[Clinical studies on pinguecula. IV. On the comparative observations between slit-lamp and histological findings].
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Adolescent↗
Biomedical subjects
M Akimoto
Publications and source records attributed to M Akimoto.
[Clinical studies on pinguecula. 3. Observation of limbus portion in the living body, and other studies].
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Adolescent↗
Comparison of stepwise and simultaneous estimations of population pharmacokinetics and pharmacodynamics of TS-943.
The prediction performances of population pharmacokinetic-pharmacodynamic analysis of the two methods (a stepwise and a simultaneous estimations) were evaluated with respect to their accuracies and precisions. A study was designed to investigate the safety and efficacy of TS-943 by a 4 hours constant infusion in 36 healthy male subjects. Population analysis was performed using pharmacokinetic and pharmacodynamic models with NONMEM. The mean of the prediction error (MPE) and the root mean squared error (RMSE) served as a measure of accuracy and precision. In addition, a bootstrap validation was also performed. The results indicate that those population pharmacokinetic-pharmacodynamic parameters for the two methods were comparable. The results of simultaneous estimations are similar to those obtained using a stepwise estimation. The mean parameter estimates obtained with the additional 200 bootstrap replicates of data were within 15% of those obtained with the final model in both methods. The present results demonstrated that the accuracy of pharmacodynamic evaluations using a stepwise end a simultaneous estimations was comparable.
Adult↗
Effects of a gastric mucosal protecting agent in rats with liver cirrhosis.
Male Sprague-Dawley rats were fed a 0.1% ethionine-added choline-deficient diet for 8 weeks to induce liver cirrhosis. At the same time 100 mg/kg/day teprenone was administered orally in order to evaluate its effects on the liver and gastric mucosal blood flow. Blood flow increased not only in gastric mucosa but also in liver tissues in the teprenone group. Serum transaminase levels and histopathologic findings of the liver also improved. These findings suggest that teprenone alleviates hepatocellular injuries. This effect may be partly attributable to cytoprotective effects of the catenoid isoprenoid moiety of teprenone on liver cells.
Animals↗
Nitric oxide as a second messenger in phagocytosis by cultured retinal pigment epithelial cells.
PURPOSE: To investigate a possible role of the nitric oxide (NO)-cGMP signal transduction system in phagocytosis of rod outer segments (ROS) by cultured retinal pigment epithelial (RPE) cells. METHODS: Primary cultures of RPE cells from 10-day-old Brown Norway rats were used to study the phagocytosis of ROS by these cells. Phagocytosis of ROS was evaluated with or without an inhibitor of nitric oxide synthase (NOS), N(G)-nitro-L-arginine (L-NNA), and the reverse effects of L-NNA by L-arginine and 8-bromo-cGMP on phagocytosis were also studied. NO-associated cGMP production by RPE cells was monitored during phagocytosis using L-NNA. NOS activity was assayed in RPE cells and ROS to locate the source of NO. RESULTS: Phagocytosis of ROS was inhibited by L-NNA but not by D-NNA. L-NNA inhibited the ingestion in a dose-dependent manner, but not the binding of ROS. The inhibition was reversed by L-arginine and also by an NO donor, SIN-1. RPE cells challenged with ROS showed increased cGMP activity, which was significantly reduced by L-NNA and again restored by an overdose of L-arginine. NOS activity was found in RPE cells but not in ROS. CONCLUSIONS: Our data show that cGMP plays a role in the ingestion phase of ROS phagocytosis by RPE cells via a cGMP second-messenger system.
Animals↗
Tissue-specific induction of metallothionein by bismuth as a promising protocol for chemotherapy with repeated administration of cis-diamminedichloroplatinum (II) against bladder tumor.
