[Targeting NMDAR/AMPAR: a promising pharmacotherapeutic approach for depressive disorders]. / Targetirovanie NMDAR/AMPAR ­ perspektivnyi podkhod farmakokorrektsii depressivnykh rasstroistv.

Depression is a leading cause of disability and reduced work capacity worldwide. The monoamine theory of the pathogenesis of depression has remained dominant for many decades, however, drugs developed on its basis have limited efficacy. Exploring alternative mechanisms underlying this pathology could illuminate new avenues for pharmacological intervention. Targeting glutamatergic pathways in the CNS, particularly through modulation of NMDA and AMPA receptors, demonstrates promising results. This review presents some existing drugs with glutamatergic activity and novel developments based on it to enhance the efficacy of pharmacotherapy for depressive disorders.

[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.

[Characteristics of purchases of hypoglycemic agents in pharmacy retail sector in 2016-2020 years dynamics].

BACKGROUND: Procurement of medicines reflects the demand and frequency of prescribing certain drugs, which makes it possible to assess the quality of medical care and compliance with standards. The Russian pharmaceutical market is dynamically developing and expanding, therefore, the commercial sector of drug circulation is a significant part of it and should be studied along with public procurement. Given the significant number of patients diagnosed with diabetes mellitus (DM) in our country, we considered it appropriate and interesting to analyze the structure and volume of turnover of antidiabetic drugs in the retail trade over five years. AIM: to assess the dynamics of the cost and sales volumes of hypoglycemic drugs in the commercial sector for 2019-2020 compared to 2016. MATERIALS AND METHODS: The analysis was made on the basis of the data of antidiabetic drugs purchases in Russian pharmacies in 2016 and 2019-2020, according to 95257 pharmacies data. RESULTS: In 2020, compared to 2016, we see a significant increase in the number of packages purchases (+14,952,897 rub.) and the purchases total amount (+9,377,975,722 rub.), in parallel with the increase in average price per box of the hypoglycemic drug +199, 57 rub. The average price for DPP4 decreased. The cost per pack of metformin remains one of the lowest, second only to glibenclamide and gliclazide. The most expensive drugs include GLP1 group representatives. Insulin purchases have halved, when budget for GLP1 have increased by 10 times, for SGLT2 by 9.5 times, and for DPP4 by 2.1 times. In 2020, metformin gliclazide, a combination of glibencladimide with metformin, glibenclamide and vildgaliptin remain leaders in the number of purchased packages. The purchase leaders in terms of budget share are: metformin, gliclazide, liraglutide, vildagliptin and dapagliflozinCONCLUSION: There are positive trends in the demand for more effective innovative hypoglycemic drugs, however, the affordability of drugs still dominates over the feasibility of their clinical use, and a high percentage of drug turnover in the commercial sector might indicates insufficient funding for drug provision for patients with diabetes mellitus.

[Does an attempt to save a limb always prolong the patient's life?] / Vsegda li popytka sokhranit' konechnost' prodlevaet zhizn' patsienta?

AIM: The purpose of the study was to examine overall survival and the incidence of major adverse cardiovascular events, as well as economic expenditures for treatment of patients with occlusion of the femoropopliteal-tibial segment and critical ischaemia in low competence of the outflow channel, with a poor prognosis for endovascular or open revascularization of lower-limb arteries. PATIENTS AND METHODS: We studied the results of treating a total of 68 patients with lower-limb critical ischaemia and low parameters of the outflow channel competence. Primary arterial reconstruction was performed in 48 cases. At various terms after revascularization due to thrombosis of the reconstruction zone and the development of gangrene, amputation of the lower limb was performed: at 3 to 11 (n=25) and at 12 to 24 (n=25) months. Primary amputation of the lower limb was performed in 20 patients. The endpoints of the study included overall survival, the incidence of major adverse cardiovascular events, and economic expenditures for the in-hospital treatment. The average duration of follow-up amounted to 2 years. RESULTS: The obtained findings demonstrated that in patients with lower-limb critical ischaemia and low parameters of the outflow channel competence, redo arterial reconstructions and amputation within 11 months, as well as a high level of surgical risk were associated with a low overall survival rate and the development of major adverse cardiovascular events in the remote period. Secondary surgical interventions on the major vessels significantly increased the cost of treatment.

