Chemical composition and cardiotropic activity of Ziziphora clinopodioides subsp. bungeana (Juz.) Rech.f.

ETHNOPHARMACOLOGICAL RELEVANCE: Ziziphora clinopodioides subsp. bungeana (Juz.) Rech.f. is a subshrub that is widely distributed in China, Kazakhstan, Kyrgyzstan, Mongolia, Russia, Tajikistan, Turkmenistan, and Uzbekistan. The species is used in traditional medicine for the relief of symptoms connected to cardiovascular diseases like coronary heart disease or hypertension. AIM OF THE STUDY: was to validate traditional use of Z. clinopodioides subsp. bungeana for the treatment of coronary hearth diseases using in vivo models and to find active compounds responsible for the activity. MATERIALS AND METHODS: Multiple extracts were obtained from the aerial parts of Z. clinopodioides subsp. bungeana using maceration, liquid-liquid extraction, CO2 extraction and ultrasound-assisted extraction. Preliminary screening studies for the evaluation of the efficacy of Z. clinopodioides subsp. bungeana extracts on the model of hemic hypoxia were performed. The most effective samples were selected and included in the main study. Stage 2 of the study evaluated the cardiotropic activity of the selected extracts on a model of chronic heart failure. Preparations were administered to animals intragastrically once a day for 28 days. For the isolation of individual compounds plant material was extracted with 96% ethanol. The obtained crude extract was sequentially extracted with n-hexane and dichloromethane and separated by chromatography on a Diaion HP-20 column. The obtained fractions were further subjected to Sephadex LH-20 column chromatography and eluted isocratically with 96% ethanol (EtOH) to yield subfractions, which were further separated by preparative HPLC to obtain 13 individual compounds. RESULTS: Extracts obtained from Ziziphora clinopodioides subsp. bungeana (Juz.) Rech.f. herb were subjected to pharmacological screening for the evaluation of their efficacy on hemic hypoxia. Based on the obtained results, out of the sixteen tested extracts two (AR and US 60%) were selected for further evaluation of their cardiotropic activity. Modeling of chronic heart failure was carried out in accordance with the following stages: 1) anesthesia with chloral hydrate at a dose of 450 mg/kg, intraperitoneally, 2) artificial ventilation of the lungs, 3) thoracotomy, 4) modeling of permanent ischemic or ischemic-reperfusion damage. Both extracts effected the indicators of contraction and output, comparable to the reference drug - Monopril. Based on the extraction methods used to obtain RAF and US60 and data from the literature, it can be assumed that they contain compounds with medium polarity, including polyphenols and terpenoids. At the next stage three previously undescribed monoterpenoid derivatives - Ziziphoric acid (1), Ziziphoroside D (2) and 6'-malonylziziphoroside A (3), along with two previously described megastigmane glucosides - blumenol C glucoside (4), blumenol C 9-O-(6'-O-malonyl-beta-D-glucopyranoside (5) and two previously described monoterpenoids 7a-hydroxymintlactone (6), 7-hydroxypiperitone (7) together with six polyphenols - pinocembrine-7-O-rutinoside (8), chrysine-7-O-rutinoside (9), acacetin-7-O-rutinoside (10), luteolin-7-O-rutinoside (11), rutin (12) and rosmarinic acid (13) were isolated from Z. clinopodioides subsp. bungeana extracts. CONCLUSION: Our results support the traditional use of Z. clinopodioides subsp. bungeana for the treatment of coronary diseases. As a result of Z. clinopodioides subsp. bungeana extracts screening in vivo, two extracts were selected as potential cardiotropic agents. Phytochemical analysis of the plant material led to the isolation of five terpenoid derivatives, two megastigmane glycosides, five flavonoids and one cinnamic acid derivative, which could be responsible for the reported biological activity. Future experiments are required to understand the mechanisms of action for the isolated compounds.

[Stomach and spleen preserving total pancreatectomy]. / Total'naya duodenopankreatektomiya s sokhraneniem zheludka, selezenki, zheludochnykh i selezenochnykh sosudov.

