Antihistamines Modulate Functional Activity of Macrophages.

We compared the effects of the first-, second- and third-generation antihistamines in different doses on enzyme activity and cytokine production by macrophages and their death using an in vitro model. It was found that decreasing the dose led to an increase in the number of viable cells; after contact with second-generation antihistamines (loratadine, desloratadine), apoptosis of macrophages predominated. A dose-dependent increase in activity of ATPase and 5'-AMP with less pronounced effect of second-generation drugs was revealed. It was shown that under the influence of drugs, macrophages do not produce IL-1ß, but actively synthesize TNFα and IL-10, which indicates the immunomodulatory properties of these drugs.

Effect of Hypotensive Drugs on Dynamics of Nitroxide-Producing Renal Function in Rats with Nephrogenic Hypertension.

An original model of nephrogenic hypertension in rats was used for histochemical mapping of NADPH diaphorase (NO synthase) in various renal segments to examine the effect of hypotensive drugs furosemide, bendazol, and clonidine on the time course of nitroxide production in the kidneys. In various nephron segments, these drugs modulated NO synthesis in different ways. Clonidine induced a stable up-regulation of NO synthesis, which can maintain active vasodilation and gradually diminish the rennin production. Bendazol also enhanced NO synthase activity in renal glomeruli and collecting tubules, but this effect was less pronounced and short lasting. During the first week after injection of bendazol, insignificant elevation of NO synthase activity was observed in the proximal nephron segments. Furosemide exerted the least effect on NO production in kidneys.

[Systemic Antimicrobials Consumption and Expenditures in Departments of Surgery of Multi-Profile Hospitals in the Russian Federation and the Republic of Belarus: Results of Multicentre Pharmacoepidemiological Study].

The results of the systemic antimicrobials (AM) consumption and expenditures assessment in the departments of surgery of multi-profile hospitals in different regions of the Russian Federation and the Republic of Belarus in 2009-2010 based on retrospective collection and analysis of the data from the hospital expenditure notes using ATC/DDD methodology are presented. The average AM consumption and expenditure rates in the above mentioned departments varied from 24.9 DDD/100 bed-days to 61.7 DDD/100 bed-days depending on the department profile, with beta-lactams (cephalosporins and penicillins) share in the consumption being as high as 70-90%, followed by fluoroquinolones and aminoglycosides. Only 55-70% of the consumed AM belonged to the drugs of choice, whereas the improper AM consumption and expenditure rates amounted up to 10-18%. The study outputs can be used for the budget allocation and AM distribution improvement in the departments of surgery, as well as for the development and efficacy control of the local antimicrobial stewardship programs.

[Multicentre study of comparative efficacy of meropenem and combined regimens for empirical antibacterial therapy of severe nosocomial infections: results of clinical and pharmacoeconomic analysis].

Adequacy and effectiveness of empirical antibacterial therapy of severe nosocomial infections with meropenem vs. combined regimens of antibacterial therapy were investigated and the ratio of the cost and effectiveness of the compared regimens was evaluated. A prospective, randomized, open, comparative study of two initiative regimens of empirical antibacterial therapy of severe nosocomial infections was performed: meropenem in a daily dose of 1.5-3 g and the standard regimen with the use of betalactams and fluoroquinolones in combination with aminoglycosides and/or metronidazole. Patients with recorded diagnosis of nosocomial pneumonia (including the ventilator-associated one) or abdominal infection with the signs of severe sepsis and severity of APACHE II > 14 were enrolled. The patients were stratified into 2 groups subject to the disease severity, i.e. APACHE II 15-20 and APACHE II 21-25. One hundred thirty five out of 166 patients with recorded nosocomial infection were included into the final estimate of the therapy adequacy and effectiveness (Protocol Analysis): 62 patients were treated with meropenem and in the treatment of 73 patients the standard antibacterial therapy was used. In the group of the patients treated with meropenem there were stated significantly higher clinical effectiveness (recovery in 80.6% of the patients vs. the control of 46.6%, p < 0.01) and pathogen eradication (89.6 and 48.1% respectively, p < 0.01). The difference in the clinical and bacteriological effectiveness of meropenem and the standard therapy was more evident in the subgroups of more severe patients (APACHE > 20). With the use of meropenem the probability of recovery from nosocomial infection was significantly higher (RR 1.73-1.94, p < 0.001) vs. the control. Meropenem provided significantly higher eradication of the pathogens: P. aeruginosa (88 and 40% respectively, p = 0.007), E. coli (100 and 46.7%, p = 0.003), Acinetobacter spp. (90.9 and 40%, p = 0.02). The antibacterial therapy with the use of meropenem was assessed as adequate in 51 out of 56 patients (91.1%), that was 3 times as frequent as with the use of the standard antibacterial therapy (33.9%). The cost-effectiveness coefficient with the use of meropenem was 2.2 times lower vs. the control. Therefore, the empirical therapy of severe nosocomial infections with meropenem proved to be more adequate and from the economic viewpoint more advantageous vs. the standard combined regimens of antibacterial therapy, that was evident from significantly higher clinical and bacteriological efficacy of the treatment and decrease of the terms of the patients hospitalization in intensive care units (on the average by 5 days).

