Sepsis and apoptosis

The article provides an overview of the current knowledge about the immune response in sepsis. Sepsis occurs on a background of development as a systemic inflammatory response, and immunosuppression phenomena. Dysfunction of the immune system is one of the most important parts of the pathophysiology and compulsory process. One of the immunosuppression mechanisms in sepsis is lymphocyte apoptosis. The article describes the main activation pathway of this process including those in neonatal sepsis

Genetic Polymorphisms and Bacterial Infections in Neonates

© 2016, Springer Science+Business Media New York.Identifying single nucleotide polymorphisms (SNPs) in the genes involved in sepsis may help to clarify the pathophysiology of neonatal sepsis. The aim of this study was to evaluate the relationships between different forms of bacterial infections in neonates and genes potentially involved in the response to invasion by infectious agents. The study involved 20 neonates with a diagnosis of sepsis, 25 neonates with localized bacterial infections, and otherwise healthy neonates born during the study period. A total of eight SNPs in four candidate genes including Toll-like receptors (TLR2, TLR4) and pro-inflammatory cytokines (IL-1, Il-6) were genotyped. Genotypes CT and TT of IL-1β C3953T were associated with a significantly increased risk of developing sepsis (OR = 9.3; p = 0.02). The percentage of heterozygotes for the mutant allele was 65 %, while homozygotes—5 %. Among the patients with localized bacterial infections, TLR4 Asp299Gly, genotypes CT and TT IL-1β C3953T, and genotypes GC and CC IL-1β G-1473C showed the association with an increased risk of developing diseases (p = 0.05, p = 0.04, p = 0,04, respectively). These results show that genetic variability seems to play a role in sepsis and localized bacterial infections in neonates by influencing susceptibility to the disease

Comparative Assessment of Cytokine Pattern in Early and Late Onset of Neonatal Sepsis

© 2017 Kh. S. Khaertynov et al.Neonatal sepsis is a significant health issue associated with high mortality. Immune responses associated with neonatal sepsis, such as proinflammatory cytokine production, are believed to play a central role in the pathogenesis of this disease. In the present study, serum levels of the proinflammatory cytokines TNF-α, IL1-β, and IL-6 and the anti-inflammatory cytokines IL-4 and IL-10 were evaluated for 25 subjects with neonatal sepsis. We observed that subjects with late onset of sepsis (LOS), as well as those with early onset of sepsis (EOS), had a substantial increase in serum TNF-α. In contrast to EOS, subjects with LOS demonstrated a significant increase in serum levels IL-6 and IL-10. Additionally, we observed a significant difference in cytokine profiles between acute and postacute cases of neonatal sepsis. For instance, the level of proinflammatory cytokines, such as TNF-α and IL-6, was elevated in the acute phase, whereas the production of anti-inflammatory cytokines, such as IL-10, became substantially upregulated during the postacute phase. Additionally, no correlation was observed between cytokine levels and CRP levels or lymphocyte counts. Thus, in contrast to CRP levels and lymphocyte counts, examination of the cytokine profile can provide valuable information when determining the most effective therapy for treating neonatal sepsis. This information may be useful to physicians when determining if anti-inflammatory or immune stimulatory therapy is warranted

Case of meningitis in a neonate caused by an extended-spectrum-beta-lactamase-producing strain of hypervirulent Klebsiella pneumoniae

© 2017 Khaertynov, Anokhin, Davidyuk, Nicolaeva, Khalioullina, Semyenova, Alatyrev, Skvortsova and Abrahamyan. Klebsiella pneumoniae is one of the most important infectious agents among neonates. This pathogen has a potential to develop an increased antimicrobial resistance and virulence. The classic non-virulent strain of K. pneumoniae, producing an extended-spectrum beta-lactamases (ESBL), is associated with nosocomial infection mainly in preterm neonates. Hypervirulent K. pneumoniae strains are associated with invasive infection among previously healthy ambulatory patients, and most of them exhibit antimicrobial susceptibility. During the last few years, several cases of diseases caused by hypervirulent K. pneumoniae producing ESBL have been registered in different geographical regions of the world. However , reports of such cases in neonates are rare. Here, we reported that this pathogen can cause pyogenic meningitis in full-term neonate with poor prognosis. A previously healthy, full-term, 12-day-old neonate was admitted to the infectious diseases hospital with suspected meningitis. The clinical symptoms included loss of appetite, irritability, fever, seizures, and a bulging anterior fontanelle. The analysis of the cerebrospinal fluid confirmed the diagnosis of meningitis. Blood and cerebrospinal fluid cultures were positive for K. pneumoniae, producing ESBL. K. pneumoniae isolates were resistant to aminopenicillins, 3rd generation cephalosporins but were sensitive to imipenem and meropenem. The "string test" was positive. The study of the virulence factors of K. pneumoniae by PCR revealed the presence of the rmpA gene. A combination of K. pneumoniae virulence and drug resistance complicated by cerebral oedema led to the death of the neonate. We concluded that both the risk of developing severe forms of infection and the outcome of the disease due to K. pneumonia are associated with the phenotypic features of the pathogen such as its antibiotic susceptibility and virulence factors. Emergence of the ESBL-producing strain of hypervirulent K. pneumoniae could represent a new serious threat to public health, suggesting an urgent need to enhance clinical awareness and epidemiological surveillance

Isolation, Purification and Evaluation of Serological Activity of Rabies Virus Antigens

