Effect of Phytoadaptogen Administration during Early Ontogeny on Lifespan and Somatic Status of CBA Mice with High Incidence of Tumors.

We studied the influence of nontoxic phytoadaptogen complex on the lifespan and somatic status (body weight, coat state, and motor activity) of CBA mice predisposed to spontaneous hepatomas. Administration of the complex phytoadaptogen during the first month of postnatal ontogeny increased mean animal lifespan by 17.1% (p<0.001) and median of survival by 25.6% (p<0.001) and promoted maintenance of satisfactory physical status of CBA mice during spontaneous hepatocarcinogenesis.

Morphological Studies of Hepatocellular Carcinomas in Male CBA Mice with High Liability to Cancer under the Effect of Phytoadaptogen.

Treatment of CBA mice predisposed to cancer with a complex phytoadaptogen in the therapeutic and preventive modes led to the appearance of moderate and low-differentiation hepato-cellular carcinomas infiltrated by leukocytes. Destructive signs were detected in tumor tissue.

Effects of Phytoadaptogen on Hepatoma Development in Cancer-Prone CBA Mice.

The incidence, size, and number of hepatocarcinomas decreased in cancer-prone male CBA mice under the effect of preventive and therapeutic treatment with a complex phytoadaptogen.

[Liver tissue regeneration under the influence of cryoprecipitate and alloplant].

AIM: To study the effectiveness and impact of cryoprecipitate and alloplant on regeneration of liver tissue in patients with cirrhosis. MATERIAL AND METHODS: 114 patients with liver cirrhosis have been treated at the Department of Faculty Surgery of I.M. Sechenov First Moscow State Medical University from 2007 to 2014. Cryoprecipitate and alloplant were injected into cirrhotic liver tissue in the first (72 patients) and second (42 patients) groups under ultrasound control respectively. Patients' age was 48.9±12.14 years (range 18-75). There were 66 men (58%) and 48 (42%) women. Mixed (toxic and viral) etiology of cirrhosis was observed in 40.3% of patients, viral--in 25.8%, toxic--in 34.2%. RESULTS: Minimally invasive treatment under ultrasound showed significant (p>0.05) positive dynamics of hepatocellular failure, cytolytic and cholestatic syndromes, hypersplenism in 3, 6 and 12 months after cryoprecipitate administration in most patients with cirrhosis Child-Pugh class A, B and C (group 1). Alloplant injected into hepatic tissue causes less regeneration of liver tissue. It improves clinical and laboratory parameters in patients with cirrhosis Child-Pugh classes A and B. In case of class C allopolant is not effective.

Integrins LFA-1 and Mac-1 and cytokines IL-6 and IL-10 in high-cancer mice under the influence of phytoadaptogen.

The expression of leukocyte integrins LFA-1 and Mac-1 and cytokines IL-6 and IL-10 was studied in mice predisposed to spontaneous hepatocarcinomas. The efficacy of a phytoadaptogen in correcting these parameters was evaluated. The role of adhesive interactions between immune cells and target cells in the recovery of antitumor regulatory mechanisms was estimated.

Regeneration of cirrhotic liver in rabbits after intrahepatic injection of cryoprecipitate.

The stimulatory effect of cryoprecipitate on liver regeneration was studied in rabbits with cirrhosis of the liver induced by subcutaneous injection of tetrachloromethane. Cryoprecipitate stimulated the hepatocyte regeneration (appearance of binuclear and proliferating cells) in liver tissue in cirrhosis, but the initial structure of the liver was not restored. The newly formed focus of regeneration with proper girder structure of hepatocytes forced back the connective tissue. Highly concentrated solution of fibrinogen, injected by puncture method into cirrhotic hepatic tissue, stimulated its regeneration.

[Antimutagenesis of multiphytoadaptogene in yeast saccharomyces].

Multiphytoadaptogene (MPA) consists of plant extracts components including adaptogenes. Genotoxicity analysis revealed the antimutagenic activity of MPA. MPA decreased the direct mutations frequency in ADE4-ADE8 loci induced by UV radiation and nitrous acid by 3.7 and 33 times, respectively. The lethal effect of UV radiation was inhibited when the preparation was used. MPA had no effect on replicative mutagenesis. At the same time it depressed mutagenesis caused by repair errors. The data obtained suggest the antimutagenic activity of multiphytoadaptogene is associated with postreplicative repair activation.

