Репозиторий Университета

© 2018 Izdatel'stvo Meditsina. All rights reserved. The purpose of the study was to investigate gender features of abnormalities of blood serum lipid composition and their relationship with clinical and functional manifestations in patients with chronic kidney disease (CKD). The study covered patients with CKD at pre-dialysis stage of disease, aged 17-71 years (average age 37.3±13.0 years). All patients underwent complex clinical and laboratory examination. Depending on gender, the sample (n = 417) was divided into 2 groups: group I - males (n = 277) and group II-females (n = 140). Blood sampling was implemented using venipuncture of ulnar vein after 12-14 hours of fasting in morning time. The lipid analysis of blood serum was performed using the auto-analyzer "Respons 920" (Germany), including detection of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG). The atherogenic index (AI) was calculated according formula: AI = (TC - HDL-C)/HDL-C. At analysis of the results of lipidogram, the levels of TC (hypercholesterolemia), LDL-C (hyper-beta-cholesterolemia) and TG (hypertriglyceridemia) were considered as increased when their values were ≥5.0 mmol/L, ≥3.0 mmol/L and > 1.7 mmol/L respectively. The level of HDL cholesterol (hypo-alpha-cholesterolemia) was considered as decreased when its concentration was ≤1.0 mmol/L in males and ≤1.2 mmol/L in females. In the group of male patients, hypo-alpha-cholesterolemia was detected in 135 patients (48.7%), hypertriglyceridemia - in 162 (58.4%), and average value of atherogenic index was significantly higher - 3.49 (2.43-5.08) as compared with 3.12 (2.12-3.74) in female patients (p=0.001). The laboratory signs of anemia were significantly more frequent in group of females - 53 (37.8%) as compared with 63 (22.7%) than in males (p = 0.001). In males, average values of HDL cholesterol and total serum protein were significantly lower (1.07 ± 0.44 mmol/L vs. 1.23 ± 0.42, p = 0.000 and 53.3 ± 14.6 g/L vs. 57.4 ± 11.9 g/L. p = 0.007, respectively. The levels of TG - 1.92 (1.23-2.74) mmol/L vs. 1.85 (1.04-2.37);p = 0.034], sodium (140.3 ± 6.20 mmol/L vs. 138.3 ± 6.01 mmol/L, p = 0.010) and uric acid in blood serum were significantly higher (0.38 ± 0,09 mmol/L vs. 0.34 ± 0.01 mmol/L, p = 0.003) as compared with females. In the group II (females), a noticeable slowing of the glomerular filtration rate (GFR) - 68,4 (43,6-98,1) ml/min vs. 87,6 (55,0-117,6) ml/min; (p = 0.001) was detected as compared with group I (males). Among male patients, a reliably significant positive relationship was established between TC and BMI, level of diastolic blood pressure and proteinuria; LDL cholesterol level and proteinuria; concentration of TG - and BMI, level of diastolic blood pressure and level of proteinuria. No correlation was established between the concentration of HDL-cholesterol and aforementioned laboratory markers of CKD. In contrast with males, in females, TC demonstrated an inverse relationship with the concentration of Hb, values of GFR and proteinuria, and level of HDL cholesterol - with indices of BMI, thrombocytes and uric acid of blood serum. In females a positive relationship was established between LDL cholesterol and level of diastolic blood pressure, GFR and daily proteinuria, and also between concentration of serum TG and volume of daily proteinuria and BMI. In general group, a reliable positive relationship was detected between TC and BMI and proteinuria, between LDL-C level and proteinuria, and between TG concentration and BMI, level of diastolic blood pressure, sodium content and proteinuria. The negative relationship was established between concentration of HDL cholesterol and BMI and uric acid in blood plasma, and TG level with Hb concentration. In male patients with CKD at pre-dialysis stage of disease, decreasing of level of HDL cholesterol was established as an increased concentration of TG and increasing atherogenic index. The content of triglyceride of blood serum is closely related to body mass index, level of diastolic blood pressure and proteinuria. In females, slowing of glomerular filtration rate is accompanied by development of anemia and atherogenic dyslipidemia.

