[Fixed combination of latanoprost and timolol in the long-term treatment of patients with normal-tension glaucoma]. / Fiksirovannaya kombinatsiya latanoprost/timolol v dolgosrochnom lechenii patsientov s glaukomoi normal'nogo davleniya.

The most well-studied and widely prescribed fixed-combination drug for open-angle glaucoma is latanoprost/timolol. Its significant hypotensive effect is especially important in challenging cases, among which are patients with normal-tension glaucoma. With long life expectancy and the constant need for treatment, requirements are high for both the effectiveness of the drug and its tolerability. This paper presents a follow-up of 7 patients with normal-tension glaucoma who have been using the fixed combination of latanoprost/timolol for 10 years. All patients showed very good tolerability to the drug and their quality of life was preserved. A moderate rate of disease progression according to static perimetry was noted in one case. A mild degree of dry eye syndrome according to the OSDI questionnaire and an objective assessment of the state of the ocular surface was observed in one patient. The latanoprost/timolol fixed combination is a well-tolerated, highly effective and safe long-term treatment choice for normal-tension glaucoma.

[Medicated prevention of scarring after glaucoma surgery]. / Medikamentoznaya profilaktika posleoperatsionnogo rubtsevaniya v khirurgicheskom lechenii glaukomy.

Modulation of wound healing is one of the main challenges in glaucoma surgery. Modern antiproliferative agents used to reduce postoperative scarring are either insufficiently effective or inadequate in terms of safety. In the search for novel agents devoid of such drawbacks, specialists directed their attention to selective inhibitors of proinflammatory cytokines and growth factors. The article reviews pathophysiologic basis of wound healing, characteristics of inflammatory mediators affecting fibroblast proliferation and scarring, and provides description of the currently used and new, potentially promising antiproliferative agents.

[Influence of treatment adherence on the progression of primary open-angle glaucoma in clinical setting]. / Vliianie priverzhennosti k lecheniiu na progressirovanie pervichnoi otkrytougol'noi glaukomy u patsientov v usloviiakh klinicheskoi praktiki.

According to various studies, treatment adherence of patients with primary open-angle glaucoma ranges from 5% to 80% and significantly influences the effectiveness of the therapy. Some authors report higher levels of adherence in patients receiving preservative-free medications. PURPOSE: To study the influence of treatment adherence in patients receiving preservative-free and preserved medications on the progression of primary open-angle glaucoma (POAG). MATERIAL AND METHODS: This prospective multicenter non-interventional study was conducted in clinical setting and included 504 patients with primary open-angle glaucoma receiving drug therapy; 51 ophthalmologist was involved in the management of patients' diaries. RESULTS: The percentage of patients who did not reach target IOP was three times lower in the group with high adherence, in comparison to patients with medium and low adherence (7% against 22%, respectively). Development of side effects was one of the factors influencing treatment adherence, their rates and expressiveness were much lower in the preservative-free group compared with the group receiving preserved medication (13.9% against 35.4%). The rate of patients who did not reach target IOP was two times lower in the group of preservative-free medication (10% against 21%). CONCLUSION: The study confirms that preservative-free glaucoma medication promotes higher adherence to treatment in clinical setting predominantly due to the reduction of quantity and severity of side effects leading to treatment gaps, which results in increased effectiveness and better stabilization of glaucoma.

[Economic aspects of diabetic macular edema treatment at regional level in Russian Federation]. / Ékonomicheskie aspekty lecheniia diabeticheskogo makuliarnogo oteka na regional'nom urovne v Rossiiskoi Federatsii.

An assessment of economic burden of Diabetic Macular Edema (DME) in Russian Federation was conducted on the example of four pilot regions including Samara Region, Republic of Bashkortostan, Chuvash Republic and Yaroslavl Region. The assessment involved a newly developed interactive pharmacoeconomic model that uses data from questionnaire surveys of leading DME experts residing in the regions. In the course of the study, direct and indirect costs associated with DME were calculated. The highest direct costs of DME treatment were seen in the Republic of Bashkortostan - 302 482 RUB/year per patient. Direct cost of treating a single DME patient in the Samara Region was 34 271 RUB/year, in the Yaroslavl Region - 32 308 RUB/year and in the Chuvash Republic - 12 243 RUB/year. Indirect costs per DME patient in the Samara Region amounted to 67 530 RUB/year, in the Yaroslavl Region - 75 177 RUB/year, in the Republic of Bashkortostan - 102 884 RUB/year and in the Chuvash Republic - 81 082 RUB/year. Total annual costs per DME patient in the Samara Region was 101 801 RUB/year, in the Yaroslavl Region - 107 485 RUB/year, in the Republic of Bashkortostan - 405 366 RUB/year and in the Chuvash Republic - 93 325 RUB/year.

