[Fixed ratio combinations GLP-1RA and basal insulin: literature review].

The progressive nature of type 2 diabetes mellitus leads to the need for insulin therapy in a significant proportion of patients. Very often start of insulin therapy in type 2 diabetes mellitus (T2DM) is associated with weight gain and a significant increase of hypoglycemia's risk. However, innovative options, such as fixed ratio combinations of glucagon-like peptide 1 receptor agonists (GLP-1RA) and basal insulin, minimize weight gain and hypoglycemia risks and allow a greater proportion of patients to achieve individual glycemic control goals without compromising safety parameters. This review includes a description of the randomized clinical trials, as well as the results of real clinical practice of the use of two currently existing fixed ration combinations of GLP-1RA and basal insulin - iDegLira and iGlarLixi.

[Evolution of insulin therapy: past, present, future].

2021 marks the 100th anniversary of the discovery of insulin, an event that forever changed the lives of people with diabetes mellitus. At present patients around the world experience the miracle of insulin therapy every day. A disease that used to kill children and teenagers in 2 years in 1920 has become a disease that can be controlled with a possibility to lead a long productive life. Over the past century, the great discovery of Banting, Best and Collip has forever changed the world and saved millions of lives. This review is devoted to the history of the development of insulin and its further improvement: from the moment of discovery to the present days. Various generations of insulin are considered: from animals to modern ultrashort and basal analogues. The article ends with a brief review of current trends in the development of new delivery methods and the development of new insulin molecules. Over the past century, insulin therapy has come a long way, which has significantly improved the quality of life of our patients. But research is actively continuing, including in the field of alternative methods of insulin delivery, which are more convenient for the patient, as well as in the development of «smart¼ molecules that will have a glucose-dependent effect.

[Study of the effect of Unifuzol on cognitive impairment and damage to the hippocampus and cerebral cortex during course administration to rats with bilateral stenosis of the common carotid arteries, causing chronic circulatory failure]. / Vliyanie preparata Unifuzol na sostoyanie kognitivnykh funktsii v usloviyakh eksperimental'nogo khronicheskogo narusheniya mozgovogo krovoobrashcheniya.

OBJECTIVE: To study the effect of Unifuzol (L-arginine sodium succinate) on cognitive impairment, cerebral blood flow, and damage to the tissues of the hippocampus and cerebral cortex during a 10-day course of administration to rats with chronic cerebral ischemia (CCI) caused by bilateral stenosis of the common carotid arteries (CCA). MATERIAL AND METHODS: The study was conducted on male rats with CCI caused by bilateral stenosis of the CCA by 60%. 40 days after surgery, rats received Unifusol (21, 42 and 84 ml/kg), nicergoline (10 mg/kg), citicoline (500 mg/kg) or placebo (0.9% NaCl) for 10 days. Next, cognitive impairments were assessed in the Morris Water Maze and the New Object Recognition (NOR) test, as well as the level of motor and exploratory activity in the Open Field test. The level of cerebral blood flow was determined immediately after the CCA stenosis and at the end of the experiment. Animals were euthanized in a CO2 incubator, after which the brain was removed and subjected to morphometric analysis. RESULTS: In animals that were modeled with CCA stenosis, pronounced behavioral and cognitive impairments occurred as a result of a decrease in blood flow in the vessels of the brain and subsequent changes in the tissues of the hippocampus and the cerebral cortex. Intravenous course administration of Unifuzol at doses of 42 and 84 ml/kg to animals with CCI was comparable in efficiency to nicergoline and citicoline, which was expressed in greater preservation of the cognitive abilities of animals in the Morris Water Maze and NOR tests. In the Open Field test, animals injected with Unifusol at doses of 42 and 84 ml/kg performed more acts of motor and exploratory activity than animals from the placebo group, and had a higher level of cerebral blood flow (compared to animals that were injected with citicoline). Based on the results of a morphological study, it was found that the most significant neuroprotective effect was provided by nicergoline and Unifuzol (at doses of 42 and 84 ml/kg). CONCLUSION: Unifuzol at a course of administration at doses of 42 and 84 ml/kg, comparable to the reference drugs nicergoline and citicoline, reduces the severity of psychoneurological deficit in animals with CCI, comparable to them improves the microcirculation of brain tissues, preventing damage to brain tissues.

[Antioxidant effect of cortexin, cerebrolysin and actovegin in rats with chronic cerebrovascular insufficiency]. / Antioksidantnoe deistvie Korteksina, Tserebrolizina i Aktovegina u zhivotnykh s khronicheskoi ishemiei golovnogo mozga.

