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Effect of Chronic Kidney Disease on Hepatic Clearance of Drugs in Rats
Get PDFThe pharmacokinetics of some hepatically cleared drugs have been reported to fluctuate in patients with renal impairment,
but the definitive factors have not been clarified. We compared the pharmacokinetics of some drugs with different hepatic elimination processes in a chronic kidney disease (CKD) rat model, to optimize their administration during kidney injury. We chose indocyanine green (ICG), midazolam (MDZ), and acetaminophen (APAP) as reference drugs to determine changes in hepatic clearance pathways in presence of CKD. Drugs were intravenously administered via the jugular vein to the CKD model rats, previously established by adenine administration, and then, blood, bile, and urine samples were collected. The plasma concentration of ICG, which is eliminated into the bile without biotransformation, increased; and its total body clearance (CLtot) significantly decreased in the CKD group compared to the control group.Moreover, the plasma concentrations of MDZ and APAP, metabolized in the liver
by CYP3A and Ugt1a6 enzymes, respectively, were higher in the CKD group than in the control group. The biliary clearances of APAP and its derivative APAP-glucuronide increased in the CKD group, whereas their renal clearances were markedly decreased with respect to those in the control group. Altogether, plasma concentrations of some hepatically eliminated drugs increased in the CKD rat model, but depending on their pharmacokinetic characteristics. This study provides useful information for optimizing the administration of some hepatically cleared drugs in CKD patients
Pathogenetic Potential Relating to Metabolic Activity in a Mouse Model of Infection with the Chikungunya Virus East/Central/South African Genotype
Get PDFEpidemics of the Chikungunya virus (CHIKV) from 2004 onwards were caused by the East/Central/South African (ECSA) genotype. However, the pathogenesis of the genotype infection has not been fully explained. In this study, we examined the pathogenic potential of CHIKV ECSA genotype M-30 (M-30) by comparing it with that of African genotype S-27 (S-27) in mice. Following low titer infections in type-I IFN receptor KO (A129) mice, we found that the M-30 infection caused high and acute fatality compared with the S-27 infection. M-30-infected A129 mice showed higher viral loads in their central nervous systems and peripheral organs, and increased levels of IFN- responses in their brains. Interestingly, M-30-infected mice did not show the hypophagia and reductions in weight which were observed in S-27-infected mice. Our observations provide a novel explanation of the pathogenic mechanisms attributed to virus proliferation, anti-type-II IFN response and metabolic activity in the CHIKV ECSA virus in mice
Two Measurements of Business Behavior
No full textThis paper aims to advance the concept ‘centers of gravity of organizations’
through analyzing the case story of Kenya Nut Company in the light of organizational life cycle. First, reviewing two
measurements, i.e., financial and non-financial, we rethink the theoretical relation between the two especially concerning start-up processes. Second, focusing on those who gather and depart repeatedly around centers of gravity of organizations in the long run, we
try to find out a key factor which affects specific directions of either gathering or departing. Based on the two autobiographies written by the founder Yoshiyuki Sato of Kenya Nut Company, the key factor seems not to be financial but to be non-financial, that is, his/her trembling impression of individual contributors toward each center
of gravity of organizations, such as Sato's business creed or Sato in person regardless of overt or covert. Thus, as trembling impressions transform each contributors' frame of cognition and motivation
status quo into the next one respectively and cumulatively, extant organizational equilibrium will be de-structured or renewed repeatedly over and over.松本睦樹教授定年退職記念号In Honour of Prof. Mutuki Matumot
Results of laparoscopic subtotal cholecystectomy by laparoscopic linear stapler in difficult cases with severe cholecystitis
Get PDFLaparoscopic subtotal cholecystectomy (LSC) has been recognized as a safe and feasible alternative surgical procedure for a difficult laparoscopic cholecystectomy (LC) with severe inflammation in Calot’s triangle. We compared the surgical outcomes
of cholecystectomy for acute cholecystitis between standard LC and LSC using laparoscopic linear stapler. 172 patients were diagnosed as acute cholecystitis, among them, 16 patients who underwent LSC and other 156 patients who underwent standard
LC were enrolled in this study. The severity grading of acute cholecystitis in LSC group was significantly higher than LC group. Operation time was longer in the LSC group than LC group. LSC had significantly more intraoperative blood loss compared to LC. However, there was no significant difference in the postoperative complications between two groups. LSC using laparoscopic linear stapler contributes surgeons avoid common bile duct injury in difficult LC
日本の土壌伝播蠕虫は制圧されているのか？分子生物学的手法を用いた日本の土壌伝播蠕虫感染状況調査結果
No full textBackground: Japan is one of the few countries believed to have eliminated soil-transmitted helminths (STHs). In 1949, the national prevalence of Ascaris lumbricoides was 62.9%, which decreased to 0.6% in 1973 due to improvements in infrastructure, socioeconomic status, and the implementation of national STH control measures. The Parasitosis Prevention Law ended in 1994 and population-level screening ceased in Japan; therefore, current transmission status of STH in Japan is not well characterized. Sporadic cases of STH infections continue to be reported, raising the possibility of a larger-scale recrudescence of STH infections. Given that traditional microscopic detection methods are not sensitive to low-intensity STH infections, we conducted targeted prevalence surveys using sensitive PCR-based assays to evaluate the current STH-transmission status and to describe epidemiological characteristics of areas of Japan believed to have achieved historical elimination of STHs. Methods: Stool samples were collected from 682 preschool- and school-aged children from six localities of Japan with previously high prevalence of STH. Caregivers of participants completed a questionnaire to ascertain access to water, sanitation and hygiene (WASH), and potential exposures to environmental contamination. For fecal testing, multi-parallel real-time PCR assays were used to detect infections of Ascaris lumbricoides, Necator americanus, Ancylostoma duodenale and Trichuris trichiura.
