In lactating mammary glands, alveolar mammary epithelial cells (MECs) synthesize and secrete milk components. MECs also form less permeable tight junctions (TJs) to prevent the leakage of milk components. During lactation, MECs are exposed to temperature changes by metabolic heat production and air ambient temperature. In this study, we investigated whether temperature changes influence milk production ability and TJ barriers in MECs by using two lactating culture models. The results showed that 39 °C treatment activated milk production and enhanced the formation of less-permeable TJs. In contrast, 41 °C treatment caused adverse effects on the TJ barrier and cell viability, although the milk production ability of MECs was temporarily up-regulated. MECs cultured at 37 °C showed relatively low milk production ability and high proliferation activity. Furthermore, we investigated three kinds of transcription factors relating to lactogenesis, signal transducer and activator of transcription 5 (STAT5), STAT3 and glucocorticoid receptor (GR). STAT5 signaling was activated at 39 and 41 °C by an increase in total STAT5. However, long-term treatment led to a decrease in total STAT5. STAT3 signaling was inactivated by high temperature treatment through a decrease in total STAT3 and inhibited phosphorylation of STAT3. GR signaling was continuously activated regardless of temperature. These results indicate that a moderate high temperature condition at 39 °C induces a high lactation capacity of MECs through control of STAT5 and STAT3 signaling. In contrast, long-term exposure at 41 °C leads to a decline in milk production capacity by inactivation of STAT5 and a decrease in the total number of MECs.

In Japan, tuberculosis has been recognized as one of the major infections requiring urgent measures because of its high morbidity rate even now especially in elderly people suffering from tuberculosis during the past epidemic and its reactivation. Hence, many Japanese clinicians have made efforts to suppress the onset of tuberculosis and treat it effectively. The objectives of this study are to (1) identify covariate(s) that may explain the variation of rifampicin, which is the key antitubercular agent, under the steady-state by evaluating its population pharmacokinetics and (2) to propose an appropriate dosing method of rifampicin to Japanese patients. For this purpose, serum concentration–time data were obtained from 138 patients receiving rifampicin (300–450 mg) and isoniazid (300–400 mg) every day over 14 days, and analyzed using nonlinear mixed effects model. Thereby, population pharmacokinetic parameters were estimated followed by elucidating relations between the parameters and statistical factors. The analysis adopted one-compartment model including Lag-time by assuming that the absorption process is 0+1st order. The analyses demonstrate that meal affected the bioavailability, primary absorption rate constant, and zero order absorption time in the constructed model. A body weight calculated from the power model was selected as the covariate by the Stepwise Covariate Model method and found to highly affect the clearance in the range from −31.6% to 47.4%. We conclude that the dose in Japanese tuberculous patients can be well estimated by the power model formula and should be taken into consideration when rifampicin is administered.

Background: Repaglinide is widely prescribed to reduce postprandial hyperglycemia and elevated glycated hemoglobin (HbA1c) levels associated with type 2 diabetes, and clopidogrel is a thienopyridine antiplatelet agent and widely used in cardiovascular and cerebrovascular diseases. It has been suggested that the concomitant use of repaglinide with clopidogrel may inhibit repaglinide metabolism, because repaglinide is a substrate of cytochrome P450 2C8 (CYP2C8) and the main metabolite of clopidogrel acyl-β-D-glucuronide inhibits CYP2C8 activity. In this study, we retrospectively investigated the effect of clopidogrel with repaglinide on plasma glucose and the risk of hypoglycemia associated with the combination of both drugs. Method: Patients were taking clopidogrel (75 mg/day) and started taking glinide (1.5 mg/day repaglinide or 30 mg/ day mitiglinide) for the first time from April 2012 to March 2017. We targeted subjects who were hospitalized at the start of glinide and whose preprandial plasma glucose was measured by a nurse. The glucose levels were collected for up to 5 days before and after the glinide start date. Results: Average fasting plasma glucose levels (before breakfast) in the repaglinide and clopidogrel group before and after starting repaglinide were 180.1±35.5 and 136.5 ± 44.1 mg/dL, with a mean decrease of 43.6 ± 33.6 mg/dL. In contrast, there was only a moderate decrease of 11.6 ± 30.0 mg/dL in the mitiglinide and clopidogrel group. Minimum plasma glucose levels in the repaglinide and clopidogrel group before and after starting repaglinide were 145.2 ± 42.9 and 93.3 ± 36.3 mg/dL, respectively. Decrease in minimum levels after starting glinide in the repaglinide and clopidogrel group (51.9 ± 47.5 mg/dL) was more significant than those in the mitiglinide and clopidogrel group (only 2.1 ± 29.1 mg/dL), and the repaglinide group (without clopidogrel, 15.5 ± 20.0 mg/dL). Hypoglycemia was observed in 6 of 15 patients in the repaglinide and clopidogrel group, but only 1 of 15 patients in the mitiglinide and clopidogrel group, and no patients in the repaglinide group. Conclusion: These findings indicate that minimum plasma glucose levels were significantly decreased in patients taking repaglinide and clopidogrel. Considering the risk of hypoglycemia associated with taking repaglinide and clopidogrel, when a glinide is required in patients taking clopidogrel, mitiglinide may be a better choice.

