Epinephrine is an enhancer of rat intestinal absorption.

Some physiological substances, including acetylcholine and nitric oxide, are useful candidates for stimulation of intestinal absorption of drugs. In the present study, we elucidated the ability of epinephrine (Epi) to stimulate the intestinal absorption of drugs. We evaluated the ability of Epi to enhance absorption of macromolecules using dextran (Mw 4000 Da), which is poorly absorbed from the intestine, as a model compound in situ in a closed loop of the rat jejunum. Treatment of the jejunum with Epi resulted in significant increase in absorption of dextran in a dose-dependent fashion. The area under the curve (AUC) from 0 to 4 h in the Epi-treated jejunum was 13-fold higher than that in the vehicle-treated jejunum. The absorption-enhancing activity of Epi was 40-fold higher than that of caprate, a clinically used absorption-enhancer of drugs. In the experimental conditions used in this study, histological injury of the mucosa and perturbation of the mucosal membrane were not observed in the Epi-treated jejunum. Treatment with an antagonist of alpha-adrenergic receptors attenuated the stimulation of intestinal absorption by Epi, and treatment with an agonist of alpha-adrenergic receptors resulted in enhancement of intestinal absorption. While an antagonist of beta-adrenergic receptors enhanced the absorption-enhancing effect of Epi, an agonist of beta-adrenergic receptors stimulated intestinal absorption. These results indicate that stimulation of adrenergic receptors may be a novel strategy for intestinal absorption of drugs.     

Expression profile of chemokines and chemokine receptors in epithelial cell layers of oral lichen planus

BACKGROUND: To understand the immunopathological features of oral lichen planus (OLP), we analyzed the expression of chemokines in the epithelial cell layers. Methods: Epithelia from OLP or healthy gingiva were collected by laser microdissection. The chemokine and chemokine receptor expressions in the epithelia were analyzed by DNA microarray. RESULTS: High levels of MIP-3alpha/LARC/CCL20 and its receptor CCR6 were expressed in the lesional epithelia. Furthermore, DC-CK1/CCL18, ELC/CCL19, SDF-1/CXCL12 and CXCR4 expressions were also increased. Immunohistologial analysis showed that high numbers of Langerhans cells (LCs) were present in the epithelia of OLP. Lesional epithelia also expressed high levels of the ligands specific for CXCR3 (e.g. MIG/CXCL9, IP-10/CXCL10 and I-TAC/CXCL11) and CCR5 (e.g. RANTES/CCL5). CONCLUSIONS: Infiltration of LCs is orchestrated by CCR6. Further, LCs residing in the lesional epithelia may be a mature phenotype. Moreover, infiltration of T cells in OLP could be mediated by signaling pathways through CXCR3 and CCR5.     

Treatment of a malignant esophageal fistula with a Gore-Tex-covered flexible nitinol stent

In order to treat fistulated esophageal cancer using a flexible stent, a covered flexible stent was constructed by wrapping a nitinol stent with a thin sheet of Gore-Tex, preserving the stents original advantages of flexibility and a low-profile introducer system. This stent was used to perform standard radiotherapy in a case of fistulated esophageal cancer.     

Antiphospholipid antibody syndrome and vasoocclusive diseases

One hundred and thirty-four patients with vasoocclusive diseases were retrospectively tested for three kinds of antiphospholipid antibody (aPL). The mean age at onset of the disease in 58 patients with aPL was 43 years old. Seventeen, 11, and 9 patients were positive for the aCL IgA, IgM, and IgG isotypes, respectively. The rates of anti-phospholipid syndrome (APS) in patients with arterial (n=94), venous (n= 31), or both arterial and venous (n=9) occlusion were 45%, 29%, and 78%, respectively.The rates of APS in patients with autoimmune disease (n=13), thromboangiitis obliterans (TAO) (n= 36), arteriosclerosis obliterans (ASO) with lower leg involvement (n=8) or aortic arch syndrome (n=5), Raynaud's syndrome (n=15), aortitis syndrome (n= 13), ischemic heart disease (IHD) with young onset (n =12), and bilateral leg deep venous thrombosis (DVT) (n=10) were 77%, 46%, 13%, 80%, 40%, 62%, 33%, and 70%, respectively. The cumulative patency rate for reconstructive surgery in patients (n=13) with aCL was found to be considerably lower than that in those without aCL (n=13). From these results it was concluded that IgA was the most valuable aCL isotype for the diagnosis of APS and that aPL should be examined in patients with double-vessel occlusion, autoimmune disease, bilateral leg DVT, aortic arch syndrome, TAO, Raynaud's syndrome, or IHD with young onset. Furthermore, prophylaxis for graft failure is more strongly recommended for patients with aCL than for those without it.     

