Stimulation of Liver Regeneration Using a Titanium Nickelide Implant (Experimental Study)

Currently, morbidity and mortality from chronic diffuse diseases of the liver and cirrhosis continue to increase worldwide. The difficulty of stabilizing the process with pharmacological agents, lots of restrictions for liver transplantation, the palliative character of the surgical correction of complications determine the urgency of finding various ways to stimulate liver regeneration, including surgical ones. Most of the known methods of surgical stimulation of regeneration are quite traumatic, and their stimulating effect is short-lived. The methods associated with cellular technologies are mostly expensive, ineffective, or poorly understood. In the experimental study, the effect on the parenchyma of a healthy and cirrhotic liver clips for clamping parenchymal organs exerting different unit pressure on the tissue was studied. The object of the study was laboratory rats with a healthy liver and animals with simulated cirrhosis. The animals were operated on with the imposition of titanium nickelide clips on the liver. Changes in the liver were studied 3, 7, 14, and 28 days after the surgery by histological examination of various parts of the liver. It was established that the clip with a lower specific pressure did not cause tissue necrosis, led to atrophy of the marginal part of the liver, also increased hepatocytes and binuclear hepatocytes were observed in the bulk of the liver. A decrease in the proportion of connective tissue was also observed in groups with liver cirrhosis. Thus, we consider it possible to use clips with a certain specific pressure on the tissue as a method of stimulating the reparative properties of the liver in chronic diffuse diseases and cirrhosis of the live

ОЦЕНКА ПРИВЕРЖЕННОСТИ АНТИРЕТРОВИРУСНОЙ ТЕРАПИИ У БОЛЬНЫХ ВИЧ-ИНФЕКЦИЕЙ, УПОТРЕБЛЯЮЩИХ АЛКОГОЛЬ

Purpose: to analyze prevalence of alcohol abuse and influence of alcohol abuse on adherence to ARVT in HIV-positive patients.Research materials: we performed an anonymous survey of 165 HIV-positive patients hospitalized in Clinical Infectious Diseases Hospital named after S.P. Botkin in 2017.Results: more than a half of participants has hazardous alcohol use or alcohol dependence. HIV-positive patients with alcohol abuse have high level of alcohol anosognosia. According to our survey among hospitalised patients, who didn’t take ARVT, 57% wasn’t ready to start antiretroviral therapy. Among patients, who were on ARVT at the time of evaluation, 92% had history of at least one episode of treatment interruption. Most common reason for interruption of antiretroviral therapy was drug’s side effect (36,5%). Alcohol was mentioned as a cause of interruption by 7,7% of participants. Level of adherence was significantly different among patients with different alcohol consumption pattern. Adherence measured with different self-assessment tools was low among hospitalized HIV-positive patients.Conclusion: Hazardous drinking and alcohol dependence is very common among hospitalized HIV-positive patients. Suggested adherence self-assessment tools should help doctors to detect patients with insufficient level of adherence to ARVT. Цель: изучить распространенность употребления алкоголя и оценить влияние злоупотребления алкоголем на приверженность антиретровирусной терапии у ВИЧ-инфицированных больных.Материалы и методы: проведено анонимное анкетирование 165 больных ВИЧ-инфекцией, находившихся на лечении в Клинической инфекционной больнице им. С.П. Боткина в 2017 г.Результаты: более половины больных обследованной группы отмечали опасное употребление или злоупотребление алкоголем. Для ВИЧ-позитивных больных, употребляющих алкоголь, был характерен высокий уровень алкогольной анозогнозии. Среди госпитализированных больных, не получавших антиретровирусной терапии на момент госпитализации, 57%, по данным тестирования, не были готовы к началу приема антиретровирусных препаратов. Пациенты, которые получали антиретровирусную терапию на момент проведения исследования, в 92% случаев имели опыт прерывания терапии в прошлом. Самой частой причиной прерывания антиретровирусной терапии участники исследования назвали побочные действия препаратов (36,5%). С употреблением алкоголя прерывание терапии связали 7,7% опрошенных. Уровень приверженности статистически значимо различался у больных с разной степенью алкоголизации. Результаты различных шкал самооценки приверженности свидетельствуют о недостаточной приверженности антиретровирусной терапии среди госпитализированных больных ВИЧ-инфекцией.Заключение: среди госпитализированных больных ВИЧ-инфекцией широко распространены опасное употребление алкоголя и алкогольная зависимость. Предложенные методики самооценки приверженности могут помочь врачам выявить группы с потенциально недостаточным уровнем приверженности антиретровирусной терапии.

