Betulin attenuated liver damage by prevention of hepatic mitochondrial dysfunction in rats with alcoholic steatohepatitis

Betulin, a pentacyclic triterpene, possesses antioxidant, anti-inflammatory and hepatoprotective properties. The aim of this study was to evaluate the impact of liver mitochondria in hepatoprotection of betulin using a rat model of alcoholic steatohepatitis induced by ethanol administration (4 g/kg, intragastric) for 8 weeks. The treatment with betulin (50 and 100 mg/kg b.w., intragastric) during this period attenuated the histological signs of steatohepatitis and lowered the serum and liver triglyceride contents, as well as the serum activities of aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase. Betulin (100 mg/kg) decreased the liver/body weight ratio and inhibited the increase in the serum levels of TNFα, IL-1β, TGFβ, and hyaluronic acid, demonstrating hepatoprotective, anti-inflammatory, and antifibrotic potential. Betulin also inhibited the formation of superoxide anions in mitochondria and the end-products of lipid peroxidation in liver tissue, the amount of which was significantly increased in ethanol-treated rats. The disturbances in mitochondrial respiration, uncoupling of oxidative phosphorylation and decreasing of mitochondrial complex I, II, and IV activities in rats with steatohepatitis, were reverted by betulin administration. The increased susceptibility of mitochondria to Ca2+-induced permeability transition pore formation in the hepatitis group was improved in rats treated with betulin. In conclusion, betulin, having antioxidant properties, exerts a beneficial effect in the rat model of alcoholic steatohepatitis via prevention of liver mitochondria dysfunction, which may be attributed to the inhibition of mitochondrial permeability transition

Ferutinin Induces Membrane Depolarization, Permeability Transition Pore Formation, and Respiration Uncoupling in Isolated Rat Liver Mitochondria by Stimulation of Ca 2+ -Permeability

It is well known that the terpenoid ferutinin (4-oxy-6-(4-oxybenzoyloxy) dauc-8,9-en), isolated from the plant Ferula tenuisecta, considerably increases the permeability of artificial and cellular membranes to Ca2+-ions and produces apoptotic cell death in different cell lines in a mitochondria-dependent manner. The present study was designed for further evaluation of the mechanism(s) of mitochondrial effects of ferutinin using isolated rat liver mitochondria. Our findings provide evidence for ferutinin at concentrations of 5–27 µM to decrease state 3 respiration and the acceptor control ratio in the case of glutamate/malate as substrates. Ferutinin alone (10–60 µM) also dose-dependently dissipated membrane potential. In the presence of Ca2+-ions, ferutinin (10–60 µM) induced considerable depolarization of the inner mitochondrial membrane, which was partially inhibited by EGTA, and permeability transition pore formation, which was diminished partly by cyclosporin A, and did not influence markedly the effect of Ca2+ on mitochondrial respiration. Ruthenium Red, a specific inhibitor of mitochondrial calcium uniporter, completely inhibited Ca2+ -induced mitochondria swelling and membrane depolarization, but did not affect markedly the stimulation of these Ca2+-dependent processes by ferutinin. We concluded that the mitochondrial effects of ferutinin might be primarily induced by stimulation of mitochondrial membrane Ca2+-permeability, but other mechanisms, such as driving of univalent cations, might be involved

The functional condition of left atrium during the endovascular treatment of atrial fibrillation

The atrial fibrillation causes structural and functional changes of atriums. In this case, the remodeling of left atrium increases the risk of AF. One of the treatment strategy is catheter isolation of the pulmonary veins. However, the effectiveness of these operations does not exceed 70% in most of the cases that may be due to remodeling of left atrium. In this regard, the assessment of the condition of left atrium is actual for the optimization of treatment tactics and improvement of effectiveness rate.Фибрилляция предсердий вызывает структурные и функциональные изменения предсердий. При этом ремоделирование левого предсердия увеличивает риск возникновения ФП. Одна из стратегий лечения - катетерная изоляция легочных вен. Однако эффективность данных операций в большинстве случаев не превышает 70%, что может быть обусловлено, в том числе, ремоделированием левого предсердия. В связи с этим, актуальна оценка состояния левого предсердия для оптимизации тактики лечения и улучшения показателей эффективности

