Role of the water-drinking test in medically treated primary open angle glaucoma patients.

PURPOSE: The water-drinking test (WDT) has recently re-emerged as a possible way to determine the competency of the trabecular meshwork. We performed a prospective interventional study to test the hypothesis that the WDT could be useful in assessing fluctuations in patients undergoing treatment for primary open angle glaucoma (POAG). METHODS: We included 122 patients; 62 on medical treatment for POAG (n=123 eyes) and 60 controls (n=120 eyes). The study group had been on intraocular pressures (IOP) lowering treatment continuously for at least 3months with stable IOP. The WDT was performed during fasting and was considered positive if it fluctuated ≥6mmHg. RESULTS: The patients on medical treatment had a mean age of 50.56±18.45 years vs. 51.35±11.22 for the controls (P=0.34); with 71% being female in the study group and 77% in the control group. In the study group; 52% were on beta blockers (n=64), 27% combination of two or more medications (n=33), 19% prostaglandin analogues (n=24) and 2% alpha agonists (n=2). The WDT was positive in 17.07% (n=21) in the study group and 2.5% (n=3) in the control group (P=0.0001). The mean fluctuation was 7.14±2.15mmHg in the study group and 6.00±0mmHg in the controls (P=0.33). A positive WDT was found in 33.33% (n=11) of those on combination therapy; 12.5% (n=3) prostaglandin analogues and 10.94% (n=7) beta blockers (P=0.03). Combination therapy had the highest positive WDT fluctuation (7.54±2.87) followed by prostaglandin analogues (7.00±1.00) and beta blockers (6.57±0.78) with a P value of 0.44. CONCLUSIONS: The WDT can identify significant fluctuations in eyes with POAG that are medically treated.

[The circadian effects of antiglaucomatous drugs]. / Effets nycthéméraux des molécules anti-glaucomateuses.

PURPOSE: To collect data reflecting the current knowledge on the interactions of medical antiglaucomatous therapy and circadian variations. METHOD: Review of the available literature published on this topic in common electronic databases. RESULTS: The IOP-reducing effect of a molecule throughout the day depends on many parameters and still remains poorly investigated. It is well known that beta-blockers have a poor efficacy at night, while prostaglandins prevent nocturnal IOP variations because of their original mechanism. DISCUSSION: The lack of a 24-hour IOP recording device limits our ability to track the effect of antiglaucomatous drugs over 24 hours, an important point because these antiglaucomatous drugs vary in terms of their capacity to reduce IOP over a 24-hour period. CONCLUSION: Assessing the effect of antiglaucomatous therapy on a 24-hour basis remains very difficult. However, in the next few Years, this could become an emerging focus point in the management of glaucoma.

Entrapping efficiency and drug release profile of an oil-in-water (o/w) emulsion formulation using a polydimethylsiloxane-coated glass bead assay.

Evaluation of entrapping efficiency is difficult for an o/w emulsion formulation containing a lipophilic oily drug, isocarbacyclin methyl ester (TEI-9090), by commonly employed techniques (dialysis, ultrafiltration, or gel filtration), because of its adsorption to the system materials. Employing this characteristic of TEI-9090, we developed an adsorption technique with polydimethylsiloxane-coated glass beads (PDMS-GB). The assay is based on the quantitative adsorption of unentrapped TEI-9090 to the PDMS-GB. The entrapping efficiency of a 10% soybean oil emulsion containing [3H]TEI-9090 (1 microgram/mL) assayed by this method approached 100%. The PDMS-GB assay was performed for the emulsion diluted 100 times with physiological saline at different time intervals after dilution over a period of 24 hr. A plot of [3H]TEI-9090 in the emulsion particles versus time showed rapid release within 1 hr, followed by very slow release, reaching equilibrium. Applying first-order kinetics, the data were found to fit to a biexponential equation over the first hour of release. The terminal release resembled the first-order release of the drug from the phospholipid-rich infranatant, which was separated from the creamy layer by ultracentrifugation of the emulsion and contained 35% [3H]TEI-9090. These results suggest that the drug is released from two components in the emulsion.

Low doses of superoxide dismutase and a stable prostacyclin analogue protect in myocardial ischemia and reperfusion.

The effects of low dose human superoxide dismutase and low dose taprostene, a stable analogue of prostacyclin, were investigated separately and together in a model of myocardial ischemia (1.5 h) with reperfusion (4.5 h) in open chest, anesthetized cats. Taprostene (60 ng/kg per min), human superoxide dismutase (0.25 mg/kg per h), both agents together, or their vehicle, were infused intravenously in cats starting 0.5 h after occlusion of the left anterior descending coronary artery. Neither low dose taprostene nor low dose human superoxide dismutase exerted any endothelial or myocardial protection in this model. However, the two agents together showed a significant endothelial and myocardial protection in cats with myocardial ischemia and reperfusion. Compared with cats that were untreated or received only taprostene or human superoxide dismutase, cats receiving both agents exhibited a lower plasma creatine kinase activity at every time point observed after reperfusion, a reduced area of cardiac necrosis (7 +/- 2% vs. 21 +/- 5% area at risk, p less than 0.001), lower myeloperoxidase activity in the ischemic region (p less than 0.01) and a significant preservation of vasorelaxant responses of left anterior descending coronary rings to endothelium-dependent vasodilators, acetylcholine (p less than 0.001) and A-23187 (p less than 0.001). Taprostene appears to act additively with human superoxide dismutase to inhibit neutrophil adherence and activation and to inactivate superoxide radicals, and thus reduce cellular injury 4.5 h after reperfusion of the ischemic heart. Use of this agent may allow low doses of superoxide dismutase to be used more effectively in early myocardial ischemia.

