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  • 1
    ISSN: 1432-1041
    Keywords: Key words Pranidipine ; Grapefruit juice/orange ; juice interaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objectives: The study was conducted to investigate whether oral co-administration with citrus juices significantly affects the pharmacokinetics and/or pharmacodynamics of pranidipine, a new 1,4-dihydropyridine calcium antagonist, in healthy male subjects. Grapefruit juice and orange juice, which were both commercially available, were used in this study. Methods: Sixteen healthy male Japanese subjects participated in this study and were divided into two groups for grapefruit juice and orange juice treatment. The study followed an open-labelled crossover design, comparing the effects of a single oral dose of 2 mg pranidipine taken together with 250 ml citrus juice or 250 ml water. Serum pharmacokinetics of pranidipine, adverse reactions, blood pressure, heart rate, 12-lead ECG, haematology, clinical chemistry and urinalysis were measured throughout the study. Results: For grapefruit juice, mean Cmax and AUC0–24 h were significantly higher than those of water (P = 0.0003 and 0.0005, respectively, ANOVA) with the ratios of log transformed values being 1.50 and 1.74, respectively. There were no differences in tmax and t½ between the juice and water treatments. A significant increase in heart rate (P = 0.0240, ANOVA with repeated measurements) was observed in the juice treatment whereas there were no significant differences in systolic and diastolic blood pressure between the two treatments. For orange juice, a small decrease in mean Cmax was observed compared with water (P = 0.0218, ANOVA) with the ratio being 0.86, but there was no significant difference in AUC0–24 h between the two treatments. No marked differences were observed in tmax and t½. Oral pranidipine administration with orange juice did not affect heart rate, systolic and diastolic blood pressures or other parameters for safety evaluation. Conclusions: Oral co-administration with grapefruit juice and pranidipine was associated with increased bioavailability and changed the pharmacodynamics of pranidipine, particularly with regard to heart rate. Orange juice intake with pranidipine did not markedly affect the pharmacokinetics and no clinically significant changes were observed in the pharmacodynamics and safety evaluation.
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  • 2
    ISSN: 1432-0630
    Keywords: PACS: 61.48.+c; 68.35.-p; 68.35.Bs
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: 60 single crystals. The (111) and the (001) faces of C60 single crystals were illuminated with photons with energies below the band gap (generation of Frenkel-type excitons) or above the band gap. In the case of sub-band-gap illumination, reconstructed surfaces formed on the crystals. The reconstruction was represented by fringes running in the [11 ] and [0 0] directions on the (111) and (001) surfaces, respectively. As a result of supra-band-gap illumination, however, there appeared only cracks, without any fringes, which were oriented in directions characteristic of each face. The results suggest that the photo-induced surface reconstruction of C60 single crystals is induced via the recombination of Frenkel-type excitons.
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  • 3
    ISSN: 1432-0533
    Keywords: Key words Immunohistochemistry ; Polymerase chain ; reaction in situ hybridization ; HTLV-I-associated ; myelopathy/tropical spastic paraparesis ; Double ; staining ; Fresh frozen sections
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract HTLV-I-infected cells play an important role in pathogenesis HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Our previous studies of quantitative polymerase chain reaction (PCR) and in situ PCR suggested that T cells infiltrating in the spinal cord lesion were infected with HTLV-I. To elucidate the localization of HTLV-I proviral DNA directly, we performed double staining using immunohistochemistry and PCR in situ hybridization (PCR-ISH). Fresh frozen sections of the spinal cord from four HAM patients taken at autopsy were first immunostained with antibodies to pan T cells (UCHL-1), macrophages (KP-1) and helper/inducer T cells (OPD4). Then PCR-ISH was carried out with specific primers and probe for the HTLV-I pX region. UCHL-1-positive cells were noted around perivascular areas and, to some extent, in the parenchyma. Of the UCHL-1-positive cells, 9.4% (case 1), 9.6% (case 2), 1.1% (case 3) and 6.7% (case 4) became positive in HTLV-I PCR-ISH. UCHL-1-negative cells were HTLV-I PCR-ISH negative and almost all KP-1-positive cells were HTLV-I negative. HTLV-I was localized to OPD4-positive cells in examined lesions of cases 2 and 4. These data are a direct demonstration of HTLV-I proviral DNA localizing to infiltrated T cells in HAM/ TSP spinal cord lesions.
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  • 4
    ISSN: 1572-9540
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract The electronic states of Fe atoms in Co[Fe(CN)5NH3 $$\cdot x $$ H2O were studied by means of 57Fe Mössbauer spectroscopy. The Mössbauer spectra of Co[Fe(CN)5NH3 $$\cdot $$ 6H2O show the coexistence of mixed valences for the Fe atoms and a magnetic relaxation at 4 K. When water molecules were removed, electron transfer from Co to Fe occurred.