INTRODUCTION: Pancreatic surgery expands the indications and the use of total pancreatectomy. Considering a rather high rate of postoperative complications, the search for the ways to improve its outcomes is extremely relevant. The purpose of this study is justification and implementation of organ-preserving variants of total pancreatectomy. MATERIAL AND METHODS: Retrospective analysis of treatment results after classic and modified total pancreatectomy in the surgical clinic of Botkin Hospital was performed from September 2010 to March 2021. During the development and implementation of pylorus-preserving total pancreatectomy with preservation of the stomach, spleen, gastric and splenic vessels, we thoroughly analyzed aspects of exocrine/endocrine disorders and changes of the immune status after performing the modified technique. RESULTS: We performed 37 total pancreatectomies, including 12 pylorus-preserving total pancreatectomies with preservation of the stomach, spleen, gastric, and splenic vessels. General and specific postoperative complication rate in patients after the modified operation was significantly lower compared to the results of classic total pancreatectomy with gastric resection and splenectomy. CONCLUSION: Modified total pancreatectomy is a method of choice for pancreatic tumors of low malignant potential.

[Spleen-preserving total pancreatectomy for low-grade tumors]. / Pilorosokhranyayushchaya pankreatektomiya s sokhraneniem selezenki pri opukholyakh s nizkim potentsialom zlokachestvennosti.

OBJECTIVE: To justify organ-preserving variants of total pancreatectomy. MATERIAL AND METHODS: We retrospectively analyzed the results of classic and modified total pancreatectomy between September 2010 and March 2021. Implementing pylorus-sparing total pancreatectomy with preservation of stomach, spleen, gastric and splenic vessels, we thoroughly analyzed exocrine/endocrine disorders after total pancreatectomy and changes in immune status after splenectomy. Serum C-reactive protein and ferritin were assessed in 1, 3, 5, 7, 14 and 30 days after surgery in both groups. We also estimated daily glycemic profile after total pancreatectomy in classical and organ-preserving modifications. RESULTS: We performed 37 total pancreatectomies including 12 pylorus-preserving total pancreatectomies with preservation of stomach, spleen, gastric and splenic vessels. General and specific postoperative complication rate was significantly lower after modified surgery compared to classic total pancreatectomy with gastric resection and splenectomy. CONCLUSION: Modified total pancreatectomy is preferable for low-grade pancreatic tumors.

[Preoperative radiation navigation in determining surgical strategy for liver echinococcosis]. / Predoperatsionnaya luchevaya navigatsiya v opredelenii khirurgicheskoi taktiki pri ekhinokokkoze pecheni.

OBJECTIVE: To analyze the technology for diagnostic modeling of liver echinococcosis. MATERIAL AND METHODS: In the Botkin Clinical Hospital, we developed a theory of diagnostic modeling of liver echinococcosis. Treatment outcomes were analyzed in 264 patients who underwent various surgical interventions. RESULTS: A retrospective group enrolled 147 patients. When comparing the results of diagnostic and surgical stages, we identified 4 models of liver echinococcosis. The choice of surgical intervention in the prospective group was based on previous models. Diagnostic modeling reduced the number of general surgical and specific complications, as well as mortality in the prospective study group. CONCLUSION: The technology for diagnostic modeling of liver echinococcosis made it possible not only to identify 4 models of liver echinococcosis, but also determine the most optimal surgical intervention for each of model.

[Modern approaches to the treatment of patients with a complicated form of gallstone disease in the Botkin hospital]. / Protokol lecheniya bol'nykh s oslozhnennoi formoi zhelchnokamennoi bolezni v khirurgicheskoi klinike Botkinskoi bol'nitsy.