Results: Among the 682 children, no positive samples were identified, and participants reported high standards of WASH. Conclusions:
To our knowledge, this is the first STH-surveillance study in Japan to use sensitive molecular techniques for STH detection. The results suggest that recrudescence of STH infections has not occurred, and that declines in prevalence have been sustained in the sampled areas. These findings suggest that reductions in prevalence below the elimination thresholds, suggestive of transmission interruption, are possible. Additionally, this study provides circumstantial evidence that multi-parallel real-time PCR methods are applicable for evaluating elimination status in areas where STH prevalence is extremely low.長崎大学学位論文 学位記番号:博(医歯薬)甲第1250号 学位授与年月日:令和2年3月31日Author: Mitsuko Hasegawa, Nils Pilotte, Mihoko Kikuchi, Arianna R. Means, Marina Papaiakovou, Andrew M. Gonzalez, Jacqueline R. M. A. Maasch, Hiroshi Ikuno, Toshihiko Sunahara, Kristjana H. Ásbjörnsdóttir, Judd L. Walson, Steven A. Williams and Shinjiro Hamano on behalf of the DeWorm3 Project TeamCitation: Parasites & Vectors, 13, art.no.6; 202
淡明腎細胞癌におけるCD57+細胞、CD68+細胞、および肥満細胞の細胞密度と比率の病理学的意義と予後的役割
No full textThe immune system is closely associated with malignant behavior in renal cell carcinoma (RCC). Therefore, understanding the pathological roles of immune cells in tumor stroma is essential to discuss the pathological characteristics of RCC. In this study, the clinical significance of densities of CD57+ cells, CD68+ cells, and mast cells, and their ratios were investigated in patients with clear cell RCC. The densities of CD57+, CD68+, and mast cells were evaluated by immunohistochemical techniques in 179 patients. Proliferation index, apoptotic index, and microvessel density were evaluated by using anti–Ki-67, anti–cleaved caspase-3, and anti-CD31 antibodies, respectively. The density of CD57+ cell was negatively correlated with grade, pT stage, and metastasis, although densities of CD68+ cell and mast cell were positively correlated. Ratios of CD68+ cell/CD57+ cell and mast cell/CD57+ cell were significantly correlated with grade, pT stage, and metastasis. Survival analyses showed that the CD68+ cell/CD57+ cell ratio was a significant predictor for cause-specific survival by multivariate analyses (hazard ratio = 1.41, 95% confidence interval = 1.03-1.93, P = .031) and was significantly correlated with proliferation index, apoptotic index, and microvessel density (r = .47, P <. 001; r = −.31, P < .001; and r = .40, P < .001, respectively). In conclusion, CD57+ cells, CD68+ cells, and mast cells played important roles in malignancy in clear cell RCC. The CD68+ cell/CD57+ cell ratio was strongly correlated with pathological features and prognosis in these patients because this ratio reflected the status of cancer cell proliferation, apoptosis, and angiogenesis.長崎大学学位論文 学位記番号:博(医歯薬)甲第1218号 学位授与年月日:令和2年3月19日Author: Hiromi Nakanishi, Yasuyoshi Miyata, Yasushi Mochizuki, Takuji Yasuda, Yuichiro Nakamura, Kyohei Araki, Yuji Sagara, Tomohiro Matsuo, Kojiro Ohba, Hideki SakaiCitation: Human Pathology, 79, pp.102-108; 201
日本の神経発達症児における協調運動能力と認知能力、学習の習得度との関連
No full textBackground/Objective: Motor coordination impairment is common in children with neurodevelopmental disorders such as autism spectrum disorder (ASD) and attention deficit/hyperactivity disorder (AD/HD). The purpose of this study was to investigate the relationship between motor coordination, cognitive ability, and academic achievement in Japanese children with neurodevelopmental disorders. Methods: Thirty-four school-age (6–12 years old) children with neurodevelopmental disorders and 34 age-matched typically developing (TD) children were recruited in this study. Correlations between the scores of the Movement Assessment Battery for Children-2 (M-ABC2) and the Kaufman Assessment Battery for Children — Second Edition (K-ABCII) that assesses cognitive abilities, and academic achievement were analyzed. Results: The children with neurodevelopmental disorders obtained a lower total score and all component scores on M-ABC2 compared to the TD children. In children with neurodevelopmental disorders, M-ABC2 Manual Dexterity score was significantly correlated with K-ABCII Simultaneous Processing (r = .345, p = .046), Knowledge (r = .422, p = .013), Reading (r = .342, p = .048), Writing (r = .414, p = .017), and Arithmetic (r = .443, p = .009) scores. In addition, M-ABC2 Balance score was significantly correlated with K-ABCII Learning (r = .341, p = .048), Writing (r = .493, p = .004), and Arithmetic (r = .386, p = .024) scores. Conclusion: These findings stress that it is essential to accurately identify motor coordination impairments and the interventions that would consider motor coordination problems related to cognitive abilities and academic achievement in Japanese children with neurodevelopmental disorders.長崎大学学位論文 学位記番号:博(医歯薬)甲第1229号 学位授与年月日:令和2年3月19日Author: Takuya Higashionna, Ryoichiro Iwanaga, Akiko Tokunaga, Akio Nakai, Koji Tanaka, Hideyuki Nakane, Goro TanakaCitation: Hong Kong Journal of Occupational Therapy, 30(1), pp.49-55; 201