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991.
Yie W. Chien 《American heart journal》1984,108(1):207-216
When formulated as a sublingual or an oral sustained-release dosage form, nitroglycerin has certain shortcomings, i.e., decreased duration of antianginal action and extensive hepatic first-pass elimination, which limit its efficacy. The finding that administration of nitroglycerin in the form of topical ointment decreases the extent of hepatic first-pass elimination and increases the duration of therapeutic activity has pointed the way to the possibility of developing a more effective transdermal drug delivery device. Three such devices are the Nitrodisc, Nitro-Dur, and Transderm-Nitro systems. All three systems generate effective plasma drug levels within 30 minutes and maintain steady-state drug plasma levels as follows: the 16 cm2 Nitrodisc at 280.6 ± 18.7 pg/ml for 32 hours; the 20 cm2 Nitro-Dur at 201.4 ± 60.7 pg/ml for 24 hours; and the 20 cm2 Transderm-Nitro system at 209.8 ± 22.8 pg/ml for 24 hours. In vitro studies show that the drug penetrates the skin with zero-order kinetics in all three systems, the rate for Nitrodisc being 20% greater than that of the other systems. When the daily nitroglycerin dose is calculated in terms of skin permeation rate and the device's surface area, the three transdermal systems become clinically interchangeable. 相似文献
992.
Chien -Ping Ko 《Journal of neurocytology》1985,14(3):487-512
Summary Development of the presynaptic active zone was studied at neuromuscular junctions with freeze-fracture electron microscopy in larval and adult bullfrogs. In rudimentary larval neuromuscular junctions, clusters of active zone particles were scattered over the P-face of the presynaptic membrane. Vesicle openings were observed at these terminals even though active zone particles lacked the mature pattern of two double rows. Gradually, active zone particles became organized into rows, but they were still randomly located and oriented. Once junctional folds were observed in replicas, developing active zones were located opposite to the folds, as in mature terminals. Multiple terminals occupying the same junctional gutters were also observed. At the end of metamorphosis, most active zones were still immature in appearance and had only grown to one third of their mature length. After metamorphosis, the number of active zone segments aligned at the same junctional fold increased. These discontinuous short active zones then elongated, joined together, and finally formed the mature active zones. Signs suggesting synapse elimination such as disorganization of active zones, absence of intramembrane particles in varicosities, and exposed muscle membranes with patches of acetylcholine receptor aggregates were observed. In some multiply innervated junctions, one terminal had mature active zones with vesicle openings, the other in the same gutter displayed disorganized active zones without vesicle openings, although both terminals showed similar sizes and distributions of background particles. This study suggests that developing active zones, as is the case for regenerating active zones in the adult, are functional before the mature organization is formed. The sequence of development of active zones is also similar to that of regeneration except for the random location and orientation of early active zones in tadpoles. The comparison between regeneration and development further indicates that the process of active zone formation is related to junctional folds and/or associated structures. It is also suggested that synapse elimination may involve degenerative changes in presynaptic membranes, although direct evidence remains to be provided. 相似文献
993.
A ventricular perfusion technique was used to determine the rate of cerebrospinal fluid (CSF) formation in a 5-year-old child who had undergone bilateral choroid plexectomy for communicating hydrocephalus during infancy. At the time of the study, the patient had a failed ventriculoperitoneal shunt and was suffering from progressive ventriculomegaly. The calculated rate of CSF formation, 0.35 ml/min +/- 0.02 standard deviation, was within normal limits. 相似文献
994.
995.
The binding of carcinogenic 7-hydroxymethylbenz[a]anthracene (7-HOCH2-B[a]A) and 7-acetoxymethylbenz[a]anthracene (7-AcOCH2-B[a]A) to calf thymus DNA was studied in the presence or absence of microsomal enzymes or nucleoside phosphates. In the absence of microsomes or ATP little or no binding was detected for either hydrocarbon (HC). Microsomal enzymes significantly enhanced the binding of both HC's to DNA when compared to control as measured by radioactivity bound to DNA. When 7-HOCH2-B[a]A was incubated at 37 degrees with ATP there was a linear increase in binding over a six hr period. Of the nucleoside phosphates tested, ATP, and to a lesser extent ADP and CTP, mediated binding of 7-HOCH2-B[a]A suggesting formation of a reactive phosphate ester. Mutagenicity studies with 7-acetoxymethyl, 7-hydroxymethyl, 7-formyl-, 7-methyl-, and 7-methoxymethyl-B[a]A were conducted using the Salmonella reverse mutation assay. All compounds exhibited mutagenic activity in the presence of S-9; only 7-AcOCH2-B[a]A was active without S-9 indicating this compound to be an ultimate mutagen. 相似文献
996.
