Introduction: The search for and development of new highly active medications and their combinations of the appropriate direction of action remains an urgent problem due to the complications of ...diabetes mellitus, especially burdened with atherosclerosis, including skin and vascular lesions.
Materials and methods: The acute toxicity, histoprotective and dermatoprotective effects of mafusol, rexod, alprostadil and their combinations were studied in male rats with normoglycemia and alloxan diabetes complicated by exogenous hypercholesterolemia.
Results: The combination of mafusol with rexod is less toxic than mafusol. In arteriovenous insufficiency of the tail, ischemia of the skin fold and skin flap, mafusol (6.25, 12.5 and 25.0 mg/kg in terms of fumarate), rexod (0.01 and 0.02 mg/kg) and especially their combination (6.25 and 0.01 mg/kg) have significant histoprotective, dermatoprotective, hypoglycemic and lipid-lowering effects, both in normoglycemia and alloxan diabetes complicated by exogenous hypercholesterolemia. Alprostadil (10 mg/kg) and especially its combination with mafusol (6.25 mg/kg) have a dermatoprotective effect.
Discussion: Rexod reduces the acute toxicity of mafusol. The dermatoprotective effect of mafusol, rexod and, to a greater extent, their combination may be associated with increased microhemocirculation, antihypoxic properties and activation of energy processes in the skin, normalization of carbohydrate and lipid metabolism in alloxan diabetes, complicated by exogenous hypercholesterolemia, increased reserve capacity of the antioxidant system, and possibly with the ability of mafusol and rexod to reduce blood viscosity and improve rheological properties of the blood. The combination of mafusol with alprostadil increases the dermatoprotective activity of the latter.
Conclusion: Combinations of mafusol with rexod and alprostadil can be recommended for clinical study as dermatoprotective agents for treating traumatic injuries and diabetes mellitus complicated by atherosclerosis.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Women living with HIV-1 are at high risk of infection with human papillomavirus of high carcinogenic risk (HR HPVs). M. tuberculosis (TB) promotes HPV infection and increases the risk to develop ...HPV-associated cancer. Our knowledge of persisting HR HPVs genotypes, and of the factors promoting HR HPV infection in people living with HIV-1 with clinical TB manifestations is sparse. Here, we analyzed 58 women living with HIV-1 with clinical TB manifestations (WLWH with TB) followed up in specialized centers in Russia, a middle income country endemic for HIV-1 and TB, for the presence in cervical smears of DNA of twelve HR HPV genotypes. DNA encoding HPV16 E5, E6/E7 was sequenced. Sociodemographic data of patients was collected by questionnaire. All women were at C2-C3 stages of HIV-infection (by CDC). The majority were over 30 years old, had secondary education, were unemployed, had sexual partners, experienced 2–3 pregnancies and at least one abortion, and were smokers. The most prevalent was HPV16 detected in the cervical smears of 38% of study participants. Altogether 34.5% of study participants were positive for HR HPV types other than HPV16; however, but none of these types was seen in more than 7% of tested samples. Altogether, 20.7% of study participants were positive for several HR HPV types. Infections with HPVs other than HPV16 were common among WLWH with generalized TB receiving combined ART/TB-therapy, and associated with their ability to work, indirectly reflecting both their health and lifestyle. The overall prevalence of HR HPVs was associated with sexual activity of women reflected by the number of pregnancies, and of HPV 16, with young age; none was associated to CD4+-counts, route of HIV-infection, duration of life with HIV, forms of TB-infection, or duration of ART, characterizing the immune status. Thus, WLWH with TB—especially young—were predisposed to infection with HPV16, advancing it as a basis for a therapeutic HPV vaccine. Phylogenetic analysis of HPV16 E5, E6/E7 DNA revealed no common ancestry; sequences were similar to those of the European and American HPV16 strains, indicating that HPV vaccine for WLWH could be the same as HPV16 vaccines developed for the general population. Sociodemographic and health correlates of HR HPV prevalence in WLWH deserve further analysis to develop criteria/recommendations for prophylactic catch-up and therapeutic HPV vaccination of this highly susceptible and vulnerable population group.
We describe and analyze a model for time‐varying, localized reconnection in a current sheet with skewed magnetic field orientations on opposite sides. As in Petschek's description, disruption is ...initiated in a localized part of the current sheet known as the diffusion region, and the disturbances are subsequently propagated into the system at large through magnetohydrodynamic (MHD) waves. The MHD waves therefore play the dominant role in energy conversion, and collectively they form an outflow for plasma streaming toward the current sheet and a field reversal region joining magnetic field lines from opposite sides. We restrict the analysis to an incompressible plasma, in which case the Alfvén wave and the slow shock merge to form shocks bounding the field reversal or outflow region, and to the case of weak reconnection, which implies that the reconnection electric field is much smaller than the product of the characteristic values of the external field strength and Alfvén speed. It is then possible to perform a perturbation analysis of the MHD equations which govern the plasma and field behavior. The analysis can be formulated as a mixture of three well‐known problems. The problem of determining the appropriate combination of MHD waves corresponds to the Riemann problem, which also specifies the tangential field and flow components in the field reversal region. These results, it is important to note, are not sensitive to variations in the reconnection rate. Reconnection also acts as a source of surface waves, and their analysis determines the behavior of the perpendicular field and flow components and the shape of the shocks. Lastly, the field reversal region can be considered as a thin boundary layer in our treatment, and the external disturbances can therefore be solved in a way similar to the flow around a thin aerofoil. The model presented here can be applied to the Earth's magnetopause, where reconnection is considered to be the dominant process coupling the solar wind and the magnetosphere. In particular, the results can be used to interpret different manifestations of reconnection such as accelerated plasma flows along the magnetopause and flux transfer events.