[Outcomes of revascularizing operations on lower-limb arteries in patients with critical ischaemia and multifocal atherosclerosis]. / Iskhody revaskuliariziruiushchikh operatsii na arteriiakh nizhnikh konechnostei u bol'nykh s kriticheskoi ishemiei i mul'tifokal'nym aterosklerozom.

The purpose of this study was to evaluate the amputation-free survival rate and predictors of major adverse cardiovascular events (extracardiac and cardiac mortality, non-fatal myocardial infarction, non-fatal stroke) in patients with atherosclerotic occlusive-stenotic lesions of the femoropopliteal-tibial segment and critical ischaemia. We analysed the results of treating a total of 122 patients with atherosclerotic lesions of the superficial femoral artery and lower limb critical ischaemia. Of these, 35 patients had no lesions of other arterial basins, 24 patients presented with a concomitant lesion of the carotid basin, 41 subjects had lesions of the coronary basin, and 22 had lesions of the coronary and carotid basins. The patients were subjected to either bypass graft operation (n=75) or endovascular intervention (n=47). The evaluated outcome measures were amputation-free survival and the frequency of major adverse cardiovascular events. The average duration of follow up amounted to 38.2±4.3 months. The carried out multivariate logistic regression analysis demonstrated that the factors associated with lower limb amputation and the development of major adverse cardiovascular events were as follows: a concomitant lesion of the coronary (p=0.044) and coronary-carotid (p<0.05) basins, a history of endured myocardial infarction (p=0.003), a C-reactive protein level not less than 17.0 mg/l (p<0.05) and the value of the apolipoprotein B/A1 ratio above 1.0 (p=0.004).

[THE REGIONAL EXPERIENCE OF ORGANIZATION OF SELECTION AND REFERRAL OF PATIENTS TO "THE FEDERAL CENTER OF CARDIOVASCULAR SURGERY"].

The organization of accessible high-tech medical care is one of instruments of implementation of public health policy. This type of medical care decides primarily the issue of decreasing of mortality and disability of diseases of blood circulatory system increasing quality and duration of life of patients. The article presents the analysis of system of selection and referral of patients in need of specialized, high-tech included, medical care in «The Federal center of cardiovascular surgery¼ (Perm). The retrospective analysis id applied concerning functioning of this medical organization in 2012-2014.

[Diagnostic peculiarities, surgical policy, and efficacy of reconstructive operations in pathological tortuosity of internal carotid arteries].

We examined a total of 88 patients presenting with unilateral pathological tortuosity of internal carotid arteries (PT ICA), who were subjected to reconstructive interventions. The patients underwent ultrasound duplex scanning of brachiocephalic arteries, CT angiography of the brain, and assessment of cognitive functions according to the Montreal scale (MoCA test). It was proved that absolute indications for operative intervention in patients with pathological tortuosity of ICA comprise coiling, and in kinking - an increase in the linear blood velocity greater than 180 cm/s. Perfusion CT makes it possible to objectively assess the state of blood supply to the cerebral hemispheres. CT angiography of ICAs with 3D reconstruction makes it possible to reveal microaneurysms of the vascular wall in the area of pathological tortuosity. PT leads to deficit of cognitive functions, and performing reconstructive operations improves cognitive functions after 6 months in stage III chronic cerebrovascular insufficiency in 91% of cases, and in stage IV - in 55%.

[Heat and cardiovascular diseases: A review of epidemiological surveys].

The review summarizes epidemiologic data on the effects of heat on cardiovascular morbidity and mortality. Patients with heart failure and cardiac arrhythmias are most susceptible to negative heat exposure. At the same time, measures aimed at preserving the health of the population lead to a considerable reduction in losses associated with an abnormal rise in air temperature.

[Peculiarities of diagnosis and surgical policy in elderly patients with pathological tortuosity of the internal carotid artery].

