IgG Stimulates the Formation of Neutrophil Extracellular Traps and Modifies Their Structure.

We studied the neutrophils and monocytes obtained from 37 patients with various inflammatory diseases such as psoriasis, acute infectious process in the abdominal cavity (acute appendicitis/abscess of the abdominal cavity, and acute cholecystitis), acute pancreatitis, and post-COVID syndrome after mild COVID infection. The number and the morphological structure of neutrophil extracellular traps (NET) as well as the effect of IgG on NET were examined. NET were visualized and counted by fluorescence microscopy with fluorescent dye SYBR Green. All the studied types of inflammation were accompanied by spontaneous formation of NET. After application of IgG, the number of NET doubled, their size increased, and transformation of net-like traps into the cloud forms was observed. The clouds form structure of the network is not capable of capturing pathogens with subsequent retraction, the products of its enzymatic degradation can be the factors of secondary alteration. The study results demonstrate a previously unknown mechanism of infection resistance.

[Risk factors of surgical treatment of acute aortic dissection type A (in Russian only)]. / Faktory riska khirurgicheskogo lecheniia u bol'nykh s ostrym rassloeniem aorty tipa A.

AIM: To evaluate risk factors of surgical treatment of acute aortic dissection type A. MATERIAL AND METHODS: Retrospective analysis included 100 patients with acute aortic dissection type A who underwent surgery in 2007-2017. Patients were divided into 2 groups: group I (survivors, n=79) and group II (unfavorable outcomes, n=21). RESULTS: Postoperative in-hospital mortality was 21% (21/100). Preoperative risk factors were cardiac tamponade (p=0.0001), aortic rupture (p=0.0001), impaired coronary blood flow (p=0.0001), renal malperfusion (p=0.0001). Prolonged cardiopulmonary bypass (156.1±37.9 min vs 205.7±91.2 min), surgery time (5.0±1.1 vs. 6.8±2.5 h, p=0.0009) and deep hypothermia (26.1±4.6 min vs 22.4±4.4 min) were the main intraoperative risk factors influencing surgical outcomes in patients who underwent aortic arch repair. Multiple organ failure (p=0.0001), sepsis (p=0.0007), severe postoperative bleeding (p=0.0010) and disseminated intravascular coagulation (p=0.0001) were the main predictors of advanced mortality in postoperative period. CONCLUSION: Timely surgical treatment in case of cardiac tamponade and aortic rupture is essential to improve survival in patients with acute aortic dissection. Advanced aortic repair including hemi- or total arch replacement should be comprehensively measured because such procedures may be followed by increased postoperative morbidity and mortality after emergency aortic surgery.

Regularities of free radical processes and involutional changes of face and neck skin in different age groups.

AIM: The purpose of this study was to examine the role of free radical oxygen and peroxide- lipid processes along with conducting the study of blood flow level and oxygen saturation of facial tissues in patients of different ages with varying degrees of involutional changes in the skin of the face and neck. MATERIALS AND METHODS: One hundred and fifty-three people (84.3% women and 15.7% men) aged from 26 to 78 years with varying degrees of involutional changes in facial skin were examined. The clinical and laboratory evaluation was carried out dynamically and included various indicators of free radical processes, objective and subjective clinical visualization, and laser Doppler flowmetry (LDF) of the facial skin and transcutaneous oximetry (TcpO2) performed at 10 points on the face. To assess the state of free radical processes, the authors investigated the basal indicator of chemiluminescence intensity (ICb), the intensity of chemiluminescence stimulated (ICs) by zymosan, the activity coefficient (AC) of chemiluminescence, antiperoxide activity of plasma, and malondialdehyde (MDA). RESULTS: With aging, the imbalance of the oxygen constituents of free radical processes grows with the increase in ROS. Proportional to age, the ICs increased 2.1 times on average in people older than 55 years compared to that in people younger than 30 years and ICb decreased by 1.8 times. As a result, the AC increased by 5.6 times. This correlates with involuntary skin changes and with regression of microcirculation and TcpO2. According to LDF, it was established that average total blood flow in people younger than 30 years and people older than 55 years was 8.1 and 6.4 mL/min, respectively The difference between the indicators of TcpO2 in people younger than 30 years and people older than 55 years was 1.6 times (average 56 vs 35 mm Hg). The stability of the indicators of the peroxide-lipid link of oxidative stress in different age groups demonstrated that the activation of ROS formation in mitochondria is not a cause but a consequence of microcirculation and metabolic processes in the face and neck and aging in general. CONCLUSION: The tissue metabolism and microcirculation parameters naturally regress with aging, which is associated with the increase of ROS. The excess of species leads to the intensification of peroxide processes. This, in turn, is reflected in the aesthetic appearance manifested by aging.