The deep, historical-roots of Cuban anti-imperialism

Colonialism, imperialism and anti-imperialism have been decisive in shaping Cuban political identity for 150 years. US determination to control Cuba, consistent with the Monroe Doctrine, had a strong economic rationale even before Spain was defeated in the War of Independence in 1898. Debate raged between Cubans who aspired to true independence and an annexationalist minority, who favoured union with the US. The Platt Amendment imposed on Cuba by the US in 1903 ‘reduced the independence and sovereignty of the Cuban republic to a myth’. Between then and the Revolution of 1959 Cuba was effectively first a protectorate and then neo-colony of the US, which dominated the Cuban economy, politics and foreign policy. Tackling the terrible socioeconomic and political effects of Cuba’s subjugation under the Spanish empire and then US imperialism necessitated a radical transformation of the Cuban economy, political institutions and power structures. The transition to socialism inevitably meant confronting US imperialism – and vice versa. Since 1959, US imperialism, with its powerful allies in the right-wing exile community based in Miami, have relentlessly tried to destroy the Revolution and Cuban socialism. The issue of imperialism remains key today, in the post-Fidel, President Trump era

A fast genomic dictionary

Thesis (S.B. and M.Eng.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 2000.Includes bibliographical references (p. 252-254).by Valentin I. Spitkovsky.S.B.and M.Eng

CHARACTERISTICS ASSOCIATED WITH LONG-TERM MAINTENANCE OF SINUS RHYTHM AFTER PULMONARY VEINS ISOLATION

Atrial fibrillation is the most frequent supraventricular tachyarrhythmia. Pulmonary veins isolation can be performed as the first line of treatment for this arrhythmia. Unfortunately, approximately 30% of patients in the first year after ablation have recurrence of atrial fibrillation. In this regard, we have attempted to identify the characteristics associated with long-term maintenance of sinus rhythm after pulmonary veins isolation.</jats:p

Treatment for ventricular arrhythmias in the absence of structural heart disease: from guidelines to clinical practice

Objective. To determine criteria for choosing management tactics in patients with ventricular arrhythmias (VA) in the absence of structural heart disease from the point of view of physicians and patients in clinical practice and to compare the immediate results of antiarrhythmic drug therapy (ADT) and radiofrequency ablation (RFA) with the trends in arrhythmic syndrome in the non-treatment group. Subjects and methods. Examinations were made in 90 patients (23 men and 67 women) (mean age, 44 (31; 57) years) with VA in the absence of structural heart disease. Preference was given to RFA (n = 32 (36%)), ADT (n = 37 (41%)), and follow-up tactics (n = 21 (23%)). At baseline and 1 month, Holter ECG monitoring was done; quality of life (QOL) was assessed; and anxiety and depression levels were detected using the SF-36 and HADS questionnaires. In addition, 71 physicians were surveyed about their preferences to the treatment of VA in individuals without structural heart disease. Results. In the total group of patients, VA was unambiguously accompanied by the symptoms only in 47%. The signs of anxiety and depression were identified in 41 and 14% of cases, respectively. The efficiency of RFA was comparable to that of ADT (p &gt; 0.1): a positive antiarrhythmic effect was observed in 71.9% of the patients in the RFA group and in 67.6% in the ADT group. During one month, 38.1% of the patients in the follow-up group showed a spontaneous substantial reduction in the number of ventricular premature beats (VPBs) or disappearance of unstable ventricular tachycardia (UVT), which met the criteria for a positive effect. At baseline, the QOL indicators on a social functioning scale in the RFA group were worse than those in the ADT group. At the same time, most QOL indicators in the patients who have chosen a wait-and-see tactic were significantly higher than those in the RFA and ADT subgroups. The patients treated with ethacyzin in the ADT group more frequently achieved a positive effect. In the interviewed physicians’ opinion, the choice of a tactic depended on the impact of arrhythmia on health status (68%), the number of VPBs per day (61%), and the presence of UVT (56%). RFA or ADT was most often recommended when there were 10,000-15,000 or more VPBs per day ((49 and 35% of the respondents, respectively). 46.5% of the respondents stated that β-blockers were the drug of choice for idiopathic frequent VPBs. Only 30% of the respondents considered it appropriate to restrict to a follow-up in the presence of asymptomatic VPBs. Conclusion. Patient management in clinical practice generally complies with the current guidelines; however, much importance is attached to the severity of arrhythmia (the number of VPBs per day, the presence of UVT) in addition to the presence of symptoms. In the opinion of most physicians, the initiation of treatment is justified when there are 10,000-15,000 and more per day. QOL assessment may be promising in choosing the optimal management tactics for these patients. Treatment should not be initiated immediately in patients with a high level of QOL, especially in those with arrhythmia lasting less than 12 months, by taking into account that there can be a spontaneous improvement in 38% of cases within the next month. The immediate results of ADT and RFA are comparable in patients with VA in the absence of structural heart disease. The Class IC antiarrhythmic drug ethacyzin is the most effective agent that ensures positive changes in arrhythmic syndrome in 66.7% of cases with the rate of side effects being in 17.8%.</jats:p