[Investigation of multyphytoadaptogene anti-radiation efficacy in dogs experiments].

The purpose of the work was to elucidate the radioprotective efficacy of multyphytoadaptogene (MPA) in dogs in various conditions of gamma radiation and MPA application. Dogs were given 15% MPA solution with drinking water in 3,6 ml/kg dose per day 2 weeks before the radiating (preventive application), 2 weeks before and 2 weeks after the radiating (preventive and therapeutic application) as well as 2 weeks after the radiating only (therapeutic application). Animals of control groups received radiation. Dogs were exposed to 3,5 Cy acute radiation and 8,0 Gy prolonged radiation. There were no survived dogs in control groups. At the same time MPA increased dogs survival in preventive, preventive and therapeutic as well as therapeutic applications after 3,5 Gy acute radiation and after 8,0 Gy prolonged radiation. MPA improved the somatic state, interfere with leukocytes amount in blood. The data obtained suggest the radioprotective efficacy of MPA.

[Investigation of multyphytoadaptogene anti-radiation activity in mice].

The aim of the work was to elucidate the radioprotective activity of multyphytoadaptogene (MPA) in mice in various conditions of gamma radiation and MPA application. Males of CBA x C57BL/6 F1 mice were given 15% MPA solution with drinking water 2 weeks before the radiating (preventive application), 2 weeks before and 2 weeks after the radiating (preventive and therapeutic application) and also 2 weeks after the radiating only (therapeutic application). Animals of control groups received radiation or were given 5% ethanol solution in drinking water in the same application schemes. MPA increased the mice survival in preventive, preventive and therapeutic as well as therapeutic applications after 7.5 Gy radiation (66.7: 66.4 and 40.2% correspondingly). After 11.0 Gy radiation MPA increased the mice survival in preventive as well as preventive and therapeutic applications (75.0 and 76.9% correspondingly). MPA administration improved the somatic state, weight of animals, quality of life. MPA has no side effects. The data suggest the radioprotective activity of MPA.

Computer-aided Evaluation of Polyvalent Medications' Pharmacological Potential. Multiphytoadaptogen as a Case Study.

Many human diseases including cancer, degenerative and autoimmune disorders, diabetes and others are multifactorial. Pharmaceutical agents acting on a single target do not provide their efficient curation. Multitargeted drugs exhibiting pleiotropic pharmacological effects have certain advantages due to the normalization of the complex pathological processes of different etiology. Extracts of medicinal plants (EMP) containing multiple phytocomponents are widely used in traditional medicines for multifactorial disorders' treatment. Experimental studies of pharmacological potential for multicomponent compositions are quite expensive and time-consuming. In silico evaluation of EMP the pharmacological potential may provide the basis for selecting the most promising directions of testing and for identifying potential additive/synergistic effects. Multiphytoadaptogen (MPhA) containing 70 major phytocomponents of different chemical classes from 40 medicinal plant extracts has been studied in vitro, in vivo and in clinical researches. Antiproliferative and anti-tumor activities have been shown against some tumors as well as evidence-based therapeutic effects against age-related pathologies. In addition, the neuroprotective, antioxidant, antimutagenic, radioprotective, and immunomodulatory effects of MPhA were confirmed. Analysis of the PASS profiles of the biological activity of MPhA phytocomponents showed that most of the predicted anti-tumor and anti-metastatic effects were consistent with the results of laboratory and clinical studies. Antimutagenic, immunomodulatory, radioprotective, neuroprotective and anti-Parkinsonian effects were also predicted for most of the phytocomponents. Effects associated with positive effects on the male and female reproductive systems have been identified too. Thus, PASS and PharmaExpert can be used to evaluate the pharmacological potential of complex pharmaceutical compositions containing natural products.

Photodynamic therapy of classic Kaposi's sarcoma with video-fluorescence control.

