Treatment of eosinophilic granulomatosis with polyangiitis (EGPA) remains a challenge because currently available therapies, corticosteroids and immunomodulators, do not always control symptoms and are often associated with significant morbidity and relapse. Mepolizumab has been demonstrated to be an effective add-on therapy with steroid-sparing effect in cases of relapsing or refractory EGPA. Intravenous immunoglobulin (IVIG) therapy is effective against mononeuritis multiplex or heart failure in patients with EGPA who do not respond to corticosteroid-cyclophosphamide treatment. We present two cases of EGPA in which earlier add-on administration of adjunct mepolizumab and IVIG led to significant improvement in EGPA symptoms and prevention of flareup of the disease. We suggested that earlier add-on combination administration of IVIG and mepolizumab might be a useful adjunct treatment to induce clinical remission of EGPA and improve the rate of remission, decrease relapse rate, and allow for reduced glucocorticoid use without any serious adverse drug effects.
Reports regarding the effect of all-trans-retinoic acid (RA) on the cell growth of retinal pigment epithelial cells (RPE) have been contradictory. The aims of this study are to clarify the in vitro effect of RA on RPE cells and to examine polyamine metabolism after RA stimulation. A 4-day incubation of fetal-calf-serum (FCS)-stimulated RPE cells with 10 or 25 µM RA significantly increased both cell number and [3H]thymidine incorporation. RPE cells grown over an extended period for 8 days also increased in number and reached full confluency. However, if the incubation was further extended to 12 days, no further increase in cell number was detected. RA treatment of FCS-stimulated RPE cells shifted the peak of ornithine decarboxylase (ODC) activity from 16 to 4 h. S-adenosylmethionine decarboxylase (SAMDC) activity and spermidine/spermine N1-acetyltransferase (SAT) activity of RA-treated RPE cells were significantly greater until 8 and 16 h after incubation, respectively. The putrescine content was significantly increased in RA-treated RPE cells up until 24 h, while spermidine, spermine and N1-acetylspermidine contents were significantly increased until 16 h. Our findings suggest that RA treatment increases the intracellular polyamine concentration of RPE cells via activation of ODC, SAMDC and SAT and that this results in the promotion of RPE cell growth until the cells reach full confluency.
Optical properties of carotenoids in photoreceptor systems for vision, phototaxis and phototropism are studied by LCAO-ASMO-SCF-CI theory, using ZDO approximation for the n"-electrons and CNDO /2 method for the valence-shell electrons. The most important point of our n"-electron approximation is that the tT-n' interactions indispensable to derive the bond alternation are taken into account explicitly.The conclusions are as follows:(1) the wavelengths of absorption maximum (i'l.max) calculated as the function of the number of double bonds are brought into a very satisfactory agreement with the experiments; (2) the wide distribution of the i'l.max's of known visual pigments is reasonably explained by the protonated Schif£-base binding of retinal with opsin; (3) the cis-trans isomerization is a non-adiabatic transition, at which the intersection of adiabatic potentials between a singlet and a triplet state plays an important role; (4) the origin of the cis-peaks is the steric hindrance of a hydrogen to a methyl branch or another hydrogen.
§1. Carotenoids in photoreceptor systemsIn the retinas of almost all vertebrate eyes, there exist two different kinds of visual cells called rod and cone, which are related to scotopic and photopic vision, respectively. Each of the outer segments contains photoreceptive pigments, which consist of a specific type of lipoprotein called opsin and a chromophore belonging to the carotenoid family. At present, two different kinds of native opsins and of native chromophores have been known. Namely, rod-and cone-opsin combine with retinal1 or retinalz (being the aldehyde of vitamin A1 or Az) to yield four photoreceptive pigments, among which rhodopsin composed of rod-opsin and retinal1 has most extensively been studied.
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