To investigate underlying mechanisms responsible for the impaired nitric oxide (NO)-dependent vascular relaxation in the insulin-resistant state, we examined production of both NO and superoxide ...anion radical (O2-) and those modulating factors in aortas obtained from normal (CTR), insulin-treated (INS), or high fructose-fed (FR) rats. FR rats showed insulin resistance with endogenous hyperinsulinemia, whereas INS rats showed normal insulin sensitivity. Only FR aortic strips with endothelium elicited impaired relaxation in response to either acetylcholine or calcium ionophore A23187. Endothelial NO synthase (eNOS) activity and its mRNA levels were increased only in vessels from INS rats (P < 0.001), whereas eNOS activity in FR rats was decreased by 58% (P < 0.05) when compared with CTR rats. NO production from aortic strips stimulated with A23187 was significantly lower in FR than CTR rats. In contrast, A23187-stimulated O2- production was higher (P < 0.01) in FR than CTR rats. These differences were abolished when aortic strips were preincubated in the media including (6R)-5,6,7,8-tetrahydrobiopterin (BH4), an active cofactor for eNOS. Furthermore, as compared with CTR rats, aortic BH4 contents in FR rats were decreased (P < 0.001), whereas the levels of 7,8-dihydrobiopterin, the oxidized form of BH4, were increased, with opposite results in INS rats. These results indicate that insulin resistance rather than hyperinsulinemia itself may be a pathogenic factor for decreased vascular relaxation through impaired eNOS activity and increased oxidative breakdown of NO due to enhanced formation of O2- (NO/O2- imbalance), which are caused by relative deficiency of BH4 in vascular endothelial cells.
Multidrug resistance-associated protein 1 (MRP1) functions as a primary active transporter utilizing energy from ATP hydrolysis. In the central nervous system (CNS), MRP1 plays an important role in ...limiting the permeation of xenobiotic and endogenous substrates across the blood-brain and blood-cerebrospinal fluid barriers, and across brain parenchymal cells. While MRP1 contributes to minimizing the neurotoxic effects of drugs, it may also restrict the distribution of drugs for the treatment of CNS diseases. Moreover, neurodegenerative disease may be associated with abnormal expression of efflux transporters in the brain. Noninvasive measurement of MRP1 function will therefore be useful for directly evaluating the effect of modulators on enhancing the penetration of drugs into the brain and for examining the pathophysiological role of MRP1 in the brain. Positron emission tomography (PET) is a powerful molecular imaging technique. While several PET probes have been proposed for imaging function of the efflux transporter P-glycoprotein, few reports discuss the probes for imaging MRP1 function in the brain. Ideally, brain radioactivity should consist of a single radioactive compound that is selectively transported by the efflux transporter of interest, without other efflux routes. However, most PET probes for MRP1 or P-glycoprotein are eliminated by both a transporter and simple diffusion, resulting in inaccurate measurement of pump function. This review addresses a new strategy to avoid this problem, and suggests the design of a PET probe based on this strategy, particularly for MRP1 imaging. Several published reports on imaging MRP1 function with PET are also discussed.
Background
The utility of casual serum triglyceride (TG) as a predictor of type 2 diabetes mellitus (DM) is unclear, especially during the most productive years.
Methods
Participants were 3271 ...workers (913 men and 2358 women, age 20–57) without DM at baseline. They underwent consecutive annual medical check-ups for 8 years. The association between newly diagnosed DM and casual serum TG level was determined by classifying the participants into 4 groups according to casual serum TG level at baseline: below 50 mg/dL (group A), 50–100 mg/dL (group B), 100–150 mg/dL (group C), and ≥150 mg/dL (group D). The effects of casual serum TG level in combination with sex, obesity, or serum glucose level on newly diagnosed DM were also evaluated.
Results
A total of 222 newly diagnosed type 2 DM cases with a mean age of 50 years old were observed during the follow-up period, i.e., 10/406 in group A, 66/1534 in group B, 58/712 in group C, and 88/619 in group D. Compared with group A, the odds ratio (ORs) for newly diagnosed DM (after adjusting for DM-associated factors) was found to increase with casual serum TG level: 1.38 (group B), 1.79 (group C), and 2.36 (group D). Moreover, the OR for newly diagnosed DM was higher in participants with high casual serum TG levels who were also male (OR 2.46), obese (OR 4.18), or had a high serum glucose level (OR 6.96) than in the reference group.
Conclusions
Serum TG level ≥150 mg/dL when fasting or nonfasting is a significant predictor of type 2 diabetes in middle-aged Japanese workers.
Microgravity experiments of He II boiling were carried out using a drop tower. The process of bubble shrinking in He II in microgravity was observed by a high speed camera. The time duration of the ...microgravity environment less than 1 mg was about 1.3 sec. First, a large spherical bubble of about 10 mm in diameter was created by a short wire heater (Diameter 0.05 x Length 2.82 mm) for a heating time of 0.4 sec. The subsequent bubble shrinking was visualized after the heater was switched off. The time variation of the volume of bubble was estimated by image analysis. The shrinking speed of bubble was calculated from these time variation data. The shrinking speed depends on the heat flux across the liquid-vapor interface. It is found that the heat flux across the interface in microgravity can be explained by the kinetic theory with a pressure difference due to surface tension.