[The test for nitric oxide metabolites in exhaled air condensate as a method of assessing NO-reactivity of the airways in patients with bronchial asthma]. / Opredelenie metabolitov oksida azota v kondensate vydykhaemogo vozdukh kak sposob otsenki NO-reaktivnosti dykhatel'nykh putei u bol'nykh bronkhial'noi astmoi.

AIM: To estimate airways NO-reactivity in response to their stimulation with fenoterol in different clinical forms of bronchial asthma (BA). MATERIAL AND METHODS: The study included 73 patients with BA: mild disease was in 21, moderate--in 24 and severe--in 28 patients. Severe BA patients were divided into two subgroups: with a stable course (n = 15) and unstable course (n = 13). NO-producing function of the airways was estimated by concentration of stable NO-metabolites (mNO)(NO2, NO3) in exhaled air condensate. RESULTS: Spontaneous NO-producing activity of the airways increases and reaches maximum in severe unstable asthma. Fenoterol-stimulated NO-production was minimal in mild BA while the most significant augmentation of mNO was observed in unstable BA. Basal level of mNO and velocity parameters of external respiration function correlated. CONCLUSION: Estimation of NO-reactivity of the airways in the test with fenoterol with calculation of the index of airways NO-reactivity provides additional information about respiratory system condition in BA patients which may be used in clinical pulmonology.

[Significance of nitric oxide function in development of cardiac hypertrophy under condition of experimental renal hypertension]. / Znachenie oksida azota v razvitii gipertrofii serdtsa v usloviiakh éksperimental'noi pochechnoi gipertenzii.

The development of cardiac hypertrophy was studied under condition of experimental renal hypertension on the rat. The number of cardiac nitric oxide synthase (NOS)-positive neurones increased simultaneously with the increase in NOS-activity in these neurones. A connection was found between the development of cardiac hypertrophy and the activity of NOS in cardiomiocytes. The involvement of NO in the development cardiac hypertrophy as auto- and paracrine regulator is supposed.

[Nitric oxide formation by chromaffinocytes of respiratory system and its importance for catecholamine exocytosis]. / Obrazovanie okisi azota khromaffinotsitami organov dykhaniia i ee znachenie dlia ékzotsitoza katekholaminov.

Chromaffinocytes (both single and within paraganglia) located in larynx, trachea, extrapulmonary bronchi and lungs possess NADPH-diaphorase/NO-synthase activity. Chromaffinocytes and paraganglia are anatomically associated with the vagus, autonomous ganglia and the walls of small blood vessels. NO-synthase agonists, acethylcholine and Ca ionophore A23217, after intrapleural injection increase the enzyme activity, that is accompanied with the decrease of luminescence intensity and a reduction of monoamine content in cell cytoplasm. It is concluded that NO is involved in the mechanism of catecholamine release.

[Inducible nitric oxide synthase in rat lungs in experimental bronchial asthma and its status in administering drugs with adrenergic action]. / Indutsibel'naia nitrooksidsintaza v legkikh krys s éksperimental'noi bronkhial'noi astmoi i ee sostoianie pri vvedenii preparatov adrenergicheskogo deistviia.

The state of inducible NO-synthase (iNOs) in the rat lung with experimental model of bronchial asthma (BA) was studied after administrating short-acting beta 2-agonist fenoterol, long-acting beta 2-agonist salmeterol, and adrenoblocker propranolol. Administrated beta 2-agonists were observed to result in reducing iNOs activity in the rats with BA, while propranolol intensified iNOs expression.

[Plasma-modified silicone graft for scleroplasty in progressive myopia]. / Plazmenno-modifitsirovannyi silikonovyi transplant dlia skleroplastiki pri progressiruiushchei miopii.

