Predicting response to glaucoma therapy in one eye based on response in the fellow eye: the monocular trial.

OBJECTIVE: To evaluate whether the change in intraocular pressure (IOP) observed in one eye after starting a glaucoma medication regimen is predictive of the change in IOP due to the same medication in the fellow eye. METHODS: A retrospective medical record review of 22 patients with primary open-angle glaucoma (POAG) and 27 glaucoma suspects who underwent monocular drug trials before the drug was added to the second eye. The absolute change in IOP from baseline and the relative change (change in treated eye minus change in fellow eye) in the first eye treated were compared with the second eye after binocular treatment. RESULTS: The absolute and relative decreases in IOP of the first eye were poorly correlated with those of the second eye in patients with POAG (r(2) < 0.001; P = .97 and r(2) = 0.040; P = .38, respectively). However, they were well correlated in glaucoma suspects (r(2) = 0.348; P = .001 and r(2) = 0.396; P < .001, respectively). CONCLUSIONS: The change in IOP of one eye due to a medication may be predictive of the subsequent response of the fellow eye to the same medication in glaucoma suspects, but not in patients with POAG. Using the fellow eye as a control may confer a more accurate portrayal of the true therapeutic effects of a medicine, although further study is needed to support both of these findings.

Avaliaçäo da resposta tecidual frente a diferentes materiais de fixaçäo em enxertos ósseos autógenos: análise microscópica morfológica / Evaluation of tissue response due to different fixation materials in autogenous bone grafts: microscopic morphological analysis

Os enxertos ósseos autógenos têm sido largamente empregados para a reconstruçäo de rebordos atróficos. A fixaçäo destes enxertos é fundamental no fenômeno de reparaçäo óssea, propiciando a incorporaçäo ao leito receptor e rápida revascularizaçäo. Placas e parafusos sintéticos reabsorvíveis têm sido desenvolvidos na tentativa de minimizar alguns pontos negativos dos materiais metálicos rotineiramente utilizados para esta finalidade. O presente estudo avaliou comparativamente as condiçöes ósseas locais de enxertos ósseos autógenos oriundos da regiäo mentoniana quando em contato com parafusos de ácido poliglicólico (PGA)/ácido poli (L-láctico) (PLA) e de titânio. Para esta avaliaçäo, participaram sete pacientes apresentando atrofias maxilar e mandibular severas, impossibilitando a reabilitaçäo com implantes osteointegráveis. Após quatro meses das cirurgias de enxerto, as áreas onde se localizavam os parafusos de teste foram biopsiadas com brocas trefinas, obtendo-se os espécimes a serem submetidos a procedimento histotécnico de rotina e corados em H.E. e Tricrômico de Mallory para avaliaçäo morfológica em microscopia óptica de luz. A partir desta análise observou-se, adjacente aos parafusos de titânio, tecido ósseo viável, com eventuais áreas recobertas por células de revestimento e ausência de reabsorçäo. Adjacente aos parafusos reabsorvíveis, o tecido ósseo também apresentou viabilidade morfológica, porém, com presença de extensa faixa de tecido conjuntivo fibroso interposto, e eventuais células gigantes. Estes resultados sugerem que ambos os métodos de fixaçäo proporcionaram condiçäo de reparo no local de enxertos, contudo, os parafusos reabsorvíveis induziram reaçäo inflamatória mais extensa que os de titânio, caracterizada por reaçäo tipo corpo estranho

Eicosanoids as a new class of ocular hypotensive agents. 3. Prostaglandin A2-1-isopropyl ester is the most potent reported hypotensive agent on feline eyes.

It has been shown that prostaglandin A2 (PGA2) is a more potent ocular hypotensive agent in cats than other PG free acids. We report here that significant IOP reduction can be achieved in normotensive cat eyes with the use of even lower doses of PGA2-1-isopropyl ester (PGA2-IE) than with PGA2, PGF2 alpha-1-isopropyl ester (PGF2 alpha-IE), or any other known ocular hypotensive agent. Furthermore, single applications of 0.5 microgram of PGA2-IE maintain significant IOP reductions for at least 24 hr. This hypotensive effect is enhanced during the first 3-5 days of daily treatment. Significant IOP reductions were maintained for several months as long as PGA2-IE was applied daily or at least once every 48 hr. None of the cats manifested signs of discomfort in response to treatment with doses ranging from 0.10 to 1.25 micrograms of PGA2-IE. Moreover, the extent of anterior chamber flare was less than that typically observed after the topical application of hypotensive doses of PGE2, PGD2, PGF2 alpha, or the esters or tromethamine salt of PGF2 alpha. Although it is possible that the human eye would respond differently to PGs of the A type, the results of these studies suggests that PGA2-IE or other esters of derived PGs of the A type, and probably the B type, may offer significant therapeutic advantages over the PGF2 alpha tromethamine salt and PGF2 alpha-IE, which have been shown to exert significant hypotensive effects on normal and glaucomatous human eyes.