Small molecules targeted to the microtubule–Hec1 interaction inhibit cancer cell growth through microtubule stabilization

Highly expressed in cancer protein 1 (Hec1) is a subunit of the kinetochore (KT)-associated Ndc80 complex, which ensures proper segregation of sister chromatids at mitosis by mediating the interaction between KTs and microtubules (MTs). HEC1 mRNA and protein are highly expressed in many malignancies as part of a signature of chromosome instability. These properties render Hec1 a promising molecular target for developing therapeutic drugs that exert their anticancer activities by producing massive chromosome aneuploidy. A virtual screening study aimed at identifying small molecules able to bind at the Hec1–MT interaction domain identified one positive hit compound and two analogs of the hit with high cytotoxic, pro-apoptotic and anti-mitotic activities. The most cytotoxic analog (SM15) was shown to produce chromosome segregation defects in cancer cells by inhibiting the correction of erroneous KT–MT interactions. Live cell imaging of treated cells demonstrated that mitotic arrest and segregation abnormalities lead to cell death through mitotic catastrophe and that cell death occurred also from interphase. Importantly, SM15 was shown to be more effective in inducing apoptotic cell death in cancer cells as compared to normal ones and effectively reduced tumor growth in a mouse xenograft model. Mechanistically, cold-induced MT depolymerization experiments demonstrated a hyper-stabilization of both mitotic and interphase MTs. Molecular dynamics simulations corroborate this finding by showing that SM15 can bind the MT surface independently from Hec1 and acts as a stabilizer of both MTs and KT–MT interactions. Overall, our studies represent a clear proof of principle that MT-Hec1-interacting compounds may represent novel powerful anticancer agents

Имплантаты из никелида титана в абдоминальной хирургии

Here are represented our results according to making and clinical using of different TiNi devices for treatment of digestive system diseases. Constructions for perfoming of compression anastomoses, cliping of tubular structures during laparoscopic operations and perforated ulcer plastic. Materials of experimental investigations and clinic experience of 220 cases treatment are represented.В настоящей статье приведены результаты работы по созданию и применению в клинике различных устройств из никелида титана для хирургического лечения заболеваний органов пищеварения. Описаны конструкции для наложения компрессионных анастомозов, клипирования трубчатых структур при лапароскопических операциях и пластики перфоративных язв. Представлены материалы экспериментального исследования и клинический опыт использования имплантатов при лечении 220 больных

HIV-1 gp120 Induces Expression of IL-6 through a Nuclear Factor-Kappa B-Dependent Mechanism: Suppression by gp120 Specific Small Interfering RNA

In addition to its role in virus entry, HIV-1 gp120 has also been implicated in HIV-associated neurocognitive disorders. However, the mechanism(s) responsible for gp120-mediated neuroinflammation remain undefined. In view of increased levels of IL-6 in HIV-positive individuals with neurological manifestations, we sought to address whether gp120 is involved in IL-6 over-expression in astrocytes. Transfection of a human astrocyte cell line with a plasmid encoding gp120 resulted in increased expression of IL-6 at the levels of mRNA and protein by 51.3±2.1 and 11.6±2.2 fold respectively; this effect of gp120 on IL-6 expression was also demonstrated using primary human fetal astrocytes. A similar effect on IL-6 expression was observed when primary astrocytes were treated with gp120 protein derived from different strains of X4 and R5 tropic HIV-1. The induction of IL-6 could be abrogated by use of gp120-specific siRNA. Furthermore, this study showed that the NF-κB pathway is involved in gp120-mediated IL-6 over-expression, as IKK-2 and IKKβ inhibitors inhibited IL-6 expression by 56.5% and 60.8%, respectively. These results were also confirmed through the use of NF-κB specific siRNA. We also showed that gp120 could increase the phosphorylation of IκBα. Furthermore, gp120 transfection in the SVGA cells increased translocation of NF-κB from cytoplasm to nucleus. These results demonstrate that HIV-1 gp120-mediated over-expression of IL-6 in astrocytes is one mechanism responsible for neuroinflammation in HIV-infected individuals and this is mediated by the NF-κB pathway

