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1.
Endocr Pract ; 2024 Sep 10.
Article in English | MEDLINE | ID: mdl-39265808

ABSTRACT

OBJECTIVE: Hypercalcemia of malignancy is a risk factor for mortality in patients with malignancies. Although the parathyroid hormone-related protein (PTHrP) secreted by tumor cells induces hypercalcemia, the association between serum PTHrP levels and mortality remains unclear. This study aimed to investigate the association between serum PTHrP levels and mortality in patients with malignancies. METHODS: We included patients with hypercalcemia (>10 mg/dL) and elevated PTHrP levels (>1.0 pmol/L) and analyzed mortality (overall survival after cancer diagnosis, PTHrP measurement, and 5-year survival rate). Moreover, using Cox proportional hazard model analysis, we investigated the impact of PTHrP levels on survival prognosis, assessing whether this effect varied depending on calcium concentration. RESULTS: We analyzed the data of 183 patients. The median PTHrP level, corrected calcium level, and age were 5.5 (3.0-10.6) pmol/L, 12.5 (11.5-13.4) mg/dl, and 70 (61-76) years, respectively. PTHrP was significantly and linearly associated with serum calcium levels (correlation coefficient, 0.06; 95% confidence interval: 0.039-0.081, t: 5.69; p<0.001). The group with the highest PTHrP levels had significantly worse survival rates than the group with the lowest PTHrP levels (hazard ratio: 1.68, 95% confidence interval 1.03-2.77, p=0.038). CONCLUSION: This study showed an association between PTHrP and mortality in patients with malignancy after adjusting for serum calcium levels.

2.
PLoS One ; 19(8): e0309657, 2024.
Article in English | MEDLINE | ID: mdl-39208258

ABSTRACT

BACKGROUND: Patients undergoing hemodialysis are at an elevated risk of fractures; however, substantial evidence for osteoporosis treatment in this population is lacking. We explored the efficacy of denosumab, an anti-IgG2 antibody that targets the receptor activator of nuclear factor-kappa B ligand, in reducing fracture incidence and all-cause mortality in patients undergoing hemodialysis. METHODS: This retrospective cohort study-conducted from December 2013 to December 2022-evaluated the effects of denosumab on fracture incidence and all-cause mortality. Patients who initiated denosumab treatment during the study period were defined as the denosumab group, while those without a history of denosumab administration were defined as the non-denosumab group. Kaplan-Meier curves and log-rank tests were used to assess survival and fracture/mortality risks, respectively. Cox proportional hazards models were used to analyze both fractures and all-cause mortality. RESULTS: Among 214 patients undergoing hemodialysis, 52 (24.3%) received denosumab. The median age was 73.0 ± 11.5 years, with 92 (43.0%) females, and the median dialysis duration was 59 months (interquartile range, 6-126). During the study, thirty-seven non-denosumab-treated patients had fractures compared to eight in the denosumab group. No significant differences were observed in the unadjusted model (HR, 0.53; 95% confidence interval (CI), 0.24-1.14). Adjusting for competing mortality and clinical factors, the HR remained at 0.64 (95% CI, 0.27-1.51). Regarding all-cause mortality, we found a statistically significant difference in the unadjusted model (HR, 0.61 [95% CI, 0.38-0.98]). A significant reduction in mortality was observed in the adjusted model (HR, 0.46 [95% CI, 0.26-0.80]). Notably, the denosumab group showed a significant decrease in mortality, particularly in cardiovascular disease-related cases (HR, 0.33 [95% CI, 0.14-0.78]). CONCLUSIONS: Denosumab may reduce all-cause mortality in patients undergoing hemodialysis, particularly in those with cardiovascular complications. This finding offers a promising direction for osteoporosis treatment in patients undergoing hemodialysis.


