Markers for obese and non-obese Type 2 diabetes identified using whole blood metabolomics

Definitive differences in blood metabolite profiles between obese and non-obese Type 2 diabetes (T2D) have not been established. We performed an LC–MS-based non-targeted metabolomic analysis of whole blood samples collected from subjects classified into 4 types, based on the presence or absence of obesity and T2D. Of the 125 compounds identified, 20, comprising mainly nucleobases and glucose metabolites, showed significant increases or decreases in the T2D group. These included cytidine, UDP-glucuronate, UMP, 6-phosphogluconate, and pentose-phosphate. Among those 20 compounds, 11 enriched in red blood cells (RBCs) have rarely been studied in the context of diabetes, indicating that RBC metabolism is more extensively disrupted than previously known. Correlation analysis revealed that these T2D markers include 15 HbA1c-associated and 5 irrelevant compounds that may reflect diabetic conditions by a different mechanism than that of HbA1c. In the obese group, enhanced protein and fatty acid catabolism causes increases in 13 compounds, including methylated or acetylated amino acids and short-chain carnitines. Our study, which may be considered a pilot investigation, suggests that changes in blood metabolism due to obesity and diabetes are large, but essentially independent.journal articl

Radiological evaluation of joint space width in medial knee osteoarthritis

Background. Although joint space width on weight-bearing radiographs of the knee is critical for early diagnosis and grading knee osteoarthritis, the optimal method with which to accurately measure this value remains controversial. The purpose of this study was to investigate and quantify the effects of the radiographic technique on joint space width in medial knee osteoarthritis.Materials and Methods. We compared maximum plateau gaps and minimum joint space widths on bilateral weight-bearing plain radiographs acquired using three different methods in 31 patients with medial knee osteoarthritis (56 knee joints): standing with the knee extended (standard imaging); SynaFlexer method; and Rosenberg method. Measured values were compared statistically, with values of P < 0.05 considered significant.Results. Maximum plateau gap in the medial compartment was significantly lower with the SynaFlexer method (3.2 ± 1.5 mm) and Rosenberg method (2.2 ± 1.2 mm) than with standard imaging (4.7 ± 2.2 mm; P < 0.05 each). Minimum width of the medial joint space was also significantly lower with the SynaFlexer method (3.1 ± 1.4 mm) and Rosenberg method (2.3 ± 1.4 mm) than with standard imaging (4.1 ± 1.4 mm; P < 0.05 each).Conclusion. The Rosenberg method appears beneficial for diagnosing early knee osteoarthritis, while the SynaFlexer method seems more appropriate for assessing disease severity or progression in patients with painful intermediate to severe knee osteoarthritis

Fetal and Neonatal Goiter in Cynomolgus Monkeys Following Administration of the Antithyroid Drug Thiamazole at High Doses to Dams During Pregnancy

To evaluate morphologic alterations in the thyroid gland in the second generation in cynomolgus monkeys, pregnant dams were exposed to high doses of thiamazole. In Experiment A, dams received thiamazole intragastrically via a nasogastric catheter from gestation day (GD) 50 to GD 150 or on the day before delivery. Initially, the dose level was 20 mg/kg/day (10 mg/kg twice daily); however, the dose level was subsequently decreased to 5 mg/kg/day (2.5 mg/kg twice daily), since deteriorated general conditions were observed in two dams. Six out of seven neonates died on the day of birth. The cause of neonatal death was tracheal compression and suffocation from goiter. The transplacental exposure to thiamazole affected the fetal thyroid glands and induced goiter in all neonates. The surviving neonate was necropsied 767 days after discontinuation of thiamazole exposure and showed reversibility of the induced changes. In Experiment B, dams were intragastrically administered thiamazole at 5 mg/kg/day (2.5 mg/kg twice daily) for treatment periods from GDs 51 to 70, 71 to 90, 91 to 110, 111 to 130 and 131 to 150. All fetuses showed enlarged thyroid glands but were viable. Histopathologically, hypertrophy and/or hyperplastic appearance of the follicular epithelium of the thyroid gland was observed at the end of each treatment period. The most active appearance of the follicular epithelium, consisting of crowded pedunculated structure, was demonstrated at end of the treatment period from GD 131 to 150. This is the first report on the morphology of fetal and neonatal goiter in the cynomolgus monkey

Paraganglioma that caused sinus arrest

Paragangliomas are neural-crest-derived nonepithelial neuroendocrine tumors distributed along the parasympathetic and sympathetic nerves. To our knowledge, no studies were reported regarding sinus arrest on day 4 after paraganglioma resection. A 66-year-old female patient with a history of pulmonary vein isolation visited our department for sigmoid colon cancer treatment. Enhanced computed tomography revealed an enhanced small nodule-like lymph node near the root of the inferior mesenteric artery. The patient underwent laparoscopic colectomy with regional lymph node dissection. Postoperatively, paroxysmal atrial fibrillation attacks developed, and the patient resumed oral medication. Additionally, sinus arrest after tachycardia developed. Changing the oral medication could maintain her circulatory dynamics. Pathological examination revealed that differentiated tubular adenocarcinoma infiltrated the submucosa. Immunohistochemically, the excised nodule as a lymph node was considered a functional paraganglioma. Our case indicates that paraganglioma resection and oral medication resumption may contribute to sinus arrest. When arrhythmias affecting the circulation occur perioperatively, the presence of a catecholamine-producing tumor should be considered in addition to cardiac disease

Progression of microstructural deterioration in load-bearing immobilization osteopenia