Formation of biliodigestive anastomoses with the TiNi compression device

In our research, we evaluated the effectiveness of the device for the valve compression anastomoses formation in animals. The implant is made of the titanium nickelide alloy (TiNi) in the form of two loops of the TiNi wire. In the area of the bent turns, compression is not carried out, the tissue is not squeezed, and later the valve is formed in the zone of anastomosis. Twenty-six antireflux biliodigestive compression anastomoses on the small bowel have been created during the experiment. They include 13 choledochojejunostomies and 13 cholecystojejunostomies. We studied the terms of the compression devices failure, the mechanical and biological durability of these anastomoses, the primary permeability of anastomoses and carried out the microscopic examination of the compression suture. We proved that all valve compression anastomoses created with TiNi shape-memory implant have been mechanically and biologically tight. The compression devices were eliminated from the zones of anastomoses on the 7th-8th day after the surgery in all cases. The microscopic examination showed the insignificant development of sclerosis in the compression zone and full adaptation of all organ layers. The created valve reduced the reflux of intestinal contents that lessened the probability of development of acute and chronic cholangitis in the postoperative period. The use of the TiNi implant allows to carry out the operation twice quicker. Such anastomosis has high physical durability and low bacteriological permeability. The new way of the formation of valve biliodigestive compression anastomoses allows to create stronger and more reliable anastomoses and prevent the development of typical complications

ASSESMENT OF ADHERENCE TO ARVT IN HIV-POSITIVE PATIENTS WITH ALCHOHOL ABUSE

Purpose: to analyze prevalence of alcohol abuse and influence of alcohol abuse on adherence to ARVT in HIV-positive patients.Research materials: we performed an anonymous survey of 165 HIV-positive patients hospitalized in Clinical Infectious Diseases Hospital named after S.P. Botkin in 2017.Results: more than a half of participants has hazardous alcohol use or alcohol dependence. HIV-positive patients with alcohol abuse have high level of alcohol anosognosia. According to our survey among hospitalised patients, who didn’t take ARVT, 57% wasn’t ready to start antiretroviral therapy. Among patients, who were on ARVT at the time of evaluation, 92% had history of at least one episode of treatment interruption. Most common reason for interruption of antiretroviral therapy was drug’s side effect (36,5%). Alcohol was mentioned as a cause of interruption by 7,7% of participants. Level of adherence was significantly different among patients with different alcohol consumption pattern. Adherence measured with different self-assessment tools was low among hospitalized HIV-positive patients.Conclusion: Hazardous drinking and alcohol dependence is very common among hospitalized HIV-positive patients. Suggested adherence self-assessment tools should help doctors to detect patients with insufficient level of adherence to ARVT

HIV-1 decreases the levels of neurotrophins in human lymphocytes

none9noneValeriya Avdoshina;Alfredo Garzino-Demo;Alessia Bachis;Maria CG Monaco;Pauline M Maki;Rochelle E Tractenberg;Chenglong Liu;Mary A Young;Italo MocchettiValeriya, Avdoshina; GARZINO DEMO, Alfredo; Alessia, Bachis; Maria CG, Monaco; Pauline M., Maki; Rochelle E., Tractenberg; Chenglong, Liu; Mary A., Young; Italo, Mocchett