Subject(s)
Denosumab , Fractures, Bone , Renal Dialysis , Humans , Denosumab/therapeutic use , Female , Male , Retrospective Studies , Aged , Incidence , Fractures, Bone/mortality , Fractures, Bone/epidemiology , Aged, 80 and over , Middle Aged , Bone Density Conservation Agents/therapeutic use , Kaplan-Meier Estimate , Osteoporosis/drug therapy , Osteoporosis/mortality , Osteoporosis/epidemiology , Proportional Hazards Models , Kidney Failure, Chronic/therapy , Kidney Failure, Chronic/mortality
3.
Clin Exp Nephrol ; 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38954308

ABSTRACT

BACKGROUND: The relationship between chronic kidney disease-mineral and bone disorder (CKD-MBD) and cognitive function remains largely unknown. This cross-sectional study aimed to explore the association between CKD-MBD and cognitive function in patients on hemodialysis. METHODS: Hemodialysis patients aged ≥ 65 years without diagnosed dementia were included. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE). CKD-MBD markers, serum magnesium, intact parathyroid hormone (PTH), 25-hydroxyvitamin D (25-OHD), fibroblast growth factor (FGF)-23, and soluble α-klotho were measured. RESULTS: Overall, 390 patients with a median age of 74 (interquartile range, 70-80) years, mean serum magnesium level of 2.4 ± 0.3 mg/dL, and median MoCA and MMSE scores of 25 (22-26) and 28 (26-29), respectively, were analyzed. MoCA and MMSE scores were significantly higher (preserved cognitive function) in the high-magnesium group than in the low-magnesium group according to the unadjusted linear regression analysis (ß coefficient [95% confidence interval (CI)] 1.05 [0.19, 1.92], P = 0.017 for MoCA; 1.2 [0.46, 1.94], P = 0.002 for MMSE) and adjusted multivariate analysis with risk factors for dementia (ß coefficient [95% CI] 1.12 [0.22, 2.02], P = 0.015 for MoCA; 0.92 [0.19, 1.65], P = 0.014 for MMSE). CONCLUSIONS: Higher serum magnesium levels might be associated with preserved cognitive function in hemodialysis patients. Conversely, significant associations were not observed between cognitive function and intact PTH, 25-OHD, FGF-23, or soluble α-klotho levels.

4.
Clin Exp Nephrol ; 28(9): 917-924, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38594468

ABSTRACT

BACKGROUND: Calcium supplements are commonly prescribed to prevent fractures in patients with osteoporosis. Nonetheless, they are generally eschewed in hemodialysis patients because they increase vascular calcification and induce cardiovascular disease. This retrospective cohort study aimed to investigate the effect of calcium-based phosphate binders (CBPB) on bone mineral density (BMD) in hemodialysis patients. METHODS: Outpatients on dialysis who underwent BMD measurement from January to December 2017, whose data on BMD trends and CBPB administration were recorded over the next 4 years, were enrolled. Patients receiving anti-osteoporotic medications were excluded. The association between the presence and duration of CBPB administration and changes in BMD was evaluated. RESULTS: The femoral neck's BMD decreased from 0.836 g/cm2 (0.702-0.952) to 0.764 g/cm2 (0.636-0.896) (P < 0.001) in the non-CBPB group (patients who never received CBPB over 4 years, n = 32). The CBPB group (n = 56) exhibited only a minute decrease from 0.833 g/cm2 (0.736-0.965) to 0.824 g/cm2 (0.706-0.939) (P = 0.004). Multivariate linear regression analysis revealed better BMD maintenance in the CBPB group [ß-coefficient (95% CI): 0.033 (0.001-0.065); P = 0.046] than in the non-CBPB group. Additionally, the prolonged-CBPB administration group showed superior BMD preservation [ß-coefficient (95% CI): 0.038 (0.001-0.076); P = 0.042]. CONCLUSION: CBPB administration may be associated with BMD maintenance.


