Determination and correlation of in vitro viability for hairless mouse and human neonatal whole skin and stratum corneum/epidermis.

BACKGROUND AND DESIGN: Viable tissue is essential to assess the rate and extent of biotransformation during percutaneous absorption in vitro. We assessed the viability of hairless mouse whole skin (WS) and stratum corneum/epidermis (SCE) and human neonatal SCE following separation from the dermis by EDTA phosphate-buffered saline (EDTA-PBS) incubation or by heat treatment by measuring the conversion of dextrose to lactate. Lactate concentrations in receptor fluid samples were determined using a Sigma diagnostic lactate determination kit. A standard curve was prepared and samples assayed spectrophotometrically at 340 nm using a lambda 2 beta spectrophotometer. Standard curves were prepared for each experiment and correlation coefficient values (r) were calculated. RESULTS: Our results showed that hairless mouse SCE was associated with glucose conversion to lactic acid at an increased rate if incubated in EDTA-PBS for 4 h and used immediately. Lactate production was greater with the dermis present (EDTA-PBS WS). The rate of glucose to lactate conversion in hairless mouse SCE was 20-25% of that found in WS. Compared with Dulbecco's modified PBS (DMPBS)-treated WS controls, the rate of lactate production in EDTA-PBS-treated WS was nearly a 50% less. Heat treatment in water at 60 degrees C to separate SCE from hairless mouse WS appeared to eliminate viability. Viability of hairless mouse SCE, as measured by glucose conversion to lactate, was comparable to human neonatal SCE. CONCLUSIONS: These results suggest that the dermis is a significant contributor to glucose metabolism and that incubation in EDTA-PBS is a contributing factor to the overall decrease in metabolic capacity of the tissue. As a result of these findings, hairless mouse SCE appears to be useful as a model for human neonatal SCE in percutaneous absorption studies.

Evaluation of transdermal theophylline pharmacokinetics in neonates.

Theophylline may be administered by several routes, but problems are associated with neonatal dosing. The transdermal route may provide a safer and noninvasive method of administration, yet produce therapeutic concentrations in a consistent and reliable manner. To study the feasibility of this in the apnea of prematurity, stable neonates were administered a subtherapeutic transdermal dose for 24 hours in order to assess pharmacokinetics and bioavailability. This was followed with routine intravenous theophylline therapy according to institutional policy. Six of nine neonates had detectable serum theophylline concentrations that increased slowly after patch application. Mean (+/- SD) maximum serum concentration was 2.4 +/- 1.3 micrograms/ml, mean time to maximum serum concentration was 22 +/- 8.2 hours, and mean latency period was 8.0 +/- 4.9 hours. Mean total amount of theophylline delivered to the skin was 18.6 +/- 4.1 mg. Mean fractional absorption at 30 hours was 0.25 +/- 0.12. These data demonstrate that it is possible to produce systemic theophylline concentrations with a transdermal patch in preterm infants sufficient to study pharmacokinetics and bioavailability, and that transdermal delivery of therapeutic doses is technologically feasible.

Mechanism of production of experimental scoliosis in rabbits.

The hypothesis for the mechanism of production of scoliosis, advanced on the basis of morphometric and morphologic studies in human thoracic skeleton, finds further support in the results of an experimental study in rabbits described herein. The removal of transverse processes alone resulted in the production of scoliosis and lordosis. When both transverse processes and facet joints were removed, scoliosis developed rapidly and was considerable. When paraspinal muscles were incised on one side only, however, this resulted in the development of lordosis alone. The convexity of the curve was always toward the operated side, and the apex was almost always at the lowest operated segment. Lordosis was limited to within the operated area. The results of the experiment indicate that scoliosis resulted because of the asymmetry in load transmission through the ribs to the vertebral column in rabbits.

Relationship between the tendon of the long head of biceps brachii and the glenoidal labrum in humans.

The relationship between the tendon of the long head of the biceps brachii muscle and the glenoidal labrum was investigated in a large number of dissected human shoulder joints. In about 70% of the specimens examined, the labrum was deficient at the posterosuperior margin of the glenoid because the tendon of the biceps coursed over this margin to blend with the labrum. Because of this, a small crescentic accessory facet was observed at the posterosuperior margin of the glenoid. In the majority of cases, the tendon of the biceps blended with the glenoidal labrum, and only a small part of the tendon attached to the supraglenoid tubercle. However, in 25% of the specimens, the major portion of the tendon was attached to the supraglenoid tubercle.