Plasma-chemical modification of synthetic transplant material (proliferous silicone) intended for scleroplasty in progressive myopia was theoretically substantiated, developed in the experiment and tested in practice. This treatment was shown to enhance the biocompatibility of a graft which tightly joins the sclera through the connective tissue intergrown from the surrounding capsule into the graft. The efficacy of the proposed plasma-modified grafts in stabilizing progressive myopia in 18 patients operated on (33 eyes) aged 6 to 49 years (spherical equivalent myopia degree 3.0-28.0 D) during 3- year followup was 97%. There was an elevation of uncorrected and corrected visual acuity, are active course of the postoperative period.

[Nitric oxide synthase in neurons of the vagal nucleus dorsalis and ganglion nodosum and its changes following acetylcholine inhalation in the norm and in experimental bronchial asthma]. / Nitrooksidsintaza neironov zadnego iadra i uzlovatogo gangliia bluzhdaiushchego nerva i ee izmeneniia pri ingaliatsiiakh atsetilkholina v norme i pri éksperimental'noi bronkhial'noi astme.

The expression NADPH-diaphorase and inducible NO-synthase (NOS) was studied in vagal nucleus dorsalis and ganglion nodosum neurons following acethylcholine inhalation in healthy rats and rats with ovalbumin-induced experimental bronchial asthma (BA). It was found that NOS activity regulation is mediated by cholinoreceptors; functioning of this mechanism is disturbed in hypoxic state. It is shown that both in conditions of physiological norm and in experimental BA, changes in NOS activity are determined by its constitutive, neuronal isoform.

Regulation of NO-producing function of the lungs with salmeterol.

The state of epithelial nitric oxide synthase, bronchomotor reaction, and concentration of NO metabolites (NO(2)(-) and NO(3)(-)) in bronchoalveolar lavage fluid were studied in healthy rats and rats with experimental bronchial asthma induced by inhalations of long-acting beta(2)-agonist salmeterol. The effects of salmeterol on NO-producing function of the lung in healthy animals and in animals with bronchial asthma were studied.

[NO synthase activity in epitheliocytes of the rat bronchi following inhalation administration of adrenergic agonists and guanosine triphosphate]. / Aktivnost' NO-sintazy épiteliotsitov bronkhov krys pri ingaliatsionnom vvedenii adrenoagonistov i guanozintrifosfata.

NO synthase was studied in intact rats and in rats with bronchial asthma epitheliocytes after inhalation of phenotherol, propranolol, guanosine triphosphate (GTP) and combined inhalation of GTP with phenotherol. NO synthase mediator action on bronchial patency during adrenoagonists and GTP inhalation was demonstrated.

[Regulation of the functional state of mediastinal pleural mast cells by adrenergic agents]. / Reguliatsiia funktsional'nogo sostoianiia tuchnykh kletok mediastinal'noi plevry preparatami adrenergicheskogo deistviia.

The adrenoactivity of the mast cells (MC) in the albino rats mediastinal pleura was studied during the experiment with the use of the pharmacological preparations of adrenergic effect in vivo and in vitro. While injecting adrenolytics and adrenomimetics presence of heparin and biogenic monoamines (catecholamines and serotonin) was observed. Adrenomimetic substances in vivo and in vitro were observed to intensify the synthetic process, decrease degranulation, concentrate the density of heparin granules and increase the number of biogenic monoamines while adrenolytic substances were noticed to produce contrary effect.

Refractive tunnel keratoplasty with synthetic implants modified by a gas-discharge plasma.

Various methods of refractive interlamellar tunnel keratoplasty with synthetic implants modified by low-temperature gas-discharge plasma were used for correction of myopia and myopic astigmatism. Experiments carried out with laboratory rabbits revealed that pretreatment of hydrogel, silicon, and polymethylmethacrylate by gas-discharge plasma enhances the tolerance of corneal stroma to these synthetic materials. Clinical studies with hydrogel have shown that gas-discharge plasma treatment of traditional polymer materials is a promising method for achieving improved biocompatibility of synthetic materials to corneal stroma. Forty-four clinical tunnel keratoplasties have been conducted on humans with gas-discharge-plasma-treated hydrogel. The patients had a high degree of myopia (from 7.0 to 28.0 D) and myopic astigmatism (within the range of 5.0 to 11.0 D). Surgical methods were similar to those developed during the experimental stage of work. The patients were followed postoperatively for up to 8 years. According to these observations, circular tunnel keratoplasty with synthetic implants reduced spherical myopia up to 20.0 D. Methods for correcting of both simple and complex myopic types of astigmatism have been developed. Arc-type sectoral tunnel keratoplasty and elliptical tunnel keratoplasty allowed correction of myopic astigmatism up to 11.0 D.

