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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: 1432-1041
    Keywords: β-Adrenoceptor blocker ; intrinsic sympathomimetic action ; muscle cramps ; CPK ; CPK-MB ; propanolol ; carteolol ; metoprolol ; arotinolol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract We have assessed the propensity of β-adrenoceptor blockers to cause muscle cramps and to raise the serum creatine phosphokinase (CPK) level in 78 patients with essential hypertension. After a control period, a β-adrenoceptor blocker without intrinsic sympathomimetic activity (ISA; propranolol, metoprolol or arotinolol) was administered for three months. Thereafter, the patients were randomised to receive a β-adrenoceptor blocker with ISA (pindolol or carteolol) for three months or a β-adrenoceptor blocker without ISA for a further three months. This pattern was continued until all β-adrenoceptor blockers had been given. At the end of each period, CPK and CPK-MB levels were measured. Of the 78 subjects, muscle cramps occurred in 27 during treatment with pindolol and 32 during treatment with carteolol. No complaints were made by subjects treated with propranolol and arotinolol, but muscle cramps were reported in 2 treated with metoprolol. While muscle cramps were caused both by pindolol and carteolol in 16 subjects, they were caused by either of these drugs in the remainder of the subjects. Muscle cramp occurred mainly in the calves when the patients were in bed at night. Serum CPK and CPK-MB levels increased significantly during treatment with pindolol (control period vs pindolol, CPK=96 vs 133 IU · ml−1, CPK-MB=14 vs 18 IU · ml−1) or carteolol (CPK=117 IU · ml−1, CPK-MB=18 IU · ml−1) while the levels during treatment with propranolol, arotinolol and metoprolol did not change from those in the control period. The change in serum CPK during treatment with carteolol or pindolol was significantly correlated with the control serum CPK level. No correlation was observed between muscle cramps and serum CPK level. There were individual differences in the severity of muscle cramps, with some subjects complaining frequently of severe muscle cramps. Because muscle cramps are frequently experienced at night, they disturb sleep and lower the quality of life in patients. This problem should be considered during treatment with β-adrenoceptor blockers with ISA.
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  • 3
    ISSN: 1440-1681
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: 〈list xml:id="l1" style="custom"〉1The age-related changes in mean arterial pressure (MAP), heart rate (HR), and baroreflex sensitivity (BRS) were studied in spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats from 4 to 20 weeks of age.2Intra-arterial blood pressure (BP) was continuously recorded for 24 h in conscious, freely moving rats. Twenty-four hour MAP and HR were calculated by an online computer. Baroreflex sensitivity was measured by phenylephrine infusion.3In SHR, BRS was significantly lower than in WKY as early as 4-5 weeks, at which time MAP in SHR was only slightly raised. During subsequent weeks, rapid increase in MAP occurred in SHR, in association with progressive bradycardia.4It was concluded that a reduced BRS may be detected in young prehypertensive SHR and this impairment of BRS may be central in origin.
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  • 4
    ISSN: 1420-9071
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Zusammenfassung Es ist anzunehmen, dass CDP-Cholin (Cytidin-Diphosphat-Cholin) auf Verminderung von Dopamin im Nucleus caudatus einen signifikanten (0.001〈p〈0.01) Abwehreffekt ausübt, was durch homolaterale Destruktion der Substantia nigra verursacht wird.
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  • 5
    ISSN: 1741-0444
    Keywords: Autonomic nervous system ; Baroreflex ; Blood pressure ; Chronic renal failure ; Heart rate ; Power spectrum ; Transfer function
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract Rhythmic blood pressure (BP) and R-R interval (R-R) oscillations at low-mid and high-frequency bands (LF: 0·02–0·06 Hz; MF; 0·07–0·14 Hz; HF; 0·15–0·40 Hz) were compared between uraemic patients maintained on haemodialysis and control subjects. The LF and MF powere spectra of BP were attenuated more in patients than in controls. With subjects standing, the MF power spectrum of BP increased significantly in both groups. With subjects supine, the plasma norepinephrine concentration was higher, and its increment upon standing was greater in patients than in controls. Each R-R frequency power spectrum decreased more in patients than in control subjects. The HF power spectrum of R-R, i.e. a vagal tone index, systematically decreased upon standing in the control subjects but not in the patients. The linear coupling between BP and R-R oscillations was strongest in the HF band, decreasing in the MF and LF bands. Transfer function analysis indicated that, in uraemic patients, linear BP/R-R relationships were altered in the HF band but remained normal in the LF and MF bands. The present results suggest that, first, the decreased amplitude of Mayer waves, i.e. the MF power spectrum of BP, observed in uraemic patients can be attributed to low sensitivity of the vasculature to sympathetic stimuli, and, secondly, autonomic modulation of linear BP/R-R relationships is frequency-dependent.
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  • 6
    ISSN: 1438-2199
    Keywords: Amino acids ; α-Endorphin accumulation ; Uremic toxin ; Uremic patient ; Carbohydrate intolerance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A 16-residue peptide was isolated from filtrate of uremic patients with carbohydrate intolerance by ultrafiltration with an Amicon Centriflo DM-5 membrane, followed by gel-filtration on Sephadex G-50 and Sephadex G-25, droplet countercurrent chromatography and high performance liquid chromatography. The hexadecapeptide thus obtained was identical as the entire amino acid sequence ofα-endorphin by amino acid analysis, application of the Edman degradation analysis and measurement of physical constants and analytical data of the synthetic hexadecapeptide. This result seems to suggest that an accumulation ofα-endorphin in uremic patients might cause carbohydrate intolerance.
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  • 7
    ISSN: 1438-2199
    Keywords: Amino acids ; Thymosinβ 4 family ; Immunological activity ; Uremic patient ; Impaired immunological deficiency ; Restoring effect
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Four peptides related to thymosinβ 4 family and its six fragments were synthesized by the solution method. Among them, the four peptides related to thymosinβ 4 family and its two fragments were found to have restoring activity on the impaired blastogenic response of T-lymphocytes isolated from uremic patients, but the other four fragments had no effect. Studies on the structureactivity relationships suggest that the tricosapeptide moiety corresponding to amino acids 16–38 of thymosinβ 4 is found to be an important moiety on impaired immunological deficiency.
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  • 8
    ISSN: 1438-2199
    Keywords: Amino acids ; Melanotropin-potentiating factor ; Melanosis ; Uremic patient ; Uremic toxin ; Melanotropic activity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Following the characterization of a hexadecapeptide,α-endorphin, melanotropin-potentiating factor (MPF) was isolated from the filtrate of uremic patients suffering from melanosis and carbohydrate intolerance. The structure of MPF has been determined on the bases of chemical and physicochemical examinations which included HPLC, Edman sequence analysis combined analysis of the amino acid composition and FAB-MS analysis. An accumulation of MPF might be a cause of melanosis in uremic patients.
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  • 9
    ISSN: 0006-291X
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology , Physics
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 0006-291X
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology , Physics
    Type of Medium: Electronic Resource
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