Evidence for the First Excited State of

The ^{7}H system was populated in the ^{2}H(^{8}He,^{3}He)^{7}H reaction with a 26 AMeV ^{8}He beam. The ^{7}H missing mass energy spectrum, the ^{3}H energy and angular distributions in the ^{7}H decay frame were reconstructed. The ^{7}H missing mass spectrum shows a peak, which can be interpreted either as unresolved 5/2^{+} and 3/2^{+} doublet or one of these states at 6.5(5) MeV. The data also provide indications of the 1/2^{+} ground state of ^{7}H located at 1.8(5) MeV with quite a low population cross section of ∼25 µb/sr within angular range θ_{c.m.}≃(17°-27°).

Towards the Limits of Existence of Nuclear Structure: Observation and First Spectroscopy of the Isotope

The most remote isotope from the proton dripline (by 4 atomic mass units) has been observed: ^{31}K. It is unbound with respect to three-proton (3p) emission, and its decays have been detected in flight by measuring the trajectories of all decay products using microstrip detectors. The 3p emission processes have been studied by the means of angular correlations of ^{28}S+3p and the respective decay vertices. The energies of the previously unknown ground and excited states of ^{31}K have been determined. This provides its 3p separation energy value S_{3p} of -4.6(2) MeV. Upper half-life limits of 10 ps of the observed ^{31}K states have been derived from distributions of the measured decay vertices.

[Adenosine A2A receptor as a drug target for treatment of sepsis].

Sepsis is a generalized infection accompanied by response of the body that manifests in a clinical and laboratory syndrome, namely, in the systemic inflammatory response syndrome (SIRS) from the organism to the infection. Although sepsis is a widespread and life-threatening disease, the assortment of drugs for its treatment is mostly limited by antibiotics. Therefore, the search for new cellular targets for drug therapy of sepsis is an urgent task of modern medicine and pharmacology. One of the most promising targets is the adenosine A(2A) receptor (A(2A)AR). The activation of this receptor, which is mediated by extracellular adenosine, manifests in almost all types of immune cells (lymphocytes, monocytes, macrophages, and dendritic cells) and results in reducing the severity of inflammation and reperfusion injury in various tissues. The activation of adenosine A(2A) receptor inhibits the proliferation of T cells and production of proinflammatory cytokines, which contributes to the activation of the synthesis of anti-inflammatory cytokines, thereby suppressing the systemic response. For this reason, various selective A(2A)AR agonists and antagonists may be considered to be drug candidates for sepsis pharmacotherapy. Nevertheless, they remain only efficient ligands and objects of pre-clinical and clinical trials. This review examines the molecular mechanisms of inflammatory response in sepsis and the structure and functions of A(2A)AR and its role in the pathogenesis of sepsis, as well as examples of using agonists and antagonists of this receptor for the treatment of SIRS and sepsis.

[ANTIVIRAL ACTIVITY OF THE DIHYDROQUERCETIN DURING THE COXSACKIEVIRUS B4 REPLICATION IN VITRO].

A study of the antiviral activity of antioxidants against viral infections is believed to be essential for creating complex antiviral agents. Dihydroquercetin is considered as the most active antioxidant extracted from Larix gmelinii. In this work, we present results of experiments of the antiviral properties of dihydroquercetin against a member of the family Picarnaviridae--Coxsackievirus B4 in vitro. We have estimated that dihydroquercetin reduces viral titers at 100 µg/ml concentration as compared with control of virus. We have shown using the plaque assay that CPE of virusis reduced in the presence of dihydroquercetin at 100 µg/ml. Study of the phase of viral lifecycle, in which dihydroquercetin acted, demonstrated that the highest efficacy of the antiviral therapy was reached at early stages of virus reproduction (1-3 hours post infection). These results show that dihydroquercetin has antiviralproperty against Coxsackievirus B4. This drug and other antioxidants can be tested as inhibitors of viral replication.

[Oncolytic potential of recombinant influenza A virus vectors on a model of malignant glioma in vivo].