BackgroundInformation about the relationship between the number of established cardiovascular disease risk factors and medical costs is limited.MethodsA linked analysis of the medical costs and ...health examination measures was performed in Shiga, Japan. Medical costs information for the period April 2000–May 2006 was collected from the Shiga National Health Insurance Organization database. Corresponding data for 38 890 individuals (age, ≥40 years) generated during annual health examination conducted between 2000 and 2003 were collected from the local municipalities in the Shiga prefecture. These data were merged by name, sex, and dates of birth. Median and interquartile were used to compare the annual medical costs among groups with different number of risk factors. The risk factors were hypertension (SBP ≥140 or DBP ≥90), high cholesterol (total cholesterol ≥240) and blood glucose levels (casual blood glucose ≥126), and smoking.ResultsThe median total annual medical cost in the group with no risk factors was 217 149 Yen for men and 147 880 Yen for women. The median total annual medical cost in the group with four risk factors was 1.28 times higher in men (278 651 Yen) and 1.80 times higher in women (265.788 Yen), as compared to that in the group with no risk factors. These trends were most apparent in outpatients (men: 1.47 times (127 205 Yen vs 186 811 Yen); women: 2.23 times (94 648 Yen vs 211 123 Yen)).ConclusionAnnual medical costs increase with an increase in the number of cardiovascular disease risk factors in the Japanese population.
Aims/hypothesis
High fasting blood glucose is one of the well-known risk factors for CHD. However, in certain settings, patients cannot always be expected to fast. For example, community screenings ...for cardiovascular disease (CVD) risk factors in Japan are performed under non-fasting conditions to achieve high participation rates. Thus, we examined a representative cohort of the Japanese population (
n
= 9,444, follow-up period 17.3 years) to clarify whether high casual blood glucose (CBG) can predict CVD mortality.
Methods
We defined CBG groups as follows: high CBG ≥ 11.1 mmol/l or participants with a history of diabetes mellitus; borderline high, 7.77 ≤ CBG < 11.1 mmol/l; higher normal, 5.22 ≤ CBG < 7.77 mmol/l); and lower normal, CBG < 5.22 mmol/l. The multivariate-adjusted hazard ratios (HRs) for CHD, CVD and all-cause mortality were calculated.
Results
The crude CHD mortality rate was 0.84 per 1,000 person-years. Age- and sex-adjusted HRs for CHD mortality were high among participants with CBG levels ≥ 7.77 mmol/l, regardless of time since last meal. Multivariate-adjusted HRs (95% CI) of CHD mortality in high and borderline high CBG groups were 2.62 (1.46–4.67) and 2.43 (1.29–4.58), respectively. Similar results were observed for both CVD and all-cause mortality. Even within the normal blood glucose range, each 1 mmol/l increase in CBG was associated with a statistically significant increase in the HR for CVD mortality (1.12, 95% CI 1.02–1.22). Population-attributable fractions of the combined groups of high and borderline high CBG for CHD, CVD and all-cause mortality were 12.0, 4.9 and 3.5%, respectively.
Conclusions/interpretation
Increases in CBG, even within the normal range, predict CVD mortality.
The International Linear Collider (ILC) plans to make use of ten cryoplants for its main linacs, each providing 19 kW at 4.5 K equivalent and among of it 3.6 kW at 2 K. Each cryoplant will consist of ...various cryogenic components such as a 4.5 K refrigerator cold box, a 2 K refrigerator cold box, and helium compressors and so on. In the technical design report (TDR) of the ILC, due to the mountainous topology, almost all cryogenic components would be installed in underground cryogenic caverns next to the main linac tunnels and only cooling towers on surface area. However, we would like to find a more effective and sophisticated configuration of the cryoplant components (cryogenic configuration). Under several constraints of technical, geographical, and environmental points of view, the cryogenic configuration should be considered carefully to satisfy such various conditions. After discussions on this topic conducted at various workshops and conferences, an updated cryogenic configuration is suggested. The proposed updated configuration may affect the total construction cost of the ILC and the entire structure of the ILC conventional facilities. The updated cryogenic configuration is presented and the on-going discussions with the conventional facilities and siting (CFS) colleagues for further improvement of the cryogenic configuration is introduced.
Positron separators in Superomega muon beamline at J-PARC Ikedo, Y.; Miyake, Y.; Shimomura, K. ...
Nuclear instruments & methods in physics research. Section B, Beam interactions with materials and atoms,
12/2013, Letnik:
317
Journal Article
Recenzirano
•Three stage positron separators was installed onto the U-line in the MLF/J-PARC.•The separators can be applied 400kV to the both electrodes.•The separators were tested and were confirmed to ...successfully eliminate the positrons from the beam.
A positron separator is one of the essential components of a muon beamline to eliminate contamination in the beam, mainly positrons that have the same momentum as muons and are transported together with the beam. In order to eliminate positrons efficiently, we selected a Wien filter type three-stage positron separator for the new muon beamline, called Superomega, that is under construction in the Materials and Life Science Experimental Facility (MLF) of the Japan Accelerator Research Complex (J-PARC). The Superomega muon beamline is the second muon beamline at MLF/J-PARC, and started operation in October of 2012. Here, we report on the features and the test results of the positron separators installed in the Superomega muon beamline.
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