Subject(s)
Bone Density , Renal Dialysis , Humans , Renal Dialysis/adverse effects , Retrospective Studies , Bone Density/drug effects , Female , Male , Middle Aged , Aged , Femur Neck/diagnostic imaging , Osteoporosis/prevention & control , Osteoporosis/etiology , Phosphates , Chelating Agents/therapeutic use
5.
Ther Apher Dial ; 28(4): 599-607, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38504452

ABSTRACT

INTRODUCTION: Vaccination is the effective strategy for coronavirus disease 2019 (COVID-19). However, few studies have investigated the association between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunoglobulin (Ig)G and vitamin D. METHODS: This study aimed to investigate the association between SARS-CoV-2 IgG and active vitamin D analogs in hemodialysis patients. Blood samples were collected four times: before vaccination and 30, 60, and 90 days after vaccination, BNT162b2 (Pfizer©). RESULTS: A total of 418 patients were enrolled. The mean age was 71.1 ± 12 years. Almost two thirds of the patients were prescribed active vitamin D analogs. The distribution of SARS-CoV-2 IgG before vaccination was 235 (93-454) AU/mL. After multiple regression analyses, active vitamin D analog use was found to be associated with higher SARS-CoV-2 IgG levels from prevaccination to 90 days postvaccination. CONCLUSION: This study demonstrated an association between higher SARS-CoV-2 IgG and active vitamin D analog use in hemodialysis patients. CLINICAL TRIAL REGISTRATION: The study information was registered in the UMIN-CTR (UMIN 000046906).


Subject(s)
Antibodies, Viral , BNT162 Vaccine , COVID-19 , Immunoglobulin G , Renal Dialysis , Vitamin D , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Antibodies, Viral/blood , COVID-19/prevention & control , COVID-19/immunology , Immunoglobulin G/blood , SARS-CoV-2/immunology , Vaccination , Vitamin D/analogs & derivatives , Vitamin D/blood
6.
J Bone Miner Metab ; 42(2): 264-270, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38512458

ABSTRACT

INTRODUCTION: Denosumab, a fully human anti-RANKL monoclonal antibody, is a widely used osteoporosis treatment that is increasingly being used in patients undergoing dialysis; however, its long-term efficacy and safety in these patients remain unknown. MATERIALS AND METHODS: This observational study comprised individuals aged ≥ 20 years undergoing hemodialysis and receiving denosumab. After denosumab administration, we analyzed the long-term changes in bone mineral density (BMD) and levels of bone turnover markers (BTMs) and calcium. RESULTS: The study included 45 patients who have been receiving denosumab for a median duration of 3.8 (interquartile range, 2.5-6.7) years. Tartrate-resistant acid phosphatase 5b (TRACP-5b) levels decreased from a median of 595 (434-778) mU/dL at baseline to 200 (141-430) mU/dL after 6 months of denosumab administration (P < 0.001) and remained low thereafter. Similarly, bone-specific alkaline phosphatase (BAP) levels decreased from a median of 18.2 (15.9-25.8) µg/L at baseline to 12.4 (9.9-15.6) µg/L after 6 months (P < 0.001) and remained low thereafter. Meanwhile, BMD, as assessed with dual energy X-ray absorptiometry and measured at the distal 1/3 of the radius, did not decrease (0.465 ± 0.112 g/cm2 at baseline vs. 0.464 ± 0.112 g/cm2 after administration; P = 0.616). Regarding hypocalcemia, corrected calcium levels reached were the lowest at 7 days after administration and normalized within 30 days. CONCLUSION: The study showed long-term suppression of TRACP-5b and BAP levels and sustaining BMD after denosumab administration over an extended period in patients undergoing hemodialysis.


Subject(s)
Bone Density Conservation Agents , Bone Density , Humans , Denosumab/pharmacology , Bone Density Conservation Agents/pharmacology , Bone Density Conservation Agents/therapeutic use , Calcium/pharmacology , Tartrate-Resistant Acid Phosphatase , Bone Remodeling , Alkaline Phosphatase , Renal Dialysis , Biomarkers
7.
Front Nutr ; 10: 1260506, 2023.
Article in English | MEDLINE | ID: mdl-38045811