[The Qualitative Analysis of the Amide Derivative of HLDF-6 Peptide and Its Metabolites with the Use of Tritium- and Deuterium-Labeled Derivatives].

The goal of the study was to elaborate the pharmacokinetics methods of the amide derivative of peptide HLDF-6 (TGENHR-NH2) and its range of nootropic and neuroprotective activity is wide. The hexapeptide 41TGENHR46 is a fragment of the HDLF differentiation factor. It forms the basis for the development of preventive and therapeutic preparations for treating cerebrovascular and neurodegenerative conditions. Pharmacokinetic and molecular mechanisms of the action of the HLDF-6 peptide were studied using tritium- and deuterium-labeled derivatives of this peptide, produced with the use of the high-temperature solid-state catalytic isotope exchange reaction (HSCIE). This reaction was employed to produce the tritium-labeled peptide [3H]TGENHR-NH2 with a molar radioactivity of 230 Ci/mmol and the deuterium-labeled peptide [2H]TGENHR-NH2 with an average deuterium incorporation equal to 10.5 atoms. It was shown by the NMR spectroscopy that the isotope label distribution over the labeled peptide's molecule was uniform, which allowed qualitative analysis ofboth the peptide itself and its fragments in the organism's tissues to be conducted. The newly developed pharmacokinetics method makes it possible to avoid almost completely losses of the peptides under study due to biodegradation during the analysis of tissues. These labeled peptides were used in mice, rats and rabbits to study the pharmacokinetics of the peptide and to calculate the values of its principal pharmacokinetic parameters. Characteristics of its pharmacokinetic profile in the blood were obtained, the hypothesis of pharmacokinetics linearity tested, its metabolism analyzed and its bioavailability value, 34%, calculated. It has been shown that the studied TGENHR-NH2 peptide shows high resistance to hydrolysis in the blood plasma, with dipeptidyl aminopeptidases making the largest contribution to its hydrolysis.

[Medication assisted activation of unveoscleral outflow of intraocular fluid in glaucoma: pathogenic aspects].

The article provides an overview of the main groups of IOP-lowering drugs which activate uveoscleral outflow in glaucoma and this activation is a key component of mechanism of action of these drugs. The issues related to the change of tone of ciliary muscle and its participation in uveoscleral outflow, and also relationship of accommodation and aqueous flow in glaucoma pathogenesis and possible pharmacological effects of these processes are being discussed.

[Temperate Legionella bacteriophage: discovery and characteristics].

For the first time, temperate Legionella bacteriophage was isolated from organs of guinea pig infected with Philadelphia 1 strain of Legionella pneumophila. Negative colonies of bactriophage from 1.5 to 2.5 mm in diameter were detected. Central part of them was transparent and surrounded by peripheral zone of partial lysis. Electron microscopy showed that corpuscles of the phage consist from multifaceted elongated head of stretched hexagonal form and short tail. The bacteriophage lyzed bacteria, which cause Legionnaires' disease, and also had certain lytic activity against causative agent of tularemia.

[Surgical treatment for recurrent pterygium with plastic repair by means of silicone-dried amniotic membrane].

By taking into account the pathogenesis of the pterygium, the treatment of choice is surgical removal of the latter with plastic repair of the conjunctiva with allogenic tissues. The authors used the allogenic silicone-dried amniotic membrane "Flexamer" to replace the formed defect in order to create conditions for regeneration of the mucosal membrane of the eyeball. The conclusions of the study are based on the analysis of the results of surgical treatment in 106 patients with primary and recurrent pterygium. The unique properties of the implant "Flexamer" made formed from the silicone-dried amniotic membrane promote a rapid corneal epithelial regeneration and create conditions for making the eyeball mucosa good at the site of the excised abnormal conjunctiva, reducing the likelihood of a recurrent. Thus, the use of the silicone-dried amniotic membrane "Flexamer" is safe and effective and the findings allow the implant "Flexamer" to be recommended for use in the removal of both primary and recurrent pterygium.

[Photodynamic visudyne therapy for subretinal neovascularization].

A total of 199 sessions of photodynamic therapy (PDT) with visudine were performed in 119 patients (227 eyes) at the Laser Center, T. I. Yeroshevsky Samara eye diseases hospital. Analysis of the changes occurring in visual function in the presence of the subretinal neovascular membrane developing in age-related macular dystrophy and high complicated myopia showed an increase in visual functions in the first 3-6 months after PDT, which is, in the authors' opinion, associated with the diminution of macular edema and the resolution of hemorrhage. In the subsequent months, visual acuity tended to slightly lower. The late follow-up periods (after 1.5 years) saw visual function stabilization. Visudine PDT for subretinal neovascularization is an effective, safe, technically simple, well-tolerable procedure that makes it possible not only to stabilize, but, in many cases, to improve visual functions. A follow-up of patients for as long as 18 months demonstrated that stable visual functions were retained with a slight tendency for their reduction during continued PDT sessions.

