435 research outputs found

    Beam range uncertainty and its clinical management in particle therapy

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    The full theoretical advantages of particle beams in external beam radiotherapy have not been fully exploited, in large part due to uncertainties of the beam range in the patient. For this reason, efforts are underway, either for more precise in-vivo detection of Bragg peak positions or for further reduction of beam range computation errors in treatment planning. Meanwhile, management of the range uncertainty issues with mitigation techniques based on existing technology is critical in providing safe and effective treatments in clinical practice. This paper briefly reviews the definition and causes of particle range uncertainty, the uncertainty estimates currently used in clinical practice, and the corresponding mitigation techniques. It is intended to provide references for clinical practices at new and existing particle therapy centers

    Evidence of d-phenylglycine as delivering tool for improving l-dopa absorption

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    <p>Abstract</p> <p>Background</p> <p><it>l</it>-Dopa has been used for Parkinson's disease management for a long time. However, its wide variety in the rate and the extent of absorption remained challenge in designing suitable therapeutic regime. We report here a design of using <it>d</it>-phenylglycine to guard <it>l</it>-dopa for better absorption in the intestine via intestinal peptide transporter I (PepT1).</p> <p>Methods</p> <p><it>d</it>-Phenylglycine was chemically attached on <it>l</it>-dopa to form <it>d</it>-phenylglycine-<it>l</it>-dopa as a dipeptide prodrug of <it>l</it>-dopa. The cross-membrane transport of this dipeptide and <it>l</it>-dopa via PepT1 was compared in brush-boarder membrane vesicle (BBMV) prepared from rat intestine. The intestinal absorption was compared by <it>in situ </it>jejunal perfusion in rats. The pharmacokinetics after i.v. and p.o. administration of both compounds were also compared in Wistar rats. The striatal dopamine released after i.v. administration of <it>d</it>-phenylglycine-<it>l</it>-dopa was collected by brain microdialysis and monitored by HPLC. Anti-Parkinsonism effect was determined by counting the rotation of 6-OHDA-treated unilateral striatal lesioned rats elicited rotation with (+)-methamphetamine (MA).</p> <p>Results</p> <p>The BBMV uptake of <it>d</it>-phenylglycine-<it>l</it>-dopa was inhibited by Gly-Pro, Gly-Phe and cephradine, the typical PepT1 substrates, but not by amino acids Phe or <it>l</it>-dopa. The cross-membrane permeability (Pm*) determined in rat jejunal perfusion of <it>d</it>-phenylglycine-<it>l</it>-dopa was higher than that of <it>l</it>-dopa (2.58 ± 0.14 vs. 0.94 ± 0.10). The oral bioavailability of <it>d</it>-phenylglycine-<it>l</it>-dopa was 31.7 times higher than that of <it>l-</it>dopa in rats. A sustained releasing profile of striatal dopamine was demonstrated after i. v. injection of <it>d</it>-phenylglycine-<it>l</it>-dopa (50 mg/kg), indicated that <it>d</it>-phenylglycine-<it>l</it>-dopa might be a prodrug of dopamine. <it>d</it>-Phenylglycine-<it>l</it>-dopa was more efficient than <it>l-</it>dopa in lowering the rotation of unilateral striatal lesioned rats (19.1 ± 1.7% vs. 9.9 ± 1.4%).</p> <p>Conclusion</p> <p>The BBMV uptake studies indicated that <it>d</it>-phenylglycine facilitated the transport of <it>l</it>-dopa through the intestinal PepT1 transporter. The higher jejunal permeability and the improved systemic bioavailability of <it>d-</it>phenylglycine-<it>l</it>-dopa in comparison to that of <it>l</it>-dopa suggested that <it>d-</it>phenylglycine is an effective delivery tool for improving the oral absorption of drugs like <it>l</it>-dopa with unsatisfactory pharmacokinetics. The gradual release of dopamine in brain striatum rendered this dipeptide as a potential dopamine sustained-releasing prodrug.</p

