Pharmacokinetic investigation of branched oligohexamethyleneguanidine hydrochloride in a liquid composition for the treatment of stomatitis and gingivitis.

Branched oligohexamethyleneguanidine hydrochloride (branched OHMG-HC) possesses high biocidal activity. This study aimed at evaluating the pharmacokinetics of branched OHMG-HC and is mandatory for obtaining permission to conduct clinical studies. The thermal activation method was used to obtain radioactive-labeled drugs for the investigation of substance distribution in various tissues of experimental animals (rats and rabbits). Substance administration was carried out both orally (a dose was split into two equal volumes that were applied to buccal zones of the oral cavities of the animals) and intravenously to get a clear pharmacokinetic profile. In this research, the drug was applied in the concentration of 0.77 mg/kg with the addition of 0.037 mg/kg 3H-OHMG for rats, and 0.42 mg/kg with the addition of 0.015 mg/kg 3H-OHMG for Chinchilla rabbits. The selected samples of blood, organs, and urine underwent alkaline mineralization. A quantitative determination of 3H-OHMG was carried out using a liquid ß-, γ-counter according to the level of scintillation in the sample. Branched OHMG-HC displayed uniform distribution within all main organs and tissues upon oral administration. The highest concentrations were found in liver and kidney tissues, whereas the lowest in blood, cardiac muscle tissue, and brain. The closeness of the fabs values obtained from different animals (24.5% for rats and 29.0% for rabbits) demonstrated the absence of the species specificity in response to the pharmaceutical substance. The main parameters of excretion were established, and the half-life time was estimated to be 15 h.

[Preventative repair of postoperative ventral hernia considering the markers of connective tissue dysplasia]. / Opredelenie pokazaniia k preventivnomu éndoprotezirovaniiu na osnovanii markerov displazii soedinitel'noi tkani u bol'nykh s posleoperatsionnymi ventral'nymi gryzhami.

OBJECTIVE: To define the indication for preventive mesh implantation in patients scheduled for laparotomy. MATERIAL AND METHODS: There were 108 patients divided into the control (52 patients without anterior abdominal wall hernia) and the main (56 patients with ventral hernia) groups. RESULTS: Predominance of collagen type III over type I was observed in patients older 60 years in the main group. The maximum ratio of collagen types I and III was 1.4 in the main group. The minimum number of inter-fiber spaces (n=5) was noted in patients aged 30-40 years. The maximum density of connective tissue was 250 pixels per inch. CONCLUSION: Analysis of connective tissue structures revealed some important age-related features and markers of connective tissue dysplasia in the main group. An indication for preventive mesh implantation in patients scheduled for laparotomy was determined.

[Collagen types ratio in prediction of postoperative ventral hernias]. / Sootnoshenie tipov kollagena v prognozirovanii posleoperatsionnykh ventral'nykh gryzh.

AIM: To analyze collagen types ratio in skin and aponeurosis in order to predict postoperative ventral hernias. MATERIAL AND METHODS: The trial included 141 patients for the period 2012-2015. Group I (n=65) of patients without ventral hernias was divided into subgroup AI (primary operation, n=41) and BI (re-operation, n=24). Group II consisted of 76 patients with ventral hernias. We performed histological examination of skin and aponeurosis to define the collagen structure of connective tissue. RESULTS: There were significant differences between collagen type I/III ratio in skin (2.81±0.52 in group I vs. 1.13±0.48 in group II) and aponeurosis (2.69±0.41 vs. 1.09±0.21, respectively, p≤0.05). We revealed strong direct correlation (r=+0.92) between aponeurosis and skin specimens in one group. Collagen type I level was 73.81±2.74% in subgroup AI and 72.03±2.47% in subgroup BI. Collagen type I was predominant (p≤0.05). CONCLUSION: In patients with ventral hernias collagen type I/III ratio in skin is 2.54 times lower than in patients without hernias. Significant correlation of collagen types in skin and aponeurosis (r= +0.92) allows to predict the risk of postoperative ventral hernias on basis of skin fragment.

[The influence of 'potassium orotate' on neocollagenogenesis in implantation of polypropylene endoprosthesis and polypropylene combined with polylactic acid endoprosthesis]. / Vliyanie orotata kaliya na neokollagenogenez pri implantatsii polipropilenovogo endoproteza i endoproteza iz polipropilena s polimolochnoi kislotoi v eksperimente.

