Oral prednisone in guarded filtration procedures supplemented with antimetabolites

BACKGROUND AND OBJECTIVE: To evaluate whether a three-day course of oral prednisone perioperatively improves the surgical outcome of guarded filtering procedures supplemented with antifibrosis agents. DESIGN, MATERIALS AND METHODS: A prospective, randomized, double-masked, placebo-controlled, clinical trial was designed. Adult patients with non-inflammatory glaucoma undergoing a guarded filtration procedure supplemented with antimetabolite were enrolled. Patients received a three-day course of prednisone (50 mg BID) or placebo perioperatively. The main outcome measures were intraocular pressure (IOP) and number of antiglaucoma medications. Surgical success was defined before data collection according to two different criteria: 'success- I': IOP level = 15 mmHg with no more than one anti-glaucoma medication, and 'success-II': IOP reduction of at least 20% of baseline level with no more than one antiglaucoma medication. RESULTS: Thirty-five subjects were enrolled. Seventeen patients were treated with prednisone and eighteen with placebo. Mean follow-up was 9.2 months ± 6.2 months. The probability of success-I at 9 months was 63.0% in the study group and 65.6% in the control groups (p>0.05). The probability of success-II at 9 months was 60.2% in the study group and 55.0% in the control groups, (p>0.05). The difference in frequency of postoperative complications between groups was not statistically significant. The most common complication was choroidal detachment (n=2) in the prednisone-treated group and bleb leak (n=2) in the control group. CONCLUSION: The perioperative use of oral prednisone did not alter the surgical outcome of filtering procedures associated with antifibrosis agents in this population of glaucoma patients.

Effect of pH on the in vitro susceptibility of planktonic and biofilm-grown Proteus mirabilis to the quinolone antimicrobials

To examine the effect of elevated pH, as reported during urinary catheter infections, on quinolone activity against the urease-producing pathogen Proteus mirabilis.

Development of novel oral formulations prepared via hot melt extrusion for targeted delivery of photosensitizer to the colon

Colon-residing bacteria, such as vancomycin-resistant Enterococcus faecalis and Bacteroides fragilis, can cause a range of serious clinical infections. Photodynamic antimicrobial chemotherapy (PACT) may be a novel treatment option for these multidrug resistant organisms. The aim of this study was to formulate a Eudragit®-based drug delivery system, via hot melt extrusion (HME), for targeting colonic release of photosensitizer. The susceptibility of E. faecalis and B. fragilis to PACT mediated by methylene blue (MB), meso-tetra(N-methyl-4-pyridyl)porphine tetra-tosylate (TMP), or 5-aminolevulinic acid hexyl-ester (h-ALA) was determined, with tetrachlorodecaoxide (TCDO), an oxygen-releasing compound, added in some studies. Results show that, for MB, an average of 30% of the total drug load was released over a 6-h period. For TMP and h-ALA, these values were 50% and 16% respectively. No drug was released in the acidic media. Levels of E. faecalis and B. fragilis were reduced by up to 4.67 and 7.73 logs, respectively, on PACT exposure under anaerobic conditions, with increased kill associated with TCDO. With these formulations, photosensitizer release could potentially be targeted to the colon, and colon-residing pathogens killed by PACT. TCDO could be used in vivo to generate oxygen, which could significantly impact on the success of PACT in the clinic.

Role of nitric oxide in maintenance of basal oral tissue blood flow in anesthetized cats

Experiments were undertaken to determine if nitric oxide (NO) plays a role in regulation of basal blood flow in the oral cavity of pentobarbital anesthetized cats and, if so, to quantify this effect using dose-response relationships. Blood flow was continuously measured from the surface of the tongue and mandibular gingiva (laser-Doppler flowmetry) and from the lingual artery (ultrasonic flowmetry). Cardiovascular parameters also were recorded. Administration of the nonselective inhibitor of nitric oxide synthase (NOS), L-NAME (0.08-20 mg/kg i.v.), produced a dose-related increase of blood pressure associated with decreases of blood flow at all three measurement sites. Maximal blood flow depression of 50-60% was seen 30-60 min after administration of 1.25 mg/kg of L-NAME. D-NAME (1.25 mg/kg i.v.) was inactive at all sites. Subsequent administration of L-arginine partially reversed effects of L-NAME in the lingual artery and tongue, but not in the gingival circulation. The neuronally selective NOS inhibitor, 7-nitroindazole (7-NI, 30 mg/kg i.p.), was devoid of effect on any of the measured parameters. These results suggest that endothelial (but not neuronally derived) NO plays an important role in control of basal blood flow in oral tissues of the cat.

Microscopic Examination of Biofilm Destruction by Atmospheric Pressure Plasma

Objective: The aim of this study is to examine microscopically the destruction of bacterial biofilms mediated by atmospheric pressure non-thermal plasma (APNTP) at cellular level as well as at the level of biofilm structure as a whole. Methods: 3-day old bacterial biofilms were grown on polycarbonate coupons in a dual channel flow cell and were treated with an in-housed designed atmospheric pressure non-thermal plasma jet for up to 4 minutes of exposure before being examined by both confocal laser scanning microscopy (CLSM), preceded by Live/Dead bacterial viability staining, and scanning electron microscopy (SEM). Results: Differential live/dead staining followed by confocal microscopy examination revealed that biofilm eradication by APNTP was mediated by varying levels of both cell killing and physical removal. Relative extent of each mechanism was dependent on plasma operating conditions, bacterial species, growth conditions and biofilm thickness. On the other hand, SEM examination of plasma-exposed biofilms revealed a series of morphological changes exhibited by biofilm cells ranging from increased roughness of cell surface to complete cell lysis. Conclusions: Interesting mechanistic insights have been revealed by microscopic examination of plasma-treated bacterial biofilms that, when coupled with more specific biochemical studies, will not only contribute significantly to our understanding of the mechanism of plasma mediated biofilm destruction but also will help in better application-guided development of this novel anti-biofilm approach.

Pharmacokinetics of a CCR5 inhibitor in rhesus macaques following vaginal, rectal and oral application

Objectives: This study measured and compared the pharmacokinetics of CMPD167, a small molecule antiretro- viral CCR5 inhibitor with potential as an HIV microbicide, following vaginal, rectal and oral administration in rhe- sus macaques.
Methods: A vaginal hydroxyethylcellulose (HEC) gel, a rectal HEC gel, a silicone elastomer matrix-type vaginal ring and an oral solution, each containing CMPD167, were prepared and administered to rhesus macaques pretreated with Depo-Provera. CMPD167 concentrations in vaginal fluid, vaginal tissue (ring only), rectal fluid and blood plasma were quantified by HPLC–mass spectrometry.
Results: CMPD167 concentrations measured in rectal fluid, vaginal fluid and blood plasma were highly depend- ent on both the route of administration and the formulation type. Although rectal and vaginal fluid concentra- tions were highest when CMPD167 was administered locally (via either gel or ring), lower concentrations of the drug were also measured in these compartments following administration at the remote mucosal site or orally. CMPD167 levels in the vaginal and rectal fluid following oral administration were relatively low compared with local administration.
Conclusions: The study provides clear evidence for vaginal – rectal and rectal – vaginal drug transfer pathways and suggests that oral pre-exposure prophylaxis with CMPD167 may be less efficacious at preventing sexual trans- mission of HIV-1 than topically applied products.