A Novel Extravascular Input Function for the Assessment of Drug Absorption in Bioavailability Studies

Purpose. Flexible parametric models describing the input process after extravascular drug administration are needed for the assessment of absorption rate and the use of population methods in bioavailability and bioequivalence studies. Methods. The oral concentration-time curve modeled as the product of the input and disposition function in the Laplace domain was obtained by numerical inversion methods for parameter estimation. The utility of the inverse Gaussian input density was examined using bioavailability data of an extended-release dosage form. Measures of rate of absorption and the cumulative absorbed amount profile were defined in terms of the estimated model parameters. Results. Accurate estimation of absorption parameters was achieved by simultaneous fitting of the extravascular and intravascular data (describing the latter by a triexponential function). The new input function allowed a direct estimation of both extent of absorption and mean absorption time. Conclusions. The findings suggest that the inverse Gaussian density is a useful input function. Its flexibility may reduce the effect of model misspecification in parameter estimation. All parameters can be readily interpreted in terms of the absorption process.     

双氯灭痛药膜体外透皮速率的实验研究

作者选择乙基纤维素、聚乙烯醇等高分子材料制成涂膜剂，用大鼠皮进行双氯灭痛药膜的体外透皮速率测定。结果表明，氮酮与丙二醇可以促进药物渗透。不同的高分子材料可影响药物的扩散与释放，从而影响其透皮速率。与无膜无促透剂处方相比，药物在乙基纤维素中的透皮速率没有增加，在聚乙烯醇膜中的透皮速率有显著增加。     

免疫反应在实验性游离型腰椎间盘突出自然吸收中的意义

目的：通过检测CD3和IgG在实验性游离型腰椎间盘突出自然吸收中的表达，探讨腰椎间盘突出后能否自然吸收及其可能的吸收机制。方法：将25只成年狗平均分成5组，从L2/3切取髓核组织，置于L5处的硬脊膜外，于术后2，4，6，8，12周，取动物标本以及正常部位的髓核组织，用CD3抗体和抗IgG进行免疫组化检测。结果：约30%的标本局部为脂肪组织，54%的标本局部硬脊膜与骨粘连，16%的标本既无粘连也无脂肪，免疫组化测定显示，随着时间的推移，CD3^ 细胞的浸润程度呈递减趋势，而IgG沉积的分布程度呈递增趋势，正常髓核无CD3^ 细胞浸润，IgG沉积分布极少。结论：在椎管内，狗游离的髓核组织8-12周后可部分或全部自然吸收，其吸收机制是机体自身免疫反应的结果。     

Small-dose oral iron absorption test in anaemic and non-anaemic elderly hospitalized patients

Abstract: The small-dose (20 mg) oral iron absorption test (OIAT) was performed in 76 hospitalized elderly patients and 30 healthy adults. Of the elderly patients, 34 were considered as iron deficient (serum ferritin level <20 μg/L) of whom 23 were anaemic and 11 not anaemic, 21 had the anaemia of chronic disorders (ACD) and another 21 were non-anaemic patients with a normal serum ferritin level. There was a significant inverse correlation between the serum ferritin level as a measure of iron store and the maximum increase in serum iron during a 3-h test (C_max), in the elderly as well as in the healthy adult group. A decision limit of 80 μg/dL for C_max is a good discriminant between absent (serum ferritin <20 μg/L) and adequate body iron stores. Sixty-eight per cent of the patients with a serum ferritin level <20 μg/L but virtually none of the ACD patients, non-anaemic elderly inpatients with normal serum ferritin levels and healthy adults had a C_max level >80 μg/L. Although further investigation is needed before the OIAT can be recommended as a valuable test for evaluating iron absorption, predicting mild iron deficiency and differentiating between different categories of anaemia, it seems worthwile that more effort should be done to validate this simple and safe test.     

The natural history of untreated phenylketonuria over 20 years

Fifty-one adults with untreated phenylketonuria (PKU), have been reviewed after a 20 year interval, at ages ranging from 28.8 to 71.8 years. Five died of causes unrelated to PKU. Three severely affected individuals had shown a progressive loss of motor function and three had developed epilepsy, bringing the total with this problem to 12. No loss of abilities was apparent in 41 patients. Other health problems, including cataracts, were not frequent. Serum phenylalanine levels had decreased over the 20 year period. Untreated PKU does not generally cause progressive loss of abilities during adult life.     

Auditory Perception and the Control of Spatially Coordinated Action of Deaf and Hearing Children

From birth onwards, auditory stimulation directs and intensifies visual orientation behaviour. In deaf children, by definition, auditory perception cannot take place and cannot, therefore, make a contribution to visual orientation to objects approaching from outside the initial field of view. In experiment 1, a difference in catching ability is demonstrated between deaf and hearing children (10-13 years of age) when the ball approached from the periphery or from outside the field of view. No differences in catching ability between the two groups occurred when the ball approached from within the field of view. A second experiment was conducted in order to determine if differences in catching ability between deaf and hearing children could be attributed to execution of slow orientating movements and/or slow reaction time as a result of the auditory loss. The deaf children showed slower reaction times. No differences were found in movement times between deaf and hearing children. Overall, the findings suggest that a lack of auditory stimulation during development can lead to deficiencies in the coordination of actions such as catching which are both spatially and temporally constrained.     

Plasma concentrations and bioavailability of propranolol by oral, rectal, and intravenous administration in man

Eight normal male volunteers received 80 mg doses of propranolol by the oral and rectal routes and 2.2 mg by intravenous administration in a crossover fashion. Plasma concentrations of propranolol were measured by a gas chromatographic method using an electron capture detector. Individual subject concentration-time data were analysed and results indicated that the data fit a two compartment model with first order absorption. An approximately two-fold higher plasma propranolol concentration was observed after rectal administration as compared with oral dosing. Statistical analysis of the difference in the total AUCs indicates a significantly higher bioavailability of propranolol administered by the rectal route. The reduced bioavailability after oral administration indicates a substantial first pass effect but that it is possible to bypass the liver, at least partially, by giving the drug rectally to man.     

农村公共卫生投融资机制存在的问题及对策

当前,农村公共卫生投融资规模不能适应农村居民的卫生服务需要,投融资结构不合理,致使投融资效果不佳,不利于农村卫生事业的发展。为此,需要从四个方面改革农村公共卫生投融资机制:一是要建立健全国家财政投资保障制度,发挥财政在农村公共卫生投资中的主体作用;二是要改革运行模式,拓宽融资渠道;三是要改善投资结构,优化资源配置;四是要创新管理体制,提高农村公共卫生服务能力。     

An investigation of the neuropsychological profile in adults with velo-cardio-facial syndrome (VCFS).

Velo-cardio-facial syndrome (VCFS) is associated with deletions on the long arm of chromosome 22, mild intellectual disability, poor social interaction and a high prevalence of psychosis. However, to date there have been no studies investigating the neuropsychological functioning of adults with VCFS. We compared 19 adults with VCFS with 19 age, gender and IQ matched controls using a comprehensive neuropsychological battery. Compared to controls, adults with VCFS had significant impairments in visuoperceptual ability (Visual Object and Space Perception Battery), problem solving and planning (Tower of London) and abstract and social thinking (Comprehension WAIS-R). It is likely that haploinsufficiency (reduced gene dosage) of a neurodevelopmental gene or genes mapping to chromosome 22q11 underlies the cognitive deficits observed in individuals with VCFS.