© 2018 Bentham Science Publishers. Patients with Parkinson’s disease (PD) are looking forward to new therapeutic strategies that may gradually decelerate the rate of neurodegenerative decline, associated with mobility restrictions and related morbidity. Its continuous neurodegenerative process, exacerbated by genetic mutations or environmental toxins, involves a progressive reduction in the dopamine neurotransmission levels, synaptic uptake density, oxidative glucose intake, deficient striatal lactate accumulation and chronic inflammation. Over the last decade, novel bioproducts have received considerable interest due to their unique potential of unifying nutritional, safety and therapeutic natural effects. Some nutraceuticals play a crucial role in the control of the signaling transduction pathways in neurotransmission and inflammation affected in PD, and some natural compounds can beneficially interact with each one of these biological mechanisms to slow down disease progression. Atremorine, a novel plant-derived nutraceutical, probably with a neuroprotective effect in the dopaminergic neurons of the substantia nigra (pars compacta), is a prototype of this new category of bioproducts with potential effects in PD. The major focus of this review will be on the current knowledge and biomedical investigation strategies through a plant-derived neuroprotective approach to improve life quality in PD patients, being of paramount importance for health providers, caregivers and the patients themselves.

© The Author(s) 2018. Objective: Chondrospheres represent a variant of tissue spheroids biofabricated from chondrocytes. They are already being used in clinical trials for cartilage repair; however, their biomechanical properties have not been systematically investigated yet. The aim of our study was to characterize chondrospheres in long-term in vitro culture conditions for morphometric changes, biomechanical integrity, and their fusion and spreading kinetics. Results: It has been demonstrated that the increase in chondrospheres secant modulus of elasticity is strongly associated with the synthesis and accumulation of extracellular matrix. Additionally, significant interplay has been found between biomechanical properties of tissue spheroids and their fusion kinetics in contrast to their spreading kinetics. Conclusions: Extracellular matrix is one of the main structural determinants of chondrospheres biomechanical properties during chondrogenic maturation in vitro. The estimation of tissue spheroids’ physical behavior in vitro prior to operative treatment can be used to predict and potentially control fusogenic self-assembly process after implantation in vivo.

© 2018 SPIE.  We have investigated the influence of indium content (x) increase on spectral characteristics of In x Ga 1-x As photoconductor. To avoid the mismatch between crystalline parameters of In x Ga 1-x As and GaAs wafer we proposed to incorporate a step-graded metamorphic buffer layer. We showed that x increase strongly enhances THz emission and broadens THz spectrum of In x Ga 1-x As. Since no polarity rehearsal of the THz waveform occurs and electron diffusion mobility increases up to 90% with x increase we attribute the increase of THz intensity to photo-Dember effect contribution. The maximum efficiency of optical-to-THz conversion was obtained for In 0.72 Ga 0.28 As at optical fluence ∼0.01 μJ=cm 2 . The fabricated photoconductors can be used as promising photo-Dember or lateral photo-Dember THz emitters in pulsed THz spectroscopy and imaging, in particular, operating with long wave optical pump.

© 2018 Media Sphera Publishing Group.All right reserved. Purpose: to study clinical-functional features of remodeling of carotid arteries and its relation to restructuring of the left ventricle (LV) in patients with chronic glomerulonephritis at pre-dialysis stage. Materials and methods. We examined 269 patients (189 men, 80 women) with chronic glomerulonephritis (CGN) aged 17-71 years, at pre-dialysis stages of the disease. We analyzed biochemical parameters of peripheral blood with the determination of daily proteinuria and glomerular filtration rate (GFR). For identification of structural changes of carotid arteries (CA) and LV we used Doppler ultrasound and echocardiography. Results. Atherosclerotic changes of CA were found in 79 patients (29.3 %). Four patients (1.4 %) had history of acute disturbance of cerebral circulation. Concentric type of left ventricular hypertrophy (LVH) was significantly more prevalent among patients with CA remodeling compared with those without (37.84 vs. 18.75 %; p=0.006). Eccentric variant of LVH was significantly more prevalent among patients without atherosclerotic lesions in CA compared with those with CA remodeling (81.25 % vs. 62.16 %; p=0.001). Increased CA intima media thickness positively correlated with body mass index (r=0.273; p=0.014) and negatively-with GFR (r=-0.222; p=0.048). Statistically significant relationships were also found between the presence of carotid atherosclerosis and structural rearrangements of the heart. Conclusion. We demonstrated a clear relationship between GFR, restructuring of CA and concentric type of change of LV geometry, regardless of the presence of traditional risk factors.

