Clothianidin (CLO), a neonicotinoid that is widely used in forests and agricultural areas, was recently reported to cause toxicity in mammals. Although sensitivity to chemicals varies between sexes ...and developmental stages, studies that comprehensively evaluate both males and females are limited. Therefore, in this study we utilized murine models to compare the sex-specific differences in behavioral effects following CLO exposure at different developmental stages. We orally administered CLO to male and female mice as a single high-dose solution (80 mg/kg) during the postnatal period (2-week-old), adolescence (6-week-old), or maturity (10-week-old), and subsequently evaluated higher brain function. The behavioral battery test consisted of open field, light/dark transition, and contextual/cued fear conditioning tests conducted at three and seven months of age. After the behavioral test, the brains were dissected and prepared for immunohistochemical staining. We observed behavioral abnormalities in anxiety, spatial memory, and cued memory only in female mice. Moreover, the immunohistochemical analysis showed a reduction in astrocytes within the hippocampus of female mice with behavioral abnormalities. The behavioral abnormalities observed in female CLO-treated mice were consistent with the typical behavioral abnormalities associated with hippocampal astrocyte dysfunction. It is therefore possible that the CLO-induced behavioral abnormalities are at least in part related to a reduction in astrocyte numbers. The results of this study highlight the differences in behavioral effects following CLO exposure between sexes and developmental stages.
Summary
objective Neurokinin B (NKB) is a neuropeptide with a vasopressor effect belonging to the tachykinin family. This neuropeptide has attracted attention since recent reports indicated that it ...is also secreted in the placenta and is probably a cause of pre‐eclampsia. To provide a basis for elucidation of the relationship between pre‐eclampsia and NKB, this study aimed to clarify the trend of changes in blood NKB levels during normal pregnancy by measuring NKB concentrations in maternal blood during various gestational periods and in umbilical blood.
methods Fifty‐nine normal pregnant women, 12 normal puerperal women and 24 nonpregnant women were studied. The normal pregnant women comprised of 24 at 8–20 weeks’ gestation (early), 11 at 28–34 weeks (middle) and 24 at 35–40 weeks (late). Plasma was separated from peripheral blood samples, umbilical venous blood samples (n = 24) and umbilical arterial blood samples (n = 9). Peptide fractions were extracted from each plasma sample and NKB concentrations were measured by the radioimmunoassay method.
results The NKB concentration in early pregnancy was not significantly different from that in the nonpregnant state. During pregnancy, the blood NKB concentration increased with advance in gestational week, and a correlation was demonstrated by a linear regression equation. The concentration during puerperium was significantly lower than that in late pregnancy. The umbilical blood concentration was significantly higher than the maternal blood concentration in late pregnancy. There was no significant difference between umbilical venous and arterial blood.
conclusion This study demonstrated that NKB secreted from the placenta during pregnancy enters both the maternal and fetal circulation. These results suggest that NKB may modulate fetoplacental haemodynamics through a paracrine mechanism.
To measure both volume and signal intensity of the fetal lung at magnetic resonance (MR) imaging and to evaluate the clinical use of this method to predict fetal pulmonary hypoplasia.
A total of 87 ...fetuses evaluated with MR imaging at 24-39 weeks of gestation were classified into a control group with good respiratory outcome (group A, n = 58) or a poor outcome group with severe respiratory disturbance after birth (group B, n = 29). Planimetric measurement of total lung volume and calculation of the ratio of lung signal intensity to spinal fluid signal intensity (L/SF) were performed on MR images by using region-of-interest analysis. Regression analysis, analysis of covariance, analysis of variance, and receiver operating characteristic (ROC) analysis were performed.
The best fit for group A lung volume was represented by the regression line V = (2.41 x G) - 37.6 (r = 0.537, P <.001), in which V is lung volume and G is gestational weeks; that for group B, by V = (0.97 x G) - 14.0 (r = 0.378, P <.05). Results of analysis of covariance with gestational weeks used as a covariate showed a significant difference in lung volume between the two groups (P <.001). Mean +/- SEM for L/SF ratio was 0.817 +/- 0.013 and 0.598 +/- 0.019 in groups A and B, respectively (P <.001). For prediction of postnatal respiratory outcome, the area under the ROC curve for lung volume and L/SF ratio combined was 0.990, significantly higher than that for lung volume alone (P <.05).
Simultaneous measurement of fetal lung volume and signal intensity on MR images is a promising method for predicting fetal pulmonary hypoplasia.
To prepare nomograms for normal fetal lung volume using three-dimensional ultrasonography and to evaluate the possibility of clinical applications of this procedure.
