174 research outputs found

    Study on relation between spatial distribution and release rate of hydrophobic compounds incorporated in polymer micelles with anomalous small angle X-ray scattering

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    Amphiphilic block copolymers in aqueous solution undergo self-assembly into polymer micelles composed of hydrophobic core and hydrophilic shell. The polymer micelles can solubilize hydrophobic compounds in aqueous solution by incorporating them in the hydrophobic core. Therefore, they have been expected to be a drug career in drug delivery system (DDS). In DDS, controlling of the drug release behavior and retention stability are critical issues. However, tuning release rate and stability of retention of drug molecules is significantly difficult. Since the hydrophobic molecules must pass through the hydrophobic cores and hydrated corona layers to go out the polymer micelles, their release properties should strongly depend on spatial distribution of drug molecules in polymer micelles. Therefore, to elucidate the relation between spatial distribution of drug molecules and release properties of drug molecules is of significant importance to design a novel DDS. Thus, the aim of this study is to clarify the relation between spatial distribution of hydrophobic compounds in polymer micelles and their release and retention property. Poly(methyl methacrylate)-block-poly(N,N-(dimethylamino)ethyl methacrylate) (Poly-1) as amphiphilic block copolymer was synthesized by reversible addition-fragmentation radical polymerization. The weight- and number-average molecular weights of the resulting Poly-1 were 1.6104 g mol-1 and 1.9104 g mol-1, respectively. Three kinds of compounds (9-bromofluorene (BrF), 4-bromobenzyl alcohol (BrBzOH), 4-bromophenol (BrPh)) were employed as bromine-labeled hydrophobic compounds. Poly-1 and a hydrophobic compound were mixed at 10 wt% of a hydrophobic compound against Poly-1. Please click Additional Files below to see the full abstract

    Effect of the angiotensin-converting enzyme inhibitor imidapril on reactive hyperemia in patients with essential hypertension: relationship between treatment periods and resistance artery endothelial function

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    AbstractOBJECTIVESThe purpose of this study was to evaluate the effects of the angiotensin-converting enzyme (ACE) inhibitor imidapril and the calcium antagonist amlodipine on endothelial function before and after 2, 4, 8, 12, 24 and 48 weeks of treatment.BACKGROUNDThere are limited data on whether and how long endothelial function is improved after initiation of ACE inhibitor treatment and how the grade of endothelial function further progresses after improvement of endothelial dysfunction in patients with essential hypertension.METHODSThe forearm blood flow (FBF) was measured in 25 patients with essential hypertension and in 25 normotensive subjects by using strain-gauge plethysmography during reactive hyperemia (RH) (280 mm Hg for 5 min) and after sublingual administration of nitroglycerin (NTG, 0.3 mg).RESULTSThe FBF of patients with essential hypertension during RH was significantly less than that of normotensive subjects. The increase in FBF after sublingual NTG was similar in both groups. Both imidapril (n = 13) and amlodipine (n = 12) significantly reduced systolic blood pressure and diastolic after eight weeks of treatment from the pretreatment values. Forearm vascular resistance was significantly decreased after two weeks of treatment. Imidapril significantly augmented RH after 12 weeks of treatment from the pretreatment values (31.6 ± 5.7 to 38.2 ± 6.0 ml/min per 100 ml tissue, p < 0.05), whereas amlodipine did not alter RH for each treatment period. The ability of imidapril to improve RH was maintained throughout the 48-week treatment period. There was no significant difference in RH at 12, 24 and 48 weeks. The increase in FBF after sublingual administration of NTG was similar in all treatment periods for the two groups. The infusion of NG-monomethyl-L-arginine, a nitric oxide (NO) synthase inhibitor, abolished the enhancement of RH in hypertensive patients treated with imidapril.CONCLUSIONSThese findings suggest that the ACE inhibitor imidapril augments RH after 12 weeks of treatment in patients with essential hypertension and that this ACE inhibitor-induced augmentation of RH may be due to an increase in NO

    Continuous release of O2−/ONOO− in plasma-exposed HEPES-buffered saline promotes TRP channel-mediated uptake of a large cation

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    Although the externally controllable extracellular supply of the short-lived reactive oxygen and nitrogen species, such as O2•−, •NO, and ONOO−, could potentially manipulate cellular functions, their simple administration to cells is likely to be ineffective due to their rapid deactivation. In this study, we found a method of a continuous supply of O2•−/ONOO− over a few minutes, which is triggered by irradiation of a nonequilibrium atmospheric pressure plasma to commonly used organic buffers (e.g., 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid, HEPES). In addition, a continuous low-dose O2•−/ONOO− supply was shown to induce a physiologically relevant Ca2+ response and subsequently the uptake of a large cation mediated by transient receptor potential channel family member(s). Our results provide a novel approach to the continuous O2•−/ONOO− supply, requiring controllable and mass-volume treatments

    Repetitive Passive Finger Movement Modulates Primary Somatosensory Cortex Excitability

