Properties and Activity of Peptide Derivatives of ACE2 Cellular Receptor and Their Interaction with SARS-CoV-2 S Protein Receptor-Binding Domain.

The aim of this work was to design and characterize peptides based on the α-helices h1 and h2 of the ACE2 receptor, forming the interaction interface between the receptor-binding domain (RBD) of the SARS-CoV-2 S protein and the cellular ACE2 receptor. Monomeric and heterodimeric peptides connected by disulfide bonds at different positions were synthesized. Solubility, RBD-binding affinity, and peptide helicity were experimentally measured, and molecular dynamics simulation was performed in various solvents. It was established that the preservation of the helical conformation is a necessary condition for the binding of peptides to RBD. The peptides have a low degree of helicity and low affinity for RBD in water. Dimeric peptides have a higher degree of helicity than monomeric ones, probably due to the mutual influence of helices. The degree of helicity of the peptides in trifluoroethanol is the highest; however, for in vitro studies, the most suitable solvent is a water-ethanol mixture.

[PAIN AFTER CHILDBIRTH AND ITS IMPACT ON QUALITY OF LIFE].

BACKGROUND: Public attitude towards labor pain and pain relief in labor is not fully formed. PURPOSE: To study the frequency of formation of acute and chronic pain during delivery. MATERIALS AND METHODS: Retrospectively we surveyed 300 women 18-48 years old, who had childbirth naturally or by caesarean section for 4-6 months before the survey and analyzed the history of their childbirth. RESULTS: The obtained data showed that the problem with generic pain has real medical and social consequences, significantly altering the quality of life of women as during childbirth and the postpartum period. Of those surveyed, 74.9% of women in childbirth experienced severe pain during labor; which had 16.7% of women had led to a complete loss of mobility. With approximately 20% of women believed the use of methods of anaesthesia was dangerous and 63% thought that anaesthesia is possible only under strict obstetric indications. Only 20% of pregnant women expected to give birth without pain. In 3-6 months. after labor representation mothers opinion was not changed significantly. In 1 month or more after delivery or cesarean section pain was presented in 21% of women, in 2-3 months--13.7%, in more than 3 months--7%. In 4.3% of the patients the pain persistedfor 5-6 months. CONCLUSIONS: Significant relationship between persistent for a long time after childbirth pain and the way the urgency of delivery, the method of anesthesia for caesarean section, the expression of acute pain during childbirth was not revealed.

[Designing of hybrid human interferon alfa-2 strain-producers and the use of enteropeptidase for obtaining N-terminal methionine-free interferons].

A system for production of human interferon-alpha2a (IFN-alpha2a) and IFN-alpha2b lacking N-terminal methionine has been developed. Plasmids containing genes of hybrid IFN-alpha2 under the control of different promoters were constructed; a sequence encoding the enteropeptidase hydrolysis site being introduced in proximal part of the genes. As the result, 4 strains of Escherichia coli producing hybrid IFN-alpha2 have been obtained. The methodology for IFN-alpha2 renaturation, hydrolysis of its N-terminal part, chromatographic purification of N-terminal methionine-free IFN-alpha2 has been developed.

[Patient-controlled postoperative analgesia in obstetrics and gynaecology].

A prospective study researches features of patient-controlled epidural analgesia (PCEA) in 42 women after cesarean section, mid- and high-traumatic gynaecological surgery. It was found out that the quality of while using the PCEA is significantly better than while using a traditional parenteral infusion of analgesics. Use of PCEA favours the circulatory and breathing systems functioning. Compared to continuous epidural infusion of analgesics and anaesthetics, use of PCME returns the expenses better due to less consumption of the drugs up to 35% during the first 24 hours after the surgery. This method is suitable for continuous estimation of the pain therapy.

[Complications of endoscopic video-assisted surgical interventions in gynaecology].

An analysis of specific complications in gynaecological endovideosurgery has been conducted, such as occurrence of extra-abdominal gas after laparoscopic surgery or resorption of the irrigation solution in hysteroscopy. Possible mechanisms of subcutaneous emphysema, pneumothorax, mediastinal emphysema and hyperhydration development are presented along with discussion of diagnosing and treatment methods.

A case of HHV-8-associated HIV-negative primary effusion lymphoma in Moscow.

Primary effusion lymphoma is a rare tumor of B-cell derivation which is associated with human herpes virus type 8 (HHV-8) in 100% and with human immunodeficiency virus (HIV) in most of cases. The paper describes the first case in Russia of HIV(-) HHV-8(+) Epstein-Barr virus (EBV)(+) primary effusion lymphoma in a male patient aged 56 years. The tumor was located in the pleural cavity. Interestingly, the patient was HIV-negative while having a positive tumor HHV-8 test. There are only 22 similar cases described worldwide.