[Scleroplasty with plasma-modified homoslceral grafts: experimental morphological study]. / Skleroplastika s ispol'zovaniem plazmenno-modifitsirovannykh gomoskleral'nykh transplantantov v eksperimente (morfologicheskoe issledovanie).

Healing of homoscleral grafts treated by gas discharge low-temperature plasma has been studied. Such treatment leads to formation of a modified surface layer in scleral tissue; the presence of such a layer improves the hydrophilic properties and biocompatibility of the sclera, thus promoting better adaptation of the graft to further restructuring and healing during the postoperative period. Experiments on 32 eyes of chinchilla rabbits showed that after scleroplasty with thus treated transplants, complete replacement of fibroblasts and collagen carcass of the graft was observed as early as after 7.5 months (vs. 12 months in the control); the graft was stabilized and tightly grown into the sclera to form a solid sclera-graft complex which fortifies the scleral membrane of the eye. Use of plasma-modified transplants may improve the efficiency of scleroplastic operations in progressive myopia and ocular injuries.

Nitric oxide synthase in bronchial epithelium and nitric oxide metabolites in the lungs of rats with bronchial asthma after fenoterol inhalation.

Nitric oxide synthase of the bronchial epithelium and concentrations of nitric oxide metabolites (NO(2)(-)and NO(3)(-)) in bronchoalveolar lavage fluids were measured in rats with bronchial asthma after fenoterol inhalation. It was suggested that nitric oxide-ergic mechanisms can mediate the effects of inhaled beta(2)-adrenergic agonists.

[The NADPH-diaphorase activity of the bronchial epithelium in chronic lung diseases]. / Aktivnost' NADPH-diaforazy épiteliia bronkhov pri khronicheskikh zabolevaniiakh legkikh.

Topochemistry and activity of NADP-H diaphorase co-localized with NO synthase was examined in operative material of lungs from patients with bronchial asthma (BA), chronic nonobstructive bronchitis (CNO) and chronic obstructive bronchitis. The enzyme activity was found to be dependent upon the types of obstruction and inflammation. In CNO the state of NO synthase was not changed. In conditions of progressive irreversible airway obstruction the enzyme activity was augmented in small bronchi epithelium and alveolar macrophages (AM). In reversible obstruction the activity of NO synthase was not changed in the epithelium but appeared high in resident cells of inflammation--AM and mast cells.

[Nitric-oxidergic mechanisms in the regulation of the bronchi and their significance in the pathogenesis of bronchial asthma]. / Nitrooksidergicheskie mekhanizmy reguliatsii bronkhov i ikh znachenie v patogeneze bronkhial'noi astmy.

AIM: Assessment of NO-synthase (NOS) activity in bronchial asthma (BA) basing on cytochemical identification and quantitation of NADPN-diaphorase. MATERIALS AND METHODS: Operative samples from 12 BA patients and biopsies from 8 patients free of bronchial inflammation or obstruction. Experimental data on control and BA rat males injected either with NOS agonist acetyl choline (AC) or beta-2-agonist fenoterol (F). RESULTS: A direct relationship was found between BA severity and activity of NADPN-diaphorase resultant from activation of inducible NOS (iNOS) mediating constrictive effect via different cellular and humoral mechanisms. AC treatment caused bronchial relaxation and severe constriction in control and BA rats, respectively, though NADPN-diaphorase activity was enhanced in both groups. Introduction of F brought about bronchial relaxation in both groups. However, there were some cases of constriction in the bronchi with impaired epithelium and high baseline iNOS activity. CONCLUSION: In intact bronchial epithelium, administration of cholino- and adrenoreceptors agonists induced bronchial myocyte relaxation due to activation of constitutive NOS. In impaired bronchial epithelium, AC stimulates iNOS induction provoking severe constriction of small bronchi.

[The monoaminergic innervation of the mediastinal pleura in human fetuses]. / Monoaminergicheskaia innervatsiia mediastinal'noi plevry plodov cheloveka.

Mediastinal pleura was studied in pregnancy second part abortive human fetuses using histological and histochemical technique. It was found to have a well-developed monoaminergic apparatus that includes adrenergic axons and mast cells. Electron microscope study confirmed monoaminergic and single peptidergic vesicles presence in axons. Luminescent method revealed that mast cells of nerve plexuses and blood vessels contain catecholamines and indolalkylamines. Monoaminergic axons and mast cells were shown to constitute a functionally integrative apparatus that regulates local hemodynamics and trophics.