The effects of bismuth nitrate pretreatment on the toxicity and antitumor activity of repeatedly administered cis-diamminedichloroplatinum (Cisplatin; CDDP) were examined using nude mice inoculated with human bladder tumor tissues. Lethal and renal toxicities exerted by the repeated administration of CDDP were effectively prevented by pretreatment with bismuth (Bi) without affecting its antitumor activity against transplanted human bladder tumor as in the case of single dose of the drug reported previously. The renal Bi level was gradually increased with the frequency of Bi administration, and metallothionein (MT) induced by Bi in the kidneys maintained its substantially high level during the treatment. It was confirmed that MT was not induced in the tumors even by the 5 cycles of repeated Bi administration. This specific protection shown by the Bi preadministration against the toxicity of repeatedly injected CDDP can be explained by the fact that Bi markedly induces MT in the kidney, a major target organ of CDDP toxicity, but not in the tumor tissues inoculated in the nude mice, probably because Bi is efficiently taken up by the kidney but hardly incorporated into the tumor tissues as reported previously. These data obtained by repeated doses of CDDP as described above strongly suggest a promising protocol for chemotherapy using CDDP with Bi compounds, a tissue specific MT inducer, against advanced bladder tumor in human.
Animals↗
Right perirenal biloma due to a common bile duct stone: CT demonstration.
Most reported extrahepatic bilomas have been located around the liver, especially in the intraperitoneal cavity. A case of a right perirenal biloma due to a common bile duct stone is presented. Intraoperative cholangiography revealed extravasation of bile from the branch in the caudate lobe. CT accurately demonstrated the fluid around the inferior vena cava and in the right perirenal space, which indicated continuity of the liver and right perirenal space.
Aged↗
Role of eicosapentaenoic acid in lipid metabolism in the liver, with special reference to experimental fatty liver.
Choline-deficient feed was given to three groups (n = 7 in each) of male Sprague-Dawley rats for 4 weeks to induce the development of fatty liver. In addition, two of the groups received eicosapentaenoic acid (EPA), 1000 mg/kg/d, administered orally either for all 4 weeks or for only the last 2 weeks of the study, respectively. The third group received the choline-deficient diet but no EPA. The untreated control group (n = 7) received only normal feed. The efficacy of EPA in preventing fatty liver was assessed based on the evaluation of pathologic and biochemical parameters and hepatic blood flow. EPA markedly improved fatty liver, probably due to both direct effects (inhibition of the synthesis of triglyceride in the liver) and indirect effects (increased hepatic blood flow). Decreased blood flow due to sinusoidal block is responsible for the progression of fatty liver. EPA has been shown to decrease thromboxane A2 production and blood viscosity and to enhance red cell deformability. These effects are thought to have contributed to the increases in hepatic blood flow.
Animals↗
Hepatic granuloma with progressive calcification: CT appearance.
Calcification in the liver is uncommon but not rare in clinical practice, and may be caused by many pathological conditions. We report a patient with hepatic mass on abdominal sonogram and CT scan. The mass was shown as a hypoechoic lesion on abdominal sonogram and as a well-marginated hypodense mass on pre- and postcontrast CT. Inflammatory granuloma was diagnosed by pathological examination following percutaneous needle biopsy. A follow-up precontrast CT scan was performed 22 months after the initial examination, and the hepatic granuloma could be the cause of hepatic parenchymal calcification.
Adult↗
Inhibitory effect of ursodeoxycholic acid on the progression of chronic hepatic disorders with special reference to increases in blood flow.
Ursodeoxycholic acid (UDCA), which is commonly used as a cholesterol-gallstone-dissolving agent, is now expected to be effective not only for primary biliary cirrhosis but for chronic active hepatitis as well. In this study, we administered 0.1% ethionine-added, choline-deficient diet for 8 weeks to male Sprague-Dawley rats to prepare an animal model of chronic hepatic disorders. At the same time, UDCA (50 mg/kg/day) was administered orally to these animals, and its effects on the liver, including effects on hepatic blood flow determined with a laser Doppler blood flow meter, were evaluated. Hepatic blood flow increased significantly in the UDCA group compared with the untreated groups. Transaminase levels decreased significantly in the UDCA group compared with the untreated group. Histologic differences were noted between the UDCA and untreated groups in histopathologic examinations of the liver, with liver cirrhosis or early liver cirrhosis being present in the untreated group, compared with only chronic active hepatitis in the UDCA group. These findings suggest that UDCA is able to prevent or inhibit the progression of chronic hepatic disorders, an effect that may be due in part to increases in hepatic blood flow.
