The frequency of exposure to strong magnetic fields has increased as the magnetic-resonance image-diagnostic technique (MRI) and passenger transport systems based on the principle of magnetic levitation have come into wider use. Accordingly, it has become necessary to more systematically assess their influence on the body and set strict guidelines on acceptable limits of magnetism exposure. Therefore, we have assessed the influence of an uniform static magnetic field (8 T in maximum) on normal erythrocytes. The erythrocytes were oriented with their disk plane parallel to the magnetic field direction. These erythrocytes were influenced even by 1 T and almost 100% of them were oriented when exposed to 4 T. Furthermore, the degree of orientation was not influenced by the state of hemoglobin (oxy: diamagnetic, deoxy and met: paramagnetic). The dependence of the measured degree of orientation on the intensity of the magnetic field was in good agreement with the theoretical equation for the magnetic orientation of diamagnetic substances. As a result of a numerical analysis based on the equation, the anisotropic diamagnetic susceptibility of erythrocytes was found to be delta chi = 8 x 10(-22) electromagnetic units/erythrocyte. It was almost in agreement with the calculated value delta chi = 6 x 10(-22) emu/erythrocyte estimated from the diamagnetism of the membrane constituents of erythrocyte.
Recent studies suggest the linkage of hypertension and insulin resistance. High fructose diet is known to induce hyperinsulinemia and hypertension in rats. In a previous study, however, high fructose (66%) diet failed to elevate blood pressure but increased left ventricular weight in Sprague-Dawley rats. In the present study, we investigated the precise mechanism of high fructose diet-induced changes in the cardiovascular system in rats. Intake of fructose-enriched diet for 2 weeks increased serum insulin and plasma angiotensin II levels. Urinary excretion of sodium and norepinephrine was not changed. Blood pressure measured directly through an indwelling catheter was not increased, but left ventricular weight and protein content were increased by high fructose diet To further elucidate the role of the renin-angiotensin system, an angiotensin II type 1 receptor antagonist, TCV-116, was given orally at 1 nig/kg per day with either normal or high fructose diet Concomitant administration of TCV-116 did not affect plasma glucose or serum insulin levels. Plasma angiotensin II was increased, but neither urinary sodium nor norepinephrine was changed by TCV-116. 3 Inhibition of insulin secretion by a somatostatin analogue 4 or reduction of insulin resistance by exercise 5 prevents hypertension, suggesting an etiological role of hyperinsulinemia in the elevation of blood pressure. In a preliminary study, 6 we showed that high fructose diet failed to increase blood pressure but induced left ventricular (LV) hypertrophy in rats. Serum insulin and plasma angiotensin II (Ang II) were increased by high fructose diet, suggesting a possible role of either insulin or Ang II in LV hypertrophy. However, the precise mechanism is not clear.The present study examined the mechanism of the development of LV hypertrophy induced by high fructose diet. Insulin causes sodium retention by increasing proximal tubular reabsorption 7 and activating the sym-
CYP3A5 expression is regulated by single-nucleotide polymorphisms (SNPs). The CYP3A5 genotype might contribute to a marked interindividual variation in CYP3A-mediated metabolism of drugs. Nifedipine is a typical substrate of CYP3A4 and CYP3A5 in vitro. The aim of this study was to elucidate the influence of the CYP3A5 genotype on nifedipine disposition in healthy subjects. A single capsule containing 10 mg of nifedipine was administered to 16 healthy male Japanese subjects (eight subjects: CYP3A5*1/*3; eight subjects: CYP3A5*3/*3). Blood samples were collected to analyze the pharmacokinetics of serum nifedipine and nitropyridine metabolite (M-I). The area under the plasma concentration-time curve (AUC), the peak plasma concentration (C max ) and the terminal half-life (t 1/2 ) of nifedipine, and the ratio of the nifedipine AUC to M-I AUC showed large intragroup variations, but no significant differences between the two genotypes. Based on the present findings, the functional relevance of CYP3A5 polymorphism should be re-evaluated in clinical trials. 