Malignant glioma is the most frequently occurring primary brain tumor. Despite significant progress in the diagnostics and treatment of neoplastic diseases the prognosis for patients with III-IV grade gliomas, remains extremely unfavorable. Rapidly developing area in oncology is the employment of therapeutic viruses with natural or genetically engineered oncolytic activity. In the present study we demonstrated the oncolytic potential of a recombinant influenza A virus vector with impaired interferon antagonism function of NS1 protein in treatment of malignant glioma. Recombinant influenza A virus (HA-DS-GFP) expressing green fluorescent protein from the NS1 open reading frame was used as a model vector. HA-DS-GFP virus has shown infectivity towards glioma cells both in vitro, and in vivo (experimental glioma model in rats). Intratumoral inoculation of HA-DS-GFP resulted in a substantial inhibition or complete regression of tumor growth. Our data demonstrate that recombinant influenza vectors have promising potential in therapy of malignant gliomas.

CHRONIC HEPATITIS WITH DOUBLE B/C INFECTION: VIROLOGICAL, CLINICAL, MORPHOLOGICAL CHARACTERISTICS.

AIM: To estimate the r, virological and clinical characteristics of chronic viral hepatitis (CVH) with double B/C infection. MATERIALS AND METHODS: We examined 282 patients with CVH. Genomes of hepatitis B virus (HBV) and hepatitis C virus (HCV) were studied by PCR in blood and liver (AmpliSens HBV and Amplisens HCV Russia), nuclear proteins (HBcorAg HBV and NS3 HCV) were determined by immunohistochemical method (Novocastra, UK), HBVgenome was sequenced by the Sanger method using ABI prism BigDye Terminator v3.1 kits and ABIPRISM 3100 analyzer (AppliedBiosystems, USA). Indices of histological activity (HAI), fibrosis, and portal vein (PV) congestion index (CI) were calculated by formula CI=SBB/LB V where S is P V cross section area in cm2 and LB V - linear blood flow velocity in cm/s (Vivid Pro- 7 apparatus, USA). RESULTS: CVH with double B/C infection was diagnosed in 85 (30.1%) patients including 44.7% with viral genomes and proteins in the live; 42.4% with HCVviremia, and 12.9% with HBJV/HCVviremia. Maximum CVH activity was documented in patients with latent HBV/HCVviremia (ALT 157.2±59.2 U/, HAI 11.6±1.3,fibrosis 2.8±0.7, C1 0.059±0.005); it was minimal inpatients.without viremia (Alt 76.25±63.0 U/I, HAI 6.7+-0.6,fibrosis 1.7±0.5, CI 0.042±0.001;p <0.05). Patients with latent HBV infection had precore/ore and pres/s mutations in HBVgenome and cytoplasmic localization ofHBcorAg. CONCLUSION: Double B/C infection was diagnosed in 30.1% of the patients with CVH dominated by HCV Patients with latent HBVhadprecore/ore and pres/s mutations. The highest intensity of hepatic cellular inflamation,fibrosis, and PV congestion was associated with HBV/HCV viremia and the lowest with intrahepatic localization of both viruses.

Observation and Spectroscopy of New Proton-Unbound Isotopes ³°Ar and ²9Cl: An Interplay of Prompt Two-Proton and Sequential Decay.

Previously unknown isotopes (30)Ar and (29)Cl have been identified by measurement of the trajectories of their in-flight decay products (28)S+p+p and (28)S+p, respectively. The analysis of angular correlations of the fragments provided information on decay energies and the structure of the parent states. The ground states of (30)Ar and (29)Cl were found at 2.25(-0.10)(+0.15) and 1.8±0.1 MeV above the two- and one-proton thresholds, respectively. The lowest states in (30)Ar and (29)Cl point to a violation of isobaric symmetry in the structure of these unbound nuclei. The two-proton decay has been identified in a transition region between simultaneous two-proton and sequential proton emissions from the (30)Ar ground state, which is characterized by an interplay of three-body and two-body decay mechanisms. The first hint of a fine structure of the two-proton decay of (30)Ar*(2(+)) has been obtained by detecting two decay branches into the ground and first-excited states of the (28)S fragment.