    Isotopic Fractionation of Nitrogen in Ammonia in the Troposphere of Jupiter

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    Laboratory measurements of the photoabsorption cross section of ^(15)NH_3 at wavelengths between 140 and 220 nm are presented for the first time. Incorporating the measured photoabsorption cross sections of ^(15)NH_3 and ^(14)NH_3 into a one-dimensional photochemical diffusive model, we find that at 400 mbar, the photolytic efficiency of ^(15)NH_3 is about 38% greater than that of ^(14)NH_3. In addition, it is known that ammonia can condense in the region between 200 and 700 mbar, and the condensation tends to deplete the abundance ratio of ^(15)NH_3 and ^(14)NH_3. By matching the observed ratio of ^(15)NH_3 and ^(14)NH_3 at 400 mbar, the combined effect of photolysis and microphysics produces the ratio of (2.42 ± 0.34) × 10^(-3) in the deep atmosphere, in excellent agreement with the Galileo spacecraft measurements. The usefulness of the isotopic composition of ammonia as a tracer of chemical and dynamical processes in the troposphere of Jupiter is discussed

    Vacuum-Ultraviolet Absorption Spectra of Icy C2H4 at 13–60 K

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    The thermal variation of absorption spectra of icy ethene in wavelength range 105–220 nm was measured from 13 to 100 K using a synchrotron as light source. Sublimation of icy ethene began above 62 K, resulting in decreasing absorption. The absorption of icy ethene increased at wavelengths less than about 150 nm with increasing temperature from 13 to 60 K, but decreased beyond above 150 nm. According to detailed examination, the absorption spectra of icy ethene intersected at isosbestic point 147.0 nm from 13 to 17 K, whereas those varied absorption profiles crossed at another point, 150.6 nm, from 23 to 60 K. These results indicate that ethene ices might exhibit three structures within temperature range 13–60 K. This work enhances our understanding of the spectra of icy ethene at low temperatures and our knowledge of its astrochemistry and astrophysics in cold astro-environments

    Integration of Chinese Herbal Medicine into Routine Care Was Related to Lower Risk of Chronic Kidney Disease in Patients with Rheumatoid Arthritis: A Population-Based Nested Case–Control Study in Taiwan

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    Objective Non-steroidal anti-inflammatory drugs (NSAIDs) are frequently used as the first-line agents for the symptomatic relief of rheumatoid arthritis (RA), but it may insidiously provoke the onset of renal diseases, especially chronic kidney disease (CKD). While Chinese herbal medicine (CHM) has become an increasingly popular adjunctive therapy among RA groups, there are currently no available data on the effect of CHM use towards risk of CKD. This study aimed to explore on a population-level whether CHM use decreases sequent CKD risk among them. Methods In this nested case–control study retrieved from the nationwide insurance database of Taiwan from 2000 to 2012, we looked at the association between CHM use and the likelihood of developing CKD, with a focus on usage intensity. Cases with CKD claims were defined and matched to one randomly selected control case. Conditional logistic regression was then applied to estimate odds ratio (OR) of CKD from CHM treatment measured before the index date. For each OR, we calculated a 95% confidence interval for CHM use relative to the matched control. Results This nested case–control study included 5464 patients with RA, where after matching comprised 2712 cases and 2712 controls. Among them, there were 706 and 1199 cases that ever received CHM treatment, respectively. After the adjustment, CHM use in RA individuals was related to a lower likelihood of CKD, with an adjusted OR of 0.49 (95% CI: 0.44–0.56). Additionally, a dose-dependent, reverse association was found between the cumulative duration of CHM use and risk of CKD. Conclusion Integrating CHM into conventional therapy may reduce the likelihood of developing CKD, which could be a reference in instituting novel preventive strategies to improve treatment outcomes and reduce related fatalities for RA subjects
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