AIM: To study neocollagenogenesis after implantation of polypropylene endoprosthesis and polypropylene combined with polylactic acid endoprosthesis on background of «potassium orotate¼ administration. MATERIAL AND METHODS: We used two different types of endoprosthesis in the experiment. The first type was made of just polypropylene, the second type was made of polypropylene combined with polylactic acid. Histological examination was performed using polarizing microscopy. Collagen types I and III ratio in connective tissue around the prosthesis was analyzed according to the color that was individual for each type. RESULTS: The results were significantly better in case of collagenogenesis stimulation with Potassium orotate within 30 days and later for one type of endoprosthesis. Also we revealed that collagenogenesis and paraprosthesis capsule formation were more active in case of combined endoprosthesis. We revealed stimulating action of «Potassium Orotate¼ for collegenogenesis process, this fact was proved by increased collagen I/III ratio. CONCLUSION: Optimization of collagenogenesis was based on persistent 1,37-fold increase of collagen I/III ratio in case of combined endoprosthesis after 90 days. It was manifested by accelerated formation of connective tissue capsule and facilitated early isolation of the implant from surrounding tissues.

THE INFLUENCE OF VITAMIN C ON THE DYNAMIC OF RELATION OF COLLAGEN I AND III TYPES IN THE PERIPROSTHESIS AREA.

The aim of the study was to learn the degree of biocompatibility of synthetic herniological prostheses «Progrip¼, with collagen-stimulating effect of ascorbic acid on the growth of connective tissue in the experiment. We examined characteristics of collagenogenesis in the anterior abdominal wall depending on the effect of vitamin C using the method of polarization microscopy. We suggest a new way to stimulate reparation process by ascorbic acid which would help to optimize forming functionally matured structures of connective tissue of the anterior abdominal wall surrounding endoprosthesis. Due to the results of our investigation it has been clear that modification effect of vitamin C is positive for synthesis of collagen in the periprosthetic capsule for any type of endoprosthesis. It has been proves by statistically reliable increase in ratio of collagen types I and III when vitamin C is used in the diet of experimental animals.

Effect of dihydroquercetin on the tone of isolated rat veins.

Dihydroquercetin effects on the tone of isolated segments of the portal vein of rats were studied. Dihydroquercetin did not modify the basal venous tone, but reduced the amplitude of contractions induced by KCl and norepinephrine hydrotartrate.

[Dynamics of cytokine profile in patients with postoperative hernias the abdominal wall in prosthesis with polytetrafluoroethylene and polyvinylidene fluoride application].

The results of experimental and clinical studies for the comparative evaluation of implants used in herniology of polytetrafluoroethylene (PTFE) and polyvinylidene fluoride (PVDF) are presented. Experimental investigations conducted on 200 mice, which in the anterior abdominal wall mesh prosthesis implanted. All animals, regardless of the type of implanted prosthesis, deduced from the experiment at 10, 30 th and 60 th day. Histological investigation of the submissions received. The clinical part is based on an analysis of surgical treatment results of postoperative abdominal wall hernia (POGBS) in 121 patients during the period from 2003 to 2011 patients were divided into 2 groups. The control group included 73 patients who were operated during the period 2005-2007, used PTFE graft "Ecoflon", in the main - 48 patients who from 2008 to 2011 the prosthesis was implanted PVDF - "Uniflex" firm "Linteks". In each group, selected patients whom have examined the profile of cytokines. The results of the studies found that both the material cause marked inflammatory reaction with a characteristic stepwise increased levels of proinflammatory and antiinflammatory cytokines, the dynamics of cytokines indicative of a less pronounced local inflammatory reaction to the prosthesis from the PVDF. In the application of the implant "Uniflex" a lower incidence of exudative complications in comparison with that when using the prosthesis "Ecoflon" it is preferable in clinical use.

[Comparative morphology of tissues when using polypropylene and polytetrafluoretilen prostheses].

The synthetic mesh is widely used for treatment of hernias. We conducted a comparative study of the morphological pattern of inflammation, the cellular composition of tissues and dynamics of scar formation in mice when using implants "Esfil" and "Unifleks" under influence of single and double injection of cultured fibroblast and without such injection to the region of stents location. A more pronounced inflammatory reaction during the study period of investigation was observed in the case of "Esfil". In the late period of the study, a higher percentage of fibroblasts was observed in the case of the prosthesis "Unifleks" compared to the prosthesis "Esfil". Injection of cultured fibroblasts modifies the curve of the dynamics of the inflammatory process by making it smoother in the case of both prostheses. So, more preferred is the use of prostheses "Unifleks".