© 2018, Bionika Media Ltd. All rights reserved. The implementation of the INTERGROWTH-21st fetal growth and newborn size for gestation age standards into clinical practice in Russia were discussed and debated. The INTERGROWTH-21st Project was implemented in more than eight countries from 2009 to 2018. All study protocols and primary findings are available online (intergrowth21. org). Briefly, eight diverse urban populations living in demarcated geographical areas were selected where: environments were free from major known pollutants; altitude was less than 1600 m; most women accessed antenatal and delivery care in institutions; mean birth weight was greater than 3100 g; rates of low birth weight (< 2500 g) were less than 10%, and perinatal mortality was less than 20 per 1000 births. The INTERGROWTH-21st study comes as a high-quality response to the common dilemma of lack of standardization in fetal growth assessment. Its use should be encouraged among Russian specialists in maternal-fetal medicine, obstetricians and radiologists.

© 2018 Bentham Science Publishers. Background: It was previously shown that inactivation of gamma-synuclein which is a small soluble neuronal protein affects psycho-emotional status and cognitive abilities in knock-out mice. Objective: Determine the role of gamma-synuclein inactivation on memory performance in aging animals. Method: We used the passive avoidance test and acute amphetamine administration in aging gammasynuclein knock-out mice. Results: As a result, we found moderate aging-unlinked deficit of dopaminergic neurotransmitter system of gamma-synuclein knock-out mice. At the same time, the evidence of progressive synaptic vesicle trafficking machinery impairment was obtained. Conclusion: Therefore most likely these dysfunctions are associated with a reduction in the highefficient learning performance in tests that require intact working memory.

© 2018 Journal of Pathology Informatics. Background: Interest has grown into the use of multidetector computed tomography (CT) and magnetic resonance imaging as an adjunct or alternative to the invasive autopsy. We sought to investigate these possibilities in postmortem CT scan using an innovative virtual autopsy approach. Methods: Twenty-five postmortem cases were scanned with the Philips Brilliance CT-64 and then underwent traditional autopsy. The images were interpreted by two blinded forensic pathologists assisted by a radiologist with the INFOPSY® Digital Autopsy Software System which provides three-dimensional images in Digital Imaging and Communications in Medicine format. Diagnostic validity of virtual autopsy (accuracy rate, sensitivity, specificity, and predictive values) and concordance between the two forensic pathologists (kappa intraobserver coefficients) were determined. Results: The causes of death at traditional autopsies were hemorrhage due to traumatic injuries (n = 8), respiratory failure (5), asphyxia due to drowning (4), asphyxia due to hanging or strangulation (2), heart failure (2), nontraumatic hemorrhage (1), and severe burns (1). In two cases, the cause of death could not be ascertained. In 15/23 (65%) cases, the cause of death diagnosed after virtual autopsy matched the diagnosis reported after traditional autopsy. In 8/23 cases (35%), traditional autopsy was necessary to establish the cause of death. Digital data provided relevant information for inferring both cause and manner of death in nine traumatic cases. The validity of virtual autopsy as a diagnostic tool was higher for traumatic deaths than other causes of death (accuracy 84%, sensitivity 82%, and specificity 86%). The concordance between the two forensic pathologists was almost perfect (>0.80). Conclusions: Our experience supports the use of virtual autopsy in postmortem investigations as an alternative diagnostic practice and does suggest a potential role as a screening test among traumatic deaths.

© 2018, Romanian Society for Pharmaceutical Sciences. All rights reserved. It has been reported that hepatitis B virus (HBV) is 10 times more infectious than hepatitis C virus (HCV) and 100 times more infectious than human immunodeficiency virus (HIV). Although there are two approved and very effective antivirals that quickly reduce the viral load (HBV DNA) and the risk of liver damage, vaccination prevention still represents the ideal intervention to reduce the spread of the disease and to protect public health. A literature review of the studies published in English on hepatitis B vaccination coverage of healthcare professionals in Greece during the 2006-2016 period was conducted. The literature review highlighted 12 studies. Healthcare professionals’ vaccine rate ranged between 55% and 88%. Doctors had the higher vaccination rate among healthcare professionals and registered nurses compared to nurses’ aides (p < 0.05). Higher educational level, knowledge of hepatitis B and a positive attitude toward vaccines (p < 0.05) revealed as the variables that affect positively healthcare professionals to be vaccinated. Mandatory vaccination of professionals within a health policy with regard to vaccination, as well as the implementation of information programs for them, are two important interventions that may increase vaccination coverage rates.