Electroactive gels based on polyaniline (PANI) and polyacrylamide (PAAm) were prepared by polymerization of aniline in the solution of linear PAAm and subsequent precipitation of PANI/PAAm dispersion ...in acetone. It has been shown that the composite gels are capable to swelling in water acid and base solutions and dimethyl sulfoxide. It was established by mechanical tests and dynamic oscillatory measurements that the swollen gels demonstrate the elastic response like a covalently crosslinked network but with strong physical interactions between the chains. It is supposed that the observed mechanical elasticity is due to the certain number of elastically effective chemical bonds between PANI and PAAm chains. It is proved that the structure of the samples containing space continuous phase of PANI in the network of PAAm provides them mechanical integrity, good-quality mechanical response, swelling ability and electrical activity.
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•A new approach to form the electroconductive hydrogels is described.•Dispersion of two polymers can be chemically crosslinked by deposition in acetone.•The hydrogels demonstrate electroactivity and elastic deformation.
Introduction: Changes in the microcirculation (MC) system reflect abnormalities of physiological processes in the body and serve as a diagnostic and prognostic factor in a number of pathological ...conditions, including inflammatory lesions of periodontal tissues. Since in the pathogenesis of microcirculatory disorders an important role is played by the processes of free-radical oxidation, medications with antioxidant effects are of certain interest in terms of pharmacological correction of blood flow disorders in the periodontal complex. It was of interest to conduct a comparative assessment of the effects of Soderm®-Forte, Cytoflavin® and their combination on MC in the gingival mucosa in rats. The aim of the study was to identify whether Soderm®-Forte, Cytoflavin® and their combination can improve microcirculation in the gingival mucosa in rats. Materials and Methods: The study of MC in the gingival mucosa in rats was carried out by using the laser Doppler Flowmetry method. Four groups of rats with 10 animals in each were formed: Group 1 – control; Groups 2-4 – experimental groups, in which Soderm®-Forte gel was applied to the gingival mucosa of the lower incisors, Cytoflavin®(100 mg/kg intraperitoneally – i.p.) was injected, and gel Soderm®-Forte was applied to the gingival mucosa against the background of injecting Cytoflavin®, respectively. The indicators of blood flow were recorded 30 and 60 minutes later. Results and Discussion: Soderm®-Fote improved MC in the gingival mucosa by increasing the basal level of NO, the activity of precapillary sphincters and metarteriolas and decreasing the activity of adrenergic vasomotors. Cytoflavin®increased the activity of precapillary sphincters and metarteriolas, the extravascular components of MC, without changing perfusion of the gingival mucosa. The combination of Soderm®-Forte and Cytoflavin® improved MC to a lesser extent than only Soderm®-Forte, but to a bigger extend than Cytoflavin®. Conclusion: According to the capacity to increase blood flow in the gingival mucosa in rats, the tested substances and their combination can be arranged in the following way: Soderm®-Forte > Soderm®-Forte+Cytoflavin® > Cytoflavin®.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Introduction: The therapeutic effect of commercially available domestic and foreign drugs for the treatment of various skin injuries is far from optimal. These drugs have no universal effects, but ...cause pronounced side reactions. There is a clear demand for development of innovative wound-healing drugs with antimicrobial properties, which increase the natural protective function of the skin. Pharmaceutical compounds with zinc nanoparticles have been increasingly recognized as a promising therapeutic direction. These drugs can easily penetrate into damaged tissues and stimulate metabolic processes. Zinc complexes with imidazole derivatives are of a particular interest. Imidazole acts as a structural fragment of many natural physiologically active compounds, thus providing targeted delivery of this essential trace element into the wound for inclusion in the multicascade mechanism of wound healing. The aim of the study: to provide experimental evidence for effects of recently developed zinc complexes with N-alkenylimidazole as wound healing agents.
Materials and Methods: Wound-healing effects of six 1% gels containing distinct N-alkenylimidazole zinc complexe derivatives based on the Na-carboxymethylcellulose (Na-CMC) were comparatively studied in 128 outbred white rats of both genders. The Na-CMC-based Zinc Sulfate 1% gel, Methyluracil and Solcoseryl served as reference drugs. After performing the local tolerance study of zinc complexes, linear and planar sterile wounds of comparable size were inflicted in anesthetized animals. The degree of healing was evaluated on the day 8 and day 28 after the treatment start by wound sizes and histological examination of inflammatory response, epithelization, granulation tissue, angiogenesis, and necrosis. The skin microcirculation system was evaluated using the laser Doppler Flowmetry (LDF), whereby the blood flow indicators were recorded 30 and 60 minutes after intraperitoneal administration of the trial compound. The antimicrobial activity of the zinc compounds was determined in vitro by means of their minimum inhibitory concentration suppressing the bacteria and fungi growth using the double serial dilution method in liquid culture media. The statistical data processing was performed using the Statistica 12 software package.
