Prospects for the Use of Intranasally Administered Insulin and Insulin-Like Growth Factor-1 in Cerebral Ischemia.

Current approaches to the treatment of stroke have significant limitations, and neuroprotective therapy is ineffective. In view of this, searching for effective neuroprotectors and developing new neuroprotective strategies remain a pressing topic in research of cerebral ischemia. Insulin and insulin-like growth factor-1 (IGF-1) play a key role in the brain functioning by regulating the growth, differentiation, and survival of neurons, neuronal plasticity, food intake, peripheral metabolism, and endocrine functions.

Hot Spots for the Use of Intranasal Insulin: Cerebral Ischemia, Brain Injury, Diabetes Mellitus, Endocrine Disorders and Postoperative Delirium.

A decrease in the activity of the insulin signaling system of the brain, due to both central insulin resistance and insulin deficiency, leads to neurodegeneration and impaired regulation of appetite, metabolism, endocrine functions. This is due to the neuroprotective properties of brain insulin and its leading role in maintaining glucose homeostasis in the brain, as well as in the regulation of the brain signaling network responsible for the functioning of the nervous, endocrine, and other systems. One of the approaches to restore the activity of the insulin system of the brain is the use of intranasally administered insulin (INI).

Association of the Serum Folate and Total Calcium and Magnesium Levels Before Ovarian Stimulation With Outcomes of Fresh Fertilization Cycles in Normogonadotropic Women.

Background: Women of reproductive age are recommended to consume folic acid and other supplements before conception and during pregnancy. We aimed to investigate the association of the serum folate and total magnesium (Mg) and calcium (Ca) levels before ovarian stimulation with the outcomes of assisted reproductive technology (ART) in normogonadotropic women.

Methods: We used a subanalysis of data obtained from a multicentre, randomized prospective study (NCT03088137).

Insulin and α-Tocopherol Enhance the Protective Effect of Each Other on Brain Cortical Neurons under Oxidative Stress Conditions and in Rat Two-Vessel Forebrain Ischemia/Reperfusion Injury.

Clinical trials show that insulin administered intranasally is a promising drug to treat neurodegenerative diseases, but at high doses its use may result in cerebral insulin resistance. Identifying compounds which could enhance the protective effects of insulin, may be helpful to reduce its effective dose. Our aim was thus to study the efficiency of combined use of insulin and α-tocopherol (α-T) to increase the viability of cultured cortical neurons under oxidative stress conditions and to normalize the metabolic disturbances caused by free radical reaction activation in brain cortex of rats with two-vessel forebrain ischemia/reperfusion injury.

The effect of metformin treatment on the basal and gonadotropin-stimulated steroidogenesis in male rats with type 2 diabetes mellitus.

Type 2 diabetes mellitus impairs reproductive functions in men, and important tasks are deciphering the mechanisms of testicular dysfunctions in diabetes and the search of effective approaches to their correction. The purpose was to study the effect of four-week metformin treatment (120 mg kg  day ) of male Wistar rats with high-fat diet/low-dose streptozotocin-induced type 2 diabetes on basal and gonadotropin-stimulated steroidogenesis, intratesticular content of leptin and the leptin and luteinising hormone receptors and on spermatogenesis. Diabetic rats had hyperleptinaemia, androgen deficiency and reduced sperm count and quality, and in the testes, they had the increased leptin level and the decreased content of the leptin and luteinising hormone receptors and 17-hydroxyprogesterone.

Normalization of Testicular Steroidogenesis and Spermatogenesis in Male Rats with Type 2 Diabetes Mellitus under the Conditions of Metformin Therapy.

One of the complications of type 2 diabetes mellitus in men is steroidogenic and spermatogenic dysfunctions. There is evidence of a restoring effect of the antidiabetic drug metformin on them. We studied the effect of MF therapy (4 weeks, 200 mg/kg/day) on the hormonal parameters of the gonad axis and on the morphological characteristics of epididymal spermatozoa in male rats with a severe form of T2DM caused by a high-fat diet and a low-dose streptozotocin.

Intranasal Administration of Insulin and Gangliosides Improves Spatial Memory in Rats with Neonatal Type 2 Diabetes Mellitus.

We analyzed the effects of intranasal administration of insulin (0.48 U/rat) and gangliosides (6 mg/kg) on spatial memory in rats with the neonatal model of the type 2 diabetes mellitus. The development of diabetes was verified by the glucose tolerance test.

[The effect of high-dose metformin on the metabolic parameters and functional state of the liver of agouti-mice with the melanocortin obesity.].

