Enhancement of transdermal delivery of phenylbutazone from liposomal gel formulations through deer skin.

Phenylbutazone (PBZ) is a nonsteroidal anti-inflammatory drug used in the treatment of chronic pain and arthritis. Topical and transdermal administration of PBZ would be beneficial in large animals in terms of minimizing gastro-intestinal ulcerations and other side effects, easy administration to legs and joints and minimizing the dose to reduce systemic toxicity of the drug. A topical liposomal preparation with different concentrations of a mono-substituted alkyl amide (MSA) and PBZ was formulated. The formulations were evaluated by in vitro skin-permeation kinetics through deer skin using Franz diffusion cells. By increasing drug loading from 1% to 5% w/w, the steady-state flux (microg/cm(2)/h) of PBZ was increased twofold (P < 0.001). Similarly, by increasing the MSA concentration from 0% to 4%, the steady-state flux (microg/cm(2)/h) of PBZ was increased twofold (P < 0.001). Overall, by increasing the drug load and the use of an appropriate amount of the penetration enhancer, the steady-state flux of PBZ through skin was increased fourfold (P < 0.001). MSA at both 2% and 4% w/w concentrations significantly increased the skin levels of PBZ as compared with control (P < 0.05). In conclusion, MSA served as an effective skin-penetration enhancer in the liposomal gel of PBZ for deer.

Fetal weights and measurements as determined by postmortem examination and their correlation with ultrasound examination.

Two hundred fifty fetuses from healthy singleton pregnancies terminated other than on health grounds at 21 to 26 weeks gestation were examined by ultrasound in utero and by autopsy. No significant maturational difference between male and female fetuses was noted, although larger biparietal distances (0.2 cm) and smaller femur lengths (0.2 cm) were seen in female fetuses at 23 weeks gestation, and heavier body weights were also noted (80 g). No maturational difference was noted between white and nonwhite populations. Maternal age was not a significant variable. Organ weights and fetal anthropometric measurements are provided. Biparietal diameter as determined by ultrasound examination of the fetus in utero is an excellent predictor of gestational age and correlated well with actual caliper measurements on the fetus (coefficient of variation [CV] < 5%). Femur length determined by ultrasound examination of the fetus in utero is significantly low compared with actual length (CV = 23%) and is not a reliable indicator of fetal development. A large CV (17%) was also seen for calculated fetal weight.

Characteristics of dimer formation, excision and DNA strand growth in Yoshida sensitive and resistant cells after ultraviolet irradiation.

The sedimentation properties of the nascent DNA of Yoshida sarcoma cells, sensitive and resistant to methylene dimethane sulphonate and cross-resistant to U.V. light, have been studied after irradiation with U.V. light at 11 and 22J/m2. It has been shown that the DNA formed immediately after irradiation with 11J/m2 is some eight to nine times longer than the calculated inter--dimer distance in both cell-lines. Differences were, however, observed between the two cell-lines, in that the absence of excision of dimers in the sensitive cells was accompanied by the formation of a DNA component of low molecular weight, whereas excision in the resistant line was not so accompanied. There are some similarities between the Yoshida tumour line sensitive to methylene dimethane sulphonate and the U.V.-sensitive line of Xeroderma pigmentosum.