Trabeculectomy with mitomycin C in glaucoma associated with uveitis

The patients with uveitic glaucoma are at high risk for failure following drainage surgery because of young age of these patients, preoperative long-term control of inflammation and postoperative complications. Twenty-two trabeculectomies performed in 22 patients with uveitic glaucoma were retrospectively evaluated to analyze the effect of intraoperative application of mitomycin C (MMC). Success rates, postoperative levels of intraocular pressure (IOP) and postoperative complications were studied. After a mean follow-up of 10.6 months (range, 5-28 months), 15 patients (68.2%) achieved IOP of 21mmHg or less without antiglaucoma medications. There were statistically significant reduction in IOP postoperatively during the period studied (p < 0.001). Early postoperative complications included chorioidal detachment (9.1%), shallow anterior chamber (9.1%), hyphema (13.6%), macular edema (4.5%) and raised IOP (27.3%). Late postoperative complications included exacerbation of uveitis (4.5%), macular edema (4.5%), cataract (22.7%) and raised IOP (31.8%). The eyes with raised IOP needed additional antiglaucoma medication. The results of this retrospective and uncontrolled study suggest that intraoperative application of MMC may be a good option for enhancement of short-term trabeculectomy success rates in patients with uveitic glaucoma.     

Full-thickeness anterior blepharotomy and transpalpebral fat decompression in Graves' orbitopathy

A chief morbidity of Graves eye disease is eyelid retraction and exophthalmus. Transpalpebral orbital fat removal accomplished with full thickness anterior blepharotomy was performed in 4 patients (5 orbits). Preoperative and postoperative ocular exposure symptoms, visual acuity, upper eyelid retraction and proptosis were evaluated. In all 5 operated orbits preoperative symptoms resolved; good results were achieved from the functional and cosmetic point of view. Full-thickness anterior blepharotomy combined with fat decompression is a safe and effective surgery for patients with upper eyelid retraction and exophthalmus due to enlarged orbital fat compartment.     

Morphological, histochemical and immunohistochemical study of the gill epithelium in the abyssal teleost fish Coelorhynchus coelorhynchus

Histochemical and immunohistochemical study was carried out on nitrinergic innervation and neuroendocrine system in the gill epithelium of the abyssal fish Coelorhynchus coelorhynchus. The results showed that nNOS-positive nerve fibers, originating from the branchial arch were present in the subepithelial tissue of branchial primary filament. nNOS-positive neuroendocrine cells were also present in the primary filaments and secondary lamellae. Numerous mucous cells in the gill epithelium were AB/PAS-positive, while sialic acid was absent as confirmed by neuraminidase reaction and WGA lectin histochemistry. The mucus compounds in abyssal teleost fish are different from those found in pelagic species, being related to their living conditions. In abyssal species, greater numbers of chloride and neuroendocrine cells are involved in the movement of water and electrolytes. Neuroendocrine cells possess oxygen receptors which mediate the cardiovascular and ventilatory response to oxygen deficiency, as reported in teleost species. Besides, NO contributes through nervous stimulation to the regulation of vascular tone and blood circulation in the gill.     

The structure of the TrmE GTP-binding protein and its implications for tRNA modification

TrmE is a 50 kDa guanine nucleotide-binding protein conserved between bacteria and man. It is involved in the modification of uridine bases (U34) at the first anticodon (wobble) position of tRNAs decoding two-family box triplets. The precise role of TrmE in the modification reaction is hitherto unknown. Here, we report the X-ray structure of TrmE from Thermotoga maritima. The structure reveals a three-domain protein comprising the N-terminal alpha/beta domain, the central helical domain and the G domain, responsible for GTP binding and hydrolysis. The N-terminal domain induces dimerization and is homologous to the tetrahydrofolate-binding domain of N,N-dimethylglycine oxidase. Biochemical and structural studies show that TrmE indeed binds formyl-tetrahydrofolate. A cysteine residue, necessary for modification of U34, is located close to the C1-group donor 5-formyl-tetrahydrofolate, suggesting a direct role of TrmE in the modification analogous to DNA modification enzymes. We propose a reaction mechanism whereby TrmE actively participates in the formylation reaction of uridine and regulates the ensuing hydrogenation reaction of a Schiff's base intermediate.     

