Chemical modification of chitosan for developing of new hemostatic materials: A review.

Uncontrolled bleeding that occurs during surgery, trauma, and in combat conditions is critical and require immediate action. Chitosan is a polysaccharide, obtained from natural sources with unique biological properties. It is often used as basis for local hemostatic agents (LHA). We summarized the data on hemostatic properties of chitosan, commercially available chitosan-based products with focus in the field of chemical modification of chitosan. Various approaches are used to enhance hemostatic activity of chitosan-based materials. The approach with chemical modification of chitosan allows changing the properties of the polymer in order to obtain an active macromolecule that contributes to hemostasis. Ongoing research on the mechanism of interaction with blood components in the case of different chitosan derivatives will make it possible to identify promising directions for chemical modification to obtain an effective LHA.

[Possibilities of differential diagnosis of chronic diseases of the nasal cavity after surgical treatment and topical antibiotic therapy]. / Vozmozhnosti differentsial'noi diagnostiki khronicheskikh zabolevanii polosti nosa posle khirurgicheskogo lecheniya i topicheskoi antibakterial'noi terapii.

OBJECTIVE: The study was performed to assess the endoscopic state of the nasal mucosa after the use of local anti-inflammatory and antibacterial therapy, in particular, Polydexa nasal spray with phenylephrine containing Dexamethasone sodium metasulfobenzoate + Neomycin + Polymyxin B + Phenylephrine, and for the treatment of granulomatosis with polyangiitis. MATERIAL AND METHODS: The study included 940 patients who underwent examination and treatment for chronic rhinosinusitis in the clinic of otorhinolaryngology of I.P. Pavlov SPbSMU surgical treatment of the paranasal sinuses underwent 907 patients. In the postoperative period, the first group (211 patients) underwent toileting of the nasal cavity. The second group (307 patients) received irrigation therapy. The third group (389 patients) received a topical treatment combined of Polydexa with phenylephrine. The dynamics of the condition was assessed on the 1st, 3rd and 7th days of treatment, the evaluation of the effectiveness of the treatment was carried out on the 3rd and 7th days. Differential diagnosis with granulomatosis with polyangiitis was carried out in 33 patients. All patients with granulomatosis with polyangiitis showed signs of chronic rhinosinusitis. Patients were prescribed local anti-inflammatory and antibacterial therapy with Polydexa with phenylephrine for 7 days with endoscopic control of the nasal cavity. CONCLUSION: The use of the combined topical drug Polydexa with phenylephrine in patients with chronic rhinosinusitis and in patients with granulomatosis with polyangiitis has a positive effect, which reduces the clinical manifestations of chronic rhinosinusitis.

Influence of the cumulative effect of zoledronic acid on periodontal microcirculation in rats.

PURPOSE: To evaluate the effect of repeated administration of zoledronic acid (ZA) on the development and severity of osteonecrosis of the jaws. METHODS: In the experiment, 36 rats were used, which were divided into 4 groups: group 1 was injected with saline for 6 weeks, group 2 was injected with ZA once, group 3 was injected zoledronic acid for 3 weeks once a week, group 4 was injected with ZA for 6 weeks once a week. While taking medications, the tooth was removed. The volumetric blood flow rate was studied using laser and high-frequency ultrasound Doppler in the area of the periodontium of an extracted tooth in rats with the application of acetylcholine. Bone tissue was examined out using CBCT. RESULTS: In group 2, there was a violation of blood flow in the mucous membrane, bone microcirculation, but no reliable data was obtained in the bone defect in comparison with group 1. In groups 3 and 4, there was significantly disrupted blood flow. This led to an increase of the osteonecrosis (maximum at the 4th group), which was confirmed by data obtained using CBCT. An inverse relationship was observed between the blood flow of bone tissue and the size of the defect after tooth extraction. CONCLUSION: The introduction of ZA in a dose-dependent fashion resulted in impaired endothelial vasodilation and impaired blood flow to extraction sockets. These findings might explain the development of osteonecrosis of the mandible following removal of a first molar.

