Locomotor characteristics of obese children

The gait patterns of 10 obese and four normal-weight, prepubertal children were used to evaluate characteristics of varying weight groups. Analyses of temporal and distance parameters were conducted on representative gait cycles at slow, normal and fast speeds of walking. Obese subjects showed longer cycle duration (P less than 0.001), lower cadence (P less than 0.001), lower relative velocity (statures/sec) (P less than 0.001) and a longer stance period (P less than 0.001) than normal-weight subjects. Differences were also found in gait symmetry measures, with the obese displaying asymmetry in step length and step factor. In all cases, the right limb was favoured. Obese subjects displayed greatest instability at the slow speed of walking.     

Release of peptides from sustained delivery systems (microcapsules and microparticles) in vivo

Sustained delivery systems (microcapsules, microparticles, or implants) developed for once a month administration of peptides are efficacious and convenient. Long acting formulations of several bioactive peptides are based on microcapsules of a biodegradable polymer poly(dl -lactide-co-glycolide) (PLG), but a better understanding is required of the mechanism of the peptide release from the microcapsules, which is assumed to be primarily by diffusion through pores. In order to clarify this mechanism, microcapsules and microparticles of the agonist [d -Trp⁶]-LHRH and microcapsules of the LHRH antagonist SB-75 were given i.m. to rats 2 h and 1, 2, 4, 7, 14 and 21 days before histological and immunohistochemical investigation. Signs of biodegradation of the PLG matrix could be seen the first day after the injection, in a form of vacuole development in the interior of the particles and connected with the presence of macrophages within the matrix. The microcapsules showed excellent tissue-compatibility, and no significant foreign body reaction was detected. Immunohistochemical study on the microcapsules revealed no visible decrease in peptide concentration in the remnants of the matrix even 2 weeks after the injection. Evaluation of serum [d -TrP⁶]-LHRH showed that after an initial burst, both microcapsules and microparticles maintained elevated serum [d -Trp⁶]-LHRH levels for more than 3 weeks. Our results suggest that the previously proposed mechanisms do not reflect the experimental findings, particularly for the insoluble peptides. The peptide release from the PLG microcapsules or microparticles appears to be controlled mostly by the speed of the biodegradation of the polymer matrix and the diffusion of the peptides from the PGL is negligible.     

PHARMACOKINETICS OF PROPOFOL IN CHILDREN

The pharmacokinetics of propofol were studied in 12 healthyChinese children, aged 4–12 yr, undergoing circumcisionunder inhalation an-aesthesia. All patients received a singlei.v. bolus dose of propofol 2.5 mg kg^–1 and blood concentrationsof propofol over the subsequent 24 h were measured using highpressure liquid chromatography with fluorimetric detection.Data were consistent with a three-compartment model with a mean(SEM) elimination half-life of 209 (29) min and total body clearanceof 40.4 (3.6) ml min^–1 kg^–1. The mean (SEM) apparentvolume of distribution at steady state was 5.0 (2.7) litre kg^–1and volume of the central compartment was 0.6 (0.1) litre kg^–1.The mean (SEM) ratio of k₁₂: k₂₁ was 1.4 (0.2), suggesting that,after injection of a single bolus dose in children, propofolis distributed rapidly to the shallow compartment. The meanratio of k₃₁: k₁₀ suggests that lipophilicity constrains returnof the drug to the central compartment.     