Behavioural characterisation of young adult transgenic mice overexpressing galanin under the PDGF-B promoter

The behavioural phenotype of transgenic mice (3- to 5-months old) overexpressing galanin (GalOE) under the platelet-derived growth factor B (PDGF-B) promoter was evaluated in a battery of tests, including open field, locomotor cages, light-dark exploration test, elevated plus-maze and the Porsolt forced swim test. Learning and memory were assessed in the passive avoidance and the Morris water maze tasks. No difference between genotypes was found in exploratory activity in the open field. GalOE mice showed a slight increase in spontaneous locomotor activity assessed in the locomotor cages, but the amphetamine-induced increase in locomotor activity was somewhat lower in GalOE mice. Anxiety-like behaviour in the three different tests including open field, light-dark exploration and elevated plus-maze did not differ between genotypes. In the Porsolt forced swim test, GalOE mice displayed an increased time of immobility, indicative of increased learned helplessness possibly reflecting increased stress-susceptibility and/or depression-like behaviour. GalOE mice showed normal learning and memory retention in the passive avoidance and the Morris water maze tasks. These data support the hypothesis that galanin may have a role in functions related to mood states including affective disorders.     

A peptide carrier with a built-in vaccine adjuvant: construction of immunogenic conjugates

A multifunctional carrier combining B/T cell epitopes (i), a built-in vaccine adjuvant (ii), and a universal T cell epitope (iii) for the construction of potent and specific immunogenic conjugates is presented. The IL-1beta(163-171) fragment known to reproduce the immunostimulatory and adjuvant effects of the whole IL-1beta without possessing any of the pro-inflammatory properties of IL-1beta was covalently anchored to the N-terminus of the Sequential Oligopeptide Carrier, SOC(n), formed by the repeating tripeptide unit Lys-Aib-Gly. A promiscuous T cell epitope derived from the tetanus toxin, TT(593-599), was also positioned in the carboxy terminus of SOC(n) as a universal immunogen to provide broad immunogenicity. Selected B/T cell epitopes from the Sm and La/SSB autoantigens, against which is directed the humoral autoimmunity in patients with systemic lupus erythematosus and Sj?gren's Syndrome, respectively, were coupled to the Lys-N(epsilon)H2 groups of the carrier, and the formulated constructs were administered in animals following the conventional immunization protocol of complete/incomplete Freund's adjuvant. The induced immune responses were compared with that produced when the Sm- and La/SSB-reconstituted immunogenic conjugates were injected alone. High titers of specific antibodies recognizing the priming construct, as well as the cognate autoantigen, were obtained when administered alone without the assistance of Freund's adjuvant. It is concluded that our approach provides the conceptual and experimental framework for the development of multifunctional immunogenic conjugates eliciting enhanced, specific, and prolonged humoral response for usage as human vaccine candidates.     

6-(2-Furanyl)-9H-purin-2-amine derivatives as A2A adenosine antagonists

Structure-activity relationships have been investigated through substitutions at the 9-position of the 2-amino-6-(2-furanyl) purine (5) to identify novel and selective A(2A) adenosine receptor antagonists. Several potent and selective antagonists were identified. In particular, compounds 20, 25, and 26 show very high affinity with excellent selectivity.     

Innovative, multifunctional sequential oligopeptide carriers Soc(n)-I and SOC(n)-II: functions-technology-perspectives

An innovative type of multifunctional helicoid artificial carriers, formed by the repetitive Lys-Aib-Gly (SOC(n)-I) or by the Aib-Lys-Aib-Gly (SOC(n)-II), with structural rigidity and regularity were successfully applied in our laboratory for anchoring antigenic/immunogenic peptides. The carriers, designed to display a predetermined 3D structure, adopt the 3(10) helical conformation, while the attached peptides preserve their original "active" conformation. The constructed conjugates were used as substrates in solid phase immunoassays, as well as for generating potent and specific immune responses.