Decrease in intracellular Zn²⁺ level by propranolol : A model experiment using rat thymocytes

Propranolol is a representative β-blocker used for the treatment of cardiovascular diseases. Because the use of propranolol expands for some clinical purposes that are not related to its β-blocking action, it is necessary to further examine cellular actions of propranolol. We revealed that propranolol decreased the intracellular Zn2+ level in rat thymocytes by the use of cytometric technique with FluoZin-3, a fluorescent indicator of intracellular Zn2+. Propranolol decreased the influx of extracellular Zn2+. However, the agent decreased the intracellular Zn2+ level even in the presence of DTPA, a chelator of extracellular Zn2+. Thus, the decrease in intracellular Zn2+ level by propranolol was not due to the decrease in Zn2+ influx by propranolol. Propranolol increased the cellular content of nonprotein thiol that was estimated by the use of 5-chloromethylfluorescein fluorescence, an indicator for non-proteinous thiol. Since non-proteinous thiols can make a complex with Zn2+, propranolol may increase the cellular content of nonprotein thiol, resulting in the decrease in intracellular Zn2+ level. Since the concentrations of propranolol to affect both intracellular Zn2+ level and cellular content of nonprotein thiol are higher than those reported under clinical conditions, it is difficult to emphasize clinical implications from present results

The Actual Conditions and Technical Problems of Dairy Farming in Setana District, Hokkaido Prefecture

わが国の酪農は,多頭化の中で牛乳生産過剰,消費の停滞,生産費の高騰による負債の累積,濃厚飼料多給やその他の飼育管理技術の不確立による疾病の発生など,多くの問題をかかえている. 北海道は,わが国で最も多頭化の進んだ地域であり,草地酪農が展開されている地域である. そこで,本研究は,北海道の酪農の実態を調査し,その結果を通して酪農技術の問題点を明らかにするために行なわれた. 調査農家は,北海道の中でも比較的歴史が浅く,地域的に本州と似通った道南の瀬棚地区の酪農家で,無作為に選択された飼育規模の異なる6戸である. 調査表に基いて直接聞き取りによって調査が行なわれた. 調査農家をアルファベット順に表わすと,飼育頭数は成牛換算でA：64,B：26,C：25,D：22,E：12,F：7であった. 成牛換算1頭当りの飼料作付面積(a)はA：64,B：65,C：72,D：92,E：62F：96であった. 山林原野の酪農への利用は行なわれていなかった. F以外の5戸の農家ではサイレージ用にデントコーンを,また3農家(A,B,C)ではサイレージ用の牧草を栽培していた. 飼育形態はいずれの農家も夏期放牧,冬期舎飼いで,牛舎での管理方式はAではフリーストールバーン方式,他の5戸ではスタンチョン方式であった. 各農家とも,維持飼料と牛乳生産飼料を区別し,いわゆる｢2本立て｣給与法を採用していたが,基礎飼料不足により,この方法は十分には実行されていなかった. いずれの農家も多量の濃厚飼料を購入しており,濃厚飼料多給農家では繁殖障害の発生が高かった. 各農家の成牛換算年平均乳量(千㎏)は,A：5.2,B：6.6,C：5.4,D：5.1,E：3.7,F：4.8であった. 駄牛淘汰は一定の基準を設けて行なっていたが,B,C以外の農家では十分実行されていなかった. いずれの農家も,搾乳施設や牧草の栽培収穫用の機械類の大部分を所有し,高い減価償却費と,高い負債をかかえていた. Eを除き飼育規模の大きい農家ほど比較的高い純益を得ていた. 以上より,調査地区の酪農技術の問題点として,(1)飼料生産技術の不確立から生ずる良質飼料の不足,(2)飼育管理技術の低水準,(3)駄牛淘汰の不徹底,(4)過剰の設備投資による多額の負債の累積が指摘された

Amphotericin B assembles into seven-molecule ion channels: An NMR and molecular dynamics study

Amphotericin B, an antifungal drug with a long history of use, forms fungicidal ion-permeable channels across cell membranes. Using solid-state nuclear magnetic resonance spectroscopy and molecular dynamics simulations, we experimentally elucidated the three-dimensional structure of the molecular assemblies formed by this drug in membranes in the presence of the fungal sterol ergosterol. A stable assembly consisting of seven drug molecules was observed to form an ion conductive channel. The structure is somewhat similar to the upper half of the barrel-stave model proposed in the 1970s but substantially different in the number of molecules and in their arrangement. The present structure explains many previous findings, including structure-activity relationships of the drug, which will be useful for improving drug efficacy and reducing adverse effects

Cryosurgical Hemorrhoidectomy: Technique and Method

The key to gain successful results with cryosurgical hemorrhoidectomy is based on the prevention of prolapse of the edematous tissue after freezing. To prevent the edema, it is important to pull out the hemorrhoid as much as possible during freezing, to freeze only on the rectal side of the anal verge, to avoid freezing the anal verge, and to freeze the hemorrhoids in two or three separate stages when they are large such as the fourth-degree. The anal discomfort and discharge in these patients are related to prolapse of frozen tissue. Cryosurgery is an effective method of treatment for hemorrhoids if care is taken to use the proper techniques

Lymphangioma of the Small Intestine : A Case Report

Lymphangiomas of the small intestine are rare tumors arising from masses of dilated lymphatic vessels in the submucosa. There are 11 cases of lymphangioma of the small intestine in the Japanese literature. We report a case of lymphangioma of the jejunum seen in a 76-year-old female and discuss with clinical feature

SORL1 Is Genetically Associated with Late-Onset Alzheimer’s Disease in Japanese, Koreans and Caucasians

To discover susceptibility genes of late-onset Alzheimer’s disease (LOAD), we conducted a 3-stage genome-wide association study (GWAS) using three populations: Japanese from the Japanese Genetic Consortium for Alzheimer Disease (JGSCAD), Koreans, and Caucasians from the Alzheimer Disease Genetic Consortium (ADGC). In Stage 1, we evaluated data for 5,877,918 genotyped and imputed SNPs in Japanese cases (n = 1,008) and controls (n = 1,016). Genome-wide significance was observed with 12 SNPs in the APOE region. Seven SNPs from other distinct regions with p-values ,261025 were genotyped in a second Japanese sample (885 cases, 985 controls), and evidence of association was confirmed for one SORL1 SNP (rs3781834, P=7.3361027 in the combined sample). Subsequent analysis combining results for several SORL1 SNPs in the Japanese, Korean (339 cases, 1,129 controls) and Caucasians (11,840 AD cases, 10,931 controls) revealed genome wide significance with rs11218343 (P=1.7761029) and rs3781834 (P=1.0461028). SNPs in previously established AD loci in Caucasians showed strong evidence of association in Japanese including rs3851179 near PICALM (P=1.7161025) and rs744373 near BIN1 (P = 1.3961024). The associated allele for each of these SNPs was the same as in Caucasians. These data demonstrate for the first time genome-wide significance of LOAD with SORL1 and confirm the role of other known loci for LOAD in Japanese. Our study highlights the importance of examining associations in multiple ethnic populations