Morphological consequences of bisacodyl on normal human rectal mucosa: effect of a prostaglandin E1 analog on mucosal injury.

Bisacodyl causes acute injury to the human rectal mucosa. Our objectives were to test whether pretreating the human rectum with an enema of 400 micrograms of a prostaglandin E1 analog (misoprostol) would ameliorate the mucosal injury provoked by an enema of 10 mg of bisacodyl, and to follow the evolution of the bisacodyl-induced injury in normal volunteers. Mucosal biopsies were taken 10 cm from the anus with an endoscopic forceps through a straight sigmoidoscope. Histological sections were interpreted blindly. In a preliminary experiment without bisacodyl, biopsies obtained from six subjects after misoprostol administration were indistinguishable from those taken from another six subjects after enemas of saline. In a parallel treatment experiment involving 30 subjects, all subjects sustained injury to the superficial epithelium and upper third of the crypt within 30 min after bisacodyl. Pretreatment with misoprostol also failed to prevent deeper injury to the lower third of colonic crypts. In a cross-over trial, a subset of four volunteers had biopsies at five different intervals after an enema of bisacodyl or saline. For up to 30 hours after bisacodyl, there was histological evidence of mild inflammation. Bisacodyl-induced colitis might confound the assessment of patients with suspected inflammatory bowel disease.

Effects of new chemically and metabolically stable prostacyclin analogues (iloprost and ZK 96480) on early consequences of a transient cerebral oligemia, in the rat.

Transient incomplete cerebral ischemia (oligemia) has been obtained in rats by associating mild systemic hypotension with bilateral carotid artery occlusion for 60 min. Continuous i.v drug administration for 3 days, performed with Alzet osmotic minipumps so that to deliver 167 ng.kg-1.min-1 Iloprost, 5 ng.kg-1.min-1 ZK 96480 or their respective vehicle, started 1 hour post-oligemia. Both compounds which are stable prostacyclin analogues reduced the edematous reaction and the post-oligemic accumulation of calcium in the brain tissue but above all they improved, mainly ZK 96480, the learning capacity of injured animals. These results indicate that regarding its therapeutic effect toward early consequences of a transient cerebral oligemia, ZK 96480 has the same profile as Iloprost at a dose 20-fold lower. Thus, these data encourage further clinical studies, in ischemic stroke, in which PGI2 and Iloprost have been shown promising.

[Second-trimester abortion: a difficult, unresolved problem]. / L'avortement du deuxième trimestre: un problème difficile, non résolu.

The authors review the various methods proposed for the late evacuation of the uterus. They report their experience of intra-amniotic injection of prostaglandins and, more recently, the use of extra-amniotic injections. They have found this latter technique to be unsatisfactory. Evacuation following dilatation under local anaesthetic, despite a few complications, appears to be effective... but the problem is far from being resolved.

Stimulative effect of prostaglandins on production of hexosamine-containing substances by cultured fibroblasts (2) early effect of various prostaglandins at various doses.

Early effects of various prostaglandins on the production of hexosamine-containing substances by cultrued fibroblasts, which were derived from a rat carrageenin granuloma, were studied. At hte stationary phase, the cells were exposed for 6 h to one of the prostaglandin A1 (PGA1), A2, B1, B2, D2, F1 alpha, E1, E2 or arachidonic acid in various concentrations ranging from 0.01 to 10 microng/ml for all the stimuli and from 10 pg to 10 microng/ml for PGF2alpha. The activity of the cells in incorporating 3H-glucosamine into hexosamine-containing substances (acidic glycosaminoglycans and glycoproteins) during this period was compared with that of control cells. All the stimuli tested showed more or less stimulative effect on the synthesis of hexosamine-containing substances at their specific concentrations. PGF2alpha was found to be the most potent stimulant and its stimulative effect was found significant even at the low concentration of 100 pg/ml. PGD2, F1alpha and E2 were the next potent stimuli. Their optimum dose were aroung 1 microng/ml but they still had significant stimulation at the concentration of 0.01 microng/ml. Effect of PGE2 was rather mild. Stimulation by PGA1, A2, B1 and B2 or arachidonic acid was seen at high dose, and it seemed to be non-specific. The results suggested that these prostaglandins such as PGF2alpha, D2, F1alpha and E2 play some important role on regulating the production of intercellular ground substances.