ABSTRACT

Introduction: Medium-chain fatty acids (MCFAs) have attracted considerable attention for preventing or improving obesity, which is a recognized risk factor for lifestyle-related diseases. Medium- and long-chain triglycerides (MLCTs) are expected to improve the metabolism of ingested long-chain triglycerides (LCTs). However, previous studies have reported mixed results. In this study, the effect of ingestion of MLCTs was evaluated on the metabolism of LCTs and compared to the ingestion of rapeseed oil (control oil). Methods: A randomized, double-blind, placebo-controlled crossover study was performed among sedentary participants with BMIs ranging from 25 below 30 kg/m2. Thirty participants were asked to ingest either 14 g of MLCTs or a control oil for 4 weeks. The metabolism of ingested LCTs was evaluated by measuring isotopically labeled carbon dioxide released by the degradation of carbon-13 (13C)-labeled LCTs. Results: Ingestion of MLCTs markedly enhanced the metabolism of ingested LCTs by comparison to the control oil. Conclusion: The findings of this study suggest that ingestion of MLCTs may enhance the metabolism of dietary LCTs through activation of ß-oxidation in liver mitochondria, which may increase the metabolic kinetics of ingested long-chain fatty acid (LCFAs). Clinical trial registration: https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000053101, identifier: UMIN000046604.

8.
BMC Nephrol ; 24(1): 244, 2023 08 22.
Article in English | MEDLINE | ID: mdl-37605118

ABSTRACT

BACKGROUND: Patients with chronic kidney disease (CKD) present high mortality and morbidity rates despite the availability of various therapies. Although CKD-mineral and bone disorder (MBD) and renal anemia are important factors in patients with CKD, only few studies have analyzed the relationship between them. Therefore, this study aimed to evaluate the relationship between CKD-MBD and anemia in patients with CKD who did not receive erythropoiesis-stimulating agent or iron therapies. METHODS: This retrospective cross-sectional study included patients with CKD aged ≥ 20 years with estimated glomerular filtration rate (eGFR) categories G2a to G5 who were referred to the Fuji City General Hospital between April 2018 and July 2019. The exclusion criterion was ongoing treatment for CKD-MBD and/or anemia. RESULTS: The data of 300 patients with CKD were analyzed in this study. The median age of patients was 71 (range, 56.5-79) years. The median eGFR was 34 (range, 20-48) mL/min/1.73 m2, and the mean hemoglobin (Hb) level was 12.7 g/dL (standard deviation, 2.3), which decreased as the CKD stage increased. In a multivariate linear regression analysis of anemia-related factors, including age, renal function (eGFR), nutritional status, inflammation, and iron dynamics (serum iron level, total iron-binding capacity, ferritin levels), the serum phosphate levels were significantly associated with the Hb levels (coefficient [95% confidence interval], -0.73 [-1.1, -0.35]; P < 0.001). Subgroup analysis revealed a robust association between serum phosphate levels and Hb levels in the low-ferritin (coefficient [95% confidence interval], -0.94 [-1.53, -0.35]; P = 0.002) and advanced CKD groups (coefficient [95% confidence interval], -0.89 [-1.37, -0.41]; P < 0.001). CONCLUSIONS: We found an association between high serum phosphate levels and low Hb levels in patients with CKD not receiving treatment for anemia. These results underscore the possibility of a mechanistic overlap between CKD-MBD and anemia.


Subject(s)
Anemia , Chronic Kidney Disease-Mineral and Bone Disorder , Phosphates , Renal Insufficiency, Chronic , Aged , Humans , Middle Aged , Anemia/epidemiology , Cross-Sectional Studies , Ferritins , Iron , Phosphates/blood , Renal Insufficiency, Chronic/epidemiology , Retrospective Studies , Male , Female
9.
Clin Chim Acta ; 538: 157-163, 2023 Jan 01.
Article in English | MEDLINE | ID: mdl-36417978