BACKGROUND: Kaposi's sarcoma (multiple idiopathic hemorrhagic sarcoma, Kaposi's angiosarcoma) is an angioproliferative neoplasm of endothelial origin associated with human herpes virus 8 (HHV - 8) and human immunodeficiency virus (HIV). The incidence of the classical form of Kaposi's sarcoma (КS) varies significantly in different geographical areas from 0.14/1 million people (both men and women) to 10.5 per 1 million men and 2.7 per 1 million women. The onset of КS is typical at the age of 35-39 in men and 25-39 years in women. CASE REPORT: A case of successful treatment of a recurrent non-HIV and non-HHV-8 Kaposi's sarcoma with PDT in a 79-year old man. RESULTS: After the recieved photodynamic treatment, complete pathologic response was achieved, i.e., Grade 5 tumor response according to Miller-Payne histological grading system (1999). The overall condition has significantly improved with no clinical tumor signs. CONCLUSION: This report describes a good outcome with PDT in the treatment of Kaposi's sarcoma. The results obtained are initial, but encouraging, demonstrating good tolerance, safety and high efficacy of PDT in classical КS. The successful use of PDT in cutaneous manifestations of HIV-associated KS is also described in literature.

[Possibilities of in silico estimations for the development of pharmaceutical composition phytoladaptogene cytotoxic for bladder cancer cells]. / Vozmozhnosti otsenok in silico dlia razrabotki farmkompozitsii fitoladaptogen, tsitotoksichnoi dlia kletok raka mochevogo puzyria.

Based on the prediction of biological activity spectra for several secondary metabolites of medicinal plants using the PASS computer program and validation in vitro of the predictions results the priority direction of the pharmaceutical composition Phytoladaptogene (PLA) development was determined. PLA is a complex of structurally diverse small organic compounds including biologically active substances of phytoadaptogenes (ginsenosides from Panax ginseng, rhodionin from Rhodiola rosea and others) compiled considering previously developed pharmaceutical compositions. Two variants of the pharmaceutical composition were studied: - the major and minor variants included 22 and 13 compounds, respectively. The probability of activity exceeds the probability of inactivity for 1400 out of 1945 pharmacological effects and mechanisms predicted by PASS for the major variant of PLA. The wide range of predicted activities is mainly due to the low structural similarity of constituent compounds. An in silico prediction indicates the possibilities of antitumor properties against bladder, stomach, colon, ovarian and cervical cancers both for minor and major PLA compositions. It was found that the highest probability values of activity were predicted for three mechanisms: apoptosis agonist, caspase-3 stimulant, and transcription factor NF-κB inhibitor. According to the PharmaExpert program they are associated with the antitumor effect against bladder cancer. Experimental validation was using the human bladder cancer cell line RT-112. The results of the MTT test have shown that the cytotoxicity of the major PLA variant is higher than that of the minor PLA variant. In vitro experiments performed using two methods (double staining with annexin V and propidium iodide and detection of active caspase-3 in cells) confirmed that the death of bladder cancer cells occurred via the apoptotic mechanism. The data obtained correspond to the results of the prediction and indicate advantages of the major PLA composition. Thus, PLA can become the basis for the development of a drug with the antitumor activity against bladder cancer. The antitumor activity predicted by PASS for other cancers may be the subject of further studies.

Prospects of using phytoadaptogen in the treatment of diffuse stomach cancer.

The efficiency of treatment of diffuse stomach cancer can be improved by using a complex phytoadaptogen. In groups receiving phytoadaptogen, the level of tumor marker CA 19-9 decreased and the mean life span of patients increased by 2.5 times. The drug exhibited immunomodulating (including interferonogenic and adhesiogenic), antioxidant, and hormone-modulating effects.

[Composite phytoadaptogens in oncology and gerontology].

The article describes results of research devoted to Phytomix-40, a mixture of plant adaptogens. It focuses on immunobiological criteria for its formulation, chemical composition and manufacture procedures, biological standartization tests, in vitro and in vivo preclinical studies, clinical trials in patients with non-malignant tumours (benign prostatic hyperplasia), precancer (oral leukoplakia), advanced cancer (malignant gastric cancer), and age-related neurodegenerative disease (parkinsonism). Prospects for the development of other plant preparations for non-toxic prevention and treatment of cancer and prolongation of life span of the affected subjects are discussed.

[Neuroprotective features of phytoadaptogens].