Influence of pharmacological preconditioning on the results of lifting operations efficiency.

The main aim of the study is to determine the effectiveness and safety of lifting operations in women with varying degrees of involuntary changes of facial skin, in particular when applying pharmacological conditioning, with the objectification of the role of the latter. MATERIALS AND METHODS: A research and surgical treatment were conducted to eliminate involutional changes of various degrees in the facial skin of 461 women aged 35-75 years. Surface lifting was performed in 20.2% of patients, SMAS-lifting - 49.0%, SMAS-lifting with a three-level endoscopic assist lift of the lower face zone was performed in 30.8% of women. Before the surgery in 13.2% of cases, I degree of involutional changes in facial skin was registered, 47.9% - grade II, 38.9% - grade III. Patients were divided into two comparable groups. With the standard preparation without additional drug correction, 299 women (64.9%) were operated on in the preoperative period, they made up a comparison group. The main group included 162 (35.1%) women who underwent therapeutic conditioning before the lifting operation (Cytoflavin, n = 86; Actovegin n = 23; Ethylmethylhydroxypyridine succinate, n = 32; Meldonium, n = 21; Pentoxifylline, n = 31; Vinpocetine n = 27). Instrumental evaluation of the skin dermal microcirculation was performed using laser Doppler flowmetry and estimation of transcutaneous oxygen tension. In the blood plasma, the parameters of free radical processes (FRP) were studied. FRP were studied in terms of generation of active oxygen forms by leukocytes - intensity of chemiluminescence basal and intensity of chemiluminescence stimulated, as well as antiperoxide plasma activity and malondialdehyde. Early postoperative complications were analyzed, the number of repeated lifting surgical corrections on the face was studied for 5 years. RESULTS: The role of FRP in the pathogenesis of involuntary changes in the facial skin has been established. The imbalance of FRP was expressed in the intensification of the reactive oxygen species generation and products of lipid peroxidation. This correlated with disorders of cutaneous microcirculation and a decrease in the saturation of the facial tissues with oxygen, manifested by an increasing energy deficit and the severity of involutional skin changes. The obtained data justify the expediency of using pharmacological conditioning with energy correcting antioxidant medicine. Preoperative conditioning allowed to reduce the number of early postlifting complications associated with tissue trophism in a quarter, especially during surface lifting. In addition, in the preconditioning group, the scar was more cosmetic already at the seventh day after the operation. Based on the study of postoperative catamnesis, self-assessment data and laboratory-instrumental methods of skin system examination in people of different ages, it was revealed that while using SMAS-lifting with a three-level endoscopic-assisted lifting of the lower part of the face, the lowest frequency of complications and the best 5-year effectiveness were established.

[Expression of genes for neurotransmitter transporters in astrocytes in different brain regions in experiment]. / Ékspressiia genov transporterov neiromediatorov v astrotsitakh raznykh otdelov golovnogo mozga v éksperimente.

AIM: To investigate the expression of transporters of different neurotransmitters (glutamate, aspartate, lactate, choline) in the culture of astrocytes isolated from different regions of the brain (cortex, hippocampus and brainstem) in 3- and 11-day rats. MATERIAL AND METHODS: An experimental study was performed on 24 3- (n=12) and 11-days (n=12) old rats (Rattus norvegicus). The results of high-performance sequencing were analyzed. RESULTS: The expression of glutamate and aspartate transporters in the brainstem of 3-day rats was higher than in other regions, however, an opposite effect was observed in 11-day rats. The expression of lactate transporters with age became identical to those of the cortex. CONCLUSION: The data demonstrate the particular qualities of neuro-astrocytic connections and the important role of astrocytes in signal transmission. Results of the study performed by using genetic methods developed by the authors for the study of neurotransmitter transporters make it possible to recommend these methods to control the neurogenesis and neurohomeostasis, including in cerebrovascular and neurodegenerative diseases.

[Efficacy and safety of collagen biomaterial local application in complex treatment of the diabetic foot syndrome (final results of the multicenter randomised study)]. / Éffektivnost' i bezopasnost' mestnogo primeneniia kollagenovogo biomateriala v kompleksnom lechenii sindroma diabeticheskoi stopy (itogi mnogotsentrovogo randomizirovannogo klinicheskogo issledovaniia).

