Thermal reversible microemulsion system for poorly water-soluble YH439 for oral delivery.

To improve bioavailability of poorly water-soluble YH439, a thermal reversible microemulsion system was prepared using modified fatty acids such as capric acid and palmitic acid with PEG 400. A combination of Capric-PEG 400 and Palmitic-PEG 400 with a ratio of 1 : 3 used as a lipid matrix and Cremophor RH40 and Neobee M-5 were selected as an oil and a surfactant, respectively. The microemulsion with melting point of 36.5 degrees C was produced by mixing the lipid matrices, Cremophor RH40 and Neobee M-5 with a volume ratio of 5 : 4 : 1. After the microemulsion was dispersed in the aqueous medium, the average particle size of 28 nm was obtained. At the release measurements of YH439 after 45 min suspension in pH 1.2 aqueous medium, about 80%, 65%, 10% and less than 5% of drug were released from the thermal reversible microemulson, Gelucire formulation, 5% Ca-carboxymethylcellulose (CMC) suspension and YH439 powder, respectively. The apparent permeability of YH439 in microemulsion either from apical to basolateral or basolateral to apical after measuring YH439 across a Caco-2 cell monolayer in a Transwell larger than Gelucire formulation or 5% Na-CMC suspension. The area under the drug concentration-time curves (AUC) and maximal blood concentration (C(max)) after oral administration of YH439 loaded on thermal reversible microemulsion were significantly increased than drug loaded on either Gelucire formulation or 5% Na-CMC suspension. Thus, the present work demonstrates that the thermal reversible microemulsion system of YH439 greatly enhances the bioavailability of YH439 after oral administration due to the improvement of solubility and dispersion of the drug in the artificial gastrointestinal tract without pepsin.

The effect of papaverine on ion channels in rat basilar smooth muscle cells.

OBJECTIVES: Papaverine has been used in treating vasospasm following subarachnoid hemorrhage (SAH). However, its action mechanism for cerebral vascular relaxation is not clear. Potassium and calcium channels are closely related to the contraction and relaxation of cerebral smooth muscle. Therefore, to identify the role of potassium and calcium channels in papaverine-induced vascular relaxation, we examined the effect of papaverine on potassium and calcium channels in freshly isolated smooth muscle cells from rat basilar artery. METHOD: The isolation of rat basilar smooth muscle cells was performed by special techniques. The whole cell currents were recorded by whole cell patch clamp technique in freshly isolated smooth muscle cells from rat basilar artery. Papaverine was added to the bath solution. RESULTS: Papaverine of 100 microM into bath solution increased the amplitude of the outward K(+) current which was completely blocked by BKCa blocker, IBX (iberiotoxin) and a calcium chelator, BAPTA (1,2-bis(o-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid) in whole cell mode. Papaverine (100 microM) also inhibited L type Ca(2+) current recorded in isolated smooth muscle cells from rat basilar artery. DISCUSSION: These results strongly suggest that Ca(2+)-activated potassium channels and L type Ca(2+) channels may be involved in papaverine-induced vascular relaxation in rat basilar artery.

Extradural Thoracic Spinal Meningioma Arising from a Nerve Root

Extradural meningiomas are relatively rare and those arising from spinal root are even rarer. Recently, a case of extradural meningioma arising from a spinal nerve root was surgically treated in our institution. This patient was a 19-year-old female presented with paraparesis and paresthesia. The mass was compressing the spinal cord at the level of fourth thoracic spine, and it was extended to the nerve root. At operation it was found to be originated from the fourth thoracic spinal nerve root. After removal of the tumor, the neurologic symptom and sign were recovered completely. Histoligic examination of tumor revealed as transitional type of meningioma.