[Influence of exogenous embryonic fibroblasts on collagen type I and type III ratio in the tissues of paraprosthetic capsule (experimental work)].

Nowadays, the use of synthetic prosthesis is obligatory method in surgical treatment of large and giant ventral hernias. We have fulfilled comparative investigation of the dynamics of collagen Type I to Type III ratio in paraprosthetic region in mice when using implants, Esphyl - polyethylene, Ecophlon - polytetrafluorethylene, and Uniflex - polyvinylidenfluoride, with a one- and two-time introduction of cultured fibroblasts into paraprosthetic region at different times after implantations and without the introduction. Use of Sirius Red dye staining and polarization microscopy revealed that, in short period (10 days after endoprosthesis implantation), the implication of fibroblasts and the number of implications did not affect the collagen Types ratio. In later stages (30-60 days after endoprosthesis implantation) a significant increase in collagen Type I was observed when using all the materials. The ratio of collagen Type I to Type III was maximal at all stages of the experiment in the case of the implant Uniflex. Double implication of exogenous fibroblasts accelerated the increase in the collagen Type I to Type III ratio to a greater extent.

Antioxidant composition causes antiexsudorific effect in the model of chronic venous insufficiency.

Venous hypertension and swelling of the hind limbs was demonstrated to develop in rat model of chronic venous insufficiency. It was found that 14-day course of dihydroquercetin (50 mg/kg) and lipoic acid (50 mg/kg) administered intragastrically prevented the increase in hind limb volume and reduced the severity of edema of rat muscle tissue in chronic venous insufficiency.

[Hepatoprotective effect of thiophane in rats with experimental carbon tetrachloride-induced hepatitis].

A hepatoprotective effect of thiophan was studied on the model of carbon tetrachloride-induced hepatitis in rats. Therapeutic administration of thiophan repairs the antitoxic function of liver, normalizes cytolysis marker activity, and improves the synthetic function of liver and the carbohydrate and lipid metabolism. The hepatoprotective activity of thiophan is similar to effect of silimarin.

Hemorheological effects of ortho-isobornyl phenol derivative under conditions of brain ischemia in rats.

Hemorheological activity of 4-methyl-2,6-di-isobornyl phenol, a new o-isobornyl phenol derivative, was studied under conditions of experimental prolonged partial cerebral ischemia. Brain ischemia is associated with hemorheological disorders which can be characterized as blood hyperviscosity syndrome: increased viscosity of the whole blood (within a wide range of shear rates), plasma viscosity, fibrinogen content in blood plasma, and platelet aggregation; deterioration of platelet deformability and reduced availability of oxygen for tissues. A course (5 days) of intragastric 4-methyl-2,6-di-isobornyl phenol (100 mg/kg) prevented the development of blood hyperviscosity syndrome by modulating blood macrorheology (reduction of plasma viscosity and fibrinogen content) and microrheology (reduction of erythrocyte aggregation and improvement of their deformability).

[Hemorheological effects of thiophane on tetrachloromethane induced hepatic damage].

Carbon tetrachloride-induced hepatitis in rats is accompanied by blood hyperviscosity syndrome development. A course intragastric administration of thiophane under these conditions prevents the increase in whole blood viscosity by normalizing the microrheological indices (deformability and aggregation of erythrocytes), which is manifested by increasing oxygen availability for tissues.

Morphological changes in retinal neurons in streptozotocin-induced diabetes mellitus and their correction with an isobornylphenol derivative.

Along with microangiopathy, one of the main causes of blindness in diabetic retinopathy consists of degeneration of retinal neurons. Electron microscopy and morphometric analysis were used to study structural changes in neurosensory cells, associative, and ganglion neurons in the retina in 30 while mongrel male rats with streptozotocin diabetes for two months and the effects of a new semisynthetic antioxidant 4-methyl-2,6-diisobornylphenol, a screened phenol, were evaluated. Destructive changes were found to affect the outer segments of neurosensory cells and ganglion neurons. The number density of neurosensory and ganglion cells decreased, and the proportion of these cells with pyknotic nuclei increased. 4-Methyl-2,6-diisobornylphenol had neuroprotective actions, preventing destructive changes to neurosensory cells and ganglion neurons.

[Neuroprotective effects of dibornol and mechanism of its action in rats with cerebral ischemia].