ABSTRACT

BACKGROUND: The chronic abnormal production of testosterone (T) is associated with many disorders in men. Fingernail clippings might be more suited for the diagnosis and medium-to-long term therapeutic monitoring for the T-related chronic disorders than the blood-derived specimens. The objective of this study was to characterize a thumbnail clipping as the specimen for assessing the several months-old T status. METHODS: Thumbnail clippings from various subjects were analyzed by liquid chromatography/electrospray ionization-tandem mass spectrometry to evaluate the gender difference, and changes caused by aging and androgen deprivation therapy (ADT) in the thumbnail T concentration. RESULTS: There was an evident gender difference in the thumbnail T concentrations [male; 2.55 ± 0.85 ng/g and female; 0.48 ± 0.29 ng/g, mean ± SD (n = 25 each), Welch t-test]. The thumbnail T concentrations significantly decreased with age in men (n = 268, Scheffé F-test), which was similar to those of the free or bioavailable T in serum/plasma. The thumbnail T concentrations sharply decreased by a 6-months ADT (especially the effect of the luteinizing hormone-releasing hormone agonist/antagonist) for patients with prostate cancer (n = 10). CONCLUSIONS: The thumbnail clipping can be a specimen to retrospectively assess the average T production.


Subject(s)
Nails , Testosterone , Humans , Male , Androgen Antagonists/therapeutic use , Nails/chemistry , Retrospective Studies , Testosterone/analysis
10.
Ther Apher Dial ; 27(3): 552-561, 2023 Jun.
Article in English | MEDLINE | ID: mdl-36507605

ABSTRACT

INTRODUCTION: We conducted an observational study to test the hypothesis that intact parathyroid hormone (PTH) levels are independently associated with pulse wave velocity (PWV), indicating arteriosclerosis progression. METHODS: In this cross-sectional study, patients on hemodialysis in whom brachial-ankle PWV (baPWV) was measured from November 2020 to November 2021, were included. RESULTS: One hundred seventy-four patients, with a mean age of 69.9 years (standard deviation [SD], 11.9), were included in this study. In multivariate linear regression analysis, serum intact PTH levels were correlated with baPWV (ß coefficient: 95% confidence interval [CI], 2.1 [0.22, 3.99]; p = 0.029). The subgroup analysis, which was divided according to the presence of diabetes, showed that diabetes has a significant interaction between PTH and PWV. CONCLUSION: These results suggest that intact PTH is independently associated with PWV. Moreover, physiological mechanisms characteristic of diabetes may be involved in the association between PTH and arteriosclerosis.


Subject(s)
Arteriosclerosis , Diabetes Mellitus , Humans , Aged , Pulse Wave Analysis/methods , Cross-Sectional Studies , Renal Dialysis , Parathyroid Hormone , Ankle Brachial Index
11.
Gan To Kagaku Ryoho ; 49(5): 520-524, 2022 May.
Article in Japanese | MEDLINE | ID: mdl-35578925

ABSTRACT

This paper reports the 5-year operational status of the third phase of the"All Japan E-Learning Cloud of the Training Program for Oncology Professionals"by tabulating the viewing trends of available lecture contents. In this phase, the goal was to train cancer genome medical professionals in this new, advanced medical technology field as well as train personnel to treat rarely encountered pediatric, adolescent/young adult, and other life stage cancers. Additionally, new lecture items have been added to the e-learning cloud in collaboration with 7 oncology specialist centers, contributing to the development of human capital in cancer care(including graduate student education)and faculty development for local medical professionals.


Subject(s)
Computer-Assisted Instruction , Neoplasms , Adolescent , Child , Humans , Japan , Learning , Medical Oncology/education , Neoplasms/therapy , Young Adult
12.
Nutrients ; 14(3)2022 Jan 26.
Article in English | MEDLINE | ID: mdl-35276897

ABSTRACT

Increasing fat burning during physical activity is thought to be an effective strategy for maintaining health and preventing lifestyle-related diseases, such as obesity and diabetes. In recent years, medium-chain triglycerides (MCTs) have gained attention as a dietary component for increasing fat-burning. However, this fat-burning effect has been unclear in people with high body mass index (BMI). Therefore, we aimed to clarify the effects of 2 g of daily ingestion of MCTs over 2 weeks on substrate oxidation during low-intensity physical activity in sedentary (i.e., with no exercise habit) subjects with a BMI from 25 (kg/m2) to less than 30, which is classified as obese in Japan. A placebo-controlled, randomized, double-blind, crossover study with a 2-week washout period was conducted. The rate of fat oxidation as well as the respiratory exchange ratio (RER) during exercise (with a cycle ergometer at a 20-watt load) were measured with a human calorimeter. MCTs ingestion significantly increased fat oxidation during physical activity and decreased RER compared to long-chain triglycerides ingestion. In conclusion, we suggest that daily ingestion of 2 g of MCTs for 2 weeks increases fat burning during daily physical activities in sedentary persons with a BMI ranging from 25 to less than 30.