Research review: DNA polymerases as molecular markers of the regenerating capacity of hepatocytes

Hepatocyte regeneration has been widely investigated, with the mitotic index and the incorporation of [³H]thymidine being used as regeneration markers. We focused on the induction of DNA replication enzymes, particularly DNA polymerases (pol) α, δ, and ε. Using rat models, we have shown that the activity of pol α in crude liver extract well represents the regenerating capacity of hepatocytes. Using pol α as an indicator, we analyzed liver regeneration in rat models under various conditions: obstructive jaundice, external or internal biliary drainage, and the obstruction of portal vein branches. It has been revealed that the ligation of the common bile duct alone induces a certain amount of hepatocyte proliferation. It was striking that external biliary drainage suppressed regeneration capacity in cholestatic rat liver after partial hepatectomy. The strong regeneration in nonligated lobes induced by portal branch ligation was similar to the liver regeneration seen after partial hepatectomy with respect to the induction of DNA polymerases. Taken together, the aspects of DNA replication, particularly the induction of DNA polymerases, may contribute to shedding new light on the regeneration of human liver. This work was supported in part by a Grant-in-Aid for General Scientific Research and for Cancer Research from the Ministry of Education, Science and Culture, Japan, and by grants from the Uehara Memorial Foundation     

Volume of tarsal bones in congenital clubfoot

To elucidate the growth of the tarsal bones in congenital clubfoot, relative to the growth of these bones in the unaffected feet and compared to growth in the feet of normal volunteers, we used a computed tomography (CT) scanner to measure the volume of all tarsal bones. The subjects of the study were 10 adults (7 men and 3 women) with unilateral congenital clubfoot (average age 20 years and 1 month). As controls, we examined 11 healthy volunteers. We calculated the ratio of the volume of each tarsal bone to the total bone volume and the ratio of the volume of each tarsal bone in clubfoot to the corresponding bone in the unaffected foot. The volume ratio of each tarsal bone was compared between clubfeet and unaffected feet because the differences of each tarsal bone ratio between the normal foot group and unaffected foot group were not significant. In the clubfeet (n=10), the talus and the medial cuneiform bones were smaller than those in the unaffected feet (n=10) but the cuboid bone was larger. The growth of the navicular did not differ from as that in unaffected feet. Our results suggested hypoplasia on the medial side of the foot in adult patients with congenital clubfoot. The 3 patients who had undergone medial release showed particularly marked hypoplasia of the medial side. In congenital clubfoot cases with severe deformities who had undergone wide soft-tissue release operations, there were clear growth suppressions in the talus and the medial cuneiform. We could not determine whether the cause of the growth suppression was the hypoplastic nature of tarsal bones themselves or the surgical obstacles to tarsal bone growth.     

Testicular macromolecular synthesis in men with varicocele.

The synthesis of DNA, RNA, and protein by varicocele testes with spermatogenic dysfunction was studied by examination of the levels of incorporation of [3H]thymidine, [14C]uridine, and [14C]leucine into the testicular tissue at 31 degrees C in vitro. The results suggest that DNA synthesis by the testis with moderate tubular damage is impaired whereas synthesis of RNA and protein is not. The cell regenerative ability of the testis with moderate tubular damage may be poor in spite of the preservation of testicular cell RNA and protein synthesis.     

The results and problems of reoperation for coronary artery disease]

In six hundred and six consecutive patients undergoing coronary artery bypass grafting (CABG) within the past 17 years (May 1974 to March 1991), repeated CABG were performed on 10 patients (1.65%). The main reasons for repeated CABG were graft failure (GF) in 8, progression of native disease (NP) in 5 and incomplete revascularization (IR) in 3 patients. The incidence of GF was high either within a half year or around 5 years after CABG. Although all patients survived from reoperation, four patients continued to have mild angina pectoris. When the recurrence of angina is noted after CABG, coronary arteriography and if necessary PTCA should be done as soon as possible. If a second surgery is inevitable, maximum utilization of arterial graft and accomplishment of complete revascularization are emphasized.     

Clinical significance of selective middle hepatic venography

Selective middle hepatic venography was performed in 86 patients who had been scheduled to undergo liver resection because of hepatobiliary diseases. Special catheters were used of which tips were bended counterclockwise at an angle of 45 degrees. Successful middle hepatic venograms were obtained in 65 cases (76%). Abnormal findings were observed in 27 cases (42%), and it was difficult to diagnose them by ultrasonography or computed tomography. Selective middle hepatic venogram is very useful to understand surgical anatomy of the liver in each case preoperatively. In 5 cases of giant tumor, middle hepatic venography is necessary to identify the exact site of the tumor. Selective middle hepatic venography is considered to be one of the indispensable, examinations for liver resection.