Neuroprotective activity of the new sterically hindered phenolic antioxidant 4-methyl-2,6-diisobornylphenol (dibornol) in rats with total transient cerebral ischemia was investigated. Dibornol decreased mortality of rats and the number of animals with severe neurological deficit; moreover, it accelerated restoration of neurological status in the survived rats. Neuroprotective activity of dibornol is based on its ability to diminish lipid peroxidation in ischemic brain, suppress cerebral tissue hypoxia and protect functional activity of endothelium. Improved oxygen delivery was a consequence of reduced hyperviscosity syndrome (enhanced deformability of erythrocytes and their decreased aggregation).

[Immunomorphological reaction of organism in prosthetic plasty of the anterior abdominal wall using polypropylene mesh in patients, suffering postoperative abdominal hernia].

Clinico-experimental studying the immunomorphological reactions variants in the prosthesis of anterior abdominal wall using synthetic polypropylene mesh was conducted. In 70 patients, operated on for postoperative hernia of abdominal wall using "on lay" method and the immune state were studied up by means of investigation of proinflammatory and anti-inflammatory cytokines content, in part, of tumor necrosis factor-alpha; (TNF-alpha), IL-8, IL-4. Morphological investigations were conducted in experiment on 100 the Vistar line mices, there were studied reactions of fibroblasts, macrophages, lymphocytes and leucocytes. The results of the immunological and morphological reactions on polypropylene obtained trust the necessity of differentiated approach application for the choice of the synthetic prosthesis kind, taking into account its biocompatibility, physical properties, the hernial defect size etc.

[Morphological changes in retinal neurons in rats with streptozotocin diabetes and their correction by O-isobornylphenol derivative].

Along with microangiopathy, degeneration of retinal neurons is one of the basic causes of blindness in patients with diabetic retinopathy. Using the electronic microscopy and morphometric analysis, the structural changes of neurosensory cells, associative and ganglionic retinal neurons were studied in 30 albino outbred male rats with long term (2 months) streptozotocin diabetes and the effect of a new semisynthetic antioxidant belonging to a group of strictly hindered phenols (4-methyl-2,6-diisobornylphenol) on these parameters was evaluated. In diabetic rats, the destructive changes of external segments of neurosensory cells and ganglionic retinal neurons were found. The numerical density of neurosensory and ganglionic cells was reduced, while the proportion of these cells with pyknotic nuclei was increased. 4-Methyl-2,6-diisobornylphenol demonstrated neuroprotective effect by preventing destructive changes of neurosensory cells and ganglionic retinal neurons.

Antithrombogenic and antiplatelet activity of optho-isobornyl phenol derivative.

We studied antithrombogenic and antiplatelet properties of 4-methyl-2,6-diisobornyl phenol, a new promising compound belonging to ortho-isobornyl phenol derivatives, under conditions of intravascular thrombosis and acute cerebral ischemia. It was found that 4-methyl-2,6-diisobornyl phenol prevents intravascular thrombus formation by reducing platelet aggregation and improving antiplatelet activity of the vascular wall.

Stimulation of the growth of human tumor by low-power laser irradiation.

We studied the effect of low-power laser on the growth of human gastric adenocarcinoma transplanted to athymic mice. Irradiation shortened the latency of tumor growth in recipients from 4-6 months to 21-24 days. After 17 serial passages on athymic mice, the size of tumor node in irradiated recipients on day 33 after transplantation was 161.1 mm(3) (vs. 10.2 mm(3) in nonirradiated mice). These findings suggest that low-power laser irradiation can stimulate the growth of metastases in patients with a history of malignancy.

[Experience in rendering medical care to infectious patients in Afghanistan]. / Opyt okazaniia meditsinskoi pomoshchi infektsionnym bol'nym v Afganistane.

For the first time it was Afghanistan where the 40th Army had faced with mass polyinfection morbidity which had a severe course and unfavourable outcome. In these conditions a new effective system of medical care to infectious patients was elaborated and applied. This system comprised a four-staged complex of medical and diagnostical measures. That made it possible to reduce the number of fatal cases by 16 times (from 0.49 to 0.03%) in 1983-1989. The total number of servicemen returned to active duty was brought up to 99.6%. The most important factors in this new system were the following: at prehospital stage--new methods in early definition of infectious patients, opportune diagnosis and emergency care; at hospital phase--new methods of triage, schemes of complex treatment for various nosological forms working principles of intensive therapy.