Alanine Transaminase↗
Experimental use of pravastatin in patients with primary biliary cirrhosis associated with hypercholesterolemia.
Primary biliary cirrhosis (PBC) is a refractory liver disease for which no medical treatment has been established. The investigators administered 20 mg/day of pravastatin, a 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor, to 2 PBC patients with hypercholesterolemia (1010 and 306 mg/dl) for 3 years and 10 months in order to decrease the blood concentration of bile acids and prevent adverse effects on the hepatocellular membrane. The drug markedly decreased not only cholesterol levels but also total bile acid levels, producing particularly pronounced decreases in cholic acid and chenodeoxycholic acid. Histologically, progression was inhibited in one patient, whereas improvement was seen in the other. Bile duct enzymes and other biochemical parameters showed improvement in both cases. General pruritus and blepharal and palmar xanthoma also improved. These findings suggest that pravastatin may be useful in the treatment of PBC associated with hypercholesterolemia.
Biopsy↗
Long-term surgical results of combined trabeculotomy ab externo and cataract extraction.
Trabeculotomy ab externo has been demonstrated to be effective in controlling intraocular pressure (IOP) in adult patients with either primary open-angle glaucoma or pseudoexfoliation syndrome. We evaluated the surgical outcome of 60 eyes with either primary open-angle glaucoma or pseudoexfoliation syndrome that underwent combined trabeculotomy ab externo and cataract extraction. All patients were at least 40 years old, and were followed for at least 1 year. At the final examination, IOP was well controlled (21 mm Hg or less) in 54 (90%) of the 60 eyes, with or without medication. Also, "overall success" (ie, stabilization of IOP, visual field, and optic nerve status) was achieved in 49 (81.7%). Complications included fibrin exudation (22%), transient IOP elevation (17%), early perforation of the probe into the anterior chamber (10%), and detachment of Descemet's membrane (5%). We recommend combined trabeculotomy ab externo and cataract extraction in selected cases of glaucoma with coexisting cataract. For cases in which the target IOP level is in the low teens, or for patients who may not tolerate postoperative fluctuations in IOP, we do not recommend trabeculotomy ab externo. Also, in eyes that have normal-tension glaucoma, or that have already sustained severe damage to the optic nerve, visual dysfunction caused by glaucomatous changes may progress even after successful combined trabeculotomy ab externo and cataract extraction.
Aged↗
Herpes simplex virus thymidine kinase/ganciclovir-mediated killing of tumor cell induces tumor-specific cytotoxic T cells in mice.
Transfer of the herpes simplex virus thymidine kinase (HSV-TK) gene into cancer cells followed by treatment with ganciclovir (GCV) is an attractive strategy of cancer gene transfer. HSV-TK-transduced cells are efficiently killed by the direct cytotoxic effect of GCV-triphosphate, which is generated by HSV-TK from GCV. In addition, the bystander effect kills adjacent nontransduced tumor cells, although this mechanism is not fully understood. We addressed whether the systemic immune response is involved in tumor regression in vivo. Renca cells, from a renal carcinoma cell line transduced with a retroviral vector bearing the HSV-TK gene driven by the cytomegalovirus early promoter, were inoculated into BALB/c mice. After complete regression of inoculated tumors with GCV treatment, the animals were challenged with nontransduced tumor cells. Rejection or significant growth inhibition of challenged tumor cells was observed. In these animals, tumor-specific cytotoxic T cells were efficiently induced. CD8+ cells appeared to be a main component in this cytotoxic T cell fraction. Expression of class I major histocompatibility complex antigens increased in HSV-TK+ cells treated with GCV. These results suggest that suicide gene therapy may be useful not only for short-term tumor regression mediated by direct cell killing and bystander effect, but also, due to the vaccination effect, may be an aid in long-term tumor regression and prevention of recurrence.
Animals↗