One hundred twenty-five healthy ...neonates with birth weights within +/-1.5 SD (group A), 9 neonates with intrauterine growth restriction (birth weight less than -1.5 SD) but no severe respiratory disturbance at birth (group B), and 10 neonates with severe respiratory disturbance but no intrauterine growth restriction (group C) were studied. With the use of a three-dimensional ultrasonographic device, continuous B-mode images centering on the fetal thorax were acquired as volume data. Analytical software was used to repeatedly trace the contours of bilateral fetal lungs on transverse slices to calculate the lung volume.
In group A, the total volume of normal fetal lungs can be expressed by the second-degree regression equation: 0.08 x (gestational week - 30.1)2 + 3.28 x gestational week - 67.2 (R = 0.909; P < .001). The lung volumes of groups B and C were below the 25th and 2.5th percentiles, respectively, of this regression curve. For the same case, the lung volume increased with gestational week in group B but remained unchanged or even decreased in group C. The total volume of normal fetal lungs can also be expressed by the linear regression equation: 0.02 x estimated fetal weight + 0.29 (R = 0.902). The lung volumes of groups B and C were distributed below and above, respectively, the 2.5th percentile of the regression line.
This analytical method may be applied to evaluate lung development.
Although drug-eluting stents (DES) for percutaneous coronary intervention (PCI) have dramatically reduced the incidence of in-stent restenosis, their deployment for large-size coronary lesions is ...still controversial because of problems such as late in-stent thrombosis and late catch-up in DES. We aimed to evaluate the long-term outcome beyond 2 years of bare metal stents (BMS) as compared with DES in large vessels. Consecutive 228 patients who underwent PCI with large-size stents (>3.5 mm in diameter) in our hospital were enrolled in this study. The end points of this study are target lesion revascularization (TLR) and occurrence of major adverse cardiac events (MACE) for subject patients. We analyzed 183 patients (152 men, mean age 65.8 ± 10.5 years) whose outcome could be followed up for at least 2 years. At the first 8-month follow-up, clinically driven TLR rate was significantly higher in patients who received BMS than those who received DES (17.2 vs. 2.2 %,
p
< 0.05), although the rate of TLR was not different between the 2 groups beyond 8 months. Thus, overall rate of TLR was higher in BMS than in DES (22.7 vs. 5.4 %,
p
< 0.05). Under these conditions, the higher rate of TLR for BMS was observed in simple as well as complex lesions with or without diabetes, although there were no significant differences in MACE between BMS and DES. Multivariate analysis showed that BMS was an only independent factor of TLR at the 8 month follow-up period
p
= 0.004, odds ratio 9.58, 95 % confidence interval (2.10–43.8). These results demonstrate that the rate of in-stent restenosis in large-size coronary lesions was transiently higher in the first 8 months for patients implanted with BMS compared with DES in which no in-stent thrombosis and TLR beyond 2 years were observed. We suggest using the DES even in large-size coronary lesions in terms of short- and long-term outcomes.
Objective Type 2 diabetes is a progressive disease characterized by insulin resistance and insulin secretory dysfunction. In this study, we assessed the factors contributing to an insulin secretory ...defect in type 2 diabetes patients. Methods The subjects consisted of 382 patients with type 2 diabetes, aged 57±13 years. We estimated the β-cell function using 6-min post-glucagon increments in C-peptide (ΔCPR). Results A significant inverse correlation was observed between the time since the diagnosis of diabetes and ΔCPR. A simple liner regression analysis showed that ΔCPR decreases at a rate of 0.056 ng/mL/year. According to a multiple regression model, body mass index (BMI) and log (triglyceride) were positively correlated with ΔCPR. Time since the diagnosis of diabetes, diabetes in 1st degree relatives, the presence of diabetic retinopathy, and HbA1c were inversely correlated with ΔCPR. In 50 patients who underwent the glucagon stimulation test twice, the ΔCPR decreased from 2.27±1.47 to 1.72±1.08 ng/mL over a period of 6.5±0.9 years. A multiple regression analysis revealed the BMI and fasting plasma glucose level to be significant contributing factors to the decline in ΔCPR. Conclusion The duration of diabetes, a low BMI, genetic factors, and the presence of microangiopathy may be associated with β-cell dysfunction in diabetic patients. The observations in this study suggest that obese subjects showed a rapid decline in the β-cell function despite an initial high CPR response. Environmental factors causing insulin resistance and glucotoxicity may therefore be involved in progressive β-cell failure.
