Ciliochoroidal effusions after neodymium:YAG posterior capsulotomy: association with pre-existing glaucoma and uveitis

Two patients with a history of glaucoma and a propensity for uveitis developed ciliochoroidal effusions following Nd:YAG laser posterior capsulotomy. Both patients experienced a waxing and waning course with eventual resolution of symptoms after a steroid regimen. The ciliochoroidal effusions were presumed to be secondary to uveitis induced by the YAG laser surgery. The role of glaucoma, previous surgeries, and an open posterior capsule is uncertain but may have predisposed these patients to ciliochoroidal detachment. We advise caution in performing YAG posterior capsulotomy in patients with glaucoma and a known propensity for uveitis.     

Efficacy and tolerability of norfloxacin vs. ciprofloxacin in complicated urinary tract infection.

This prospective, open, randomized clinical study compared the efficacy and tolerability of norfloxacin and ciprofloxacin in adult patients with complicated urinary tract infection, defined as infection in the presence of an underlying anatomic or functional abnormality of the urinary tract. Seventy-two patients were randomized, 37 received norfloxacin (400 mg orally twice daily for 10-21 days) and 35 received ciprofloxacin (500 mg orally every 12 hours for 14-21 days). Patients were clinically assessed, and urine cultures were obtained following two to four days of therapy, and five to nine days and four to six weeks after discontinuation of therapy. Seventy-two percent of the norfloxacin group and 79 percent of the ciprofloxacin group were considered cured. This difference was not significant. One failure of norfloxacin therapy was associated with the emergence of resistant Pseudomonas aeruginosa. Following norfloxacin therapy, in 2 patients superinfections developed with resistant organisms (Staphylococcus epidermidis [1] and Pseudomonas maltophilia [1]). Twelve patients, 6 in each group, experienced adverse reactions, which were considered related to the study drug therapy in only four instances. Our results indicated comparable efficacy and tolerability of norfloxacin and ciprofloxacin in the treatment of complicated urinary tract infection in adults.     

Protection Against Chemically-Induced Oxidative Gastrointestinal Tissue Injury in Rats by Bismuth Salts

Oxygen free radicals (OFR) are implicated in thepathogenesis of stress, chemically induced gastriclesions, and gastrointestinal injury. Theconcentration-dependent scavenging abilities of bismuthsubsalicylate (SBS), colloidal bismuth subcitrate (CBS), andselected OFR scavengers, including superoxide dismutase(SOD), catalase, mannitol, and allopurinol were examinedagainst biochemically or chemically generated superoxide anion, hydroxyl radical, andhypochlorite radical plus hypochlorous acid based on achemiluminescence assay. Furthermore, both gastric (GM)and intestinal mucosa (IM) were individually exposed in vitro to these free radical generatingsystems, and the concentration-dependent protectiveabilities of SBS and CBS against lipid peroxidation (LP)were compared with selected OFR scavengers. In addition, 24-hr fasted rats were orally treated with thenecrotizing agents 0.6 M HCl, 0.2 M NaOH, 80% ethanol,and aspirin (200 mg/kg). The extent of tissue injury inthe GM and IM was determined by assessing LP, DNA fragmentation, and membrane microviscosity.Dose- and time-dependent in vivo protective abilities ofCBS (100 mg/kg) and SBS (15 mg/kg) were also assessed.Following incubations with superoxide anion and hydroxyl radical generating systems in thepresence of 125 mg SBS/liter, approximately 47% and 61%inhibitions were observed in the chemiluminescenceresponse, respectively, while 48% and 46% inhibitions were observed with 125 mg CBS/liter. SBS andCBS exerted similar abilities towards hypochloriteradical plus hypochlorous acid. Approx. 3.1- and3.7-fold increases in LP were observed in the GM and IMof rats following oral administration of 0.6 MHCl. Pretreatment of the rats with SBS and CBS decreased0.6 M HCl-induced LP in the GM by approx. 39% and 27%,respectively, with similar decreases in LP in the IM. SBS exhibited better protectiveabilities towards 0.6 M HCl and 0.2 m NaOH-induced GMand IM injury as compared to CBS. SBS and CBS providedsimilar protection towards 80% ethanol-induced gastric injury, while CBS exerted a superior protectiveability towards aspirin-induced gastric injury. Theresults demonstrate that both SBS and CBS can scavengereactive oxygen species and prevent tissue damage produced by OFR.     

Synthesis,Physicochemical Properties,and Cytotoxicity of a Series of 5′-Ester Prodrugs of 5-Iodo-2′-deoxyuridine

Five aliphatic 5-esters of 5-iodo-2deoxyuridine (IDU) were synthesized via an acid chloride alcoholysis reaction. The solubility in pH 7.4 phosphate buffer, lipophilicity as determined by partition experiments in octanol/pH 7.4 buffer, and cytotoxicity of these potential prodrugs were evaluated. The esters showed a 43- to 250-fold increase in lipophilicity and a 1.6- to 14-fold decrease in aqueous solubility relative to IDU. At a concentration of 50 µM, all esters showed reduced cytotoxicity toward uninfected Vero cells relative to IDU.     

Prodrugs of 5-Iodo-2′-Deoxyuridine for Enhanced Ocular Transport

Problems associated with the use of 5-iodo-2-deoxyundine (IDU) in the treatment of herpes simplex keratitis can be attributed largely to the polar nature of IDU resulting in its poor permeability across the lipoidal epithelial layer of the corneal membrane. Five aliphatic 5-esters of IDU were synthesized and evaluated as prodrugs for potential use in the treatment of deep ocular infections such as stromal keratitis, iritis, and even retinitis. A parabolic relationship between in vitro corneal membrane permeability and carbon chain length of prodrugs is evident. For a given prodrug, enzymatic hydrolysis proceeded most readily in iris–ciliary body, followed by cornea and aqueous humor. An increase in carbon chain length made the prodrugs more enzymatically labile but more resistant to chemical hydrolysis at pH 7.4 and 34°C. The 5-butyryl ester of IDU exhibited an approximately fourfold increase in aqueous humor IDU concentration relative to IDU at 25 min following instillation of 25-µl 5 mM solutions.