[Capsaicin-sensitive afferents in the vagus nerve]. / Kapsaitsin-chuvstvitel'nye afferenty bluzhdaiushchego nerva.

Vanilloids were shown to interact with over 70% of vagal C-afferents first causing an excitation followed by desensitisation and a lasting destruction of nerve fibres. Capsaicin induces a secretion of some neuropeptides from 10-30% of vagal sensory terminals and therefore serves as a pharmacological tool for testing local "effector function" of primary afferents. Vagal afferents seem to have their own subtype of vanilloid receptors (VR), not completely identical with the VR receptors in the dorsal root ganglia. Considering potentiation of the capsaicin receptors sensitivity by some factors such as local heating, pH, free oxygen radicals, a possible role of the VRs as integrators of chemical and physical components of nociceptive stimuli, is discussed.

AE2 anion exchanger polypeptide is a homooligomer in pig gastric membranes: a chemical cross-linking study.

Although considerable information is available on the oligomeric states of the AE1 (band 3) anion exchanger, little is known about the physiological state of the polypeptides encoded by the nonerythroid AE genes, AE2 and AE3. We have previously characterized the proteolytic susceptibility of native pig gastric AE2. In the course of studies in which pig gastric membranes were treated with the AE2 transport antagonist, DIDS, we noted evidence for cross-linking of AE2 proteolytic fragments to higher-order oligomeric forms. We have characterized the ability of DIDS and of selected N-hydroxysuccinimide cross-linking agents to increase the proportion of SDS-resistant oligomers of pig gastric AE2 and its proteolytic fragments. Cross-linking exhibited time and concentration dependence. N-Terminal protein sequencing proved that DIDS treatment created AE2 homodimers. Putative homotetramers were also observed. Protomers were cross-linked via residues within the C-terminal 40 kDa of AE2. Prior proteolytic cleavage of AE2 in membranes resulted in decreased yield of subsequently cross-linked products. AE2 cross-linking could not be detected in membranes pretreated by hypotonic wash and freeze-thaw. The results are interpreted in light of the deduced amino acid sequence of the transmembrane domain of pig AE2.

HCO3(-)-dependent conformational change in gastric parietal cell AE2, a glycoprotein naturally lacking sialic acid.

Although the AE1 chloride/bicarbonate exchanger of the red blood cell is among the most thoroughly investigated of membrane transport proteins, less is known about the related AE2 polypeptide of parietal cells. We have studied enzymatic deglycosylation of native AE2 polypeptide in gastric mucosal membranes from pig and rabbit. Deglycosylation of AE2 was maximal at low ionic strength. Deglycosylation of AE2 in membranes was preferentially inhibited by bicarbonate compared with other anions. This inhibition was maximal at alkaline pH and was not evident after detergent solubilization of AE2. Deglycosylation of AE2 increased its susceptibility to proteolytic degradation, but the presence of bicarbonate protected against this degradation. Bicarbonate failed to inhibit deglycosylation of the membrane glycoproteins AE1 and gastric H(+)-K(+)-adenosinetriphosphatase beta-subunit or deglycosylation of the soluble glycoproteins fetuin and ribonuclease B. These data suggest that bicarbonate induces a conformational change in AE2 that can protect the polypeptide from deglycosylation and proteolysis. Pig AE2 was purified in sodium dodecyl sulfate, and its monosaccharide composition was determined after blotting onto polyvinylidene fluoride membrane. AE2 was found to be devoid of sialic acid, with a composition suggestive of the presence of lactosamine-type chains.

Proteolytic cleavage sites of native AE2 anion exchanger in gastric mucosal membranes.

The AE2 anion exchanger in pig and rabbit gastric mucosal membranes was subjected to limited proteolysis with trypsin, chymotrypsin, and papain, and to enzymatic N-deglycosylation. A monoclonal antibody to the AE2 C-terminal peptide was raised, characterized, and used to purify pig AE2 and its C-terminal cleavage products. Five distinct proteolytic cleavage sites within the AE2 transmembrane domain were defined by amino acid sequencing. The amino acid sequence of pig AE2 in the region encompassing the N-glycosylated Z-loop was also determined by RT-PCR. Tryptic cleavage of pig AE2 in the Z-loop produced C-terminal glycopeptides and was unaffected by deglycosylation, whereas the smaller rabbit AE2 C-terminal tryptic peptide lacked oligosaccharide, consistent with the respective amino acid sequences. The third consensus N-glycosylation site in pig Z-loop was heterogeneously glycosylated. Rapid papain cleavage in the Z-loop and slower cleavage in loop 7-8 produced C-terminal peptide products which were not N-glycosylated. Chymotryptic cleavage of the rabbit AE2 Z-loop required prior deglycosylation. Chymotryptic cleavage in the pig AE2 Z-loop produced C-terminal glycopeptides. Prior deglycosylation of pig AE2 unmasked novel, ionic strength-sensitive chymotryptic cleavage sites in the adjacent exofacial loop 7-8. These results provide experimental confirmation for some aspects of AE2 topography previously predicted from primary structure alone.