PurposeImmobilization osteopenia is a major healthcare problem in clinical and social medicine. However, the mechanisms underlying this bone pathology caused by immobilization under load-bearing conditions are not yet fully understood. This study aimed to evaluate sequential changes to the three-dimensional microstructure of bone in load-bearing immobilization osteopenia using a fixed-limb rat model.Materials and methodEight-week-old specific-pathogen-free male Wistar rats were divided into an immobilized group and a control group (n = 60 each). Hind limbs in the immobilized group were fixed using orthopedic casts with fixation periods of 1, 2, 4, 8, and 12 weeks. Feeding and weight-bearing were freely permitted. Length of the right femur was measured after each fixation period and bone microstructure was analyzed by micro-computed tomography. The architectural parameters of cortical and cancellous bone were analyzed statistically.ResultsFemoral length was significantly shorter in the immobilized group than in the control group after 2 weeks. Total area and marrow area were significantly lower in the immobilized group than in the control group from 1 to 12 weeks. Cortical bone area, cortical thickness, and polar moment of inertia decreased significantly after 2 weeks. Some cancellous bone parameters showed osteoporotic changes at 2 weeks after immobilization and the gap with the control group widened as the fixation period extended (P < 0.05).ConclusionThe present results indicate that load-bearing immobilization triggers early deterioration of microstructure in both cortical and cancellous bone after 2 weeks

Reduced mortality during the COVID-19 outbreak in Japan, 2020: a two-stage interrupted time-series design.

BACKGROUND: Coronavirus disease 2019 (COVID-19) continues to be a major global health burden. This study aims to estimate the all-cause excess mortality occurring in the COVID-19 outbreak in Japan, 2020, by sex and age group. METHODS: Daily time series of mortality for the period January 2015-December 2020 in all 47 prefectures of Japan were obtained from the Ministry of Health, Labour and Welfare, Japan. A two-stage interrupted time-series design was used to calculate excess mortality. In the first stage, we estimated excess mortality by prefecture using quasi-Poisson regression models in combination with distributed lag non-linear models, adjusting for seasonal and long-term variations, weather conditions and influenza activity. In the second stage, we used a random-effects multivariate meta-analysis to synthesize prefecture-specific estimates at the nationwide level. RESULTS: In 2020, we estimated an all-cause excess mortality of -20 982 deaths [95% empirical confidence intervals (eCI): -38 367 to -5472] in Japan, which corresponded to a percentage excess of -1.7% (95% eCI: -3.1 to -0.5) relative to the expected value. Reduced deaths were observed for both sexes and in all age groups except those aged <60 and 70-79 years. CONCLUSIONS: All-cause mortality during the COVID-19 outbreak in Japan in 2020 was decreased compared with a historical baseline. Further evaluation of cause-specific excess mortality is warranted

Markers for obese and non-obese Type 2 diabetes identified using whole blood metabolomics

Definitive differences in blood metabolite profiles between obese and non-obese Type 2 diabetes (T2D) have not been established. We performed an LC–MS-based non-targeted metabolomic analysis of whole blood samples collected from subjects classified into 4 types, based on the presence or absence of obesity and T2D. Of the 125 compounds identified, 20, comprising mainly nucleobases and glucose metabolites, showed significant increases or decreases in the T2D group. These included cytidine, UDP-glucuronate, UMP, 6-phosphogluconate, and pentose-phosphate. Among those 20 compounds, 11 enriched in red blood cells (RBCs) have rarely been studied in the context of diabetes, indicating that RBC metabolism is more extensively disrupted than previously known. Correlation analysis revealed that these T2D markers include 15 HbA1c-associated and 5 irrelevant compounds that may reflect diabetic conditions by a different mechanism than that of HbA1c. In the obese group, enhanced protein and fatty acid catabolism causes increases in 13 compounds, including methylated or acetylated amino acids and short-chain carnitines. Our study, which may be considered a pilot investigation, suggests that changes in blood metabolism due to obesity and diabetes are large, but essentially independent

Inhibition of Angiogenic Factor Productions by Quercetin In Vitro and In Vivo

Background: Angiogenesis is well known to be an important event in the tissue remodeling observed in allergic diseases. Although there is much evidence that quercetin, one of the most abundant dietary flavonoids, exerts anti-allergic effects in both human and experimental animal models of allergic diseases, the action of quercetin on angiogenesis has not been defined. Therefore, in this study, we first examined the action of quercetin on the secretion of angiogenic factors from murine mast cells in vitro. We also examined the action of quercetin on angiogenic factor secretion in the murine allergic rhinitis model in vivo. Methods: Mast cells (1 × 105 cells/mL) sensitized with ovalbumin (OVA)-specific murine IgE were stimulated with 10.0 ng/mL OVA in the presence or the absence of quercetin for 24 h. The concentrations of angiogenic factors, vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), tumor necrosis factor-α, IL-6 and IL-8 in the supernatants were examined by ELISA. BALB/c male mice immunized with OVA were challenged intranasally with OVA every other day, starting seven days after the final immunization. These mice were then orally administered quercetin once a day for five days, starting seven days after the final immunization. Clinical symptoms were assessed by counting the number of sneezes and nasal rubbing behaviors during the 10 min period just after OVA nasal provocation. The angiogenic factor concentrations in the nasal lavage fluids obtained 6 h after nasal antigenic provocation were examined by ELISA. Results: Quercetin significantly inhibited the production of angiogenetic factors induced by IgE-dependent mechanisms at 5.0 µM or more. Oral administration of 25.0 mg/kg quercetin into the mice also suppressed the appearance of angiogenetic factors in nasal lavage fluids, along with the attenuation of nasal symptoms. Conclusions: These results strongly suggest that the inhibitory action of quercetin on angiogenic factor secretion may be implicated in the therapeutic action of quercetin on allergic diseases, especially allergic rhinitis