ABSTRACT
Several 2-anilino- and 2-benzylamino-3-deaza-6-oxopurines [3-deazaguanines] and selected 8-methyl and 8-aza analogs have been synthesized. 7-Substituted N(2)-(3-ethyl-4-methylphenyl)-3-deazaguanines were potent and selective inhibitors of Gram+ bacterial DNA polymerase (pol) IIIC, and 7-substituted N(2)-(3,4-dichlorobenzyl)-3-deazaguanines were potent inhibitors of both pol IIIC and pol IIIE from Gram+ bacteria, but weakly inhibited pol IIIE from Gram- bacteria. Potent enzyme inhibitors in both classes inhibited the growth of Gram+ bacteria (MICs 2.5-10µg/ml), and were inactive against the Gram- organism Escherichia coli. Several derivatives had moderate protective activity in Staphylococcus aureus-infected mice.
Subject(s)
Anti-Bacterial Agents/chemical synthesis , DNA Polymerase III/antagonists & inhibitors , Enzyme Inhibitors/chemical synthesis , Guanine/analogs & derivatives , Animals , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , DNA Polymerase III/metabolism , Enzyme Inhibitors/pharmacology , Enzyme Inhibitors/therapeutic use , Escherichia coli/drug effects , Gram-Positive Bacteria/drug effects , Gram-Positive Bacteria/enzymology , Guanine/chemistry , Guanine/pharmacology , Guanine/therapeutic use , Mice , Microbial Sensitivity Tests , Staphylococcal Infections/drug therapyABSTRACT
<p><b>OBJECTIVES</b>To study the mechanism of Labbé vein injury, and its effect on traumatic cerebral infarction and prognosis in patients of craniocerebral trauma.</p><p><b>METHODS</b>The clinic imageology and data of 16 patients of craniocerebral trauma with Labbé vein injury approved intraoperatively from June 2006 to February 2009 were analyzed. To compare the effect of the intraoperative finding of Labbé vein damage and blood vessel treatment on traumatic cerebral infarction, and to analyze the traumatic cerebral infarction size and prognosis.</p><p><b>RESULTS</b>All the 16 patients had acute subdural hematoma and(or) intracerebral hematoma. And 15 of all the 16 patients with Labbé vein injury suffered from skull fractures. All patients accepted hematoma cleaning and intracranial decompression procedure by removing skull. The preoperative Glasgow coma scale (GCS) were as following: 5 patients being between 9 - 12, 7 patients being between 6 - 8 and 4 patients being between 3 - 5. Eight patients had cerebral hernia before operations on admission, and among them, 3 patients had corectasis of both sides and 5 patients had corectasis of only one side, the other 8 patients had no corectasis. Postoperatively, 14 patients suffered from traumatic cerebral infarction of different grades. After follow-ups of 24 months, 8 patients had relatively good prognosis, with 4 patients having good recoveries and 4 having middle disability; the other 8 had bad prognosis, including 3 patients being seriously disable and 5 kept vegetative state.</p><p><b>CONCLUSIONS</b>Impact injury and counterblow are the main reasons to the injury of Labbé vein, which consequently leads to serious traumatic cerebral infarction and bad prognosis. Intraoperatively, it is quite important to protect Labbé vein during the surgery, which should not be easily cut or obstructed by electric coagulation, and this is an effective way to improve the prognosis of these patients.</p>