Physicochemical and biological characteristics of chitosan/κ-carrageenan thin layer-by-layer films for surface modification of nitinol.

Thin films based on the natural polysaccharides κ-carrageenan (Carr) and chitosan (Chit) were formed by layer-by-layer deposition technique. Surface topography and mechanical characteristics (Young's modulus, adhesion strength) of the polymer films with different number of layers were determined using various modes of atomic force microscopy (AFM). Polymer films were used to deposit on the surface of nitinol (NiTi) plates. The creation of polysaccharide coatings on nitinol led to a change in surface properties, such as hydrophilicity and root mean square roughness. in vitro cytotoxicity assay for nitinol plates with and without polymer coating by the MG-63 osteoblast-like cell line was conducted and was shown that all the studied samples are not toxic. A decrease in cytotoxicity for samples with a polymer film consisting of 4 layers of chitosan and carrageenan was shown as compared to an uncoated nitinol plates.

Disorders of microcirculation in the mechanism of bisphosphonate osteonecrosis: preliminary study in rats.

We investigated the possibilities of angioprotection and the reduction of osteonecrosis in rats that had been given bisphosphonates. In our experiment, 27 rats were divided into three groups: Group 1 was injected with saline; Group 2 was given zoledronic acid for six weeks; and Group 3 was given zoledronic acid for six weeks, with added doses of sulodexide after three weeks. After that we constructed a model of how the teeth should be extracted. The velocity of linear blood flow in the periodontal area of an extracted tooth in rats was studied using laser and high-frequency Doppler ultrasound (with the application of the vasoactive substance acetylcholine 3% for 1min). We evaluated changes in the structure of the bony tissues of the head using computed tomography, comparing the control group with the saline group. A rapid reduction in microcirculation was detected during the use of zoledronic acid for six weeks. A smaller reduction in microcirculation was detected after three weeks of treatment with sulodexide and zoledronic acid. There was a reduction in blood flow in the mucous membranes and, to a greater extent, in bony tissue. Zoledronic acid causes significant impairment of the periosteal blood flow to the mucous membranes because of a complex of disorders, which includes both the cellular component (impaired endothelium-dependent vasodilation of the mucous membrane vessels) and by reducing the intensity of microcirculation in the mucous membranes and bony tissues. Sulodexide, however, improves the restoration of blood flow and reduces the severity of osteonecrosis.

Involvement of Actin Filaments in the Cytotoxic Effect of GD2-Specific Antibodies.

Induction of direct cell death is one of the mechanisms of the antitumor effect of GD2-specific antibodies used for the therapy of high-risk neuroblastoma. The mechanisms of the cytotoxic signal triggered by antibody binding to GD2 ganglioside on the surface of the tumor cell remain insufficiently studied. Using inhibitor analysis we demonstrated that actin microfilaments are involved in the cell death induced by GD2-specific antibodies. Specifically, a strong antagonistic influence of cytochalasin D on the cytotoxic effect induced by GD2-specific antibodies was demonstrated in GD2+ tumor cell lines, which was expressed in at least 20% increase in cell survival and a significant decrease of the fraction of cells with fragmented DNA.

[The potential of cone beam computed tomography of the temporal bones in the patients presenting with otosclerosis]. / Vozmozhnosti konusno-luchevoi komp'yuternoi tomografii visochnykh kostei u patsientov s otosklerozom.