© 2018 Media Sphera Publishing Group. All rights reserved. Purpose of the study. To provide demographic, clinical, laboratory, ultrasound, radiological, morphological/ immunomorphological phenotype of IgG4-related ophthalmic diseases, which allowsmaking a differential diagnosis with granulomatous, autoimmune, inflammatory, endocrine and hematologic diseases affecting the eye and orbits. Materials and methods. From 2004 to 2016 108 (78.2%) of the 138 patients were diagnosed with non-tumoral lesions of eye and orbits. In 48 patients (35%) at admission and 5 patients in the follow were diagnosed IgG4-related ophthalmic disease. In the analysis of 82 (f-44, m- 38) patients with IgG4-related disease, localization of lesions in orbit observed in 53 (f-36, m-17) and it was the most frequent involvement in patients with IgG4-related disease (64.5%). Only 7 patients had isolated IgG4-related ophthalmic disease, whereas 46 patients (87%) had involvement of 2-7 locations, as a manifestation of IgG4-related systemic disease.During the examination, the average age of patients with IgG4-related ophthalmic disease was 47.5 years (19-73 years). Median time to diagnosis was 52.8 months before 2004 and 36 months 2004-2016. Results. We noted the predominance of females in the ratio 2: 1 inthe group of patients with IgG4-related ophthalmic disease. Edema of the eyelids, nasal congestion (55-60%), tumor-like formations of the upper eyelids and increased lacrimation prevailed at the onset of the disease, whereas such functional impairment like limited mobility and pain in eyeballs, exophthalmos, ptosis and diplopia appeared later at 15-38% with a loss visual acuity in one case. Bilateral lesion (86%), mainly affecting the lacrimal glands (93.5%), infiltration of the extraocular muscles (83.5%) and retrobulbar tissue with a thickening of the optic nerve in one third of patients were the main localizations IgG4-related ophthalmic disease. Clinical symptoms were accompanied by the appearance of moderate inflammatory activity (38%), increased levels IgG (44%), IgG4(88%) and IgE (61%). Indicators of autoimmune disorders observed in 6-22% of patients, most often in patients with simultaneous involvement of the salivary glands. Significant lymphoplasmacytic infiltration (94%) with a ratio of plasma cells (IgG4/IgG) secreting IgG4> 40% (90%) with fibrosis formation (94%) and follicle formation (71%) with a moderate amount of eosinophils (34%) were the major morphological / immunomorphological manifestations of IgG4-related ophthalmic disease. Signs of vasculitis and obliterative phlebitis were found in a small amount of patients. Conclusion. Determination of elevated levels of IgG-4 / IgE in patients with edema, pseudotumor of the eyelid, sinusitis and increase of the palpebral lobe of the lacrimal gland suggests the presence of IgG4-related ophthalmic disease. Minimally invasive incisional biopsy of lacrimal glands and salivary glands followed by morphological / immunomorphological research is needed for the correct diagnosis. Diagnostic orbitotomy in ophthalmic hospitals in such cases is inexpedient, since it leads to the development of dry eye. Massive lymphoplasmacytic infiltration with IgG4 / IgG ratio more than 40%, advanced fibrosis in biopsiesof the orbits tissue or salivary glands when combined lesions are required for the making the diagnosis of IgG4-related ophthalmic disease.

© 2018 Media Sphera Publishing Group. All rights reserved. The analysis of publications devoted to the Russian Consensus on the Diagnostic and Treatment of Autoimmune Hepatitis (AIH), which was considered at the 43rd annual Scientific Session of the CNIIG From Traditions to Innovation (March 4, 2017) is carried out. The presence of clear algorithms and recommendations for the diagnosis and treatment of AIH significantly help the doctor in real clinical practice, but do not exclude a personified approach to the patient.