The study was aimed at optimizing surgical treatment management of elderly patients presenting with pathological tortuosity of the internal carotid artery (ICA). We examined a total of 94 patients with unilateral haemodynamically significant tortuosity of the ICA. Depending on the age, the patients were subdivided into two groups: Group One comprising forty-six (49%) 50-to-60-year-old patients and Group Two consisting of 48 (51%) patients above 60 years (from 61 to 84 years). 37% of patients had were found to have pathological tortuosity combined with haemodynamically significant ICA stenosis. In these patients linear blood velocity in the zone of the largest deformation was by 15% less than in patients with isolated tortuosity (p<0.05). All patients underwent reconstructive operations of carotid arteries with a good clinical effect. A combination of stenosis and pathological tortuosity of the ICA was treated by eversion carotid endarterectomy with lowering down and reimplantation of the artery into the previous ostium; microaneurysms present in the ICA wall were managed by resection of the artery's portion with autovenous prosthetic repair or bringing down the artery into the previous ostium. In 77% of patients above 60 years the operation was carried out under regional anaesthesia. According to the findings of duplex scanning, rectilinearity of the ICA after surgery was restored in 100% of cases, blood flow was of major type, with no turbulence registered. It was demonstrated that surgical management of elderly patients with pathological tortuosity is an effective method of prevention of ischaemic stroke. The complications rate in patients presenting with combined atherosclerotic lesions of the ICA and its pathological tortuosity, should adequate surgical policy be employed, falls within the framework of the accepted standards and does not depend on the type of ICA lesion.

[Effect of 17ß-estradiol on bioenergetic processes in the heart mitochondria of ovariectomized rats with insulin resistance].

Тhe bioenergetic processes in the heart mitochondria of Wistar rats with fructose-induced insulin resistance was investigated in female animals with different estrogen status. Respiration studies on isolated heart mitochondria by the polarographic method revealed that estrogen deficiency reduced complex IV activity, while its combination with high-fructose diet induced additional disturbances in the coupling of respiration and oxidative phosphorylation at the level of complex I of the electron transport chain. Exogenous 17b-estradiol inhibited the development of mitochondrial dysfunction in cardiomyocytes of ovariectomized rats with insulin resistance.

[Spring water quality assessment regarding the problem of endemic fluorosis].

A possible variant for reducing the consumption of fluoride by population of Tver region is the use of water with low fluoride content, such as spring water. Assessment of drinking suitability of spring water (the content of physiologically important mineral elements and microbial purity) is relevant to our region. Water samples from 6 spring-water source of Tver region were studied during the year. The content of fluoride and calcium were measured by using an ion-selective electrodes. Microbiological purity tested by the presence of total coliform bacteria, thermotolerant coliform bacteria, coliphages and total microbial numbers. The analysis of some mineral components in spring water of Tver region showed that calcium content was in range 33-88 mg/l, that satisfied the recommended value; fluoride concentration is less then 0.5 mg/l. In all spring water samples total coliforms, thermotolerant coliforms and coliphages were absent. The total microbial number was in standard range, except of two spring-water source in the autumn and summer. The data suppose that spring water of Tver region can be used as a component of diet normalizing the fluoride consumption at risk of dental fluorosis in children.

[Toxicity modifying action of remaxol by treatment of advanced oral cancer].

The efficiency of remaxol for prevention and treatment of chemoradiotherapy toxicity effects in patients with advanced oral cancer was evaluated. Ninety-five oral cancer patients were using remaxol both locally (mouth rinse solution) and by intravenous infusion, 87 patients were included in control group. Intravenous remaxol proved to be effective for mucositis and nephrotoxicity prevention by chemoradiotherapy.

[Role of intraosteal administration of antibiotics in treatment of local oral mucinous carcinoma].

The problems of prophylaxis of infectious complications in the treatment of oral local mucinous carcinoma are considered relevant to 204 respective cases. More favourable results of the combined and complex treatment of the patients were shown when a multidisciplinary approach was used with obligatory participation of stomatologists. Special stomatologic prophylactic and therapeutic procedures with using reamberin orally and intravenously in the chemo- and radiotherapy and adequate antibiotic therapy during the surgical operation resulted in less frequent infectious complications, that was in favour of the patients life quality. Intraosteal administration of antibiotics was shown preferable.

[Supportive therapy for locally advanced cancer of the oral mucosa].

The article discusses the practice of detoxication therapy to minimize undesirable toxic effects during chemo- and radiotherapy for locally advanced cancer of the oral mucosa in 88 patients treated with 1.5% solution of reamberine. There was a significant improvement in the parameters of liver function, as well as in the general wellbeing of patients. We analyzed the main symptoms of the toxicity of chemo- and radiotherapy in both groups. Inclusion of the reamberine solution as supportive therapy for cancer patients who were receiving chemo- and radiotherapy for cancer of the oral mucosa allowed reducing the number and severity of toxic complications.

[Anxiosedative properties of heteryl(aryl)-containing hexahydrobenzofuranon derivatives].