OBJECTIVE: To compare the antioxidant effects of cortexin, cerebrolysin and actovegin in rats with chronic brain ischemia. MATERIAL AND METHODS: Chronic brain ischemia was modeled in male rats by 50% stenosis of the common carotid arteries. Forty days after surgery, the animals received 2 ten-day courses of therapy, separated by a break of 10 days. Placebo, cortexin (0.3, 1 and 3 mg/kg), cerebrolysin (0.8, 2.5 and 7.5 ml/kg) and actovegin (5 ml/kg) were administered to animals as treatment. The concentration of malondialdehyde (MDA) in the homogenates was determined by the reaction with thiobarbituric acid, the concentration of reduced glutathione was determined by the reduction reaction of 5.5-dithiobis- (2-nitrobenzoic acid); determination of catalase activity, as well as the content of lactate and pyruvate, by commercially available reagent kits. The activity of superoxide dismutase (SOD) was determined by the photometric method based on an assessment of the degree of inhibition of the epinephrine oxidation reaction. All reactions were carried out in triplicates. RESULTS: Modeling of chronic brain ischemia led to the statistically significant decrease in the content of lactate and pyruvate (p<0.001, when compared with the control group), which was not accompanied by a significant decrease in their ratio (p>0.05), as well as to the decrease in SOD, catalase activity, restored glutathione and increase in MDA concentrations. Compared with the control group, in the groups that received cortexin at a dose of 3 mg/kg/day, cerebrolysin at a dose of 7.5 ml/kg/day and actovegin at a dose of 5 ml/kg/day, there were an increase in the content of lactate and pyruvate (without a significant change in their ratio), restoration of glutathione levels and the activity of SOD and, to a lesser extent, catalase, combined with a decrease in the concentration of MDA. CONCLUSION: Course administration of cortexin (3 mg/kg), cerebrolysin (7.5 ml/kg) and, to a lesser extent, actovegin (5 ml/kg) has a positive effect on the state of the antioxidant system of the brain in rats with chronic brain ischemia.

Mycobacterium vaccae Lysate Induces Anti-Allergic Immune Response In Vitro.

Mycobacterium vaccae is a soil saprophyte which exerts anti-allergic properties. There are data that mechanism of action of M. vaccae when used in the treatment of human and animal allergic diseases is associated with Th1-phenotype switch. Here we studied the properties of sonicated M. vaccae lysate in co-cultures of dendritic cells and CD4+T cells. M. vaccae lysate stimulated IL-10 synthesis in co-cultures and CD86 expression in dendritic cells, being more potent than heat-killed M. vaccae. The reported clinical data and the mechanism of action of M. vaccae lysate suggest that its use is a feasible option for the primary prevention of allergic diseases, in particular atopic dermatitis.

[Comparative study of protective effects of Cortexin, Cerebrolysin and Actovegin on memory impairment, cerebral circulation and morphological changes in the hippocampus of rats with chronic brain ischemia]. / Sravnitel'noe izuchenie vliyaniya Korteksina, Tserebrolizina i Aktovegina na sostoyanie pamyati, mozgovoe krovoobrashchenie i strukturu gippokampa u krys s khronicheskim narusheniem mozgovogo krovoobrashcheniya.

OBJECTIVE: To compare the effects of cortexin, cerebrolysin and actovegin on memory impairment, cerebral circulation and morphological changes in the hippocampus of rats with chronic brain ischemia. MATERIAL AND METHODS: The study was conducted using male rats with chronic brain ischemia caused by stenosis of the common carotid arteries by 50%. Animals received cortexin (0,3; 1 or 3 mg/kg), cerebrolysin (0,8; 2,5 or 7,5 ml/kg) and actovegin (5 ml/kg) in two 10-day courses with 10 days of treatment break. The severity of cognitive impairment was evaluated using the Morris water maze, passive and active avoidance tests. Cerebral circulation using laser flowmetry and brain hippocampus structures were studied in the end of treatment. RESULTS: Cognitive impairment in animals with chronic brain ischemia was accompanied by the development of pathological changes in the CA1 and CA4 regions of the hippocampus. Administration of cortexin (1 and 3 mg/kg) and cerebrolysin (2.5 and 7.5 ml/kg) to rats with chronic brain ischemia had almost no effect on cerebral blood flow, but contributed to the improvement in memory formation and retrieval processes in the Morris water maze. The treatment effect was comparable for both drugs and persisted after 10 days of treatment break. Morphological assessment showed a decrease in the severity of pathological changes in the hippocampal regions. CONCLUSION: The course-administration of cortexin and cerebrolysin lead to a decrease in the severity of memory impairment and pathomorphological changes in the hippocampus in rats with chronic brain ischemia.

[Behavioral phenotyping in rats during the experimental modeling of chronic cerebral circulation disorder]. / Povedencheskoe fenotipirovanie krys pri éksperimental'nom modelirovanii khronicheskogo narusheniia mozgovogo krovoobrashcheniia.

AIM: To describe motor, adaptive and cognitive disorders in rats with chronic cerebral circulatory deficiency caused by partial stenosis of the common carotid arteries (CCA). MATERIAL AND METHODS: A study was performed on 20 white outbred male rats. This manipulation led to 40-45% and 50-60% reduction of blood flow in CCA and in the brain, respectively. Twenty days after operation, animal's condition was assessed in the following tests: open field test, rotarod performance test, marble burying test and novel object recognition. RESULTS AND CONCLUSION: After 20 days of experimental CCA stenosis, animals demonstrated several signs of neuropsychiatric deficiency including coordination disorders, a decrease in locomotor activity as well as in explorative and protective behavior. The model of CCA partial stenosis could be used during further studies of the pathophysiology and pharmacology of chronic cerebral circulatory deficiency.