[Effect of premedication on the formation of postoperative pain syndrome]. / Vliianie premedikatsii na formirovanie posleoperatsionnogo bolevogo sindroma.

The pronouncement degree and dynamics of pain syndrome were assessed after surgeries in the abdominal cavity organs with regard for a nature of the analgetic component of premedication and of the postoperative analgesic therapy (n = 155). The administration of analgesics before extra-traumatic surgeries was found to be compulsory in order to prevent the onset of a persistent postoperative pain syndrome. A combination of non-steroid anti-inflammatory drugs, i.e. ketonal, and of a high-efficiency agonist of opiate mu-receptors, i.e. bupranal, was acknowledged as most effective in coping with this task. It was demonstrated that the application of "the forestalling analgesia" by ketonal (100 mg in 30 min before the beginning of moderate- and mild-trauma surgical interventions and immediately after the finalization of such surgeries) contributed to an essentially lower pronouncement degree of the postoperative pain syndrome and made the administration of narcotic analgesics unnecessary. Finally, it is pointed out that promedol could not be regarded as a drug ensuring a safe prophylaxis of the central sensitization and hyperalgesia.

[Characteristics of hemodynamic reactions during various endoscopic surgeries for cholelithiasis in patients with concurrent cardiovascular pathologies]. / Osobennosti gemodinamicheskikh reaktsii pri razlichnykh variantakh éndovideokhirurgicheskogo lecheniia zhelchnokamennoi bolezni u patsientov s soputstvuiushchimi zabolevaniiami serdechno-sosudistoi sistemy.

A prospective study of 170 patients with concurrent cardiac pathology, who had underwent the laparoscopic cholecystectomy under the conditions of a tense carboxyperitomium, led to isolating two groups of patients with high-risk of intra- and postoperative unfavorable cardiac-vascular responses: an original high risk degree (III-IV classes according to ASA), a high value of cardiac risk indices according to Goldman (III-IV classes) and according to Detsky (II-III classes), a hypodynamic blood circulation regimen under rest conditions, and ejection fraction (according to echocardiography) amounting below 50%. Such patients are recommended to be operated on by laparolifting or by low-gas laparoscopy with a local lifting, i.e. by using the surgical techniques free of any negative effects produced on the carboxyperitomium hemodynamics, while all positive features of small-invasion surgery remain intact.

[Mathematical modeling -- an objective assessment of new medicines and treatment technologies]. / Matematicheskoe modelirovanie -- ob"ektivnaia otsenka novykh lekarstvennykh preparatov i lechebnykh tekhnologii.

An objective method of studying effectiveness of new medicines and methods of treatment is mathematical modeling. On the basis of mathematical processing of the pooled data obtained in the control group of patients an individual prognostic formula can be made which predicts the only outcome for each patient. When studying a new medicine or method of treatment in each patient under test his prognostic outcome is compared to the real one. An improvement of the real outcome as compared to the prognostic one points to the effectiveness of the new medicine used. An objective and individual approach to the assessment of the result after the end of each case of treatment allows the further perspectiveness of the work done and the number of necessary tests to be efficiently estimated.

[Diagnosis and intensive therapy of thermal and inhalation trauma]. / Diagnostika i intensivnaia terapiia termoingaliatsionnoi travmy.

The authors made an analysis of an experience with treatment of patients with a combined thermal inhalation injury in the Burn Center of the St. Petersburg Research Institute of emergency medical care named after I.I. Dzhanelidze for the recent years. A prognostic model with respect to the patient's life was worked out on the basis of complex estimation of the data of the depth and square of the injury of skin, severity of the inhalation trauma and age of the casualty. The authors propose a scale of estimation of the severity of the inhalation trauma with special reference to the probable outcome which allows a differentiated approach to choice of the treatment policy that finally favors reduction of lethality in the group under analysis.

[Early diagnosis and intensive care of acute postoperative pancreatitis]. / Ranniaia diagnostika i intensivnaia terapiia ostrogo posleoperatsionnogo pankreatita.

Diagnostic algorithm developed on the basis of multifactorial regression analysis is suggested for more objective diagnosis of acute pancreatitis after operations on the hepatopancreatoduodenal organs. This algorithm helps differentiate the strategy of intensive care in patients with pancreatitis, pancreatic disease, and uneventful postoperative period. It is impossible to single out the specific (pathognomonic) clinical signs of this complication during the immediate postoperative period. Hyperamylasemia and changes in other enzymes are important but not absolute markers of unfavorable course of disease.

[Prognostication and prevention of acute postoperative pancreatitis]. / Prognozirovanie i profilaktika ostrogo posleoperatsionnogo pankreatita.