[Ebola hemorrhagic fever: Properties of the pathogen and development of vaccines and chemotherapeutic agents].

Ebola hemorrhagic fever (EHF) epidemic currently ongoing in West Africa is not the first among numerous epidemics in the continent. Yet it seems to be the worst EHF epidemic outbreak caused by Ebola virus Zaire since 1976 as regards its extremely large scale and rapid spread in the population. Experiments to study the agent have continued for more than 20 years. The EHF virus has a relatively simple genome with seven genes and additional reading frame resulting from RNA editing. While being of a relatively low genetic capacity, the virus can be ranked as a standard for pathogenicity with the ability to evade the host immune response in uttermost perfection. The EHF virus has similarities with retroviruses, but belongs to (-)RNA viruses of a nonretroviral origin. Genetic elements of the virus, NIRV, were detected in animal and human genomes. EHF virus glycoprotein (GP) is a class I fusion protein and shows more similarities than distinctions in tertiary structure with SIV and HIV gp41 proteins and even influenza virus hemagglutinin. EHF is an unusual infectious disease, and studying the molecular basis of its pathogenesis may contribute to new findings in therapy of severe conditions leading to a fatal outcome.

[Comparison of the influenza epidemics in Russia caused by the pandemic virus A(H1N1)pdm09 within the period from 2009 to 2013].

Comparative analysis of the three past epidemics with the participation of the pandemic influenza A(H1N1)pdm09 was conducted according to the results of the epidemiological trials of two WHO National influenza centers for the morbidity, hospitalization, and mortality of the influenza in 59 cities of Russia for the period from 2009 to 2013. The first wave of the pandemic of 2009 was the most severe. Compared with this wave, during the next epidemics of 2011 and 2013, the involvement of urban population in the epidemic was reduced, as well as the morbidity in the people 15-64 years old and schoolchildren 7-14 years old. The duration of the epidemic among the adult population, the mortality rate of the total population, and the mortality rates in all age groups were also decreased. Vice versa, the incidence in the children of preschool age and the elderly people and the duration of the epidemic among children (especially preschool children) were increased. The share of patients 65 years and older, children 0-2 years old, and patients with pathology of the cardiovascular systems among the deceased patients increased to 33.6%.

[Clinical efficacy of arbidol (umifenovir) in the therapy of influenza in adults: preliminary results of the multicenter double-blind randomized placebo-controlled study ARBITR].

AIM: To evaluate the efficacy and safety of Arbidol (umifenovir) in adult patients with influenza. SUBJECTS AND METHODS: The analysis of the preliminary results of the multicenter double-blind randomized placebo-controlled post-marketing study ARBITR was performed. A total of 293 adults aged 18 to 65 years with influenza or acute respiratory tract infection of no more than 36 hours' duration were enrolled in the study. Individuals were randomized into 2 treatment groups: oral umifenovir 200 mg four times daily for 5 days or placebo four times daily for 5 days. The efficacy endpoints were time to resolution of all symptoms, severity of symptoms and illness, durations of virus shedding. RESULTS: The efficacy of umifenovir was evaluated in the group of 119 (40.6%) patients with influenza: 45 patients with laboratory-confirmed influenza and 74 patients whom diagnosis of influenza was made based on clinical and epidemiological data. Umifenovir had influence on the time to resolution of all symptoms. All symptoms were resolved within the first 60 hours after therapy initiation in 23.8% patients with laboratory-confirmed influenza in the umifenovir group and it was 5.7 times greater compared to placebo group (4.2%) (p < 0.05). Severity of illness, catarrhal symptoms and intoxication was reduced with umifenovir compared to placebo, reducing of severity was most evidently observed within the first 2-3 days following the therapy initiation. Umifenovir had a significant effect on viral shedding. The proportion of patients still shedding influenza virus on day 4 was significantly reduced in the umifenovir group compared to placebo (25 vs 53%, respectively; p < 0.05). CONCLUSION: It was found that the effect of umifenovir in the treatment of influenza in adults is most pronounced in the acute stage of the disease and appears in the reduction of time to resolution of all symptoms of the disease, reducing the severity of symptoms of the disease and durations of virus shedding.