In recent years, the effectiveness of high-dose metformin (MF) to treat the endocrine and oncological diseases has been shown. However, the use of high-dose MF may be associated with the lactic acidosis and the liver dysfunctions. The aim of the work was to study the effect of long-term (10 days) oral administration of a relatively high dose of MF (600 mg/kg per day) into yellow C57Bl/6J (Ay/a) Agouti line mice with the melanocortin type obesity on the liver function, which was evaluated by the morphology of hepatocytes and the severity of steatosis, the expression of the inflammatory and apoptotic factors of and the activity of aminotransferases, as well as on the plasma lactate level in the animals.

A multicenter, randomized, phase III study comparing the efficacy and safety of follitropin alpha biosimilar and the original follitropin alpha.

Objective: The aim of the present study was to investigate the therapeutic equivalence between the follitropin alpha biosimilar and the reference medication in women undergoing assisted reproductive technologies (ART).

Study Design: This multicenter, randomized (1:1), embryologist-blinded, parallel-group, comparative phase III study involved 110 women aged 20-35 years old with tubal and/or male factors of infertility. All of the subjects underwent controlled ovarian hyperstimulation (COH) using a gonadotropin-releasing hormone antagonist (GnRH-ant) protocol.

The Protective Effect of Insulin on Rat Cortical Neurons in Oxidative Stress and Its Dependence on the Modulation of Akt, GSK-3beta, ERK1/2, and AMPK Activities.

Insulin is a promising drug for the treatment of diseases associated with brain damage. However, the mechanism of its neuroprotective action is far from being understood. Our aim was to study the insulin-induced protection of cortical neurons in oxidative stress and its mechanism.

[The effect of different types of bariatric surgery on the metabolic and hormonal parameters in rats with decompensed form of type 2 diabetes mellitus.].

Currently, one of the approaches to correct metabolic disorders in the type 2 diabetes mellitus (DM2) with obesity are bariatric surgery (BS), including sleeve gastrectomy (SG), gastric bypass (GB) and ileal transposition (IT). However, their effectiveness and impact on the hypothalamic signaling and hormonal status in severe forms of DM2 without obesity remain little studied. The aim of the work was to study the effect of IT, SG and GB on the insulin, leptin, ghrelin and glucagon-like peptide-1 (GLP-1) levels in the blood and on the expression of the genes encoding the main components of the hypothalamic signaling systems in rats with decompensated form of DM2, which was induced by a high-fat diet (3 months) and a single low dose of streptozotocin (25 mg/kg, 2 months after the start of the diet).

An enhanced clot growth rate before in vitro fertilization decreases the probability of pregnancy.

Background: The shift towards hypercoagulation during in vitro fertilization (IVF) can lead to the impairment of embryo implantation and placental blood circulation, which is believed to be a factor in an unsuccessful IVF cycle.

Objectives: To assess coagulation in women with infertility before the start of an IVF cycle and during treatment to reveal the association between coagulation imbalance and IVF outcome.

Patients/methods: We conducted a prospective cohort observational study including 125 participants who underwent fresh IVF cycles.

The evidence of metabolic-improving effect of metformin in Ay/a mice with genetically-induced melanocortin obesity and the contribution of hypothalamic mechanisms to this effect.

In diet-induced obesity, metformin (MF) has weight-lowering effect and improves glucose homeostasis and insulin sensitivity. However, there is no information on the efficiency of MF and the mechanisms of its action in melanocortin-type obesity. We studied the effect of the 10-day treatment with MF at the doses of 200, 400 and 600 mg/kg/day on the food intake and the metabolic and hormonal parameters in female C57Bl/6J (genotype Ay/a) agouti-mice with melanocortin-type obesity, and the influence of MF on the hypothalamic signaling in obese animals at the most effective metabolic dose (600 mg/kg/day).

[Features of the changes in lipid peroxidation and activity of Na+/K+-ATPase in the brain of the aged rats in the conditions of two-vessel cerebral ischemia/reperfusion.].

The success of preclinical neuroprotection studies depends on the model used in animal research. The methodological approaches developed on young animals and widely used for modeling cerebral ischemia/reperfusion injury may not be so effective or not suitable for its modeling on senescent animals, which usage is recommended for preclinical trials. The aim of this study was to investigate the age-related features on the effect of brain reperfusion with different duration (1 and 3 h) after 2-vessel forebrain ischemia on the level of lipid peroxidation (LPO) products and on the activity of Na+/K+-ATPase in the cerebral cortex of rats aged 22-24 months.

Insulin Increases Viability of Neurons in Rat Cerebral Cortex and Normalizes Bax/Bcl-2 Ratio under Conditions of Oxidative Stress.

We studied the protective effect of insulin in various concentrations and its effect on the Bax/ Bcl-2 ratio in neurons of rat cerebral cortex under conditions of oxidative stress. The protective effect of insulin was dose-dependent within the nanomolar range (1 nM<10 nM<100 nM). Preincubation with insulin in concentrations of 100 nM and 1 μM significantly increased Bcl-2 content in neurons in 5, 30, and 45 min and 1, 2, and 4 h after the start of cell exposure to HO.

