Broad-spectrum antibacterial and pro-regenerative effects of photoactivated Photodithazine-Pluronic F127-Chitosan polymer system: In vivo study.

Emerging global danger of multidrug resistant microbes makes it essential to explore new approaches to treat infections. We studied antibacterial and pro-regenerative effects of photodynamic therapy (PDT) performed with water solutions of photodithazine and its complexes with Pluronic F127 and chitosan in rat model of full thickness wound (n = 24) infected by an associated Gram-negative and Gram-positive bacteria culture. Laboratory rats were exposed to PDT 24 and 72 h after the injury. Exudate samples were collected before and after PDT for a microbiological study. Autopsy tissues were excised and fixed in formalin on day 4 of the experiment. Fixed tissues were processed and poured into paraffin. Paraffin sections were stained with hematoxylin and eosin and studied by an experienced pathologist. Microbiological analysis revealed that the photoactivation of photodithazine and its complexes suppressed the associated microflora in vivo and inhibited suppurative inflammation in the wounds. The triple Photodithazine-Pluronic F127-Chitosan system possessed the highest antibacterial activity. The morphological study revealed that PDT with photodithazine polymer complexes accelerated wound healing, promoted restoration of microcirculation, facilitated proliferation of fibroblast and vessels and stimulated collagen synthesis. The Photodithazine-Pluronic F127-Chitosan complex may be successfully applied for PDT to prevent and treat suppurative inflammatory diseases of the skin and soft tissues.

[Dinitrosyl-iron complexes with cysteine or glutathione accelerate skin wound healing in animals].

The beneficial effect of NO-donors, dinitrosyl-iron complexes with cysteine or glutathione on the healing of skin wound in rats was demonstrated by hystological and hystochemical methods: dinitrosyl-iron complexes accelerated efficiently repair processes in wound tissue after a twofold injection of an aqueous solution of a dinitrosyl-iron complex into wound tissue at a total dose of 5 mmol on days 1 and 2 after skin wounding, and the granulocyte volume increased 3-4 times on the fourth day after wounding compared with the control. Higher doses of dinitrosyl-iron complex provoked an inflammation process in the wound. Similar experiments with of another NO donor S-nitrosoglutathione affected adversely the wound. S-Nitrosoglutathione was added to the wound at a total dose of 10 mmol, which ensured the administration of NO to the wound tissue in the amount equal to that introduced upon the injection of dinitrosyl-iron complex. The addition of dinitrosyl-iron complex with glutathione at a dose of 2.5 mmol was accompanied by the formation of protein-bound dinitrosyl-iron complex in wound tissue. The formation of dinitrosyl-iron complex was also observed after the injection of S-nitrosoglutathione. However, the amount of complexes was more than 25 times less than that after the administration of dinitrosyl-iron complex. The beneficial effect of dinitrosyl-iron complex on the wound was suggested to be due to the formation of a self-regulated chemical system in wound tissue, which is characterized by the mutual transformation of low-molecular dinitrosyl-iron complex and S-nitrosoglutathione. This system ensures a regulated delivery of NO to its intracellular targets without the formation of high amounts of peroxynitrite which could adversely affect the intracellular processes. It was assumed that the self-regulated system of dinitrosyl-iron complex and S-nitrosoglutathione is not formed after the addition of S-nitrosoglutathione to the wound, probably due to a low amount of intracellular iron which could provide the formation of dinitrosyl-iron complex. The rapid decomposition of S-nitrosoglutathione results in the appearance of high amounts of NO and hence peroxynitrite, which adversely affects the wound.

[A comparative study of the effects of laser and light-emitting diode irradiation on the wound healing and functional activity of wound exudate leukocytes].

The effects of coherent He-Ne laser and non-coherent light-emitting diode radiation on rat skin wound healing and functional activity of wound excudate leukocytes were compared. A comparative pathomorphological analysis showed that the He-Ne laser and light-emitting diode irradiation stimulated the transition of the inflammatory phase of the wound healing into the reparative (proliferative) and scarring phases sequentially. It was also detected that the functional activity of leucocytes changed in a dose-dependent manner. The leukocyte activity was found to be similar in the groups with laser and light-emitting diode irradiation. Thus, we can conclude that coherent laser and non-coherent light-emitting diode radiation have very close effects on wound healing and activity of wound exudate leukocytes, and coherence is not required for this activity.

[Ozone-ultrasonic therapy in the treatment of purulent wounds]. / Kombinirovannaia ozono-ul'trazvukovaia terapiia v lechenii gnoinykh ran.

Based on planimetric, bacteriologic and histologic study high efficiency of local ozonotherapy of wound in combination with low-frequency ultrasound was demonstrated experimentally on rat model of infected purulent skin wound. This method was used in 45 patients with purulent wounds of soft tissues (postoperative, posttraumatic, burn, sore spot) that led to fast cleaning of wound surface, decrease of bacterial contamination and granulations. It permitted to eliminate inflammation and to create optimum conditions for wound closure.