OBJECTIVE: To determine the optimal timing of laparoscopic cholecystectomy in patients with gallstone disease complicated by cholelithiasis after endoscopic retrograde papillosphincterotomy with lithoextraction. MATERIAL AND METHODS: We analyzed treatment outcomes in 229 patients with gallstone disease complicated by cholelithiasis between 2016 and 2020. Simultaneous surgery was performed in 31 patients, early cholecystectomy (after 1-3 days) - in 78 cases, delayed cholecystectomy (after 4-7 days) - in 35 cases and delayed cholecystectomy in 14-30 days after endoscopic retrograde papillosphincterotomy with lithoextraction in 85 cases. RESULTS: Simultaneous laparoscopic cholecystectomy and surgery in early period after endoscopic retrograde papillosphincterotomy with lithoextraction are followed by less surgery time, few postoperative complications and less hospital-stay. CONCLUSION: Simultaneous laparoscopic cholecystectomy and early surgery after endoscopic retrograde papillosphincterotomy with lithoextraction are preferred for patients with complicated gallstone disease. However, this requires adherence to strict criteria for patient selection.

[Echinococcosis of the liver: evolution of surgical treatment]. / Ekhinokokkoz pecheni: evolyutsiya khirurgicheskogo lecheniya.

OBJECTIVE: To analyze the development of surgical approaches for hepatic echinococcosis. MATERIAL AND METHODS: We have analyzed diagnosis and treatment of 349 patients with liver echinococcosis; 97 patients were treated at the Botkin Clinical Hospital for the period from 2009 to 2019 and 252 patients were treated in surgical hospitals of Moscow city for the period from 2014 to 2019. RESULTS: General and specific postoperative complications, relapses and surgical approaches were assessed. The number of echinococcectomies performed in surgical hospitals of Moscow is 3 times higher compared to the Botkin Hospital. The number of liver resections is comparable in both groups. The number of pericystectomies is more than 2 times higher in the Botkin Hospital. PAIR technique was more common in surgical hospitals of Moscow. CONCLUSION: Evolution of surgical treatment from open echinococcectomy to anatomical liver resections and subsequent pericystectomy with PAIR technique becomes another round of evolutionary spiral in the development of surgical treatment of liver echinococcosis.

[Preoperative biliary drainage for malignant biliary obstruction: to drain or not to drain? And if drain, in what way?] / Predoperatsionnaya biliarnaya dekompressiya pri opukholevoi zheltukhe: drenirovat' ili net? I esli drenirovat', to kakim sposobom?

On the basis of the conducted literary search, a number of conclusions can be drawn. When performing preoperative biliary drainage (PBD), it is necessary to have a clear understanding: why is this procedure performed (severe liver failure, cholangitis, long preoperative preparation is required due to comorbid status, neoadjuvant chemotherapy is necessary, etc.)? Routine use of PBD is impractical. In the presence of indications for PBB in perihilar cholangiocarcinoma, percutaneous decompression is preferable, in periampullary tumors, endoscopic. Moreover, both methods can be alternative (for example, in case of technical failure of the first priority). There is also no convincing evidence of the superiority of metal stents over plastic ones for PBD (except in cases of long-term preoperative preparation or neoadjuvate treatment) for periampular tumors. To date, a decrease in overall survival and a higher incidence of implantation metastases have not been proven when using the antegrade PBD method. Large multicenter studies are required with differentiation of patients according to the nosological principle in order to more accurately understand the place of each method, as well as to determine clear indications for PBD and those clinical situations when its implementation is impractical.

[Mechanisms and prevention of biliary stent occlusion]. / Mekhanizmy okklyuzii biliarnykh stentov i vozmozhnye sposoby ee profilaktiki.

