Pharmacokinetics and disposition of recombinant human osteoprotegerin (rhOPG) after intravenous administration in female fischer rats.

1. Osteoprotegerin (OPG) is a secreted member of the tumour necrosis factor receptor (TNFR) family that leads to the suppression of the differentiation, activation and survival of osteoclasts. The objective was to investigate the in vivo pharmacokinetics and tissue distribution of full-length recombinant human OPG (rhOPG) as well as its clearance mechanism using (125)I-labelled protein ((125)I-rhOPG) after intravenous administration to female Fischer rats. 2. (125)I-rhOPG was rapidly and predominantly distributed to the liver after dosing (3 mg kg(-1)). Immunohistochemical analysis indicated that rhOPG was located in the sinusoids of the liver. 3. The hepatic uptake of (125)I-rhOPG (0.01 mg kg(-1)) was partly regulated under a saturable process. Pre-dosing of some sulfated glycans (20 mg kg(-1)), especially dextran sulfate, heparin and fucoidan, markedly inhibited the hepatic uptake of (125)I-rhOPG. The clearance of (125)I-rhOPG was markedly reduced by the conjugation of dextran sulfate. 4. The results suggested that the hepatic clearance of (125)I-rhOPG was mainly mediated by the interaction with glycosaminoglycans.

Asynchronous breathing during sleep.

BACKGROUND: Children rarely complain of symptoms associated with sleep disordered breathing (SDB). Paradoxical inward rib cage movement (PIRCM) during sleep might prove useful for detecting SDB. AIMS: (1) To determine the correlation between the degree of PIRCM and other measures of disordered breathing during sleep. PIRCM occurs physiologically throughout rapid eye movement sleep in neonates, while no PIRCM has been reported during sleep in adolescents. (2) To determine the chronological changes in the degree of PIRCM. METHODS: PIRCM was quantified by means of the laboured breathing index (LBI). LBI was determined by respiratory inductive plethysmography; PIRCM accompanies a high LBI. Sleep recordings obtained for 101 subjects for various reasons (aged from 3.5 months to 19 years) were analysed. RESULTS: In 22 records, the minimum SaO2 value was 90% or more and no obstructive apnoea of more than 10 seconds was observed. In these 22 records, LBI during rapid eye movement sleep decreased significantly with age, reaching the mature low level at 3.3 years of age. In the other 79 records, LBI correlated well with measures of obstructed breathing during sleep. CONCLUSIONS: By paying more attention to PIRCM, more obstructed breathing during sleep might be found among children aged 3 years or more.

Sleep disordered breathing during REM sleep in Freeman-Sheldon syndrome.

OBJECTIVES: To examine the sleep-disordered breathing in patients with Freeman-Sheldon syndrome (FSS). MATERIAL AND METHODS: One night polysomnography was performed for 2 teenage FSS patients. RESULTS: They showed frequent obstructive sleep apnea exclusively during rapid-eye-movement sleep. CONCLUSION: FSS is a risk factor for the occurrence of sleep disordered breathing.

Quantitative analysis of paradoxical inward rib cage movement during sleep in children.

Paradoxical inward rib cage movement in children is quantified by the labored breathing index (LBI) on the respiratory inductive plethysmography. Labored breathing index during rapid eye movement sleep (REMS) in 59 children without obvious sleep disordered breathing (SDB) declined with age, and decreased to the mature low level at 35 months of age. The LBI was also found to reflect well the severity of SDB. Paradoxical inward rib cage movement, which was quantified by LBI, is concluded to be an important finding in diagnosing SDB in child patients.

Video analysis of gross body movements during sleep.

Gross body movements (GM) during sleep, classified into four GM types by the involved parts of body, were evaluated using two-dimensional video analysis in five normal children aged 4-12 years. The rate of occurrence of all GM types showed apparent sleep stage dependency. Among four GM types, GM-1 (GM with axial rotation) was the most frequent. Averaged duration of GM-1 was the longest. A total of 77.2% of GM-1 started with the contraction of chin muscle and 35% of total sleep changes (tSC) were related to GM. A total of 5.6% of tSC following GM shifted to the deeper stage. Further evaluation is necessary in order to understand the physiological mechanism of GM.