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    Somatosensory inputs induced by repetitive passive movement (RPM) modulate primary motor cortex (M1) excitability; however, it is unclear whether RPM affects primary somatosensory cortex (S1) excitability. In this study, we investigated whether RPM affects somatosensory evoked potentials (SEPs) and resting state brain oscillation, including alpha and beta bands, depend on RPM frequency. Nineteen healthy subjects participated in this study, and SEPs elicited by peripheral nerve electrical stimulation were recorded from the C3’ area in order to assess S1 excitability (Exp. 1: n = 15). We focused on prominent SEP components such as N20, P25 and P45-reflecting S1 activities. In addition, resting electroencephalograms (EEGs) were recorded from C3’ area to assess the internal state of the brain network at rest (Exp. 2: n = 15). Passive abduction/adduction of the right index finger was applied for 10 min at frequencies of 0.5, 1.0, 3.0, and 5.0 Hz in Exp. 1, and 1.0, 3.0, and 5.0 Hz in Exp. 2. No changes in N20 or P25 components were observed following RPM. The 3.0 Hz-RPM decreased the P45 component for 20 min (p &lt; 0.05), but otherwise did not affect the P45 component. There was no difference in the alpha and beta bands before and after any RPM; however, a negative correlation was observed between the rate of change of beta power and P45 component at 3.0 Hz-RPM. Our findings indicated that the P45 component changes depending on the RPM frequency, suggesting that somatosensory inputs induced by RPM influences S1 excitability. Additionally, beta power enhancement appears to contribute to the P45 component depression in 3.0 Hz-RPM

    Repetitive Passive Movement Modulates Corticospinal Excitability: Effect of Movement and Rest Cycles and Subject Attention

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    Repetitive passive movement (PM) affects corticospinal excitability; however, it is unknown whether a duty cycle which repeats movement and rest, or subjects’ conscious attention to movements, affects corticospinal excitability. We aimed to clarify the effect of the presence or absence of a duty cycle and subjects’ attention on corticospinal excitability. Three experiments were conducted. In Experiment 1, PM of the right index finger was performed for 10 min. Three conditions were used: (1) continuous PM (cPM) at a rate of 40°/s; (2) intermittent PM (iPM) with a duty cycle at 40°/s; and (3) iPM at 100°/s. In conditions 1 and 3, motor evoked potential (MEP) amplitude was significantly reduced. In Experiment 2, PM was performed for 30 min: condition 1 comprised cPM at a rate of 40°/s and Condition 2 comprised iPM at 40°/s. MEP amplitude significantly decreased in both conditions. In Experiment 3, PM was performed for 10 min: condition 1 comprised paying attention to the moving finger during iPM and Condition 2 was similar to Condition 1 but while counting images on a monitor without looking at the movement finger, and Condition 3 comprised counting images on a monitor without performing PM. MEP amplitude significantly increased only under Condition 1. Thus, afferent input from movements above a certain threshold may affect corticospinal excitability reduction. Furthermore, corticospinal excitability increases when paying attention to passive finger movement

    Usefulness of brain natriuretic peptide for predicting left atrial appendage thrombus in patients with unanticoagulated nonvalvular persistent atrial fibrillation

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    AbstractBackgroundThe CHADS2 scoring system is simple and widely accepted for predicting thromboembolism in patients with nonvalvular atrial fibrillation (NVAF). Although congestive heart failure (CHF) is a component of the CHADS2 score, the definition of CHF remains unclear. We previously reported that the presence of CHF was a strong predictor of left atrial appendage (LAA) thrombus. Therefore, the present study aimed to elucidate the relationship between LAA thrombus and the brain natriuretic peptide (BNP) level in patients with unanticoagulated NVAF.MethodsThe study included 524 consecutive patients with NVAF who had undergone transesophageal echocardiography to detect intracardiac thrombus before cardioversion between January 2006 and December 2008, at Hiroshima City Asa Hospital. The exclusion criteria were as follows: paroxysmal atrial fibrillation, unknown BNP levels, prothrombin time international normalized ratio ≥2.0, and hospitalization for systemic thromboembolism.ResultsReceiver operating characteristic analysis yielded optimal plasma BNP cut-off levels of 157.1pg/mL (area under the curve, 0.91; p<0.01) and 251.2pg/mL (area under the curve, 0.70; p<0.01) for identifying CHF and detecting LAA thrombus, respectively. Multivariate analyses demonstrated that a BNP level >251.2pg/mL was an independent predictor of LAA thrombus (odds ratio, 3.51; 95% confidence interval, 1.08–10.7; p=0.046).ConclusionsIn patients with unanticoagulated NVAF, a BNP level >251.2pg/mL may be helpful for predicting the incidence of LAA thrombus and may be used as a surrogate marker of CHF. The BNP level is clinically useful for the risk stratification of systemic thromboembolism in patients with unanticoagulated NVAF
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