One of significant achievements of modern endoscopy is development of retrograde biliary stenting for obstructive jaundice. This method ensured widespread application of endoscopic decompression in the treatment of patients with malignant biliary obstruction as preparation before radical surgery and final palliative care. Endoscopic retrograde transpapillary stenting firmly took its place together with antegrade and percutaneous stenting. There are certain advantages of this technique including minimally invasiveness and favorable quality of life. However, this approach is associated with some drawbacks associated with stent occlusion and difficult correction of this complication. The maximum diameter of the plastic stent (PS) is determined by the width of the working channel of the duodenoscope. In this regard, self-expandable metal stents (SEMS) were developed to increase the diameter of bile drainage channel. SEMS are associated with prolonged function. However, there is another problem. It is a germination of SEMS followed by impossible removal of the stent for its subsequent replacement. A further step in development of endoscopic biliary stents was the use of special SEMS coating to exclude tumor or granulation ingrowth. The problem of biliary stent occlusion remains relevant despite some improvement of stenting results. Mechanisms of occlusion of biliary stents and prevention of these events are discussed in this review.

[Specific complications of liver resection and their prevention]. / Rezektsiia pecheni. Spetsificheskie oslozhneniia i ikh profilaktika.

AIM: To improve the results of treatment of patients with focal liver formations by preventing the development of postoperative complications after liver resections. METHODS: The study included 304 patients with benign and malignant liver lesions. In 196 (64.4%) patients, resections were performed for malignant liver damage, in 108 (35.6%) - for a benign process. To assess the impact of ongoing measures to prevent the development of postoperative complications, patients were divided into two time periods: from 2007 to 2012 and from 2013 to 2018. RESULTS: The introduction of a protocol of preoperative examination of patients for whom resection of 3 or more liver segments is planned, with the inclusion of SPECT/CT, which allows determining the volume of the remaining functioning liver parenchyma, allowed to reduce the percentage of development of acute post-resection liver failure from 11.6% to 3.6% during the second time period (p=0.0064). The use of modern suture material, surgical binocular loops, as well as the use of the concept of predominantly performing parenchyma-saving resections, reduced the number of biliary complications from 8.1% to 5.7% (p=0.1). The use of a proprietary dissection algorithm for the liver parenchyma significantly reduced hemorrhagic complications from 5.3% to 1.04% (p=0.0074). CONCLUSION: The use of modern pre- and intraoperative technologies has reduced the number of postoperative complications after liver resections from 38.3% to 20.9% (p=0.018) and mortality from 2.6% to 0.5% (p=0.004), thereby improving the results of liver resections.

[Endoscopic septoplasty as a stage of endonasal dacryocystorhinostomy]. / Endoskopicheskaya septum-operatsiya kak etap endonazal'noi dakriotsistorinostomii.

Endoscopic endonasal dacryocystorhinostomy (EN-DCR) is a modern and effective method for the surgical treatment of distal part obstruction of lacrimal pathway. Unsuccessful outcome and dacryocystitis relapses may be associated with concomitant rhinological pathology. Deviation of the nasal septum in the surgical area can affect the operation and contribute to stenosis. Additional correction of the nasal septum is necessary to obtain free surgical approach to the lacrimal sac. Endoscopic septoplasty provides high-quality surgical approach to the lateral wall of the nasal cavity. OBJECTIVE: To evaluate simultaneous endoscopic septoplasty when performing EN-DCR. METHODS: A retrospective analysis patients clinical data was conducted who were operated at the ENT department of Pavlov First Saint Petersburg State Medical University between January 2014 and December 2019. RESULTS: 232 EN-DCR were performed in 212 patients (21 men, 191 women). The average age at the time of the operation was 54.3 years (range 19-87). Of the 212 people 192 underwent unilateral surgery, 20 - bilateral EN-DCR. Simultaneous endoscopic septoplasty was required in 36 (15.5%) cases. CONCLUSION: Performing a simultaneous endoscopic septoplasty provides comfortable surgical access and contributes to the final successful outcome of EN-DCR.

[MODIFICATION OF MESENCHYMAL STEM CELLS AS A WAY TO IMPROVE THE EFFECTIVENESS OF CELL THERAPY OF ISCHEMIC MYOCARDIAL INJURY].