Antiviral activity of a synthetic analog of prostaglandin A in mice infected with influenza A virus.

We have previously shown that prostaglandins of the A series potently inhibit virus replication in several virus-host systems in vitro. In the present report we have studied the effect of a long-acting synthetic analog of PGA, 16,16-dimethyl-PGA2(Di-M-PGA2), on virus infection in vivo, using as a model Balb/c mice infected with influenza A (PR8) virus. Depending upon the dose of viral inoculum, PR8 virus caused the death of 50 to 100% of the animals in a period of 8-20 days. Di-M-PGA2-treatment significantly increased mouse survival by an average of 40%, independently of the dose of inoculum and the age of the animals. The fact that Di-M-PGA2-treatment decreased virus titers in the lungs and did not alter the host immune response, suggested that PGA's therapeutic action was due to suppression of virus replication. Finally, two anti-inflammatory compounds, which inhibit prostaglandin synthesis, aspirin and indomethacin, were shown not to significantly alter mouse survival in this system.

Inhibition of human melanoma growth by prostaglandin A, D, and J analogues.

The relative inhibitory potency of prostaglandin A (PGA) and prostaglandin J2 (PGJ2) analogues compared to prostaglandin A1 (PGA1) was determined in a clonogenic assay system. Three human melanoma cell strains (C8146A, C8146C, and C8161), a human melanoma cell line (M1RW5) and a human neuroblastoma cell line (IMR-32) were used. Prostaglandin analogues were screened in the clonogenic assay system and the dose effect curves were analyzed by linear regression utilizing the median effect relationship. The computer-generated 50% and 95% inhibitory doses showed that 15-deoxy-16-hydroxyl-16-vinyl-prostaglandin A2 (DHV-PGA2) was from two- to three-fold more active than PGA1 in inhibiting the clonogenic growth of human melanoma cells. Based on the 50% inhibitory dose, PGJ2 and its analogues were from two to five times more potent than PGA1. The delta 12- and delta 12,14-PGJ2 were the most potent of the prostaglandins tested. However, the 95% inhibitory dose for prostaglandin D2 (PGD2), PGJ2 and its analogues against neuroblastoma did not show any enhancement in activity in comparison to PGA1, suggesting that some tumor specificity in the activity of these analogues may be signified by the neuroblastoma data. Prostaglandins which contained a fluoride substitution at position 11 were also tested for activity. As we previously observed with other analogues which did not contain an alpha, beta-unsaturated carbonyl group in the cyclopentane ring, 9 beta, 15 alpha-dihydroxy-11 beta-fluoroprosta-5-cis-13-trans-dienoic acid and 9 alpha, 15 alpha-dihydroxy-11 beta-fluoroprosta-5-cis-13-trans-dienoic acid did not inhibit the clonogenic growth of human melanoma cells. Administration s.c. to established human melanoma tumors growing in athymic nude mice caused a significant growth inhibition. The treatment schedules ranged from 1 to 8 days. Injection s.c. of PGA1 at a dose of 40 mg/kg/day resulted in a 20% suppression in tumor growth. Higher doses (100 and 200 mg/kg/day) effected an 80% reduction in tumor growth. The higher doses were associated with reversible toxicities, diarrhea and skin inflammation. Administration of DHV-PGA2 at a dose of 20 mg/kg/day resulted in 40% reduction in tumor growth. The increased in vivo potency of DHV-PGA2 corresponds to the results obtained in the clonogenic assay system.

Use of lipid microspheres as a drug carrier for antitumour drugs.

9-Oxo-15-hydroxy-delta 7,10,13-prostatrienoic acid methyl ester (delta 7-PGA1), an antitumour drug was incorporated into lipid microspheres of 0.2 micron diameter (lipo-delta 7-PGA1). In in-vivo experiments, lipo-delta 7-PGA1 had a significantly greater antitumour activity than free delta 7-PGA1 against P388 leukaemia. Lipo-delta 7-PGA1 slightly, but significantly, prolonged the survival time of mice inoculated with L1210 leukaemia, whereas free delta 7-PGA1 did not. Against MM46 ascites tumour, the survival time after treatment with 10 mg kg-1 of lipo-delta 7-PGA1 was significantly greater than that after the same dose of free delta 7-PGA1. The results suggest that lipid microspheres can be used as drug delivery carriers for lipid soluble antitumour agents.