Relationships between skin permeability and physicochemical properties of drugs were examined to establish a predictive method for the steady-state permeation rate of drugs through human skin. Human skin permeation properties fell into two categories: one in which the permeability coefficient is correlated to the partition coefficient, revealed with lipophilic drugs; and the other in which the permeability coefficients are almost constant, shown with hydrophilic drugs. The stratum corneum, the main barrier in skin, could be considered as a membrane with two parallel permeation pathways: lipid and pore pathways, and an equation for predicting the steady-state permeation rate of drugs was derived. The skin permeabilities of drugs for man were compared with those for hairless rat. The species difference in skin permeability found was suggested to be due to the difference in skin permeation pathways, since lipid content and water uptake of the stratum corneum varied between human and hairless rat skin.

A method for estimating the in-vitro permeability of human skin to drugs, based on in-vitro permeation studies using animal skins, has been developed. The skins from hairless rats, guinea-pigs, dogs and pigs were used, with nicorandil and deionized water as model drug and solvent in a drug-donor compartment. Diffusion coefficients through the skin barrier, D, and partition coefficients from the drug-donor compartment to skin, K, of the drug, in each species, were calculated by curve-fitting the in-vitro permeation data to a diffusion equation describing the drug permeation through a homogeneous membrane, using a non-linear least squares method. Each barrier thickness, L, was measured microscopically from microtomed skin sections. A positive relationship was found between the skin permeability, Kp, and K value among the four species, but species differences in the D and L values were small in spite of the Kp values being different among the four species. A positive correlation was also observed between the calculated and experimental K values among the four species, and hence it was suggested that the main factor for the species difference in the skin permeability of nicorandil would be the difference in partitioning of the drug from vehicle to stratum corneum. As a result, it has become feasible to predict and estimate skin permeability of nicorandil in humans by substituting each parameter, extrapolated from the animal skin permeation data and partition experiments, in the diffusion equation.

Carcinosarcoma of the duodenum has not been reported previously, although this type of tumor has been detected in other organs. We present here a case of carcinosarcoma of the duodenum, including immunohistochemical and electron microscopical findings. An ulcerating tumor, located in the duodenal ampullary region, contained two divergent components: ordinary differentiated tubular adenocarcinoma, and sarcomatoid tissue composed of spindle tumor cells. Immunohistochemically, the adenocarcinoma cells were stained with antibodies against epithelial markers including keratin and CA19-9. In contrast, the sarcomatoid tissue was strongly positive for vimentin and was focally positive for myoglobin, keratin, and CA19-9. We speculate that the sarcomatoid element of the carcinosarcoma arose from part of the ordinary adenocarcinoma tissue.

A direct current (DC) system and a pulsed depolarization (PD) system were evaluated for their iontophoretic permeation of sodium benzoate, as a model drug, through hairless rat and human skin. Approximately the same initial permeation of sodium benzoate through the hairless rat skin was obtained at 0.1 mA for the DC device and at 3.0 mA for the PD device. Study of the drug's permeation was performed using a two-chamber iontophoretic diffusion cell, over two cycles of three successive on-off experimental conditions [stage I (off) 0-4 h, II (on) 4-6 h, III (off) 6-10 h, saline washing 10-24 h, IV (off) 24-28 h, V (on) 28-30 h and VI (off) 30-34 h]. Skin permeation rate during stage IV of the iontophoresis as compared with the control group through hairless rat or human skin for the DC system was 2-4 times that in stage I, whereas in the same stage using the PD system it was almost the same as in stage I. Impedance of skin decreased during the application of either system (stage II); however, the value significantly recovered during stage III only in the case of the PD system use on human skin. Histological observation revealed no tissue alteration in the hairless rat skin after using either system. When the DC or PD system was applied to volunteers, the minimum current density producing pain was 0.016 or 2.7 mA cm-2, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

A 71-year-old man who developed jaundice with a high-grade fever was admitted to our hospital. The episode was ascribed to cholecysto-choledocholithiasis. In the preoperative evaluation, a cavernous transformation of the portal vein and an early gastric cancer were found. The patient thereafter underwent an operation for those pathologies after the endoscopic removal of a choledochal stone; cholecystectomy, and a distal gastrectomy with regional lymph node dissection for gastric cancer. The proposed procedures of gastrectomy and cholecystectomy were completed without any major difficulty because no markedly enlarged collateral veins were found in the area where the regional lymph node dissection was carried out. Thanks to advances in imaging modalities, an asymptomatic cavernous transformation of the portal vein coinciding with gastric cancer such as that seen in the present case may be increasingly encountered in the future. The greatest caution, however, needs to be exerted at operation to minimize any unexpected bleeding and to avoid any interruption of the porto-portal shunts in such cases. Further, the reestablishment of the portal blood supply to the liver might be required in advanced cases of gastric cancer, where regional lymph node dissection may necessitate skeletonization of the hepatoduodenal ligament for curative purposes.