Acute myocardial infarction remains to be one of the most important problems of health care. Cardiac cell therapy is a new therapeutic strategy focused on repair of the injured cardiac muscle. Mesenchymal stem cells (MSC) are considered as the most suitable candidates for cardiac cell therapy. MSC transplantation in the myocardium after ischemic injury has been shown to be cardioprotective in animal models and clinical trials. However, the beneficial effects of MSC in humans are limited because of both poor survival and impaired function of the cells in ischemic tissue. To address these issues, a number of approaches to the modification of MSCs with the aim to improve their survival and proliferation, reduce the immune reaction, enhance transdifferentiation, and optimize the profile of secreted paracrine factors have been tested. In this review, we provide detailed discussion of different methods of MSCs modification, including targeted gene overexpression, conditioning of MSCs using physical and chemical factors, and application of multicellular units for transplantation. The effectiveness of these strategies in preclinical studies is also discussed.

[CARDIOPROTFETIVE EFECTS OF NECROSTATIN-7 IN THE RAT MODEL OF PERMANENT CORONARY OCCLUSION].

The cardioprotective effects of necroptosis inhibitor necrostatin-7 were studied in the rat model of permanent coronary occlusion. It was found that intraperitoneal injection of necrostatin-7 at a dose of 14.5 mg/kg 60 minutes prior to permanent left coronary artery occlusion reduced the amount of scar tissue and scar length in the left ventricle on the 21st day after surgery. In addition, pretreatment with necrostatin-7 resulted in decreased plasma level of N-terminal pro-brain natriuretic peptide, which points to the improvement in left ventricular function.

[FEATURES OF FUNCTIONAL DISORDERS GASTRODUODENOBILIARY SYSTEM IN PATIENTS WITH CELIAC DISEASE].

The disturbances in synchronous functioning of gastroduodenal and biliary system and in their consequent interaction underlies functional disorders of the digestive tract. Motor and evacuation functioning of the gastrointestinal tract depends on the bile flow to the duodenum, which influences on digestive processes. Functional disorders of the biliary tract, contributing disturbances of the gastrointestinal motor activity, cause gastrointestinal symptoms. The cause of biliary dysfunctions often are gallbladder anomalies, which are accompanied by disturbances in drainage system of bile flow, development of the pathological refluxes, inflammation and formation of the biliary sludge. The progression of the biliary system deflux dysfunction leads to motor and evacuation dysfunction of the gut. According to the numerous data, gall bladder anomalies, which underlies functional disorders in bile deflux, are common in patients with coeliac disease. The results, obtained in the conducted research, revealed hypertonic hyperkinetic motor disorders of the upper part of the gastrointestinal tract and inflammation changes of the gastroduodenal zone in patients with coeliac disease with fixed bend in the gallbladder neck, necking and different deformation of the gallbladder, which are the visceral signs of undifferentiated connective tissue dysplasia. Disorders in every component of the digestive tract upper part motor activity lead to the corresponding clinical manifestations.

[Cellular mechanisms of regeneration of rats' liver after experimental myocardial infarction].

Morphological changes and regeneration activity of the rats' liver after an experimental myocardial infarction (MI), caused by a permanent left coronary artery occlusion, were investigated. It has been shown that in 6 months after MI there were considerable changes of the rats' liver circulatory system: the quantity of vessels per unit of area increased by 118%, thickness of their walls by 19%, and the average square of vessels lumens by 159%. The percentage of connective tissue in 6 months after MI increased more than in one and a half time in comparison with control. Inflammatory and necrotic changes in rats' liver remained for 6 months after MI. The liver injury caused by MI led to activation of regeneration processes in its parenchyma. In 6 months after MI, the number of 4c- hepatocytes decreased by 12% in comparison with control, and the number of 4c x 2- and 8c-hepatocytes increased by 45 and 71%, respectively. The mean level of hepatocytes ploidy increased in 6 months after MI by 11%. The dry mass of rats' hepatocytes increased in 6 months after MI by 19% in comparison with control. Thus, liver regeneration after MI is more due to hepatocytes hypertrophy than to their polyploidization.