潮式呼吸分析参数评价哮喘儿童气道阻塞的意义和应用

】　目的　评价潮式呼吸分析参数t     

依法加强我国新药技术市场监管的对策

本文分析了我国新药技术市场的现状。介绍了新药技术成果转化的方式,以及如何建立、健全和完善新药技术市场的管理体系。提出了依法监督管理的对策及办法。     

Intrinsic absolute bioavailability prediction in rats based on in situ absorption rate constants and/or in vitro partition coefficients: 6-fluoroquinolones

A preliminary study attempting to predict the intrinsic absolute bioavailability of a group of antibacterial 6-fluoroquinolones-including true and imperfect homologues as well as heterologues-was carried out. The intrinsic absolute bioavailability of the test compounds, F, was assessed on permanently cannulated conscious rats by comparing the trapezoidal normalized areas under the plasma concentration-time curves obtained by intravenous and oral routes (n = 8-12). The high-performance liquid chromatography analytical methods used for plasma samples are described. Prediction of the absolute bioavailability of the compounds was based on their intrinsic rat gut in situ absorption rate constant, k(a). The working equation was: where T represents the mean absorbing time. A T value of 0.93 (+/-0.06) h provides the best correlation between predicted and experimentally obtained bioavailabilities (F' and F, respectively) when k(a) values are used (slope a = 1.10; intercept b = -0.05; r = 0.991). The k(a) values can also be expressed in function of the in vitro partition coefficients, P, between n-octanol and a phosphate buffer. In this case, theoretical k(a) values can be determined with the parameters of a standard k(a)/P correlation previously established for a group of model compounds. When P values are taken instead of k(a) values, reliable bioavailability predictions can also be made. These and other relevant features of the method are discussed.     

Biodistribution, plasma kinetics and quantification of single-pass pulmonary clearance of adrenomedullin

The biodistribution, pharmacokinetics and multi-organ clearance of the vasodilator peptide AM (adrenomedullin) were evaluated in rats and its single-pass pulmonary clearance was measured in dogs by the indicator-dilution technique. Intravenously administered 125I-rAM(1-50) [rat AM(1-50)] was rapidly cleared following a two-compartment model with a very rapid distribution half-life of 2.0 min [95% CI (confidence interval), 1.98-2.01] and an elimination half-life of 15.9 min (95% CI, 15.0-16.9). The lungs retained most of the injected activity with evidence of single-pass clearance, since retention was lower after intra-arterial (13.5+/-0.6%) compared with intravenous (30.4+/-1.5%; P < 0.001) injection. Lung tissue levels of total endogenous AM were 20-fold higher than in other organs with no difference in plasma levels across the pulmonary circulation. In dogs, there was 36.4+/-2.1% first-pass unidirectional extraction of 125I-rAM(1-50) by the lungs that was reduced to 21.9+/-2.4% after the administration of unlabelled rAM(1-50) (P < 0.01). Extraction was not affected by calcitonin-gene-related peptide administration (40.6+/-2.9%), but was slightly reduced by the C-terminal fragment of human AM(22-52) (31.4+/-3.3%; P < 0.01). These data demonstrate that the lungs are a primary site for AM clearance in vivo with approx. 36% first-pass extraction through specific receptors. This suggests that the lungs not only modulate circulating levels of this peptide, but also represent its primary target.     

New 9-thiocyanatopupukeanane sesquiterpenes from the nudibranch Phyllidia varicosa and its sponge-prey Axinyssa aculeata

Two new 9-thiocyanatopupukeanane sesquiterpene isomers were isolated as major metabolites from the MeOH extract of the sponge Axinyssa aculeata and from its nudibranch predator Phyllidia varicosa. The presence of the sesquiterpenes was monitored by GC-MS, and the structures were confirmed by both 1D and 2D NMR spectroscopy. The isolated sesquiterpenes were found to be toxic toward brine shrimp at LC(50) of 5 ppm. At a dose level of 20 microg, they were found to be weakly and moderately active against B. subtilis and C. albicans, respectively.     

Positron emission tomography in a patient with Von Recklinghausen disease and left dorsal neurofibrosarcoma

The development of neurofibrosarcomas in patients with Von Recklinghausen disease is a rare complication that can appear in the daily clinical practice. We report a clinical case with Von Recklinghausen disease and recurrence of a left dorsal neurofibrosarcoma diagnosed by Positron Emission Tomography with fluorine-18-fluoro-deoxyD-glucose (FDG-PET). We believe this work is important due to the relatively uncommon clinical presentation and the discussion on the utility of 18-FDG PET and other conventional imaging methods in the diagnosis of this entity.     

Bone mineral density in children with nocturnal enuresis

In enuretic children there is a significantly higher incidence of fine and gross motor clumsiness, delayed developmental milestones, slower and poor linear growth, and these patients are shorter than normal children. Skeletal maturation of enuretic children has been determined with bone age in only two studies before, but to our knowledge bone mineral content of enuretic children has not previously been determined by bone mineral density measurement. Bone mineral density was measured by the dual-energy x-ray absorptiometry method in children with nocturnal enuresis and compared with that of a control group to detect whether there were any delay in bone development and any decrease in bone mass. Thirty enuretic children were compared with a control group of 40 healthy children with respect to body height and weight measurements, daily calcium intake, serum calcium, phosphorus and ALP levels, chronological and bone ages, and bone mineral density measurements. Of the parameters compared, bone age was significantly retarded, and bone mineral density was significantly reduced in children with enuresis (8.3 +/- 1.9 vs 9.7 +/- 2.3 years; p = 0.01, and 0.5476 +/- 0.07 vs 0.6077 +/- 0.05 g/cm2; p = 0.001, respectively). Chronological ages demonstrated a significant correlation with the bone ages in both the study and control groups (r = 0.852, p < 0.001, and r = 0.844, p < 0.001, respectively). However, the mean chronological age was significantly greater than the mean bone age in the study group (p < 0.001), whereas the mean chronological age was not significantly different from the mean bone age in the control group (p = 0.514). To clarify the exact mechanism responsible for these manifestations of skeletal maturation retardation, the relationship between the maturational delay of the central nervous system connections or the effect of any perinatal insult and the retardation in skeletal maturation remains to be determined.