Subject(s)
Adipose Tissue , Energy Metabolism , Adipose Tissue/metabolism , Cross-Over Studies , Eating , Exercise , Humans , Triglycerides/metabolism
13.
Nutrients ; 14(5)2022 Mar 07.
Article in English | MEDLINE | ID: mdl-35268094

ABSTRACT

The elimination of obesity is essential to maintaining good health. Medium-chain triglycerides (MCTs) inhibit fat accumulation. However, studies examining energy expenditure and fat oxidation with continuous ingestion of MCTs show little association with the elimination of obesity. In this study, we conducted a randomized, double-blind crossover clinical trial to investigate the effects of continuous ingestion of MCTs on postprandial energy expenditure and ingested long-chain triglycerides (LCTs) oxidation. A daily 2 g of MCTs were ingested for two weeks by sedentary participants with a body mass index (BMI) from 25 (kg/m2) to less than 30. Ingestion of a meal containing MCTs and isotopic carbon-13-labeled (13C) LCTs increased energy expenditure and consumption of diet-derived LCTs, as determined by postprandial 13C carbon dioxide excretion, compared to canola oil as the placebo control. These results indicate that continuous ingestion of MCTs could enhance postprandial degradation of diet-derived fat and energy expenditure in sedentary, overweight individuals.


Subject(s)
Eating , Postprandial Period , Body Mass Index , Cross-Over Studies , Humans , Triglycerides
14.
Nutrients ; 13(12)2021 Dec 02.
Article in English | MEDLINE | ID: mdl-34959901

ABSTRACT

Patients with chronic kidney disease (CKD) and dialysis have higher mortality than those without, and cardiovascular disease (CVD) is the main cause of death. As CVD is caused by several mechanisms, insulin resistance plays an important role in CVD. This review summarizes the importance and mechanism of insulin resistance in CKD and discusses the current evidence regarding insulin resistance in patients with CKD and dialysis. Insulin resistance has been reported to influence endothelial dysfunction, plaque formation, hypertension, and dyslipidemia. A recent study also reported an association between insulin resistance and cognitive dysfunction, non-alcoholic fatty liver disease, polycystic ovary syndrome, and malignancy. Insulin resistance increases as renal function decrease in patients with CKD and dialysis. Several mechanisms increase insulin resistance in patients with CKD, such as chronic inflammation, oxidative stress, obesity, and mineral bone disorder. There is the possibility that insulin resistance is the potential future target of treatment in patients with CKD.


Subject(s)
Insulin Resistance , Renal Insufficiency, Chronic/physiopathology , Cardiovascular Diseases/etiology , Cognitive Dysfunction/etiology , Dyslipidemias/etiology , Humans , Hypertension/etiology , Molecular Targeted Therapy , Non-alcoholic Fatty Liver Disease/etiology , Oxidative Stress , Renal Insufficiency, Chronic/therapy
15.
Xenobiotica ; 51(9): 983-994, 2021 Sep.
Article in English | MEDLINE | ID: mdl-34227923

ABSTRACT

Chimeric mice are immunodeficient mice in which the majority of the hepatic parenchymal cells are replaced with human hepatocytes.Following intravenous administration of 24 model compounds to control and chimeric mice, human hepatic clearance (CLh) was predicted using the single-species allometric scaling (SSS) method. Predictability of the chimeric mice was better than that of the control mice.Human CLh was predicted by the physiologically based scaling (PBS) method, wherein observed CLh in chimeric mice was first converted to intrinsic CLh (CLh,int). As the liver of chimeric mice contains remaining mouse hepatocytes, CLh,int was corrected by in vitro CLh ratios of the mouse to human hepatocytes according to their hepatocyte replacement index. Further, predicted human CLh was calculated based on an assumption that CLh,int in chimeric mice normalised for their liver weight was equal to CLh,int per liver weight in humans. Consequently, better prediction performance was observed with the use of the PBS method than the SSS method.SSS method is an empirical method, and the effects of coexisting mouse metabolism cannot be avoided. However, the PBS method with in vitro CLh correction might be a potential solution and may expand the application of chimeric mice in new drug development.