© 2018 Izdatel'stvo Meditsina. All rights reserved. We have studied the adaptogenic properties of Kardecaim phytopreparation based on dry extracts derived from Inula helenium L., Zingiber officinale Roscoe, Elletaria cardamomum (L.) Maton., and Caragaha spinose (L.) Wall, ex Homem, which contain phenolic compounds and terpenoids. A course of preventive administration of Kardecaim to white rats in a dose of 100 mg/kg for 7 days before the induction of acute emotional stress produced stress-protective effect by preventing the development of catabolic signs of Selye's triad in animal inner organs, including the thymus involution (40% lower than in control); degree of hemorrhagic and ulcerative defects in the stomach mucosa (5 times less than reference gastroprotector effect), and somewhat less pronounced effect on the stress-induced hypertrophy of adrenal glands, yet comparable to the effect of reference preparation (eleutherococcus extract). It was shown that the increase in the resistance to stress under the action of Kardecaim was due to the activation of synthesis of heat shock proteins (Hsp). The Hsp-70 content in the thymus of white rats undergoing emotional stress was 56% higher than in the control. The introduction of Kardecaim to intact animals had no effect on the basal level of Hsp-70. It was established that the expression of Hsp under the drug action was not connected with NO system, since the administration of Kardecaim on the background of stress impact was followed by a decrease in the NO metabolite yield.

© 2018 Medical Education. All rights reserved. The aim of this study was pharmacoeconomic evaluation of treatment with reslizumab compared to omalizumab in severe eosinophilic asthma. Methods. The study was based on indirect comparison between omalizumab and reslizumab in patients with severe asthma using published data. Costs of treatment with omalizumab, reslizumab, combinations of inhaled corticosteroids and long-acting beta-agonists (ICS/LABA), outpatient treatment, treatment of exacerbations and adverse events were also compared. Сost-effectiveness analysis and budget impact analysis were used. Results. According to results of cost-effectiveness analysis, therapy with reslizumab dominated over therapy with omalizumab in patients with severe asthma in term of exacerbation rate requiring treatment with systemic steroids. According to results of budget impact analysis, switching of 100 patients from omalizumab to reslizumab could save RUB 51.99 million per year that corresponds to 36.6% reduction in general direct costs for treatment of severe asthma. Conclusion. The results of this study demonstrated economic advantage of reslizumab over omalizumab in patients with severe eosinophilic asthma.

© ISUCT Publishing. The macrolide antibiotic oligomycin A (1), produced by actinomycetes Streptomyces,[1] is a well-known inhibitor of FO F1 ATP-synthase, which is regarded as a molecular target for new drugs in the treatment of tumors and infections. Oligomycin A (1) exhibits antifungal and cytotoxic activities, but Gram-negative and Gram-positive bacteria are resistant to 1 except actinobacteria.[2] In micromolar concentrations, oligomycin binds to FO c-subunit, blocks proton translocation and disrupts bioenergetic metabolism.[3] However, a clinical application of oligomycin A is limited by high cytotoxicity for mammalian cells. The searches of new derivatives of oligomycin A with more selective pharmacological activity and low toxicity for normal cells are of great interest. New semi-synthetic oligomycins also would be valuable for SAR studies and depicting the mechanism of FO F1 ATP-synthase inhibition. The complicity of oligomycin structure and its lability in basic conditions[4] significantly impede modifications and an applicability of this antibiotic. However, previously we have managed this challenge and developed some modifications of the side chain and chemical transformations of the lactone moiety of 1.[4-9] In this paper, throughout our research we describe synthesis and biological investigation of novel oligomycin A derivatives, namely 16,33-O,O-diformyl-16,17-dihydro-16(S),17(R)-dihydroxyoligomycin A (3) and 33-O-formyloligomycin A (4). First, we have studied Prilezhaev epoxidation of double bonds in core structure of oligomycin A. It was found that treatment 1 with m-CPBA at -17oC in dichloromethane led to 16,17-epoxyoligomycin (2). Unfortunately, all attempts for isolation of product 2 were failed due to its instability on silica gel, and, consequently, we were unable to determine the structure of 2 by direct physicochemical and spectral methods. The presence of epoxide at C16-C19 positions was confirmed by tandem mass spectrometry, but its exact localization was still elusive. We assumed that it might be at C16-C17 positions, because C18-C19 double bond is hindered by ethyl side chain at C20. In order to obtain a stable oligomycin A derivative we performed an epoxide ring-opening reaction by the treatment of the crude epoxyoligomycin 2 with formic acid. This acid-catalyzed opening of the epoxide accompanied with acylation of 33-OH group and led to16,33-O,O-diformyl-16,17-dihydro-16(S),17(R)-dihydroxyoligomycin A (3). The structure of 3 was confirmed by NMR spectroscopy and high resolution mass spectrometry. Configurations at C16 and C17 positions were determined by detecting correlations in1H-1H ROESY spectrum. Obtained results allowed to confirm an assumption about localization of the epoxide ring and establish the structure of 2 as (R,R)-16,17-epoxyoligomycin A, since inversion of configuration has taken place at the attacked carbon atom.[23] It is known that O-acyl derivatives of pharmacologically active agents are widely used as prodrugs.[24] Acylation of 2-hydroxypropyl side chain in 2 prompts us to examine the reaction of oligomycin A (1) with formic acid. Thus, stirring the solution of 1 in HCOOH (98 %) for 2 h at room temperature afforded 33-O-formyloligomycin A (4) in a good yield. The structure of 4 was confirmed by NMR-spectroscopy and high resolution mass spectrometry. Also, biological data of new derivatives were evaluated. The modification of C16-C17 positions of the macrocycle as well as acylation of C33 hydroxyl group led to the decreasing of activity against S. fradiae, Candida spp. and filamentous fungi. Obtained results were in agreement with docking studies. A simulation of an interaction of 1, 3 and 4 with the FO subunit of the ATP-synthase (PDB: 4f4s) revealed that these modifications led to a significant change in the solvation energy and an increase in the conformational capacity of the ligands during the binding with the target. This resulted in decrease of the binding affinity for derivatives 2, 3. However, 33-O-formyloligomycin A (4) showed similar antiproliferative activity against tumor cell lines (HCT-116 colon carcinoma, К562 myeloid leukemia cell lines and MDR K562/4 subline) as for 1, but less cytotoxic for non-malignant human cells.