Aim: The prospective, randomized, multicenter Myocardial Ischemia Treated with Percutaneous Coronary Intervention and Plaque Regression by Lipid Lowering & Blood Pressure Controlling assessed by ...Intravascular Ultrasonography (MILLION) study demonstrated that combined treatment with atorvastatin and amlodipine enhanced coronary artery plaque regression. Although the baseline high-sensitive C-reactive protein (hs-CRP) reportedly plays an important role in atherogenesis, few data exist regarding the relationship between hs-CRP and plaque regression in patients receiving a combined atorvastatin and amlodipine therapy.Methods: A total of 68 patients (male, 55; mean age, 64.2 years) with baseline and follow-up 3-dimensional intravascular ultrasound examinations in the MILLION study were stratified by baseline hs-CRP level quartiles. The serial measurements of lipid, blood pressure, and percentage changes in the plaque volume were compared between the groups, and the factors associated with the percentage change in the plaque volume were assessed.Results: There were no significant between-group differences in the extent of change in low-density lipoprotein cholesterol (LDL-C) or systolic and diastolic blood pressure after 18–24 months of treatment. The percentage change in the plaque volume showed a linear association with the baseline hs-CRP (p for trend ＜0.05); however, there was no correlation with changes in LDL-C or systolic and diastolic blood pressure. In the multiple regression analysis, the baseline hs-CRP level was independently associated with the percentage change in the plaque volume (β=0.29, p=0.022).Conclusions: Coronary plaque regression was associated with the baseline hs-CRP level in patients treated with a combined lipid- and blood pressure-lowering therapy.
Objective Several studies have assessed the efficacy of angiotensin receptor blockers (ARBs) on peripheral insulin sensitivity using the euglycemic hyperinsulinemic clamp technique in hypertensive ...subjects. However, these subjects were mostly non-diabetic, and some studies showed that ARB treatment did not improve insulin sensitivity. Thus, it is still uncertain whether ARBs could improve insulin sensitivity in subjects with hypertension and diabetes. Therefore, we evaluated the effect of olmesartan on peripheral insulin sensitivity in subjects with type 2 diabetes and hypertension using M/I value during the euglycemic-hyperinsulinemic clamp technique. Methods We enrolled 10 Japanese subjects with type 2 diabetes and hypertension who had never taken antihypertensive agents. Their blood pressure, fasting plasma glucose level, HbA1c and glucose utilization rate during euglycemic-hyperinsulinemic clamp (M/I value) were examined before and after 6 months of treatment with 10-20 mg/day olmesartan (mean: 13.0 mg/day). Results Blood pressure decreased significantly from 156/88 mmHg before starting olmesartan to 135/76 mmHg after 6 months of olmesartan treatment. The mean M/I value increased significantly from 6.33±3.19 (mg/kg/min/mU/L) × 100 to 8.11±4.20 (mg/kg/min/mU/L) × 100. Peripheral insulin sensitivity improved in eight out of ten subjects. Fasting glucose levels and HbA1c levels also decreased significantly. Conclusion These results indicate that olmesartan improves glucose metabolism by improving the peripheral insulin sensitivity in subjects with type 2 diabetes.
Although benefits of direct oral anticoagulants (DOAC) for treatment of non-valvular atrial fibrillation (AF) were well demonstrated, few data exist regarding cost-effectiveness between DOAC and ...warfarin uses in real-world clinical practice. Therefore, we estimated total cost of treatment for AF by authorized cardiologists in Japan. We studied consecutive 617 anticoagulated non-valvular AF patients (418 men, mean age 68.8, 54% warfarin) consulted by authorized cardiologists. The mean time in therapeutic range of warfarin was 71.8%. Under these conditions, we calculated the cost of anticoagulants, laboratory examination, and hospitalization due to thromboembolism or bleeding during follow-up for 3.1 years. Thromboembolism occurred in 26 patients (4.2%, 1.3/100 person-year) and hemorrhagic events in 20 patients (3.2%, 1.0/100 person-year). There was no significant difference in the occurrence rate of thromboembolism (log rank
P
= 0.16) or hemorrhagic events (log rank
P
= 0.83) between these two groups. Importantly, warfarin group showed lower cost than DOAC group (117,361 ± 743,710 yen/year vs. 310,436 ± 1,075,639 yen/person,
P
= 0.009) in terms of cost including drug, medical check, and hospitalization. These results demonstrate that the total cost with warfarin can be lower than DOAC in treatment for AF by authorized cardiologists in Japan, although further prospective randomized cost calculation is necessary including post-discharge care fee.
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