Subject(s)
Pharmaceutical Preparations , Animals , Chimera , Hepatocytes , Humans , Liver/metabolism , Metabolic Clearance Rate , Mice , Pharmaceutical Preparations/metabolism
16.
Xenobiotica ; 51(4): 479-493, 2021 Apr.
Article in English | MEDLINE | ID: mdl-33455494

ABSTRACT

Common marmosets (Callithrix jacchus) are small non-human primates that genetically lack cytochrome P450 2C9 (CYP2C9). Polymorphic marmoset CYP2C19 compensates by mediating oxidations of typical human CYP2C9/19 substrates.Twenty-four probe substrates were intravenously administered in combinations to marmosets assigned to extensive or poor metaboliser (PM) groups by CYP2C19 genotyping. Eliminations from plasma of cilomilast, phenytoin, repaglinide, tolbutamide, and S-warfarin in the CYP2C19 PM group were significantly slow; these drugs are known substrates of human CYP2C8/9/19.Human total clearance values and volumes of distribution of the 24 test compounds were extrapolated using single-species allometric scaling with experimental data from marmosets and found to be mostly comparable with the reported values.Human total clearance values and volumes of distribution of 15 of the 24 test compounds similarly extrapolated using reported data sets from cynomolgus or rhesus monkeys were comparable to the present predicted results, especially to those based on data from PM marmosets.These results suggest that single-species allometric scaling using marmosets, being small, has advantages over multiple-species-based allometry and could be applicable for pharmacokinetic predictions at the discovery stage of drug development.


Subject(s)
Callithrix , Omeprazole , Animals , Cytochrome P-450 CYP2C19/genetics , Cytochrome P-450 CYP2C9 , Genotype , Humans , Warfarin
17.
Nutrients ; 13(1)2020 Dec 24.
Article in English | MEDLINE | ID: mdl-33374218

ABSTRACT

Fat oxidation (FAO) during aerobic exercise and whole-body FAO via lipid intake are thought to be important for the maintenance of health, such as the prevention of type 2 diabetes and obesity in sedentary persons in their 40s and 50s. Medium-chain triglycerides (MCTs) ingestion has been attracting attention. However, the effects of difference of sex and the composition of medium-chain fatty acids (MCFAs) are unclear, so we examined the effects of these factors on FAO during aerobic exercise. We conducted a randomized, double-blind, placebo-controlled, 3-arm, within-participants crossover trial. FAO during low- to moderate-intensity exercise was compared when octanoate-rich MCTs (C8R), decanoate-rich MCTs (C10R), or carbohydrate (control) was ingested. Three 2-week interventions were separated by two 2-week washout periods. An increase of FAO during exercise after the C8R diet was found in males, but not in females. An increase of carbohydrate oxidation (CAO) and oxygen uptake during exercise after the C10R diet was found in females, but not in males. In a pooled estimate of the effect of MCTs (C8R and C10R) in women and men, FAO increased during exercise. In conclusion, short-term ingestion of MCTs by middle-aged sedentary persons could increase FAO during aerobic exercise compared to carbohydrate ingestion, but the enhancing effect of MCTs on substrate utilization and oxygen uptake might vary, depending on sex and the composition of MCFAs.