AIM: To evaluate the efficacy and safety of collagen biomaterial application during the 4-week follow-up of patients with diabetic foot syndrome. MATERIAL AND METHODS: 75 patients with diabetic foot (Wagner II (69.3%) and III (30.7%)) aged 30-80 years were included in the multicenter study, among them were 50.7% with the wound unhealed for 1.5-6 months and 49.3% over 6-48 months. Patients were randomized into 2 groups: 1) standard therapy (n=37), 2) the additional use of the collagen material Collost (n=38). Observation period was at least 4 weeks for each patient. The size of ulcers, results of general and biochemical blood tests, oximetry, microbiological testing, ultrasound of lower extremities vessels as well as a detailed medical history, social and functional status, level of cardiovascular comorbidity and ongoing therapy were estimated. RESULTS: Additional use of a collagen biomaterial has led to a significant reduction ulcers of all sizes from 13.5 to 2.1 cm2 (in the comparison group - from 12.5 to 7 cm2). The best dynamics have been registered in Wagner II (4.4-fold average wound area regress in Collost group, from 8.8 to 2.0 cm2; average wound area regress by 1.8 times, from 10 to 5.6 cm2 in the comparison group) than in Wagner III group (in the main group from 55 to 21.3 cm2; in the control group from 36 to 32.4 cm2) and in ulcers existing less than 6 months. Treatment with biological material Collost within standard therapy after 4 weeks led to increase of complete epithelialization by 2.6% (21.1% as compared to 14.7%), while decreasing the frequency of ineffective treatment by 4.1 (7.9% in primary and 32.4% in the comparison group). CONCLUSION: We have proved the efficacy and safety of collagen biomaterial topical application in a diabetic foot syndrome treatment.

[Assessment of changes in the lesions sizes and the incidence of complete epithelialization during the treatment of diabetic foot syndrome over a period of 4 weeks (multicenter study)]. / Otsenka dinamiki ploshchadi rany i chastoty sluchaev polnoi epitelizatsii pri lechenii sindroma diabeticheskoi stopy (rezul'taty mnogotsentrovogo issledovaniya).

AIM: To assess the effectiveness of the collagen biomaterial in treatment process in patients with DFS. MATERIAL AND METHODS: 71 patients 30-80 y.o. with diabetic foot syndrome of varying severity were included in prospective multicenter study. Patients were randomized into two homogeneous groups: control group (n=35) - standard therapy, other 36 patients (main group) were additionally treated with medical device (MD) Collost in accordance with the instructions for use. RESULTS: Biomaterial Collost using in complex treatment of diabetic foot syndrome resulted in more rapid and effective healing of the ulcer. The treatment success increased from 43% to 72%. Complete epithelialization was achieved by 2.6 times more rapidly in conjunction with reduction the incidence of unsuccessful treatment results by 4.1 times.

[Clinical and morphologic efficacy of a complex antioxidant and energy correction therapy of different duration in brain infarction: results of a multicenter randomized trial].

AIM: To compare clinical and morphological results of treatment of ischemic stroke in three groups of patients which differed by the forms and duration of an antioxidant therapy. MATERIAL AND METHODS: A randomized clinical trial was performed in 8 vascular centers of the Russian Federation in 2010-2014. It included 373 patients with ischemic stroke in the carotid territory. Patients were randomized into 3 groups to receive different regimens of antioxidant therapy as an adjunct to standard therapy: control group (ascorbic acid; 132 patients); cytoflavin (20 ml per day for 10 days; 133 patients); cytoflavin (the dose was decreased to 10 ml per day from 11th to 20th day) (108 patients). Patient's condition was assessed in 1, 10 and 21 day by a complex of clinical, laboratory and instrumental methods. RESULTS AND CONCLUSION: The analysis of CT in 1th and 21th day revealed a significant 1,5-1,7- fold decrease in the cerebral ischemic lesion in both groups treated with cytoflavin with no significant morphologic changes in the ascorbic acid group. The percentage of patients with ischemic lesion, increased during days 1-21, was 2-fold higher in the ascorbic acid group compared to cytoflavin groups. Morphologic changes were correlated with clinical variables and outcome. In patients with ≥14 points on NIH scale on admission, prolonged 20 day cytoflavin therapy was associated with a more prominent improvement of neurologic, functional and cognitive status compared to 10-day cytoflavin infusion. No differences in clinical variables were observed in patients with mild symptoms (<14 points on NIH scale on admission) receiving cytoflavin for 10 and 20 days.