Potentiation of Pulmonary Arteriolar Vasoconstriction to Endothelin-1 by Inhibition of Nitric Oxide Synthesis in the Intact Lung

Objective : To observe pulmonary arteriolar effects of endothelin-1 (ET-1) in the intact lung and determine if constriction to ET-1 is potentiated by inhibition of nitric oxide (NO) synthesis. Methods : In anesthetized male Sprague-Dawley rats with open chest, the lungs were ventilated with air through the lower trachea and in vivo responses of pulmonary arterioles were examined by video microscopy. Observations were made when the lungs were statically inflated with oxygen to a pressure of approximately 10 cm H₂O for brief periods. A lens with a dipping cone was held at the pleural surface. ET-1 (10^?7–10^?5 M; approximately 0.1 ml) was applied topically to the fluid layer under the dipping cone. Results : ET-1 (10^?6 M) constricted parent arterioles 60 ± 5 µm in diameter by 52 ± 12% (range: 20–100%) and branches 45 ± 3 µm in diameter by 36 ± 4% (19–48%). Constriction persisted and there was a dramatic long-lasting decrease in flow. Alveolar walls quickly became pale, indicating reduced capillary perfusion. A lower concentration of ET-1 (10^?7 M) constricted (p < 0.05) parent arterioles 61 ± 4 µm in diameter by 7 ± 3% initially, and by 13 ± 8% after 14 ± 2 minutes, while smaller branches did not respond. In separate experiments, infusion of the NO synthase inhibitor L-NAME (1 mg/kg per minute), modestly (10 ± 3%) decreased (p < 0.05) baseline parent arteriolar diameter from 72 ± 7 µm to 64 ± 5 µm. Branch diameter changed insignificantly from 42 ± 7 µm to 38 ± 7 µm. After l -NAME, ET-1 (10^?7 M) constricted (p < 0.05) parent arterioles by 17 ± 4% initially and 40 ± 14% after 14 ± 2 minutes. Concurrently, branches constricted (p < 0.05) by 14 ± 4% and 26 ± 15%. Conclusions : Arterioles less than 80 µm in diameter were very responsive to ET-1, which could be a factor in altering pulmonary microvascular resistance. Inhibition of NO synthesis appears to potentiate constriction to ET-1.     

Antigen topography is critical for interaction of IgG2 anti-red-cell antibodies with Fcγ receptors

IgG antibodies to the Rh D polypeptide on red cells are normally IgG1 or IgG3, whereas antibodies produced in response to carbohydrate antigens such as the A and B blood groups are predominantly IgG2. The consequences of this isotype restriction for the immune destruction of red cells were investigated. Human IgG2 anti-D and IgG2 anti-A were isolated by affinity purification from an unusual anti-D serum (DEL) and anti-A sera, respectively. These antibodies were compared with IgG1 and IgG3 monoclonal anti-D in in vitro functional assays of the interaction between IgG-coated red cells (EA-IgG) and cells bearing IgG Fc receptors (FcγR). Dimeric IgG2 anti-D bound efficiently to cell lines transfected with FcγRIIa-H131, an allotypic form of FcγRIIa which readily interacts with IgG2, IgG1 and IgG3. Unexpectedly, however, -D-phenotype red cells coated with IgG2 anti-D did not form rosettes with these cells, whereas EA-IgG2 anti-A and EA-IgG1 and EA-IgG3 anti-D effectively formed rosettes with these transfectants at the same sensitization level (100 000 molecules IgG/red cell). In antibody-dependent cell-mediated cytotoxicity (ADCC) assays, lysis of EA-IgG2 anti-A was mediated via FcγRIIa, whereas lysis of EA-IgG1 and EA-IgG3 anti-D was mediated via FcγRI or FcγRIII; EA-IgG2 anti-D was inactive in all functional assays. These experiments suggest that both IgG subclass and antigen structure affect functional IgG–FcγR interactions. The topography of the Rh D antigen, an integral membrane protein, ensures that anti-D is bound near the lipid bilayer surrounded by the glycocalyx. This may sterically hinder access of FcγRIIa-H131 to the FcγR recognition site on the relatively inflexible IgG2 anti-D, but not to that of IgG1 or IgG3 anti-D. In contrast, IgG2 bound to the A antigen on glycoproteins is not so constrained. The topography of the D and A antigens may thus determine whether functional interactions of red-cell-bound IgG2 anti-D and IgG2 anti-A with cells bearing Fcγ receptors can occur.