997.
Rodgers J Buchanan T Pearson C Parrott AC Ling J Hefferman TM Scholey AB 《Journal of psychopharmacology (Oxford, England)》2006,20(3):437-446
Previous work provided preliminary evidence that different patterns of use among ecstasy users may impact on perceived side-effects. Participants recruited via an ecstasy-related bulletin board differed in their responses compared to those recruited via other means. The present investigation compares self-reports of psychobiological difficulties among ecstasy users recruited either via a bulletin board or by alternative methods. Qualitative data included reports of any negative or positive changes attributable to ecstasy use and reasons for cessation of use. An Internet-based design was utilized and 209 volunteers completed the study, 117 of whom were recruited via a bulletin board devoted to discussion of ecstasy. Psychobiological difficulties attributable to ecstasy use varied, with mood fluctuation the most common. Differences between the two groups in the extent to which these problems were reported was found. Bulletin board recruits were less likely to report anxiety or poor concentration, but more likely to report tremors/twitches. For the whole sample, lifetime use was associated more with psychobiologial problems, although this pattern was stronger and more pervasive for the non-bulletin board participants. Bulletin board recruits were more aware of possible negative psychological effects and were more likely to report adopting harm reduction strategies. From the qualitative data three negative consequences of use were identified, the most common of which was "psychological problems". In support of the quantitative findings the likelihood of reporting psychological problems increased with lifetime exposure to ecstasy in both recruitment conditions but interestingly this did not appear to impact on reasons for cessation of use. Participants also reported a number of effects that they regarded as beneficial. Future research should also take these aspects of use into account. 相似文献
998.
999.
1000.
Mwinyihija M Strachan NJ Rotariu O Standing D Meharg A Killham K 《International journal of environmental health research》2006,16(1):47-58
Ecotoxicological screening of dust sampled throughout a Kenyan tannery was conducted using a luminescence (lux)-based bacterial biosensor for both solid and liquid assays. This was complemented by chemical analysis in an attempt to identify possible causative toxic components. The biosensor results showed a highly significant (p < 0.001) difference in both solid and liquid phase toxicity in samples collected from various identified sampling points in the tannery. A positive correlation was observed between results of the solid and liquid phase techniques, for most of the sampling points indicating that the toxic contaminants were bioavailable both in the solid and liquid state. However, the results generally indicated toxicity associated with liquid phase except certain areas in solid phase such as chemical handling, buffing area and weighing. The most toxic tannery area identified was the weighing area (p < 0.001), showing the lowest bioluminescence for both the solid (0.38 +/- 2.21) and liquid phases (0.01 +/- 0.001). Chromium was the metal present in the highest concentration indicating levels higher than the stipulated regulatory requirement of 0.5 mg Cr/m3 for total Cr (highest Cr concentration was at chemical handling at 209.24 mg l(-1)) in all dust samples. The weighing area had the highest Ni concentration (1.87 mg l(-1)) and the chemical handling area showed the highest Zn concentration (31.9 mg l(-1)). These results raise environmental health concerns, as occupational exposure to dust samples from this site has been shown to give rise to elevated concentrations (above the stipulated levels) of chromium in blood, urine and some body tissues, with inhalation being the main route. Health and Safety Executive (HSE), UK, and American Conference of Governmental Industrial Hygienist (ACGIH) and National Institute for Occupational Safety and Health (NIOSH), USA stipulates an occupational exposure limit of 0.5 mg Cr/m3 (8 h TWA) for total chromium. However, schedule 1 of Controls of substances hazardous to health (COSHH) regulations developed by HSE, indicate 0.05 mg m3 (8 h TWA reference periods) to be the limit for Cr (VI) exposure. The exposure limit for individual (e.g., Cr, Zn, Ni etc.) contaminants (homogeneity) was not exceeded, but potential impact of heterogeneity (multi-element synergistic effect) on toxicity requires application of the precautionary principle. 相似文献