2 Recently, single-nucleotide polymorphisms (SNPs) were identified in intron 3 (A-G: CYP3A5*3) and exon 7 (G-A: CYP3A5*6) of the CYP3A5 gene.3 In addition, CYP3A5*5 and CYP3A5*7 were reported as a defective allele of CYP3A5, which gave a substantial impact on CYP3A5 expression. 4,5 These SNPs cause a frame-shift mutation or alternative splicing and protein truncation, and result in the absence of CYP3A5, suggesting that only people with at least one CYP3A5*1 allele express large amounts of CYP3A5 protein. Therefore, these findings suggest that polymorphic CYP3A5 expression might be one factor contributing to the marked interindividual variation observed in CYP3A-mediated metabolism of drugs.We previously reported the frequencies of CYP3A5-related SNPs in 200 healthy Japanese subjects. 6 As a result, the allele frequency of CYP3A5*3 was approximately 70%, but CYP3A5*6 was not detected in the Japanese population. Accordingly, these findings suggested that about 40% of Japanese express relatively high levels of metabolically active CYP3A5 protein.
High‐speed two‐photon microscopy can be used to analyze vascular dynamics in living animals and is essential for the understanding of brain diseases. Recent advances in fluorescent probes/optical systems have allowed successful imaging of the hippocampal vasculature in the deep brain of mice (1 mm from the brain surface) under low‐speed conditions (1–2 fps); however, using high‐speed techniques (>30 fps), observation of the deep‐brain vasculature is still challenging. Here, a new nanoemulsion that encapsulates thousands of red‐emissive pyrene dye molecules while maintaining their high two‐photon brightness [1.5 × 102 GM (GM = 10−50 cm4·s·photon−1·molecule−1) at 960 nm excitation] and delivers a large amount of such pyrene dyes (65 nmol) into the blood vessels of mice is developed. Remarkably, the nanoprobe is found to exploit the inherent performance of a commonly used Ti:sapphire excitation laser and a sensitive gallium arsenide phosphide nondescanned fluorescence detector to the limit, enabling visualization of the brain vasculature under the cortex region of mice (up to 1.5 mm) under very low‐speed conditions. As a highlight, such a nanoprobe is successfully used to directly observe the blood flow in the hippocampal CA1 region (1.1 mm) through high‐speed resonant scanning (120 fps).
AimFor patients with inhalation injury, the indications for early intubation are diverse. The purpose of this study was to identify the most reliable symptoms, physical findings, and medical examinations with which to determine the indications for early intubation in patients with inhalation injury.MethodsWe retrospectively collected patient data from medical records. Collected data included age, sex, burn size, symptoms, physical findings, carboxyhemoglobin levels (COHb), and bronchial wall thickness (BWT) determined from chest computed tomography images. We analyzed the relationships between these findings and the early intubation. We performed fiberoptic bronchoscopy in all patients, and analyzed the relationships between bronchoscopic severity and other findings.ResultsOf the 205 patients, 80 patients were diagnosed as having inhalation injury, and 34 patients were intubated. Burn size, facial burns, neck burns, use of accessory respiratory muscles, and COHb seemed to be related with intubation, whereas singed nasal hair was not. If the patients suffered ≥27% total body surface area burn and BWT ≥3.5 mm, the positive predictive value for early intubation was 1.00. If the patients suffered smaller cutaneous burn without neck burn, and their COHb <4.0%, the negative predictive value for early intubation was 0.97. Fiberoptic bronchoscopy findings from above the glottis were mainly related with patients’ symptoms. Findings from below the glottis were mainly related with BWT and COHb.ConclusionsPatients’ symptoms, especially use of accessory respiratory muscles, are reliable, and BWT and COHb are also useful tools, for determining the indication for early intubation.
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