy Healthcare and Sciences certified Senior Oncology Pharmacist (odds ratio 0.29, p < 0.01) and the Japanese Society of Medical Oncology certified oncologist (odds ratio 0.48, p < 0.01). Conclusion Board certification was more prevalent in the designated (cancer specialist) hospitals than general hospitals and adherence to appropriate therapy was better when the DH was involved. Board certification was shown to be beneficial in terms of adherence to adequate chemotherapy.

Outpatient pharmacy services were established since June 2009 for educating about the signs and symptoms that required treatment, explaining how to receive an emergency service, improving a patient's adherence, and managing side effects. In this study, we evaluated the usefulness of one of our outpatient pharmacy services, which aims to help patients receiving adjuvant chemotherapy including S-1 monotherapy for gastric cancer. In total, 34 and 80 patients received S-1 monotherapy without or with the intervention of outpatient pharmacy services, respectively; additionally, the median ages of the former and latter were 68 and 65 years, respectively. The treatment completion rates(82.4% versus 67.5%)were similar between the 2 groups(odds ratio[OR]: 0.45, 95% confidence interval[CI]: 0.16-1.21, p=0.106). Their emergency visit rates were 23.5% and 8.8%(OR: 0.31, 95% Cl: 0.10-0.94, p<0.05). Emergency hospitalization was required for 8.8% and 0% of the population from each group(OR: 0.00, 95% CI: not significant, p<0.05). We suggest that outpatient pharmacy services are useful because they are likely to improve a patient's safety.