[Clinical and Pathophysiological Correlations in Acute Stroke, CT Visualized at Different Times].

Two hundred twenty one patients aged 32-93 years with brain infarction, admitted to a Vascular Neurology Center in the first 3-48 hours (mean 6 hours) after the onset of the symptoms of stroke with computed tomography (CT) verified diagnosis were enrolled in the study. According to the timing of the CT-verification the patients were divided into 2 groups: "early" visualization (EV 50.2%) and "late" visualization (LV, 49.8%). In the EV group the lesion was visualized by CT on the admission (3-6 hours after the admission), in the LV group it was visualized only when CT was repeated 2-3 days after the admission. The patients in the LV group demonstrated increased severity of the underlying pathology, increased mortality and unfavourable functional outcomes correlating with the stroke lesion volume vs. the EV group. There was observed pathophysiological correlation of the blood enzymatic spectrum and acid-base balance parameters, explaining the late lesion visualization by delayed and more pronounced intracellular energy synthesis stabilization mechanisms failure in the aerobic and anaerobic glycolysis cycles.

[Performance evaluation of integrated cytoprotective therapy of different duration in patients with cerebral infarction].

The paper reviews the preliminary results of a multicenter randomized clinical research. The aim of the study was to determine the optimal duration of different types of energy-correction therapy. 99 case report forms of patients with cerebral infarction were reviewed with their prior envelope randomization into three groups. Patients in the first group (experimental group), consisting of 32 patients, as part of combined therapy received ascorbic acid (5% solution twice a day in a recommended dosage of 20 ml/day for 20 days); the second group (37 patients) received 10 ml of cytoflavin intravenously by drop infusion twice a day for 10 days; the third group received cytoflavin for 20 days (from day 1 to day 10 - 20 ml a day, from day 11 to day 20 - 10 ml a day). The average NIH scale score on admission was 14.9 ± 2.6. Prescription of cytoflavin came with average 1.7 - 1.8 time regression (p < 0.05) of the volumes of cerebral ischemia in the of cases of the 10- and 20-day courses of treatment, while there were no significant morphologic changes in the ascorbic acid group. These results correlated with the best dynamics and outcomes of the neurological and performance status of patients receiving cytoflavin. Despite the lack of significant general differences in the clinical and morphological data of the second and third groups, the patients with underlying grave medical condition in the 20-day cytoflavin group (with NIH score of 14-20 points on admission) tended to have improved neurologic status parameters in comparison with the experimental group and the 10-day cytoflavin group. These results attest to the advantages of personalized antioxidant energy-correction therapy.

[Efficacy of antioxidant energocorreсtion in brain infarction (results of a multicenter randomized trial)].

OBJECTIVE: To determine the optimal duration of energy corrective treatment of ischemic stroke (II) with cytoflavin or ascorbic acid. MATERIAL AND METHODS: A multicenter randomized clinical trial included 185 patients, aged 40-75 years. Patients were randomized into 3 groups: the control group (n=64) received ascorbic acid; cytoflavin group 1 (n=72) was treated for 10 days and cytoflavin group 2 (n=49) for 20 days. In all groups, mean NIHSS score was 13, 42.2% of patients scored ≥14 and on admission, 42.2% of patients had consciousness impairment of different severity. RESULTS: Cytoflavin treatment was more efficient than ascorbic acid that can be explained by different pharmacologic mechanisms. Treatment with cytoflavin for 10 days resulted in a significant decrease of ischemia zone volume by 25.2%, treatment with cytoflavin for 20 days - by 29.0%, which was associated with better outcomes in neurologic and functional status. Ascorbic acid demonstrated no effect on morphologic parameters. Prolonged treatment with cytoflavin in critically ill patients led to significant improvement in clinical and morphologic variables compared to the 10-day course. In patients with less severe condition comparable results were obtained. CONCLUSION: Our data justify the need for personalized integrated antioxidant and energy correction therapy.

[Modern methods of energy homeostasis correction in elderly patients].