The objective of the present study was to analyze the potential of cone beam computed tomography of the temporal bones in the patients presenting with otosclerosis for the detection of surgically significant specific structural features of the labyrinth wall of the tympanic cavity. More than 400 tomograms of the temporal bones were obtained with the use of a cone beam tomographwere available for the investigation during the period from 2012 till 2016. The study was carried out in several steps, viz. the search for the optimal (for the given instrument) position of the patient, the experimental stage, the retrospective analysis of the tomograms and the comparison of the temporal bones of different types (pneumatic, mixed, and sclerotic) in individual patients, the comparison of the results of cone beam computed tomography (CBCT) with the intraoperative observations, and the modification of the algorithm for the analysis of temporal bone cone beam tomograms. The study included a total of 16 patients (15 women at the age from 32 to 56 years and one managed 58 years) presenting with the clinical diagnosis of otosclerosis. The results of the study were used to elaborate the algorithm for the analysis of cone beam tomograms of the temporal bones to be performed inthe stage by stage manner including the qualitative analysis of tomograms, evaluation of their quantitative parameters and additional characteristics to be taken into consideration when planning the surgical interventions on the labyrinth wall and the tympanic cavity as a preparation for the stapedoplastic treatment. The results of CBCT obtained in the present study were compared with the surgical observations. The diagnostic sensitivity and specificity of the method were estimated to be 100% and 83% respectively. It is concluded that cone beam computed tomography can be employed as a component of the diagnostic algorithm prior to the planning of surgical interventions onthe medial wall of the tympanic cavity and the assessment of dynamics of the clinical course of middle ear diseases.

[Mechanisms of the interaction of chitosan and its derivatives with the cell].

The review summarizes the data on the mechanisms of the interaction of chitosan and other molecules, as well as the drug delivery systems based on them, with mammalian cells. The mechanisms of binding, endocytosis, and the further distribution of chitosan and nanoparticles with different physic-chemical properties in cells remain unclear at the present time.

[Analysis of toxicity and biocompatibility of chitosan derivatives with different physico-chemical properties].

A comparative study of the toxicity and hemocompatibility of chitosan and its derivatives with different acetylation degrees, molecular masses, charges, and hydrophobicity has been performed. It has been shown that only positively charged chitosan derivatives activate platelets and suppress cell proliferation, regardless of the acetylation degree, molecular mass, and hydrophobicity. Chitosan quaternization decreases toxicity at a low degree of substitution and abruptly increases it at a high one. Negatively charged chitosan derivatives were nontoxic and compatible with blood components. It was concluded that the toxicity of chitosan and its derivatives is defined by their charge and solubility at a neutral pH.

Intracellular sorting of differently charged chitosan derivatives and chitosan-based nanoparticles.

Chitosan (Chi) is a biodegradable nontoxic polycation with multiple reactive groups that is easily used to obtain derivatives with a desired charge and hydrophobic properties. The aim of this work was to study the intracellular traffic of positively charged hexanoyl-chitosan (HC) or HC-based nanoparticles (HCNPs) and negatively charged succinoyl-chitosan (SC) and SCNPs in epithelial and macrophage cell lines. By using flow cytometry we demonstrated that positively charged HC adhered to cell membranes quicker and more efficiently than negatively charged SC or NPs. However confocal studies showed that SC and SCNPs penetrated cells much more efficiently than HC while HCNPs did not enter the epithelial cells. Macrophages also phagocyted better negatively charged material but were able to engulf both HC and HCNPs. Upon entering the cells, SC and SCNPs were co-localized with endosomes and lysosomes while HC was found in mitochondria and, to a lesser extent, in lysosomes of epithelial cells. Macrophages, RAW264.7, more efficiently transported all Chi samples to the lysosomal compartment while some positively charged material was still found in mitochondria. Incubation of Chi derivatives and ChiNPs at pH specific to mitochondria (8.0) and lysosomes (4.5) demonstrated the neutralization of Chi charge. We concluded that epithelial cells and, to a lesser extent, macrophages sort charged material to the organelles neutralizing Chi charge.

[A case of successful treatment of angioma of the middle and external ear]. / Nabliudenie uspeshnogo lecheniia rasprostranennoi angiomy srednego i naruzhnogo ukha.

A rare form of benign tumour (angioma of the middle and external ear) is described. The preoperative treatment with the use of embolization of the feeding vessel made possible surgical intervention on a practically "dry" operating field.