Equations for accurate prediction of the course of postoperative pancreatitis are developed by multifactorial regression analysis for purposeful prevention of this condition. An injury to the pancreas and the "readiness" of hepatoduodenal organs to a degenerative destructive process are significant for the development of pancreatitis. A differentiated strategy is developed for preventing this complication during the post- and intraoperative period by protease inhibitors, cytostatics, and other nonspecific methods.

[Objective assessment of the severity of gunshot wounds]. / Ob"ektivnaia otsenka tiazhesti ognestrel'nykh ranenii.

By the present time, many mathematical models have been developed for assessing the status of patients with grave mechanical injuries. However, comparative analysis of the efficacy of predicting the outcomes of shock and traumatic disease with the use of some models in patients with war and other than war traumas showed that these methods are not fit for cases with gunshot wounds. We consider that a differentiated approach is needed in assessment of the status of wounded and injured patients.

[A first trial of the use of human recombinant interleukin (rIL-2) in patients with tumorous diseases]. / Pervyi opyt ispol'zovaniia chelovecheskogo rekombinantnogo interleikina (rIL-2) u patsientov s opukholevymi zabolevaniiami.

Clinical approbation of human recombinant yeast human interleukin-2 (rIL-2) was carried out in 10 patients with III-IV stages of tumor that have undergone 65 intravenous drop by drop infusions of the drug as a course of 5-11 injections in the dosage of 1-8 mln/un. The drug toxicity was shown in 4 mln and especially, in 8 mln/un dose administration. That's why the dose of 1-2 mln/un is recommended. This dose was not followed by any serious complications, and the number of slightly complicated cases was significantly decreased as compared to similar rIL-2 drug made by the "Cetus Corporation" firm. Immunostimulating effect of yeast rIL-2 was found which appeared to be able to reach it's maximum by 3-4 administrations, with it's following disappearance or inversion, which may cause immunosuppression.

[Prehospital care in traumatic shock]. / Dogospital'naia pomoshch' pri travmaticheskom shoke.

Clinical investigations performed in 735 patients have shown that in addition to the improvement of organisation of the medical aid and the universally recognized resuscitation measures for trauma shock, the prophylactics and treatment of intoxication, metabolic, immune and other disorders developing in the patients soon after trauma should be started as early as at the prehospital step.

[The role of adoptive immunotherapy in the combined treatment of neglected forms of colorectal cancer (a preliminary report)]. / Rol' adoptivnoi immunoterapii v kombinirovannom lechenii zapushchennykh form kolorektal'nogo raka (predvaritel'noe soobshchenie).

Results of treatment of 24 patients with neglected colorectal tumors in the period from 1988 till 1994 are presented. Six patients had stage C and 18 patients had stage D after Dukes. Methods of combined action on the tumor including dissection of the tumor and its metastases, using immunoadoptive therapy as extracorporal connection with the donor porcine spleen, intravenous infusions of interleukin-2 and chemotherapy were employed. All the patients with stage C according to Dukes are alive: the average period of observations was 1143 +/- 206 days with intervals within the limits of 4,5-1,5 years. Seven patients of 18 with stage D after Dukes are alive with the average period of observations 1331 +/- 216 days and an interval of observations within the limits from 6 to 2 years. Dead patients with stage D after Dukes lived 525 +/-98 days on the average, i.e. about 1,4 year. The employed method of combined treatment of colorectal tumors improves survival, prolongs the lifetime of patients with neglected forms of the disease.

[Interleukin-1 in combined detoxification therapy of surgical sepsis]. / Interleikin-2 v kompleksnoi detoksikatsionnoi terapii khirurgicheskogo sepsisa.

Clinical trials of Russian yeast recombinant human interleukin-2 (yrIL-2) were carried out in 17 patients with posttraumatic and postoperative sepsis to whom 33 intravenous drip infusions of the drug were administered as a single infusion or courses of 2 to 4 injections in a dose of 1,000,000 U per .1 m2 body surface. A positive clinical effect of yrIL-2 in this dose was observed on the next day after the first injection of the drug: the signs of intoxication were reliably reduced. The immunostimulating effect of yrIL-2 consisted in activation of pharmacytizing leukocytes of blood. Addition of yrIL-2 to therapeutic complex for patients with sepsis helped reliably reduce the mortality of such patients with sepsis helped reliably reduce the mortality of such patients to 29.4% vs. 63.3% in controls.

[A point-scale assessment of the pathological changes in acute complicated cholecystitis]. / Ball'naia otsenka patologicheskikh izmenenii pri ostrom oslozhnennom kholetsistite.

The use of a present-day method of statistical investigation allowed to present the variety of pathological changes in acute cholecystitis in a parametric form, i.e. as a scale of scores. The scale allows determination of comparative severity of one or another changes characteristic of acute cholecystitis in the concrete patient. The correlation analysis as well as scores assessment show a substantial importance of the functional ability of detoxicating mechanisms for the characteristic of the degree of pathological changes.