In the multicenter randomized clinical-instrumental prospective study 185 patients aged 55-75 years (mean age 68 years) with 94 men and 91 women with cerebral infarction were included. All the patients were hospitalized in the period from 6 to 24 hours from the time of the debut of clinical symptoms, 42,2% of patients scored 14 and above on NIH scale on admission. Patients were randomized into 3 groups: 1st group consisted of 64 patients treated as an antioxidant by 5% solution of ascorbic acid 2 times a day the recommended dose (20 ml/day) for 20 days; 2nd group consisted of 72 patients who received energy monitor Cytoflavin in a daily dose of 20 ml (10.0 ml/drip 2 times a day for 10 days); 3rd group consisted of 49 patients with Cytoflavin therapy extended to 20 days, moreover from 11th to 20th day the dose was 10 ml/day. Cytoflavin treatment was more efficient than ascorbic acid, which can be explained by different pharmacologic mechanisms. Treatment with Cytoflavin for 10 days resulted in a significant decrease of ischemia zone volume by 25% in average, treatment with Cytoflavin for 20 days--by 29%, which manifested in better outcomes in neurologic and functional status. Ascorbic acid demonstrated no effect on morphologic parameters. Patients having at the time of admission 18-20 points according to the NIH and treated with Cytoflavin for 20 days demonstrated significant trend towards improvement of the parameters of the neurological status.

[Lethality after gastroduodenal ulcer bleeding].

The retrospective analysis (2006-2010 yy) of treatment of 895 patients with gastroduodenal ulcer bleeding was conducted. Lethal outcome was registered in 220 (24.6%) patients, of them directly of the ulcer bleeding died 45 (5%). The Rockall score was used as universal prognostic instrument. Of 164 lethal outcomes, did not directly connected to the ulcer bleeding, the etiological distribution was as follows: multiple organ failure - 36% (n=59), cardiovascular diseases - 24.4% (n=40), inveterate oncology - 15.9% (26). Of 45 deaths from bleeding, only 4 patients died of the uncontrolled bleeding, whereas 18 (45%) died after the emergency surgery. Signs of hemorrhagic shock were registered in 60% of died patients (in comparison with 18% among the survived). Bleeding reccurrence was registered in 28.6% of died patients (in comparison with 11% among the survived). The use of the Rockall score confirmed its prognostic value: the mean score was 4.3±2.12 points among the survived patients, whereas among the died patients it was 7.16±2.35 points (p=0.001). Authors conclude, that the leading reasons of death, considering the bleeding itself, were the hemorrhagic shock and recurrent bleeding. Though, about 80% of patients are dying of reasons, do not directly connected to the bleeding episode, but of concomitant diseases (multiple organ failure, cardiovascular and oncologic diseases). The least, nevertheless, leads to the wrong formulation of the final diagnosis and incorrect interpretation of the etiology of death.

[Treatment of hepatic insufficiency in benign mechanical jaundice].

The aim of this work was to estimate hepatic dysfunction and improve treatment of benign mechanical jaundice using an injection hepatoprotector. The study included 124 patients of whom 74 were given remaxol. 50 control subjects received basal therapy. The patients were randomized by the random sampling method. Severity of cholestasis was evaluated from the total and fractional bilirubin content and γ-glutamyl transpeptidase (GGT) level; AST and ALT activities were used to detect cytolysis. Liver synthetic function was estimated from prothrombin index (PTI) and coagulation function from fibrinogen level, PTI and APTT. Endogenous intoxication during biliary tract decompression was assessed by calculating the leukocyte intoxication index from the Kalf-Kalif formula. It was shown that remaxol suppresses cytolysis, reduces total and fractional bilirubin levels, improves bilirubin excretion in bile and decreases activity of hepatocyte excretory enzymes.

[Free radical processes in the pathogenesis of involutional skin changes].

AIM: To study the role of free radical processes (FRP) in the development of involutional skin changes and their correction. SUBJECTS AND METHODS: One hundred and twenty patients aged 18 to 74 years with various degrees of involutional facial and cervical skin changes were examined. Clinical and laboratory assessments were made over time. The oxygen and lipid peroxidase parameters of FRP were estimated; objective and subjective visualization, Doppler flowmetry of the facial skin, and colorimetric study of the skin color spectrum were done. RESULTS: The imbalance between oxygen and lipid peroxide components of FRP was found to increase with advancing age. These processes correlate with the severity of involutional skin changes and objectify the early use of energy-correcting therapy (ECT). The incorporation of ECT with cytoflavin positively affects FRP values and clinical and instrumental findings of involutional facial and cervical skin changes, by improving microcirculation. The patients with first-second degree involutional skin changes achieved the best results. CONCLUSION: The findings permit cytoflavin to be recommended as one of the components of therapy aimed to stabilize intradermal exchange processes as part cosmetic manipulations in aesthetic medicine.