First observation of the unbound nucleus 15Ne.

We report on the first observation of the unbound proton-rich nucleus 15Ne. Its ground state and first excited state were populated in two-neutron knockout reactions from a beam of 500 MeV/u 17Ne. The 15Ne ground state is found to be unbound by 2.522(66) MeV. The decay proceeds directly to 13O with simultaneous two-proton emission. No evidence for sequential decay via the energetically allowed 2- and 1- states in 14F is observed. The 15Ne ground state is shown to have a strong configuration with two protons in the (sd) shell around 13O with a 63(5)% (1s1/2)2 component.

[The use of apoptosis inducers in the therapy of experimental influenza infection and preventing of chronic post-influenza lung damage].

Influenza is a respiratory infection widely spread around the world. Influenza complications are various in nature and in most cases involve the excessive proliferation of cells in respiratory tract as a factor of pathogenesis. In the present work the efficacy of the use of apoptosis inducer 6-[3-(1-adamantyl)-4-hydroxyphenyl]-2-naphtalenecarboxylic acid (AHPN) for prophylaxis of chronic damage on the stage of post- influenza pneumonia has been studied. Mice were infected with influenza virus A/mallard/Pennsylvania/10218/84(H5N2) with further study of the level of influenza virus reproduction in the lungs, specific mortality of animals and morphology of the foci of post-influenza pneumonia on the 15th day post inoculation. AHPN was shown to decrease the infectious activity of the virus in the lungs by 1.2-1.5 log10 EID50/0.2 mL depending on the dose as compared to the control group, in a weak decrease in mortality of animals (protection index was 12.5-37.5%). The application of AHPN restricted both the proliferative and infiltrative component in chronic post-influenza lesions. It demonstrated the most pronounced effect on the lung morphology when applied on days 4 to 7 post inoculation, i. e. in the period of maximal activation of inflammatory tissue infiltration and regeneration of bronchiolar epithelium. In conclusion, the use of apoptosis inducers can partially prevent the development of chronic post-influenza lesions with proliferative component.

New constraint on the existence of the µ+ → e+ γ decay.

The analysis of a combined data set, totaling 3.6 × 10(14) stopped muons on target, in the search for the lepton flavor violating decay µ(+) → e(+)γ is presented. The data collected by the MEG experiment at the Paul Scherrer Institut show no excess of events compared to background expectations and yield a new upper limit on the branching ratio of this decay of 5.7 × 10(-13) (90% confidence level). This represents a four times more stringent limit than the previous world best limit set by MEG.

Measurement of the dipole polarizability of the unstable neutron-rich nucleus 68Ni.

The E1 strength distribution in 68Ni has been investigated using Coulomb excitation in inverse kinematics at the R3B-LAND setup and by measuring the invariant mass in the one- and two-neutron decay channels. The giant dipole resonance and a low-lying peak (pygmy dipole resonance) have been observed at 17.1(2) and 9.55(17) MeV, respectively. The measured dipole polarizability is compared to relativistic random phase approximation calculations yielding a neutron-skin thickness of 0.17(2) fm. A method and analysis applicable to neutron-rich nuclei has been developed, allowing for a precise determination of neutron skins in nuclei as a function of neutron excess.

[Intranasal co-administration of recombinant streptococcus group B polypeptides and influenza deltaNS1 vaccine].

In the present work, the immunoadjuvant properties of the influenza deltaNS1 vaccine virus after intranasal administration in combination with recombinant GBS polypeptides was tested in mice. According to our data, co-administration of recombinant GBS polypeptides and influenza deltaNS1 vaccine resulted in the increase in the immunogenicity and protective efficacy of bacterial proteins. Combined vaccination with the GBS polypeptides and influenza deltaNS1 vaccine has a potential to be used not only for prophylaxis infections caused by SGB, but also for prevention of the bacterial complications of influenza.