Metabolic parameters and functional state of hypothalamic signaling systems in A/a mice with genetic predisposition to obesity and the effect of metformin.

The metabolic parameters and functional state of hypothalamic systems in mice with the Yellow mutation in the Agouti locus and with obesity of the melanocortin type and the effect of metformin (MF) treatment (9 days, 200 mg/kg/day) were studied. The MF treatment led to decreased body weight and to normalization of glucose tolerance in mice. In the hypothalamus, MF restored the decreased activity of Akt kinase, the main component of leptin pathway, and normalized the increased expression of subtype 1B serotonin receptor.

[Metabolomic profiling in culture media of day-5 human embryos].

The aim of this study was to determine the changes of metabolomic profiles in embryonic culture media (ECM) for the evaluation of quality and implantation potential of human embryos. ECM (n=163) were collected on day 5 before transfer or cryopreservation. Some embryos were used in preimplantation genetic screening for detection of aneuploidy karyotypes.

Mitral and Aortic Valvulitis in Primary Chronic Septic Endocarditis.

Results of long-term prospective follow-up of patients with early stages of mitral and aortic valvulitis and primary chronic septic endocarditic are presented. Clinical diagnostics of the diseases is described and the key role is assigned to pathognomic (absolute) clinical symptoms. The tendency to progressive fibrosis of endocardial structures with subsequent gradual development of valve dysfunction and stenosis (especially for the mitral valve) is revealed.

[Cone-beam computed tomography in paleoanthropology].

Objective: To study the capabilities of cone-bean computed tomography (CBCT) in estimating the bone structure when analyzing anthropological findings.

Material And Methods: Twenty-four bone fragments (remains) of Napoléon Bonaparte Imperial Army soldiers who had died at a Königsberg military hospital during their retreat from Russia in the War of 1812 were examined by CBCT. A total of 28 tubular bones with different injury healing signs and a skull with maxillofacial trauma marks were investigated.

[Catecholamine content in the adrenal gland of rat offspring in the model of prenatal hyperhomocysteinemia].

Catecholamine content has been studied in the adrenal gland of rat females whose pregnant mothers were loaded daily with L-methionine administered per os during all the pregnancy period, on the first day of postnatal life, and in one and two months after birth. The animal model of hyperhomocysteinemia used in the experiment has been shown to result in the catecholamine content decreasing in the adrenal gland of both newly born rat offspring with high serum level of homocysteine and one-month old offspring with their homocysteine level decreased to the normal values. It was found that nitrotyrosine level increased significantly in the blood serum of the offspring aged one and two months.

Early echocardiographic manifestations of primary chronic septic endocarditis.

Echocardiographic manifestations of the early stages of primary chronic septic endocarditis are studied in patients with mono-, bi-, and multivalvular valvulitis. The basic morphological substrate of the disease is fibrosis; the main trend is progressive fibrosis of valvular and extravalvular endocardial structures leading in many cases to stenosis of the valvular orifices. The results in some cases do not permit us to regard fibrosis as a result of previous "healed" endocarditis ruling out the presence of an inflammatory process.

[Prenosological neuropsychiatric disorders among schoolchildren and their relationship to environmental factors].

Environmental factor is one of the most accurate indicators of determining the health of the population, especially in childhood and adolescence. A significant increase in the amount of data on the status of school health and the environment are the most precise and correct, in view of causation, to evaluate an individual's health at prenosological level in the presence of a specialized database of automated systems. The aim of our study--the study of fundamental interactions and patterns of environmental factors in general and neuropsychiatric disease in schoolchildren of the city of Chelyabinsk.

[Differential radiodiagnosis of odontogenic mandibular osteomyelitis accompanied by trigeminal neuropathy].

This paper deals with the results of radiation examination in 43 patients with clinical manifestations of mandibular osteomyelitis. In 13 of them, the disease was accompanied by trigeminal neuropathy. The radiation semiotics of the changes occurring in the mandibular bone and its adjacent soft tissues in different phases of osteomyelitis is described.

[Multislice spiral computed tomography in the diagnosis of osteomyelitis].

This paper deals with the results of a radiation study in 34 patients with the clinical manifestations of maxillofacial osteomyelitides. It describes the radiation semiotics of changes occurring in the bone and its surrounding soft tissues of the maxillofacial region in different phases of osteomyelitis. Comparative analysis of orthopantograms and images obtained by multislice spiral computed tomography revealed the benefits of the latter in detecting soft tissue changes and subtle bone alterations.

[The psychophysiological status of school children going to educational establishments of different kinds].

The paper presents the results of hygienic studies of the psychophysiological status of school children going to educational establishments of different kinds, which have established the best psychophysiological status in intensively taught schoolchildren.