Subject(s)
Dietary Fats/administration & dosage , Exercise/physiology , Sedentary Behavior , Sex Characteristics , Triglycerides/administration & dosage , Adult , Caprylates/administration & dosage , Cross-Over Studies , Dietary Carbohydrates/administration & dosage , Dietary Fats/metabolism , Double-Blind Method , Female , Humans , Japan , Male , Middle Aged , Oxidation-Reduction , Oxygen Consumption , Placebos
18.
Case Rep Nephrol ; 2020: 5698708, 2020.
Article in English | MEDLINE | ID: mdl-32509365

ABSTRACT

Systemic lupus erythematosus/antineutrophil cytoplasmic antibody-associated vasculitis overlap syndrome (SLE/AAV OS) describes a pathological condition that presents with overlapping features of two diseases. There have been few reports of SLE/AAV OS and none from Japan. We present the case of a 59-year-old woman admitted with chief complaints of fever and decreased renal function. SLE was suspected due to the identification of four items from the diagnostic criteria of the American College of Rheumatology, including positivity for anti-ds-DNA and antinuclear antibodies. However, pathological findings from the kidney biopsy suggested pauci-immune crescentic glomerulonephritis. She was also diagnosed with AAV according to the Chapel Hill Consensus Conference (CHCC) 2012 definitions and the classification algorithm of AAV. SLE/AAV OS was suspected, we started immunosuppressant therapy, and subsequently her renal function improved. In previous reports, initial immunological and pathological findings generally concur. In cases where clinical and pathological features appear to conflict, as in the present case, a treatment strategy decision should be based on pathological and immunological findings to improve the prognosis of OS.

19.
Lipids ; 55(2): 173-183, 2020 03.
Article in English | MEDLINE | ID: mdl-32058596

ABSTRACT

Previous studies in recreational and trained athletes aged mostly in their 20s have reported that short-term ingestion of medium-chain triacylglycerols (MCT) enhances fat oxidation (FAO) during submaximal exercise. However, whether the FAO-enhancing effect of MCT with a different composition of medium-chain fatty acids (MCFA) occurs in older sedentary persons is unclear. The present study investigated the effect of MCT ingestion with different proportions of MCFA in sedentary participants in their 40's and 50's. Participants ingested 0 g of MCT (control), 6 g of octanoic acid-rich MCT (OAR), or 6 g of decanoic acid-rich MCT (DAR) for 14 days separated by a 14-day washout period in random order. Cumulative FAO (Fcv ) during submaximal, fixed, and incremental exercise was evaluated at workload from 20 W to the appearance of a ventilation threshold (VT). During the 20 W fixed-load exercise, Fcv was significantly (p < 0.05) higher in the OAR than in the control. At appearance of VT, intervention effect of power output was significantly higher in the OAR and DAR than in the control. In a subgroup analysis by age, intervention effects of maximal FAO rate and oxygen uptake in the upper age subgroup were higher in the OAR and DAR than in the control. In a pooled analysis with age subgroup and diet, the integrated pooled estimate of Fcv during submaximal exercise was significantly higher in 6 g of MCT ingestion than 0 g ingestion. Our data show that the effect of MCT might differ depending on the age group and the proportion of MCFA, while MCT could enhance FAO during submaximal exercise.


Subject(s)
Caprylates/administration & dosage , Decanoic Acids/administration & dosage , Exercise/physiology , Fatty Acids/chemistry , Adult , Age Factors , Caprylates/pharmacology , Cross-Over Studies , Decanoic Acids/pharmacology , Double-Blind Method , Humans , Male , Middle Aged , Oxidation-Reduction/drug effects , Oxygen/metabolism , Sedentary Behavior
20.
Respir Med Case Rep ; 29: 100990, 2020.
Article in English | MEDLINE | ID: mdl-31908917

ABSTRACT

Rapid decline of pulmonary function in acute respiratory distress syndrome (ARDS) can make ARDS a dangerous and potentially life-threatening condition. Gadolinium-based contrast agents are considered safe alternatives to iodine-based contrast agents, with comparatively fewer adverse effects and a lower incidence of serious adverse events, such as dyspnea or hypotension. There are five reported cases of gadolinium-induced ARDS. A 59-year-old woman with respiratory failure 30 min after gadolinium administration was diagnosed with ARDS; she was admitted to the intensive care unit. Her condition improved by artificial respiration management and adrenaline and steroids administration. She was discharged on day 13. Considering ARDS occurred 30 min after gadolinium administration and findings suggesting anaphylaxis, such as wheezing and failure in organs other than the lungs, were absent, the involvement of any immediate-onset reaction was excluded; thus, a diagnosis of gadolinium-induced ARDS was made.

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