Effects of acute intermittent hypoxia on energy balance and hypothalamic feeding pathways.

This study was done to investigate the effects of acute intermittent hypoxia (IH) on metabolic factors associated with energy balance and body weight, and on hypothalamic satiety-inducing pathways. Adult male Sprague-Dawley rats were exposed to either 8h IH or normoxic control conditions. Food intake, locomotion and body weights were examined after IH. Additionally, plasma levels of leptin, adiponectin corticosterone, insulin and blood glucose were measured following exposure to IH. Furthermore, adipose tissue was removed and analyzed for leptin and adiponectin content. Finally, the hypothalamic arcuate nucleus (ARC) was assessed for alterations in protein signaling associated with satiety. IH reduced body weight, food intake and active cycle locomotion without altering adipose tissue mass. Leptin protein content was reduced while adiponectin content was elevated in adipose tissue after IH. Plasma concentration of leptin was significantly increased while adiponectin decreased after IH. No changes were found in plasma corticosterone, insulin and blood glucose. In ARC, phosphorylation of signal transducer and activator of transcription-3 and pro-opiomelanocortin (POMC) expression were elevated. In addition, POMC-expressing neurons were activated as determined by immediate early gene FRA-1/2 expression. Finally, ERK1/2 and its phosphorylation were reduced in response to IH. These data suggest that IH induces significant alterations to body energy balance through changes in the secretion of leptin which exert effects on satiety-inducing pathways within the hypothalamus.

Effectiveness of ciprofloxacin and ofloxacin in a prophylaxis model of Staphylococcus keratitis.

PURPOSE: To determine the effectiveness of prophylactic fluoroquinolone treatment against staphylococci in a rabbit keratitis model. METHODS: Prophylactic ciprofloxacin or ofloxacin was applied as one topical drop 15 minutes before infection or as one drop at three time points (19, 17, and 15 minutes) before infection. In a second experiment, rabbits were treated with two, three, or four drops of ciprofloxacin 1 hour before infection. Approximately 250 colony-forming units (CFUs) of Staphylococcus aureus were injected intrastromally, and CFUs were determined 5 hours after infection. RESULTS: The CFUs per cornea in all treatment groups were significantly less than the 5.6 +/- 0.11 log CFUs per cornea in the untreated group ( p < or = 0.0001). Rabbit eyes treated 15 minutes before infection with Ciloxan or Ocuflox had 0.96 +/- 0.48 log CFUs per cornea (three of six sterile corneas) or 1.26 +/- 0.31 log CFUs per cornea (one of six sterile corneas), respectively ( p = 0.5226). Eyes treated with Ciloxan 19, 17, and 15 minutes before infection had 0.0 +/- 0.0 log CFUs per cornea, and all eyes were sterile, whereas eyes treated with Ocuflox had 0.98 +/- 0.48 log CFUs per cornea and two of six eyes sterile ( p = 0.0435). Eyes treated 1 hour before infection with two, three, or four drops of Ciloxan had 2.61 +/- 0.69 log CFUs, 1.23 +/- 0.32 log CFUs, or 0.85 +/- 0.28 log CFUs per cornea, respectively, which was significantly less than untreated eyes ( p < or = 0.0001). CONCLUSIONS: Multiple topical drops of a fluoroquinolone administered prophylactically were effective for subsequent staphylococcal ocular infection.

The effectiveness of tobramycin and Ocuflox in a prophylaxis model of Staphylococcus keratitis.

PURPOSE: To determine the effectiveness of prophylactic antibiotic treatment prior to intra-corneal infection with Staphylococcus aureus. METHODS: One topical drop of Tobrex (0.3% tobramycin), tobramycin (0.3%) in the Tobrex vehicle with 0.05% dodecyl maltoside (DDM)/4.0% hydroxypropylmethycellulose (HPMC), Ocuflox (0.3% ofloxacin) or DDM/HPMC vehicle were applied to rabbit eyes at one or five hours prior to injection of bacteria. Approximately 500 colony-forming units (CFU) of S. aureus strain 8325-4 were injected into the corneal stroma. Rabbits were sacrificed five hours after infection and corneal homogenates were cultured to determine the number of colony forming units (CFU) per cornea. RESULTS: Rabbits treated at five hours prior to infection with tobramycin-DDM/HPMC reduced the bacterial load by approximately 2.4 log CFU/cornea as compared to the untreated control (3.47 +/- 0.98 vs. 5.71 +/- 0.14 log CFU/cornea, respectively; P = 0.0010); however, Ocuflox, Tobrex, or DDM/HPMC vehicle did not significantly reduce the log CFU (P >or= 0.4837). Rabbits treated at 1 hour prior to infection with Ocuflox or tobramycin-DDM/HPMC had significantly reduced CFU/cornea (1.31 +/- 0.86 and 0.48 +/- 0.31 log CFU/cornea, respectively) as compared to the untreated group (5.71 +/- 0.14 log CFU/cornea; P or= 0.2312). CONCLUSIONS: This pre-treatment model of Staphylococcus keratitis quantitatively measured the prophylactic effectiveness of topical antibiotic formulations. An important finding was that a tobramycin-DDM/HPMC formulation was highly effective as a prophylactic medication.

Effectiveness of ciprofloxacin-polystyrene sulfonate (PSS), ciprofloxacin and ofloxacin in a Staphylococcus keratitis model.

PURPOSE: Staphylococcus aureus causes severe corneal infections that often result in corneal scarring and blindness. Presently, therapy often involves the use of a fluoroquinolone antibiotic. This study, employing an experimental rabbit model of Staphylococcus keratitis, compared the effectiveness of two commonly prescribed formulations of fluoroquinolones to an experimental formulation, ciprofloxacin with polystyrene sulfonate (ciprofloxacin-PSS). The ciprofloxacin-PSS formulation uses an ion exchange resin to aid in the delivery of drug to the cornea. METHODS: Early (4-9 h postinfection, PI) and late (10-15 h PI) therapies were studied, employing 5 groups: ciprofloxacin-PSS, ciprofloxacin, ofloxacin, PSS vehicle. and untreated. Dosing regimens were: every 30 min, 60 min, or a single drop applied at 9 h PI. Eyes were observed by slit lamp examination (SLE) and bacterial colony forming units (CFU) per cornea were determined. RESULTS: Early phase therapy with ciprofloxacin-PSS, ciprofloxacin, or ofloxacin administered every 30 or 60 min were equally effective (P > or = 0.2880), decreasing CFU per cornea by >5 log. Ciprofloxacin was significantly more active than ciprofloxacin-PSS or ofloxacin (P < or = 0.0410) when applied as a single drop. Late therapy with ciprofloxacin-PSS, ciprofloxacin, or ofloxacin administered every 30 or 60 min resulted in >3 log decrease in CFU per cornea relative to controls (P < or = 0.0001). CONCLUSIONS: Topical treatment of experimental Staphylococcus keratitis with ciprofloxacin-PSS, ciprofloxacin, or ofloxacin was effective. The effectiveness of ciprofloxacin-PSS suggests that improved drug delivery systems employing an ion exchange resin could be useful in an ocular fluoroquinolone formulation.