The anxiosedative properties of 2-hydroxyimino-3-indolylyl(aryl)-4-oxo-2,3,4,5,6,7-hexahydrobenzofuranon derivatives have been studied using the open-field test, elevated plus-maze test, and conflict drinking procedure as developed by Vogel. It is established that all derivatives with both indole and aryl substituents produce a sedative effect. However, an anxiolytic effect is determined by the presence of indole substituent in the third position of the hexahydrobenzofuran molecule.

[Reaction of monoamine-containing structures of rat spleen to acupuncture].

Using the method of luminescent microscopy, the catecholamine (CA) and serotonin (S) content was examined in spleen structures, and the interrelations between them were traced in rats before and 15 minutes, 1, 2 and 4 hours after the acupuncture in LI 4 and GV 14 points. It was found that after acupuncture, neurotransmitter content in splenic red and white pulp was changed already in 15 minutes. The changes of CA and S content in granular luminescent cells (GLC) of the germinal centers of spleen lymphoid nodules had a wavy character. At the same time, the correlations between monoamine content in the central arteriole wall and in germinal center GLCs, as well as that one between GLCs and germinal center lymphocytes, became strong positive. The data obtained suggest the presence of an immune-stimulating component in acupuncture, which became apparent during the first hour and persisted for 4 hours after a single acupuncture in GV 14 and LI 4 points.

Microarray study of gene expression in uterine leiomyoma.

UNLABELLED: Uterine leiomyoma is a most common benign neoplasm in women of reproductive age. It arises from the myometrial compartment of the uterus and may transform in some cases to a malignant phenotype. AIM: To identify the genes involved in pathogenesis of uterine leiomyoma. METHODS: We have studied differential gene expression in matched tissue samples of leiomyoma and normal myometrium from the very same people utilizing a cDNA microarray screening method. We also compared our results with previously published microarray data to identify the overlapping gene alterations. RESULTS: Based on this comparison we can divide genes deregulated in our study into two groups. The first group comprises genes that to our knowledge have not been previously reported as deregulated in fibroids: CLDN1, FGF7 (KGF), HNRPM, ISOC1, MAGEC1 (CT7), MAPK12, RFC, TIE1, TNFRSF21 (DR6). The second group consists of genes identified also in previous studies: CCND1 (BCL1), CDKN1A (P21), CRABP2, FN1 and SOX4 (EVI16). In our study FN1 was the most up-regulated gene, occupying the place between the myometrium and fibroids ranging from 2.07 to 3.64, depending of the probe molecule used for detection. CONCLUSIONS: Newly identified genes may be regarded as potential diagnostic or prognostic markers of uterine leiomyoma and thus may be very useful as new therapeutic candidates.

[Polymerase chain reaction to determine and control drug-resistant Mycobacterium tuberculosis strains].

Real-time polymerase chain reaction was used to develop a one-stage procedure for molecular genetic analysis of Mycobacterium tuberculosis (MBT) DNA in order to determine mutations associated with drug resistance to the antituberculous agents: isoniazid and rifampicin. To analyze the spread of drug-resistance of the causative agent of tuberculosis in Russia, two thousand MBT strains were studied in 24 regions of all the federal districts. Testing 1406 MBT strains isolated by first detected and untreated patients revealed multidrug resistance (MDR) in 21.9% of cases. MRD was detected in 58.5% of the previously treated patients with MDR. The agreement of molecular genetic analysis of drug resistance with the results of cultural tests of 1096 strains was 94%.

[Results of using biocoating by means of the amniotic sac. Communication 2. Biocoating for the treatment of keratitis].

The amniotic sac has recently come into wide use to treat patients with various corneal lesions. Its suture fixation to the conjunctiva has proven to be inadequate, which limits its therapeutic effect. It is not quite expedient to use a donor corneoscleral flap for amniotic sac fixation in the existing shortage of a plastic material for keratoplasty. Longer retention of the amniotic sac on the involved cornea is achieved by the authors' technology that is to prescarify the ulcerated corneal surface, to set the preserved amniotic sac onto the surface, by grasping the limbal region of a graft, to place a ring-shaped donor layer or full-thickness corneoscleral flap cut out of a donor eye from which a corneal graft has been previously taken to be transplanted to another patient, to fix a ring-shaped flap together with the amnion with 8-00 interrupted sutures to the conjunctiva and episclera of a patient's eye. Twenty-nine patients with long non-healing corneal surface layer defect were operated on. Ten days after biocoat removal, complete corneal epithelization was revealed in 21 patients, defect substantially reduced in 8 patients, in them complete epithelization occurred in the outpatient setting following 5-7 days.