Harumi Omiya

Prediction of Skin Permeability of Drugs: Comparison of Human and Hairless Rat Skin

Abstract— 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.

Carcinosarcoma of the ampulla of Vater: a case report with immunohistochemical and ultrastructural studies.

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.

Comparison of depolarizing and direct current systems on iontophoretic enhancement of transport of sodium benzoate through human and hairless rat skin

Abstract— 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 drugs 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. These results suggested that the PD system was more appropriate for iontophoresis application than the DC system from the point of view of skin permeability of the drug and effect on the skin.

Cavernous transformation of the portal vein coinciding with early gastric cancer and cholelithiasis

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.

Focal nodular hyperplasia of the liver: A patient with two concurrent lesions that manifested different behavior on radiographic imaging tests

Focal nodular hyperplasia (FNH) of the liver is a relatively uncommon pathology, with only 68 cases having been documented to date in Japan. Here, we describe an interesting case; the patient had two concurrent lesions of FNH in segments three (S3) and five (S5), respectively. The two lesions differed from each other in their behavior on various radiographic imagings, i.e., computed tomography, magnetic resonance imaging, and hepatic angiography, leading to a misdiagnosis of hepatocellular carcinoma for the S3 lesion. The patient underwent left lateral hepatic resection, along with excision of the S5 lesion. Histological examination confirmed that these two lesions were FNH. Retrospective assessment of the correlation between the radiographic imagings and the morphological architecture suggested that the architectural differences between the two lesions (i.e., that, in the S3 lesion, the central scar was more developed than in the S5 lesion and was more prominent in the periphery than in the central area of the lesion) had contributed to the misdiagnosis.

THE MODE OF SPREAD OF PANCREAS CANCER ON MACROSCOPIC AND MICROSCOPIC INVESTIGATION AT OPERATION AND AUTOPSY

北里大学外科で昭和46年7月より昭和60年12月までに経験した膵癌 (Ductcell carcinoma) 手術症例80例, 剖検症例24例につき膵癌の進展形式を検討し以下の結果を得た.1) 切除例においても, 膵被膜浸潤, 膵後方剥離面への癌侵襲陽性のものが多かった.2) 切除剖検例6例の検討では, 全例局在再発, 肝転移がみられ, 腹膜播種も5例にみられた.3) 非切除例の検討では非切除の因子として門脈系浸潤, 動脈系への浸潤, 膵後方浸潤が多かった.また肝転移, 腹膜播種が非切除の因子となったものもみられた.これらの検討をもとに昭和61年1月より積極的に門脈合併切除を伴う拡大手術を行い膵頭部癌の切除率が26.3%より50.0%と向上した.