[Universal diagnostic oligonucleotide microarray for subtyping of human and animal influenza A viruses].

The diagnostic oligonucleotide microarray for subtyping of human and animal influenza A viruses (IAVs) was developed. We proposed a simple method of the fluorescent labeling of genomic segments of all known IAVs subtypes, the composition of the hybridization buffer, as well as the software of the data processing. 48 IAVs strains of different subtypes were analyzed using our microarray. All of them were identified, while 45 of 48 strains were unambiguously subtyped.

[Deitiforine, an antiinfluenza chemotherapeutic].

The problem of prophylaxis and therapy of influenza infections remains one of the priority goals for medical science and practical health care. The review includes the discussion of antiviral activity of Deitiforine, a Russian chemotherapeutic. The data on the toxicity and the specific activity spectrum in cell cultures, chicken embryos and laboratory animals are presented. The problem of the influenza viruses resistance to cage compounds and in particular to rimantadine and Deitiforine is also discussed.

Plant-produced recombinant influenza vaccine based on virus-like HBc particles carrying an extracellular domain of M2 protein.

Conventional influenza vaccines are based on a virus obtained in chicken embryos or its components. The high variability of the surface proteins of influenza virus, hemagglutinin and neuraminidase, requires strain-specific vaccines matching the antigenic specificity of newly emerging virus strains to be developed. A recombinant vaccine based on a highly conservative influenza virus protein M2 fused to a nanosized carrier particle can be an attractive alternative to traditional vaccines. We have constructed a recombinant viral vector based on potato X virus that provides for expression in the Nicotiana benthamiana plants of a hybrid protein M2eHBc consisting of an extracellular domain of influenza virus M2 protein (M2e) fused to hepatitis B core antigen (HBc). This vector was introduced into plant cells by infiltrating leaves with agrobacteria carrying the viral vector. The hybrid protein M2eHBc was synthesized in the infected N. benthamiana plants in an amount reaching 1-2% of the total soluble protein and formed virus-like particles with the M2e peptide presented on the surface. Methods of isolation and purification of M2eHBc particles from plant producers were elaborated. Experiments on mice have shown a high immunogenicity of the plant-produced M2eHBc particles and their protective effect against lethal influenza challenge. The developed transient expression system can be used for production of M2e-based candidate influenza vaccine in plants.

[Molecular-biological properties of the rubella virus strains isolated in St. Petersburg].

In the surveillance of rubella in the northwest region of Russia samples of nasopharyngeal swabs from 37 patients with rubella, which were treated in the 442nd district military hospital named after Z.P. Solovyov in autumn 2007 were screened for the rubella virus using RK-13 cell line, 22 strains of rubella virus were isolated. Gene sequencing of E1 region of rubella virus isolates was carried out. Rubella virus strains isolated in St. Petersburg during the 2007 outbreak belonged to rubella virus genotype 1E. The morphogenesis of RK-13 cells with formation of replication complexes and enveloped virions of rubella virus was shown.

[Effect of different water-soluble forms of the fullerene C60 on the metabolic activity and ultra-structure of cells in culture].

In view of contradictory data on the toxicity of fullerenes for live organisms we studied the effect of water-soluble complexes of C60 with N-polyvivyl-pirrolidone (C60/PVP) and gamma-cyclodextrine (C60/gamma-CD) on MA-104 cells in culture. Both complexes proved to be non-toxic for cultured cells in the dark in wide range of concentrations. Both complexes provoke changes of cellular ultra-structure which reflect the enhancement of metabolic activity. At the same time only the exposition with the complex C60/PVP leads to the essential growth of number and size of mitochondria. However, the effect of two studied water-soluble forms of C60 under intensive UV-irradiation of cells proved to be opposite: C60/PVP had a cyto-protective action while C60/gamma-CD caused a significant growth of photo-toxicity. Possible reasons of the differences in the action of different forms of C60 on living organisms are discussed.