[The risk factors for the development of the multiple organ failure syndrome in destructive pancreatitis]. / Faktory riska razvitiia sindroma poliorgannoi nedostatochnosti pri destruktivnom pankreatite.

The role of neutrophil leukocytes in the development of the polyorgan failure syndrome during an unfavorable course of destructive pancreatitis is discussed. The examinations of 52 patients demonstrated a high correlation of neutrophil functional activity tests (nitroblue tetrazolium reduction test and leukocyte-platelet aggregation) and disorders of microcirculation and hepatorenal involvement (detected clinically and by laboratory tests). The "critical mass" of leukocytosis has been estimated: at least 18 . 10(9)/liter, at which the risk of polyorgan failure appreciably increases. The authors discuss the advisability of selective cytopheresis in a complex of intensive care for critical states involving endogenous poisoning and leukocytosis.

Mutations of conserved arginines in the membrane domain of erythroid band 3 lead to a decrease in membrane-associated band 3 and to the phenotype of hereditary spherocytosis.

To elucidate the molecular basis of band 3 deficiency in a recently defined subset of patients with autosomal dominant hereditary spherocytosis (HS), we screened band 3 cDNA for single-strand conformation polymorphism (SSCP). In 5 of 17 (29%) unrelated HS subjects with band 3 deficiency, we detected substitutions R760W, R760Q, R808C, and R870W that were all coinherited with the HS phenotype. The involved arginines are highly conserved throughout evolution. To examine whether or not the product of the mutant allele is inserted into the membrane, we studied one HS subject who was doubly heterozygous for the R760Q mutation and the K56E (band 3sMEMPHIS) polymorphism that results in altered electrophoretic mobility of the band 3 Memphis proteolytic fragments. We detected only the band 3MEMPHIS in the erythrocyte membrane indicating that the protein product of the mutant, R760Q, band 3 allele is absent from the red blood cell membrane. These findings suggest that the R760Q substitution, and probably the other arginine subsitutions, produce band 3 deficiency either by precluding incorporation of the mutant protein into the red blood cell membrane or by leading to loss of mutant protein from differentiating erythroid precursors.

[Local use of retabolil in the treatment of corneal pathology in experimental animals and clinical practice]. / Mestnoe primenenie retabolila pri lechenii patologii rogovitsy v éksperimente i klinike.

Experiments with 30 rabbits revealed enhanced corneal epithelium regeneration under the effect of local (epibulbar and subconjunctival) retabolil therapy. Clinically 15 patients with epithelial-endothelial corneal dystrophy were treated with retabolil, the treatment being effective in all the cases when the initial visual acuity was at least 0.1 diopters.

[Photosystem II of rye. Nucleotide sequence of psbD, psbI genes encoding reaction center proteins]. / Fotosistema II rzhi. Nukleotidnaia posledovatel'nost' genov psbD, psbI, kodiruiushchikh belki reaktsionnogo tsentra.

Structures of the rye chloroplast DNA regions, containing psbD and psbI genes coding for the components of the reaction centre of photosystem II, D2 protein and I polypeptide, respectively, have been determined. The gene trnS for tRNA(Ser) (GCU) is located 111 bp downstream from the stop codon of the psbI gene on the opposite strand. The high homology between the rye BamHI-fragment comprising these genes and his counterpart from wheat are discussed.

[Rye photosystem II. Nucleotide sequence of the psbC gene coding 43- kDa chlorophyll(a)-binding proteins]. / Fotosistema II rzhi. Nukleotidnaia posledovatel'nost' gena psbC, kodiruiushchego 43-kDa khlorfill(a)-sviazyvaiushchii belok.

The structure of the rye chloroplast DNA, which contains psbC gene coding for 43-kDa chlorophyll(a)-binding subunit of photosystem II, is determined. The sequence of trnS (UGA) gene encoding tRNA Ser is located at a distance of 140 bp downstream from the stop codon of psbC gene on the opposite DNA strand. The 5'-terminal part of psbC gene, like in other plants, overlaps by 50 bp the 3'-terminal region of psbD gene coding for D2 protein of photosystem II. The amino acid sequence of the psbC gene product reveals common features with the structure of the psbB gene product (CPa-1 protein). The structural similarity of these two proteins seems to reflect their similar functions.