Synthesis and Antiviral Evaluation of Novel 2,3-Dihydroxypropyl Nucleosides from 2- and 4-Thiouracils

Regioselective alkylation of 2-thiouracils 1a–c and 4-thiouracils 7a,b with 2,3-O-isopropylidene-2,3-dihydroxypropyl chloride (2) afforded 2-{[(2,2-Dimethyl-1,3-dioxolan-4-yl) methyl]thio}pyrimidin-4(1H)-ones 3a–c and 4-{[(2,2-Dimethyl-1,3-dioxolan-4-yl)methyl]thio} pyrimidin-2(1H)-ones 8a,b, respectively. Further alkylation with 2 and/or 2,3-O-isopropylidine-1-O-(4-toluenesulfonyl)-glycerol (4) gave the acyclo N-nucleosides 5a–c and 9a,b whose deprotection afforded 6a–c and 10a,b. 2-(Methylthio)pyrimidin-4(1H)-ones 11a–c and 4-(methylthio)pyrimidin-2(1H)-ones 14a,b were treated with 2 and/or 4 to give 12a–c and 15a,b which were deprotected to give 13a–c and 16a,b. Pyrimidine-2,4(1H,3H)-dithiones 17a–c were treated with two equivalents of 2 to give 2,4-bis{[(2,2-dimethyl-1,3-dioxolan-4-yl)methyl]thio}pyrimidines 18a–c. Deprotection of compounds 18a–c gave 2,4-bis[(2,3-dihydroxypropyl)thio]pyrimidines 19a-c. The activity of the deprotected nucleosides against Hepatitis B virus was evaluated and showed moderate inhibition activity against HBV with mild cytotoxicity.     

Topological analysis of a haloacid permease of a Burkholderia sp. bacterium with a PhoA-LacZ reporter

Background  

2-Haloacids can be found in the natural environment as degradative products of natural and synthetic halogenated compounds. They can also be generated by disinfection of water and have been shown to be mutagenic and to inhibit glyceraldehyde-3-phosphate dehydrogenase activity. We have recently identified a novel haloacid permease Deh4p from a bromoacetate-degrading bacterium Burkholderia sp. MBA4. Comparative analyses suggested that Deh4p is a member of the Major Facilitator Superfamily (MFS), which includes thousands of membrane transporter proteins. Members of the MFS usually possess twelve putative transmembrane segments (TMS). Deh4p was predicted to have twelve TMS. In this study we characterized the topology of Deh4p with a PhoA-LacZ dual reporters system.     

Surgical treatment of bleeding esophageal varices

Massive bleeding from varices in the esophagus and stomach secondary to liver disease is a serious surgical emergency, as the patient may bleed to death. The problem is further complicated by the difficulties in making a diagnosis and the poor general condition of the patient due to the long standing liver disease. For the past two years at the San Francisco Hospital this problem has been handled by exploring the stomach and esophagus and ligating the bleeding point. No effort has been made to lower the pressure in the veins to the liver. The results have been sufficiently encouraging to warrant further trial.     

Operations upon the aged

From the point of view of the surgeon, as repeatedly emphasized in the surgical literature, the mortality rate for operations upon old persons is only slightly higher for elective surgical operations than for the same operations on younger persons when proper preoperative and postoperative precautions are taken. However, the mortality rate for emergency operations is much higher in old persons than in younger ones. Many surgeons believe, therefore, that disease for which operation is otherwise indicated should be treated surgically irrespective of the age of the patient per se. The authors' experience with operations upon old persons at the San Francisco Hospital accords with these conclusions.     

Surgical treatment of esophageal hiatus hernia by transthoracic herniotomy; a preliminary report

In view of the extensive operation required for repair of hiatus hernia by transthoracic or abdominal approach, herniotomy was done in three cases. Objectives were to (a) widen the esophageal hiatus, (b) remove the hernial sac, (c) cut the structures of the omentum and lesser curvature so that the stomach would lie flat in the chest, and (d) fix the stomach at the new level. After the operation, all three patients were free of the symptoms of indigestion of which they had previously complained.