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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 44 (1993), S. 439-444 
    ISSN: 1432-1041
    Keywords: Chlorpromazine ; Haloperidol ; scalp hair ; melanin ; dosage history
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The concentration of chlorpromazine (CPZ) in hair was measured to demonstrate its value as an index of individual dosage history and compliance. An animal study using pigmented rats was conducted to confirm the dose-dependent accumulation of CPZ in hair. The concentration of CPZ in hair, newly regrown on a denuded area of the back after the administration of CPZ for 3 weeks, was 4.6, 8.5 and 16.6 ng·mg−1 hair after daily doses of 1.25, 2.5 and 5 mg·kg−1·day−1, respectively, significantly correlated with the daily dose. The concentration of CPZ in black hairs collected from 23 Japanese patients, who had been taking CPZ in fixed daily doses (30–300 mg/day), ranged from 1.6 to 27.5 ng·mg−1, and was significantly correlated both with the daily dose and with the trough plasma concentration at steady state. Several strands of hair collected from each of 5 patients, whose doses of CPZ had been changed within several months before sampling, were cut into 1-cm pieces successively from the scalp end and the concentration of CPZ in each piece was measured. With the assumption of a hair growth rate of 1 cm per month, the individual history of CPZ doses in all patients could be deduced from the distribution of CPZ along the hair shaft. In 5 patients with grizzled hair the concentration of CPZ in white hairs was much lower (〈10%) than in black hairs, suggesting that the strong affinity of CPZ for hair melanin may explain the accumulation of CPZ in black hair. The concentration of co-administered haloperidol (HP) in plasma and hair was also measured in 11 out of 23 patients. The CPZ concentration in hair was much lower than that of HP (about 0.3 to 7.8%), whether the comparison was made on the basis of daily dose or plasma concentration. This finding is discussed in relation to the affinity of the compounds for their melanin and photochemical stability.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1434-4726
    Keywords: Inner ear microcirculation ; Photochemically induced vascular thrombosis ; Rose bengal ; Hearing loss
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A new photochemical method was employed to cause disorders in the inner ear's microcirculation, using the rat as an animal model. Hearing loss was used as a measure for establishing the altered microcirculation. Under pentobarbital anesthesia, the middle ear was opened by a ventral approach. The lateral wall of the cochlea was then illuminated with a filtered xenon lamp (wavelength 540 nm) while rose bengal was infused intravenously. Photoactivated rose bengal produces oxygen radicals and oxygen singlets, which subsequently damage the vascular epithelium to cause the adhesion and aggregation of platelets in the small vessels. Disintegration of the inner ear hair cells at the irradiated site became evident 24 h after the illumination. These findings further suggest that the photochemical occlusion in the inner ear's microcirculation led to ischemic damage of the stria vascularis and the hair cells in the inner ear. When the action potential (AP) of the cochlea was measured with an electrocochleogram a gradual decrease occurred after the illumination. When acetylsalicylic acid was injected intravenously before treatment, the time required to completely suppress the AP was prolonged in a dose-dependent manner. Findings indicate that our method causes a photochemically induced occlusion in the inner ear's microcirculation and is therefore potentially useful for evaluating the various effects of drugs on the ear.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    European archives of oto-rhino-laryngology and head & neck 250 (1993), S. 342-344 
    ISSN: 1434-4726
    Keywords: Hearing disorders ; Inner ear microcirculation ; Thromboxane A2 synthetase inhibitor ; Thromboxane A2 receptor antagonist disorder
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Since thromboxane (TX) A2 causes vasoconstriction and platelet aggregation, we evaluation the effect of a TXA2 receptor antagonist (vapiprost) and a TXAZ synthetase inhibitor (Y-20811) on a microcirculation disorder in the rat inner ear that was induced by a photochemical reaction between an intravenous injection of rose bengal (RB) and green light. A gradual decrease of the cochlear action potential (CAP) to an 8 kHz sound stimulus was measured with an electrocochleogram and occurred after the RB injection. The CAP then disappeared 5 min after the injection of RB. Both vapiprost and Y-20811 significantly prolonged the time required to complete suppression of the CAP as compared with saline as control. These findings indicate that TXAZ may play an important role in microcirculation disorders in the rat inner ear.
    Type of Medium: Electronic Resource
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