Results and Discussion: In the linear wound model, all animals treated with either of six experimental zinc compounds showed almost complete reduction in wound size (92-100%, p<0.05) on the day 8, significantly exceeding the wound healing in the control animals (reduction by 67-88 %, p<0.05) and effects of the reference drugs (reduction by 83-86%, p<0.05). In the planar wound model, the most significant wound healing effect was reached by using the gel containing N-isopropenylimidazole zinc diacetate (encoded as Pilim-1). The respective histological examination showed signs of complete epithelialization, absence of destructive changes in the epidermis, restoration of skin appendages and presence of mature granulation tissue. Intraperitoneal Pilim-1 administration at a dose of 20 mg/kg improved microcirculation in the rat skin, as judged by significant effects on perfusion and the amplitudes of the isolated rhythms of the LDF-gram. In addition, Pilim-1 exerted a moderate bacteriostatic and fungistatic activity, which was 2 times greater than the antimicrobial activity of Metronidazole.
Conclusion: Topical application of gels containing 1% N-alkenylimidazole zinc complex derivatives accelerates the healing of uninfected linear and planar wounds in comparison with the established reference drugs. The Pilim-1 zinc compound exhibited the most pronounced therapeutic effect. The observed in vitro antimicrobial action of Pilim-1 is of further interest for potential implications in treatment of infected skin wounds. The regenerative effect of this substance opens prospects for development of new drugs with improved wound healing properties.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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•Polyelectrolyte copolymers conformations in aqueous and DMSO solutions were studied.•Hydrodynamic, optical and relaxation methods were used.•Polyelectrolyte effects in non-salt ...aqueous solutions are much weaker than in DMSO.•Formation of hydrophobic shielding of the charged groups N+ in water is observed.
Copolymers of 2-deoxy-2-methacrylamido-d-glucose with N,N-dimethyl aminoethyl methacrylate were synthesized. Triple copolymers containing N,N-dimethyl-N-dodecyl-N-methacryloyl oxyethyl ammonium iodide units were obtained by alkylation of tertiary amino groups. These copolymers were studied by hydrodynamic and optical methods in various solvents. It was revealed that polyelectrolyte effect in salt-free aqueous solutions is far less pronounced than that in dimethyl sulfoxide (DMSO) solutions. The values of equilibrium rigidity A of alkylated macromolecules in salt-free solutions obtained from viscosimetry data is equal to ∼ (150±50)Å in aqueous solutions and to (750±250)Å in DMSO solutions. Change in intrinsic anisotropy of alkylated macromolecules in DMSO solutions demonstrated that in the concentration range from 2.5 to 0.5g/dL, electrostatic interactions lead to isotropic increase in dimensions of macromolecular coils. In the concentration range from 0.5 to 0.02g/dL, increase in equilibrium rigidity by almost a factor of 4 is observed. It was established that in water-salt solutions of copolymers which contain more than 10mol.% of dodecyl groups, compact structure is formed; in this structure, intramolecular fragments of polymer chain are hindered. In dimethylsulfoxide solution, in the presence of a salt, the value of intrinsic viscosity η increases by more than a factor of 6–8 as compared to that in water-salt solutions. The observed differences in conformation, optical and relaxation properties of the triple copolymers in aqueous and DMSO solutions are related to hydrophobic interactions between alkyl substituents. These interactions lead to the formation of hydrophobic “core” and shielding the charged quaternary ammonium groups (N+) in aqua solutions.
Introduction. Development of cell therapy for Parkinson's disease (PD) requires protocols based on transplantation of neurons derived from human induced pluripotent stem cells (hiPSCs) into the ...damaged area of the brain. Objective: to characterize neurons transplanted into a rat brain and evaluate neural transplantation efficacy using a PD animal model. Materials and methods. Neurons derived from hiPSCs (IPSRG4S line) were transplanted into the striatum of rats after intranigral injection of 6-hydroxydopamine (6-OHDA). Immunostaining was performed to identify expression of glial and neuronal markers in the transplanted cells within 224 weeks posttransplant. Results. 4 weeks posttransplant we observed increased expression of mature neuron markers, decreased expression of neural progenitor markers, and primary pro-inflammatory response of glial cells in the graft. Differentiation and maturation of neuronal cells in the graft lasted over 3 months. At 3 and 6 months we detected 2 graft zones: one mainly contained the transplanted neurons and the other human astrocytes. We detected human neurites in the corpus callosum and surrounding striatal tissue and large human tyrosine hydroxylase-expressing neurons in the graft. Conclusion. With graft's morphological characteristics identified at different periods we can better understand pathophysiology and temporal patterns of new dopaminergic neurons integration and striatal reinnervation in a rat PD model in the long-term postoperative period.
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