Objective of the study is to evaluate the serological activity of rabies virus antigens isolated from the brain tissue of mice by homogenization on FastPrep followed by ultracentrifugation. Materials and methods. Producer strain of the rabies virus “Ovechiy” GNKI. The rabies virus was isolated from the brain tissue of experimentally infected mice, followed by the study of the electrophoretic profile. The serological activity of the virus components was assessed by immunoblot and ELISA using specific anti-rabies sera.Results and conclusions. In the course of comparing the methods of isolation and purification of the rabies virus antigen, it was found that most optimal one is to use a homogenization on FastPrep-24, followed by fractionation in a sucrose gradient. As a result of fractionation in a graded sucrose density gradient with a concentration of 15–50 % at 25000 g for 120 min, five fractions of the rabies virus components were obtained. The maximum purified protein fraction was from 15–20 % sucrose zone, which corresponded to a molecular weight of 67 kDa. The specific antigen activity of the fraction in ELISA reached up the titers of 1:1280 (Specificity coefficient 2.2). Using immunoblot of antigens, obtained from the sucrose gradient in the range of 40–45 % and 20–35 % after ultracentrifugation, one major fraction of polypeptides (54 kDa) was detected, which showed the highest antigenic activity. The results obtained will be useful in the design of test systems for rabies screening and monitoring the effectiveness of anti-epizootic measures

Epidemiological dynamics of nephropathia epidemica in the Republic of Tatarstan, Russia, during the period of 1997-2013

Copyright © Cambridge University Press 2015.This report summarizes epidemiological data on nephropathia epidemica (NE) in the Republic of Tatarstan, Russia. NE cases identified in the period 1997-2013 were investigated in parallel with the hantavirus antigen prevalence in small rodents in the study area. A total of 13 930 NE cases were documented in all but one district of Tatarstan, with most cases located in the central and southeastern districts. The NE annual incidence rate exhibited a cyclical pattern, with the highest numbers of cases being registered once in every 3-5 years. The numbers of NE cases rose gradually from July to November, with the highest morbidity in adult males. The highest annual disease incidence rate, 64·4 cases/100 000 population, was observed in 1997, with a total of 2431 NE cases registered. NE cases were mostly associated with visiting forests and agricultural activities. The analysis revealed that the bank vole Myodes glareolus not only comprises the majority of the small rodent communities in the region, but also consistently displays the highest hantavirus prevalence compared to other small rodent species

Isolation of Rabies Virus Glycoprotein Using Three-Phase Extraction and Characteristics of its Antigenic Properties

The aim of the work was to develop an approach to isolation of rabies virus glycoprotein applying threephase extraction and to characterize its antigenic properties.Materials and methods. Infectious activity of the rabies virus (production strain, “Ovine” GNKI) after long-term storage was restored on white BALB/c mice. The strain was used for cultivation on BHK-21 cells; the culture liquid was concentrated applying ultracentrifugation followed by separation by buoyant density in a sucrose gradient, selection of visually opalescent zones, phase concentration, chromatographic separation on an ENrich™ SEC650 column (Bio-Rad, USA) and selection of monomeric fractions with high serological activity according to the results of Western blotting.Results and discussion. We have demonstrated that preliminary mechanical destruction of brain suspension, extraction of the virus-containing material from the cell suspension through successive low-speed and high-speed centrifugation, separation of the sediment produced in sucrose gradient with further phase concentration and chromatographic separation of the precipitate allows to obtain monomeric antigenic preparations with high serological activity. This methodology has made it possible to obtain an antigen, which is rabies virus glycoprotein with a molecular weight of 67 kDa, and two of its isoforms, having molecular weights of 60 and 54 kDa. The described approach can be viewed as an option for isolation of the rabies virus specific antigen when improving laboratory diagnostics techniques. The resulting antigen is a monomeric discrete containing one fraction with a molecu lar weight of 67 kDa. The data obtained corroborate the high specificity of the antigen and its suitability for the design of enzyme immunoassay and immunochromatographic tests, production of specific immunoglobulins, the study of the antigen/antibody interaction, as well as for the assessment of the protective immunity intensity after vaccination

Sepsis and apoptosis

The article provides an overview of the current knowledge about the immune response in sepsis. Sepsis occurs on a background of development as a systemic inflammatory response, and immunosuppression phenomena. Dysfunction of the immune system is one of the most important parts of the pathophysiology and compulsory process. One of the immunosuppression mechanisms in sepsis is lymphocyte apoptosis. The article describes the main activation pathway of this process including those in neonatal sepsis

Sepsis and apoptosis

The article provides an overview of the current knowledge about the immune response in sepsis. Sepsis occurs on a background of development as a systemic inflammatory response, and immunosuppression phenomena. Dysfunction of the immune system is one of the most important parts of the pathophysiology and compulsory process. One of the immunosuppression mechanisms in sepsis is lymphocyte apoptosis. The article describes the main activation pathway of this process including those in neonatal sepsis

Sepsis and apoptosis

The article provides an overview of the current knowledge about the immune response in sepsis. Sepsis occurs on a background of development as a systemic inflammatory response, and immunosuppression phenomena. Dysfunction of the immune system is one of the most important parts of the pathophysiology and compulsory process. One of the immunosuppression mechanisms in sepsis is lymphocyte apoptosis. The article describes the main activation pathway of this process including those in neonatal sepsis