[Current antiretroviral therapy: A review].

The article presents an overview of clinical recommendations for currant antiretroviral therapy. Currently, the current preferred first-line antiretroviral therapy regimens are combinations of 2 or 3 antiretroviral drugs (ARVs) in one tablet with a frequency of administration 1 time per day and, as a rule, include drugs of the 2nd generation (integrase inhibitors or non-nucleoside reverse transcriptase inhibitors). These schemes have high efficiency and a good genetic barrier in the development of HIV resistance mutations. HIV protease inhibitors are used as alternative regimens. Schemes with the least number and spectrum of side effects, no effect on metabolic processes and minimal drug interactions have advantages. Switching patients to injectable therapy regimens with a frequency of administration of drugs once every 2 months can significantly improve the quality of life of patients and, accordingly, adherence to their treatment. The development and introduction of new classes of ARVs into clinical practice ensures the suppression of HIV replication in most patients with HIV strains resistant to drugs of the main groups of ARVs (nucleoside/nucleotide reverse transcriptase.

[Description of the case of adverse pasteurellosis in a cirrhosis patient. Case report].

The article describes a clinical case of an unfavorable course of pasteurellosis in a patient with liver cirrhosis. Possible variants of the clinical course, clinical and epidemiological data, on the basis of which pasteurellosis can be suspected, modern recommendations for antibiotic therapy are considered.

[The problem of diagnosis and differential diagnosis of botulism in pregnant women. Case report].

The article describes a clinical observation of a severe course of a sporadic case of foodborne botulism in a woman at 32 weeks gestation with a successful resolution of pregnancy by independent childbirth. No adverse effects of botulism on pregnancy, delivery, and fetal development were noted. Anti-botulinum serum was administered to the patient no earlier than 96 hours from the onset of the disease. The paper analyzes the clinical picture of botulism, on the basis of which it is necessary to carry out a differential diagnosis.

[Human babesiosis: clinical cases in the european part of the Russian Federation].

The article describes four clinical observations of patients with babesiosis detected in the European part of the Russian Federation, two of whom were under the direct supervision of the authors. The analysis of epidemiological data, clinical picture, results of laboratory studies in the dynamics of the disease. Differential diagnosis and treatment are discussed.

INCREASED FORMATION OF PHOSPHORYLATED H2AX FOCI IN NUCLEI OF CELLS INFECTED BY HEPATITIS B AND B+D VIRUSES.

Liver cirrhosis and hepatocellular carcinoma are the most common outcomes of chronic hepatitis B. Hepatitis B virus (HBV) induces transformation and cell death in chronic hepatitis B (CHB). DNA double strand breaks (DSBs) represent the most dangerous type of genome damage. It was shown previously that generation of phosphorylated histone H2AX foci is a reliable marker of DSBs. The aim of this study was to analyse generation of yH2AX foci in HBV and hepatitis D virus (HDV) infection in vitro and in liver biopsies of patients with CHB and CHB with delta-agent (CHD). Human hepatoma cell line HepG2-1.1merHBV with activated HBV life cycle was used to perform real-time PCR for analysis of pregenomic RNA, HBV DNA, HBV cccDNA and for immunocytochemical analysis of yH2AX. Liver biopsies from CHB and CHD patients were analyzed to confirm the results. HBV induces multiple discrete yH2AX foci in HepG2-1.1merHBV cells in vitro and in biopsies of CHB and CHB+D patients. The ratio of hepatocytes w/o yH2AX foci is significantly lower (49,9+/-12,3% vs. 85,5+/-0,9%, p.

THE ROLE OF DNA-METHYLTRANSFERASES IN THE LIFE CYCLE OF HEPATITIS B VIRUS AND PATHOGENESIS OF CHRONIC HEPATITIS B.

Chronic hepatitis B is caused by a persistent form of hepatitis B virus, covalently closed circular DNA (cccDNA). Stability of cccDNA is associated with intracellular localization of cccDNA and formation of minichromosome, regulated by epigenetic mechanisms. One of the key mechanisms in epigenetics is methylation of DNA on CpG islands. Expression levels of DNA-methyltransferases (DNMTs) in chronic hepatitis B patients were shown to be upregulated. Nevertheless, the role of DNMTs in the life cycle of HBV and their effects on the cell remain elusive. In this review, we discuss latest achievements on the role of DNMTs in chronic hepatitis B and HBV in vitro models.

The problem of diagnosis of generalized and focal forms of salmonellosis.

The article describes the clinical observation with an unfavorable outcome of the generalized form of salmonella infection caused by Salmonella typhimurium group B in a woman of 60 years without immunodeficiency, complicated by the development of multiple abscesses of the lower parts of abdominal cavity, probably of appendicular origin. In a short literary review, the pathogenetic mechanisms that contribute to the formation of generalized and extraintestinal forms of salmonella infection are discussed.

Pets in modern society: hidden threats.

The article discusses the problem of the role of pets as a source of zoonotic infections, representing a hidden threat to modern society. Since the content is now very popular at home, both traditional and exotic animals, it is necessary to develop an interdisciplinary program to control the spread of zoonotic infections and the risks of their infection with people. Since the problem lies in the intersection of several disciplines, joint efforts of doctors, veterinarians, health organizers and laboratory specialists are necessary.

[Hepatitis C can be cured: will hepatitis B become next?] / Gepatit S stal izlechim. Gepatit V - sleduiushchii?

Chronic hepatitis B (CHB) and C (CHC) are one of the leading causes of cirrhosis and liver cancer with over a million of people dying annually from their consequences. In Russia CHB and CHC morbidity and related mortality show an upward trend. As a result of recent breakthroughs in antiviral therapeutics CHC became a curable disease. Modern therapeutics effectively suppress viral replication in CHB patients, but withdrawal of antivirals usually results in disease relapse. Loss of HBsAg required for the so called 'functional cure' is a very rare event. Moreover, 'complete cure' when the virus is entirely eliminated from the body is not possible due to a persistent form of covalently closed circular DNA (cccDNA) of hepatitis B virus (HBV) in hepatocytes refractory to modern antivirals. Today, there is a plethora of new promising medications being at different stages of development that target different steps of viral life cycle, including inhibitors of interaction between HBV and its entry receptor NTCP, inhibitors of HBV cccDNA, inhibitors of nucleocapsid assembly, technologies of genome editing (TALENs, CRISPR/Cas etc) and RNA-interference. In addition to direct acting antivirals, there is a number of approaches aimed at enhancement of the innate and adaptive immune responses. In experimental conditions, some of these approaches or their combinations help to achieve functional cure. However, complete elimination of the virus is possible only using technologies of genome editing, capable of specific cccDNA degradation. Nuclease systems are currently at their early stages of development, and there is a long way to prove their efficacy and safety. Nevertheless, highly promising results of the recent years leave no doubt that CRISPR/Cas systems and similar technologies can become the basis of CHB therapy.

Natural polysaccharide carrageenan inhibits toxic effect of gram-negative bacterial endotoxins.

The protective effect of polysaccharide carrageenan on the damaging effect of endotoxins of gram-negative bacteria was studied in vivo and in vitro. Carrageenan increased mouse resistance to the toxic effect of LPS. The degree of protection depended on polysaccharide concentration and administration time and route. Pretreatment of donor platelets with carrageenan reduced their aggregation activity caused by cooperative effect of LPS and ADP.