[Gapkol--a new osteoplastic material]. / Gapkol--novyi osteoplasticheskii material.

Hapcol, a new osteoplastic material, representing a biological composition on the basis of a natural biopolymer collagen with biologically compatible osteotropic mineral hydroxyapatite has been developed and allowed for clinical use. It is intended for use in dentistry in surgical treatment of periodontal diseases, deformations of the abutment tissues of the face, filling of bone defects after cystectomy, surgery for bone plasty, etc. Hapcol is characterized by antiinflammatory action, stimulates repair osteogenesis and collagenogenesis. Joint stock company Polistom starts commercial manufacture of the new material.

[Experimental premises and 1st experiences in the clinical use of antibacterial vascular prostheses under circumstances of increased risk of suppuration]. / Eksperimental'nye predposylki i pervyi opyt klinicheskogo primeneniia antibakterial'nykh sosudistykh protezov v usloviiakh povyshennogo riska nagnoeniia.

It was shown on the basis of laboratory and experimental data that created antibacterial vascular prostheses are marked, on the main, by local bacteriostatic and anticoagulative effect. It was found that heparin concentration of 3 to 500 U per 1 kg collagen causes a hyperadhesive effect on blood platelets and facilitates the formation of the primary thrombocytic thrombus. The free surface energy grows in this case from 34 +/- 0.8 to 66.3 +/- erg/cm2. The optimal thromboresistant effect occurs in heparin content of 1 U per 1 mg collagen. That this choice is correct is confirmed on examination of the inner surface of the prostheses with an electron microscope after being in the blood flow for 45 minutes. Bifurcation and linear antibacterial prostheses were used in 9 patients with a high risk of suppuration verified by cultures of discharge from ulcers and lymph nodes, and the presence of lymphangitis and lymphadenitis. The effect was positive in 8 patients, 2 of them had superficial suppuration of the operative wounds.

[Pharmacokinetic study of implantable gentamycin preparations. I. Antibiotic pharmacokinetics in the implantation area and an evaluation of the prolonged effect of the preparations]. / Farmakokineticheskoe izuchenie implantiruemykh preparatov gentamitsina. I. Farmakokinetika antibiotikov v zone implantatsii i otsenka prolongiruiushchego éffekta preparatov.

Gentamicin pharmacokinetics was studied in the zone of subcutaneous implantation to rats of Septopal, a dosage form based on polymethylmethacrylate stable in vivo (4.5 mg of the antibiotic) and of preparations based on biodegradable polymers such as monocarboxycellulose, alginic acid, nonmodified and modified collagens (1 and 5 mg of the antibiotic). A three-phase pattern of gentamicin level changing in the implantation zone was observed: (1) rapid increasing and decreasing of the antibiotic concentration, (2) stabilization of the gentamicin content at a practically constant level and (3) slow lowering of the antibiotic level in the tissue. Comparison of the areas under the concentration/time curves showed that the modified collagen, alginic acid and monocarboxycellulose had the highest prolongation effect among the biodegradable polymers. Their use in the compositions provided during the first hours after the implantation the antibiotic concentrations in the administration site equal to tens micrograms per 1 g of the tissue. After that during 14 days the concentration of gentamicin in the implantation zone maintained at the level higher than its MIC for the main pathogens of wound infections.

[Tetracycline hydrochloride complex formation with collagen]. / Kompleksoobrazovanie tetratsiklina gidrokhlorida s kollagenom.

The quantitative indices and regularities of tetracycline hydrochloride binding with colelagen in the process of complex formation were studied in vitro. It was found that tetracycline-interacted with collagen. The amount of the antibiotic bound depended on its initial concentration in the mixture and the aggregate state of the protein: the amount of tetracycline hydrochloride absorbed by dissloved collagen was 10 times higher than that absorbed by polymerized collagen. The antibiotic bound with collagen did not lose its specific antibacterial activity.

[Properties of a collagen and monomycin complex]. / O svoistvakh kompleksa kollagena s monomitsinom

The prolonged effect of a single application of a collagen-monomycin sponge was studied experimentally on albino rats on a model of a skin flat wound. The monomycin levels in the blood and tissues in the area of the sponge application for 14 days were determined by the biological method. The therapeutically effective concentration of monomycin, i.e. 3.8 gemma/ml was maintained in the general blood flow for 2 weeks. During this period the local antibiotic concentration was almost 5 times higher. The toxic effect of the collagen-monomycin complex was studied on rabbits and albino rats for 2 months with respect to the indices of the protein metabolism and the content of residual nitrogen and urea. The activity of cholinestrerase and the content of histamine in the blood were determined. No significant changes in the studied tests were observed during the period of the chronic experiment. The microstructure of the organs of the test animals did not differ from that of the intact animals. The collagen-monomycin complex had a prolonged antibacterial effect and was not toxic with respect to the the test animal.