An adherence based cost–consequence model comparing bimatoprost 0.01% to bimatoprost 0.03%

Abstract

Objectives:

Estimate the long-term direct medical costs and clinical consequences of improved adherence with bimatoprost 0.01% compared to bimatoprost 0.03% in the treatment of glaucoma.     

Phorbol ester-induced adhesion (binding) among human mononuclear leukocytes requires extracellular Mg++ and is sensitive to protein kinase C, lipoxygenase, and ATPase inhibitors

Under gentle shaking, the phorbol 12,13-dibutyrate (P(Bu)2)-induced adhesion among human blood mononuclear leukocytes started within a few minutes, increased with time and was almost complete after 12 h. During this moment and thereafter more than 60% of the cells were in aggregates. Induction of the cell aggregation by 20 min treatment with P(Bu)2 did not occur in Ca++/Mg++-free medium but was almost complete with Mg++ alone and reached its maximal manifestation with both divalent cations present. The intracellular Ca++ antagonist 8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate had a minimal inhibitory effect, and simultaneous treatment of the cells with Ca++ ionophore A23187 and P(Bu)2 did not increase the intercellular binding, whereas A23187 alone induced some cell aggregation. Retinal, a protein kinase C inhibitor, inhibited the intercellular adhesion by more than 50%, and treatment of intact cells with 1-oleoyl-2-acetyl-glycerol, an activator of the enzyme, induced some cell aggregation that was slightly increased when A23187 was added simultaneously. Nordihydroguaiaretic acid, 5,8,11-eicosatriynoic acid and 5,8,11,14-eicosatetraynoic acid, which inhibit lipoxygenation of arachidonic acid, reduced the cell aggregation in contrast to indomethacin and acetylsalicylic acid that had no effect. Cellular ATPases, inhibited by quercetin, but not the ouabain-sensitive Na+, K+-ATPase, appeared to participate, whereas the amiloride-sensitive plasma membrane Na+/H+ exchanger and the intracellular levels of cGMP did not seem to influence the system.     

Inactivation of expressed and conducting rCx46 hemichannels by phosphorylation

 Hemichannels of rat connexin 46 (rCx46) were expressed in Xenopus laevis oocytes and analysed by two-electrode voltage-clamp experiments. It is established that rCx46 hemichannels can be activated at low external Ca²⁺ and positive membrane potentials. Upon larger depolarizations, the hemichannels of oocytes activate in a time-dependent manner, occasionally followed by a spontaneous inactivation. We found that, in the absence of inactivation, treatment of oocytes with 1-oleoyl-2-acetyl-sn-glycerol (OAG), an activator of protein kinase C (PKC), reversibly reduced the amplitude of the rCx46-mediated current and, after an incubation time of about 30 min, induced inactivation of the voltage-dependent current. After wash-out of OAG the corresponding membrane conductance increased and the inactivation behaviour disappeared. The OAG-induced inactivation, as well as the spontaneous inactivation, could be removed by application of the specific PKC inhibitor calphostin C and also by phloretin. The data provide evidence that the activation and inhibition of PKC affect the rCx46-mediated membrane conductance as well as the voltage-dependent current inactivation in an inverse manner. Received: 13 March 1998 / Received after revision and accepted: 18 June 1998     

Modulation of human leukocyte histamine release by sn-1,2-isopropylidene-3-decanoyl-glycerol and decanoic acid cyclopentyl methylester in comparison with effects of synthetic diacylglycerols and a phorbol ester

Previous studies have shown that the glyceride derivative, sn-1,2-isopropylidene-3-decanoyl-glycerol (IpOCOC9), can trigger human leukocyte histamine release. Approximately 25% of the total cellular histamine content is extruded in the presence of 206 microM of IpOCOC9; at 69 microM, however, the secretagogue action of the compound is marginal. The characteristics of the release induced by IpOCOC9 are closely similar to those reportedly recorded at hyperosmolar triggering of basophils with mannitol, and in many respects they also mimic those observed at phorbol ester-induced histamine release. The compound decanoic acid cyclopentyl methylester (DACPME), a structural analogue of IpOCOC9, fails to induce histamine release. IpOCOC9, but not DACPME, stimulates human polymorphonuclear leukocyte cytosolic Ca2+- and phospholipid-dependent histone III-S kinase activity (unpublished observations). The secretagogue action of IpOCOC9 has therefore tentatively, at least partly, been attributed to a direct protein kinase C activation. In the present studies, we examined the influence of IpOCOC9 and DACPME on histamine release triggered by an ensuing exposure to anti-IgE, the calcium ionophore A23187, formyl-methionyl-leucyl-phenylalanine (FMLP), or 4 beta-phorbol 12-myristate 13-acetate (PMA). It is shown that IpOCOC9-treatment of cells results in either enhancement or reduction of the release induced by anti-IgE or by A23187, whereas FMLP-induced release is consistently reduced and PMA-induced release consistently enhanced by such a treatment. Treatment of cells with DACPME enhances but does not reduce anti-IgE-triggered release, whereas FMLP-induced release is not affected. Pretreatment of the cells with other putative protein kinase C activators like PMA, sn-1-oleoyl-2-acetyl-glycerol (OAG), 1,2-dioctanoyl-glycerol (DiC8) or the glycerol derivative sn-1,2-diacetyl-3-decanoyl-glycerol (DiC2OCOC9) affects secretagogue-induced basophil histamine release according to specific patterns similar to but not identical with those recorded for IpOCOC9 and DACPME. Thus, e.g., DiC2OCOC9 consistently reduces but does not enhance anti-IgE-triggered release. These data show that limited structural changes of IpOCOC9 may qualitatively affect its modulating properties in the human basophil histamine release system.     

近视与开角型青光眼(OAG)临床相关研究进展

 开角型青光眼(open-angle glaucoma,OAG)包括高眼压性原发性开角型青光眼(primary open-angle glaucoma,POAG)和正常眼压性青光眼(normal-tension glaucoma,NTG)。不少研究表明近视,特别是高度近视是OAG发生的危险因素,但近视对青光眼性损害形式及进展的影响尚不明确。近视本身也可能发生一系列器质性改变,使得近视与OAG并存时病情尤为复杂。NTG与POAG在临床表现和发病机制上有所不同,近视对两者的影响也有所不同。而不同程度的近视对OAG影响亦不同,表现在其流行病学、视神经和视野损害形式、视野进展速率上有所差异。明确近视与OAG发生、发展的关系,对OAG的诊断、治疗、预后及发病机制的研究有重要作用。