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  • 5
    ISSN: 1434-6079
    Keywords: PACS. 36.40.Qv Stability and fragmentation of clusters - 36.40.Wa Charged clusters
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract: The stability of neutral, singly and multiply ionized silicon clusters, (N = 2-7, M = 0, , , ), has been investigated using an ab initio density functional method. We show that the fragmentation effect significantly affects the structure of mass-spectra of multiply ionized silicon clusters. For clusters, the clusters with a large fragmentation energy are found to correspond to the high peaks at N = 4 and 6 in mass-spectra. For clusters, a peak at N = 5 in mass-spectra has been predicted to be especially high.
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  • 6
    ISSN: 1432-1912
    Keywords: Key words A-2545 ; Ventricular arrhythmia ; Programmed electrical stimulation ; Mexiletine ; Flecainide ; Dog
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We investigated effects of a new Na+ channel blocking antiarrhythmic drug, A-2545, N-3 (2,2,5,5-tetramethyl-3-pyrroline-3-carboxamido)-propyl-phthalimide-hydrochloride, on various canine ventricular automaticity arrhythmias induced by two-stage coronary ligation, digitalis and adrenaline, and compared them with those of mexiletine. A-2545 showed antiarrhythmic effects, significantly decreasing the arrhythmic ratio of 24-h and 48-h coronary ligation-, digitalis- and adrenaline-induced automaticity arrhythmias. The antiarrhythmic plasma concentrations (IC50) of A-2545, 2 mg kg–1 10 min–1, i.v., for 24-h and 48-h coronary ligation-, digitalis- and adrenaline-induced arrhythmias were 1.8, 1.3, 5.8 and 3.7 µg ml–1, respectively, and that calculated for oral A-2545 (25 mg kg–1) in 24-h coronary ligation-induced arrhythmia was 1.8 µg ml–1. A-2545 is specifically potent in suppressing coronary ligation-induced arrhythmias, i.e., decreasing the arrhythmic ratio nearly to zero by oral administration, and among the intravenously given experiments A-2545 was effective at lower concentrations than other arrhythmia models; A-2545, 2 mg kg–1 10 min–1, was equipotent to 5 mg kg–1 10 min–1 mexiletine in suppressing 24-h coronary ligation-induced arrhythmia, indicating that A-2545 is more potent than mexiletine. In order to determine whether A-2545 has arrhythmogenic effects, we used programmed electrical stimulation (PES)-induced reentry arrhythmias in dogs with old myocardial infarction and compared effects of A-2545 and flecainide. A-2545, 2 and 5 mg kg–1 10 min–1, significantly suppressed the PES-induced arrhythmias in all six dogs without aggravating them. These arrhythmias were not markedly suppressed by flecainide either with 1 or 3 mg kg–1 10 min–1; moreover even in one out of six dogs aggravation of arrhythmia was noted after 1 mg kg–1 10 min–1. In conclusion, A-2545 suppressed various canine ventricular arrhythmias, and the antiarrhythmic effect of A-2545 was more potent than that of mexiletine, and A-2545 did not show arrhythmogenic effects compared to flecainide.
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  • 7
    ISSN: 1432-1750
    Keywords: Key Words: Neutrophils—Apoptosis—Macrophages—Ozone—TUNEL.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. We evaluated the apoptosis of neutrophils during the resolution of acute pulmonary inflammation induced by exposure to ozone. The inflammatory response was assessed in rat lungs 0, 1, 3, and 7 days after 4-h exposure to air or 2 ppm ozone. Analysis of bronchoalveolar lavage fluid demonstrated significant increases in albumin concentrations on days 0 and 1 and in the number of lavageable neutrophils on days 0, 1, and 3, indicating the presence of acute pulmonary inflammation. These parameters returned to control values on day 7, which suggests that the acute pulmonary inflammation induced by ozone was reversible. On days 1 and 3, but not on day 0, the neutrophils showed morphologic evidence of apoptosis. Based on morphologic analysis, the proportion of apoptotic neutrophils was 23.3 ± 2.2% on day 1 and 55.7 ± 3.2% on day 3. Terminal deoxynucleotidyl transferase-mediated dUTP end labeling (TUNEL), in contrast, revealed that the proportion of apoptotic cells was 59.7 ± 9.1% on day 1 and 68.0 ± 4.3% on day 3. On day 3, light microscopy and electron microscopy demonstrated engulfment of the neutrophils by macrophages. These findings indicate that the apoptosis of neutrophils followed by their engulfment by macrophages contributes to the clearance of neutrophils from the sites of inflammation. Moreover, TUNEL detected apoptotic neutrophils with greater sensitivity compared with morphologic assessment.
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