In the article the authors demonstrated that phytoadaptogens (Panax ginseng, Eleutherococcus senticosus, Rhodiola rosea) take part in protecting brain neurons from various injuries. Ability of phytoadaptogens to have influence on neurodegenerative mechanisms at Parkinson's disease is discussed. Phytoadaptogens should be proposed for study or use as therapeutic modulators in neurodegenerative disorders including Parkinson's disease.

[Ultrasound investigation and mini-invasive ultrasound-assisted technologies in diagnosis and treatment of extra-organ separate fluid formations in abdominal cavity]. / Ul'trazvukovoe issledovanie i maloinvazivnye tekhnologii pod kontrolem UZI v diagnostike i lechenii vneorgannykh otgranichennykh skoplenii zhidkosti v briushnoi polosti.

The authors discuss the use of ultrasound-assisted percutaneous puncture and drainage for diagnosis and treatment of extraorganic separate fluid formations in abdominal cavity (abscess, limited non-infected fluid formation, hematoma with clotted blood), determination of their sizes and obtaining material for laboratory study. 307 patients with various extraorganic separate fluid in formations in abdominal cavity were examined. Ultrasonic symptoms of abscess were described in 54 patients, of limited non-infected fluid formation--in 234, of hematoma with clotted blood in 19 patients. 146 patients were cured conservatively, 75 patients underwent US-assisted puncture, 76--US-assisted drainage. Mean time of drainage was 14 days (ranged from 10 to 20). There were neither complications nor lethal outcomes. Ultrasound examination and US-assisted mini-invasive surgery permit to detect precisely the nature of fluid formation, to perform timely and low-traumatic treatment.

[Diagnosis and treatment of isolated subdiaphragmatic liquid accumulations under ultrasound control]. / Diagnostika i lechenie ogranichennykh poddiafragmal'nykh zhidkostnykh skoplenii pod kontrolem UZI.

The analysis of diagnostic abilities of ultrasound and miniinvasive treatment under ultrasound examination control in 39 patients with subdiaphragmatic local fluid accumulations in abdominal cavity has been carried out. The revealed by US examination manifestations of the abscess formation in 15 patients, local noninfected accumulation of fluid in 20 patients, haematomas (hemolized)--in 4 are described. Indications for the treatment by punctures and drainage of local subdiaphragmatic fluid accumulations under US control depending on the size, form and character of liquid accumulation are given. 11 patients were cured by a single puncture, 1--by multiple punctures, 27--by drainage under US-control. The use of miniinvasive technologies resulted in no complications and mortality in this group of patients. Laboratory examination of the material taken by punctures and drainage under US-control demonstrated in 20 patients infected material and in 14--uninfected one, in 5 patients hematoma was detected. Standard operations performed from 1946 in the surgical clinic resulted in lethality of 19%.

[Minimally-invasive combined radiosurgical interventions in diagnosis and treatment of pulmonary artery thromboembolism]. / Maloinvazivnye kombinirovannye rentgenokhirgicheskie vmeshatel'stva pri diagnostike i lechenii tromboémbolii legochno-arterial'nogo basseina.

Basing on the analysis of results obtained during the investigation and treatment of 38 patients suspected of pulmonary artery thromboembolism (PAT) the algorithm of measures applied in our hospital was developed. Its purpose was to put the PAT diagnosis and treatment in order. In our investigations the leading treatment method was the regional infusion therapy conducted through the transformation of diagnostic catheterization of pulmonary artery trunk into the treatment intervention. With the purpose of embolus hydrodynamic destruction the regional thrombolysis was conducted under conditions of fast high-pressure perfusion. It was preceded by the mechanical recanalization of thrombosis zone by the distal part of probe in order to create more favorable perfusion conditions. To prevent the repeated PAT when the source of thromboembolism was revealed the cava-filter implantation in the infra-renal part of inferior cava was performed.

[A toxicological study of the preparation Phytomix-40]. / Toksikologicheskoe izuchenie preparata Fitomiks-40.

The results of toxicological evaluation of the new plant preparation Phitomix-40 (PM-40) used in the treatment of cancer are presented. To prevent a patient's individual immunological responsiveness to some phytoadaptogens, the preparation comprises 40 plant extracts (Rhodiola r. L.; Juniperus C. L.; Helichrysum a. L; Viburnum o. L., etc.). Animal experiments demonstrated that PM-40 had a low toxicity; LD50 was more than 20 and 15 ml/kg for rats and mice, respectively.