Background Most previous reports of normal acetabular radiographic values focused on adults or elderly people. Recent reports have described premature hip osteoarthritis in adolescents not caused by acetabular dysplasia. In addition, there is a certain failure rate of surgical treatment for young patients with borderline acetabular dysplasia. Accurate indices for treatment of adolescent hips are unclear because standard measurement values of the adolescent acetabulum have not been reported. Methods This cross-sectional study involved 552 Japanese adolescents aged 12–18 years who had scoliosis or suspected scoliosis and asymptomatic hips. All persons underwent plain standing anteroposterior whole-spine radiography, and measurements were obtained using the pelvic part of the radiograph. We excluded persons who were unable to correctly perform measurements because of conditions such as pelvic rotation or lateral inclination and persons in whom closure of the triradiate cartilage or closure of the secondary ossification centers of the acetabulum had not yet occurred. In 1101 hips, we measured the lateral center–edge angle (LCEA), Tönnis angle, Sharp angle, acetabular head index (AHI), lateral subluxation (LS), vertical subluxation (VS), and peak-to-edge distance (PED). We evaluated the correlation coefficient and coefficient of determination between each parameter and age, height, body weight, and body mass index (BMI) and assessed the intra- and inter-rater reliability of each radiographic parameter. Results Among all hips, the mean of each parameter was as follows: LCEA, 27.9° ± 4.8°; Tönnis angle, 5.0° ± 3.7°; Sharp angle, 44.1° ± 3.1°; AHI, 82.1% ± 5.5%; LS, 5.4 ± 1.4 mm; VS, 0.3 ± 1.2 mm; and PED, 14.0 ± 2.3 mm. The correlation between each parameter and age, height, body weight, and BMI was considerably low. Intra- and inter-rater reliability was moderate or good for almost all parameters. Conclusions The values for each radiographic parameter of the acetabulum in this study are considered standard for the adolescent acetabulum without age-related changes. Some parameters differ slightly from the normal values for adults or elderly people in previous reports; thus, we suggest careful evaluation of these parameters for adolescents.

This paper presents a gastric contraction imaging system for assessment of gastric motility using a 3-D endoscope. Gastrointestinal diseases are mainly based on morphological abnormalities. However, gastrointestinal symptoms are sometimes apparent without visible abnormalities. One of the major factors for these diseases is abnormal gastrointestinal motility. For assessment of gastric motility, a gastric motility imaging system is needed. To assess the dynamic motility of the stomach, the proposed system measures 3-D gastric contractions derived from a 3-D profile of the stomach wall obtained with a developed 3-D endoscope. After obtaining contraction waves, their frequency, amplitude, and speed of propagation can be calculated using a Gaussian function. The proposed system was evaluated for 3-D measurements of several objects with known geometries. The results showed that the surface profiles could be obtained with an error of \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{upgreek} \usepackage{mathrsfs} \setlength{\oddsidemargin}{-69pt} \begin{document} }{}${<}{10\%}$\end{document} of the distance between two different points on images. Subsequently, we evaluated the validity of a prototype system using a wave simulated model. In the experiment, the amplitude and position of waves could be measured with 1-mm accuracy. The present results suggest that the proposed system can measure the speed and amplitude of contractions. This system has low invasiveness and can assess the motility of the stomach wall directly in a 3-D manner. Our method can be used for examination of gastric morphological and functional abnormalities.