© 2018, Nizhny Novgorod State Medical Academy. All rights reserved. The aim of the study was to investigate the morphological and metabolic features of primary hippocampal cultures formation on hydrogel films and scaffolds based on hyaluronic acid glycidyl methacrylate. Materials and Methods. Hydrogel films and scaffolds with certain architectonics were developed by micromolding technique on the basis of hyaluronic acid glycidyl methacrylate. Primary hippocampal cells obtained from C57BL/6 mouse embryos (E18) were cultured on the created constructs more than 14 days. Testing cell viability, morphometric assessment, and analysis of spontaneous calcium activity of primary hippocampal cultures were performed on day 14 of cultures development in vitro. Results. This study revealed that the material for the development of scaffolds with given architectonics is non-toxic for the nervous system cells. Dissociated hippocampal cells were actively attached to the scaffold surface and were assembled into cell conglomerates, which exhibited spontaneous calcium activity. Conclusion. Scaffolds designed on the basis of hyaluronic acid glycidyl methacrylate have a high biocompatibility with the nervous system cells. Architectonics and adhesive properties of scaffold contribute to the formation of functionally active cell conglomerates.

© 2018, Nizhny Novgorod State Medical Academy. All rights reserved. The aim of this study was to modify the chemical structure and to optimize the composition of the fibrin gel for effective cell encapsulation. Materials and Methods. We prepared PEGylated fibrin gels using different fibrinogen concentrations (25–50 mg/ml) and PEG-fibrinogen molar ratio 10:1 and 5:1 and characterized them via Fourier transform infrared spectroscopy and differential scanning calorimetry. Within the gels, we encapsulated primary culture of fibroblasts and analyzed using light and laser confocal microscopy. Results. PEGylation of fibrinogen allowed us to achieve the gel transparency and preserve its biocompatibility. We revealed that the gel prepared from PEGylated 5:1 fibrinogen (25 mg/ml) provided the most favorable microenvironment for spreading, growth, and proliferation of fibroblasts. This PEG-fibrin gel can be used for encapsulation of different cell types that is essential for various approaches in tissue engineering and diagnostic systems.

© 2018, Nizhny Novgorod State Medical Academy. All rights reserved. The aim of the study was to demonstrate a good diagnostic potential of atomic force microscopy (AFM) in tracking morphological changes in the extracellular matrix (ECM) of connective tissue due to pathological processes. Here we summarize our experience in AFM application in a number of biomedical studies on the connective tissue disease, both for the research and clinical purposes. Materials and Methods. Depending on the project application (experimental or clinical), the tissue specimens were harvested either from animals, or from patients in the course of their surgical treatment, or post mortem. AFM images of fixed tissue slices on glass slides were acquired with a Solver P47 AFM instrument (NT-MDT, Russia), in the semi-contact mode. For mechanical properties mapping, the images were acquired on air in the PeakForce Quantitative Nanomechanical Mapping mode (PeakForce QNM®), using a MultiMode 8 atomic force microscope (Bruker, USA). The regions of interest for scanning were selected in accordance with the histological assignments for the same sample, based on the view of a sample in the built-in optical microscope of the AFM instrument setup. To quantify the changes in the ECM morphology visualized by AFM imaging, we applied flicker-noise spectroscopy parameterization. Results. AFM has been shown to reveal visible deviations from the normal morphology of the ECM in diseased tissues. We found that AFM and related techniques are capable of tracking disease-related changes at different levels of collagen organization in the ECM. At the microscale, AFM may detect loosening and disorganization of collagen fibers (e.g., in a dysplastic process), or the opposite process of their packing into tight parallel bundles in a fibrotic process. AFM may also monitor the ratio between collagen and non-fibrous material of the ECM, for example, in inflammatory and neoplastic processes. At the level of collagen fibrils, AFM may reveal early signs of the matrix destruction and remodeling not visible at the microscopic level. The flicker-noise spectroscopy parameters provide quantification of the morphological changes visualized by AFM. The PeakForce QNM® and nanoindentation studies give a further insight into the state of ECM via tracking changes in the local mechanical and adhesive properties. All our AFM studies appeared in a good agreement with the histological findings and generally had a superior sensitivity to pathology-related ECM rearrangements. Conclusion. AFM may serve as a valuable complementary diagnostic tool for tracking pathological changes in the connective tissue.

© Authors. The present study was conducted in Iran and aimed to analyze the relationships among technology acquisition & exploitation, organizational innovation, and organizational performance. We selected 80 knowledge-intensive organizations as statistical population of the study. Executive managers, senior managers, operational managers, and R & D managers of the companies were considered as appropriate respondents for this study. After the distribution of 320 questionnaires among the respondents, 280 usable questionnaires were gathered. The analysis was done utilizing Structural Equation Modeling (SEM) methodology by LISREL software. The factors analysis and the findings show that technology acquisition & exploitation has a significant positive influence on both organizational innovation and organizational performance. Further, organizational innovation has a significant positive impact on organizational performance.

© Authors. The present study was conducted in Semnan Science and Technology Park and aimed to analyze the relationship among intellectual property rights, open innovation, and organizational performance of 30 New Technology Based Firms (NTBFs). Senior managers, middle managers, and business owners were considered as appropriate respondents for study. A total of 140 questionnaires were distributed among the respondents, and 126 filled questionnaires were returned. The research method used in this study is descriptive-correlation and the analysis was carried out utilizing Structural Equation Modeling. The factors analysis and the findings show that intellectual property rights have a significant positive relationship with open innovation. Further, open innovation has a significant positive relationship with organizational performance. Moreover, no significant relationship between intellectual property rights and organizational performance was established. But, intellectual property rights affect organizational performance positively, through open innovation acting as a mediator.

© 2017 Elsevier Inc. A growing body of evidence suggests that peptides may possess analgesic effects without tolerance development. The synthetic tetrapeptide Tyr-D-Arg-Phe-Gly-NH2 was modified with the inclusion of a (D-Arg)8 vector to prevent the action of endopeptidase and to increase the duration of the analgesic action of the tetrapeptide when administered orally. The aim of this study was to estimate the analgesic efficacy of the tetrapeptide with (D-Arg)8 (tridecapeptide, TDP) in experimental models of acute and chronic pain. The analgesic effects of TDP were estimated using a model of acute visceral pain in mice (writhing test) and a model of chronic neuropathic pain (chronic constriction injury (CCI) of the sciatic nerve) in rats. The intravenous administration of morphine (0.32–1 mg/kg) and TDP (0.32–1.8 mg/kg) produced significant dose-related antinociceptive effects in the writhing test. The potency of TDP after i.g. administration was lower than that after i.v. administration but comparable with that of i.g. morphine. In the CCI model, TDP (0.1, 1 and 10 mg/kg, i.g.) induced marked analgesia with repeated administration without any signs of tolerance. The single administration of TDP after morphine treatment (7 days) produced a significant analgesic effect in morphine-tolerant rats, indicating the absence of cross-tolerance between these two drugs. The combined administration of TDP and morphine resulted in the reduction of analgesic tolerance to morphine. The absence of cross-tolerance to morphine and the ability to prevent morphine tolerance allows this compound to be a prospective candidate for chronic pain therapy. In order to find the target receptors for TDP, a docking study was performed. It was found that the molecule can bind to the NMDA receptor using electrostatic, hydrogen bonding and hydrophobic interactions.