Difficulties in diagnosing atypical hemolytic uremic syndrome

The paper presents the case of clinical observation of a patient with atypical hemolytic-uremic syndrome (aHUS). aHUS is a disease characterized by an unfavorable prognosis (severe or catastrophic course with rapid development of terminal renal or multi-organ failure). The aim of the study is to evaluate the approaches to differential diagnosis of aHUS in clinical practice.Material and methods. The study was conducted on the basis of the Nephrology Department of Kemerovo Regional Clinical Hospital n.a. S.V Belyaev. The clinical observation of patient D., aged 26 years old, is discussed.Results and discussion. Diagnosing aHUS requires: 1) diagnosing thrombotic microangiopathy (TMA: thrombocytopenia or decrease in platelet count by more than 25 % of original, visceral damage (kidneys, CNS, gastrointestinal tract, heart, lungs)); 2) ruling out HUS associated with Shiga toxin-producing Escherichia coli (STEC-HUS; negative for Shiga-toxin in blood and stool), thrombotic thrombocytopenic purpura (TTP), systemic connective tissue disease, catastrophic antiphospholipid syndrome, HIV infection; 3) assessing the activity of ADAMTS13 (decrease confirms the aHUS diagnosis); 4) proving normal content of complement components C3 and C4 as an additional argument in favor of aHUS diagnosis. At the first stage, the patient was diagnosed with TMA (platelet content 37 x 109/l, hemoglobin content 59 g/l), LDH up to 824 E/l), liver damage (AST, ALT and LDH activity 55, 60 and 824 U/l, respectively), kidney damage (acute renal damage), lungs, heart, and brain damage. At the second stage the following diagnoses were ruled out: STEC-HUS (Shiga toxin in blood and stool was not detected), TTP (ADAMTS13 activity level was 66 %, whereas reference values are 93-113 %, in TTP - below 5-10 %); systemic connective tissue diseases catastrophic antiphospholipid syndrome, HIV infection sepsis. Normal values of C3 (0.9 g/l) and C4 (0.23 g/l) complement components did not rule out the diagnosis of aHUS

Results of Work of the Specialized Anti-Epidemic Teams of the Irkutsk Research Anti-Plague Institute in the Amur Region, Khabarovsk Territory and the Jewish Autonomous Region in 2013

Displayed are the major results of work of the specialized anti-epidemic teams from Irkutsk Research Anti-Plague Institute, aimed at the provision for sanitary-epidemiological welfare of the population in the Amur Region, Khabarovsk Territory and the Jewish Autonomous Region, devastated by the abnormally high water, in 2013. Represented are the data on sanitary-hygienic and epidemiological monitoring over the territory of the worst-hit areas. Revealed are the findings as regards examination of water samples obtained from the centralized and decentralized water supplies, surface water reservoirs and treatment facilities for presence of Vibrio cholerae , and of clinical material - for intestinal viruses, as well as serological screening of the decreed groups and foreign citizens temporarily working in the Russian Federation. Presented are the results of epizootiological-epidemiological inspection of the endemic areas for natural-focal infections, and also potentially hazardous areas as concerns anthrax, situated within the bonds of the flooded territories. Total of 3626 samples have been tested, 15502 analyses for 23 nosological entities have been performed

PTTG1 Attenuates Drug-Induced Cellular Senescence

As PTTG1 (pituitary tumor transforming gene) abundance correlates with adverse outcomes in cancer treatment, we determined mechanisms underlying this observation by assessing the role of PTTG1 in regulating cell response to anti-neoplastic drugs. HCT116 cells devoid of PTTG1 (PTTG1−/−) exhibited enhanced drug sensitivity as assessed by measuring BrdU incorporation in vitro. Apoptosis, mitosis catastrophe or DNA damage were not detected, but features of senescence were observed using low doses of doxorubicin and TSA. The number of drug-induced PTTG1−/− senescent cells increased ∼4 fold as compared to WT PTTG1-replete cells (p<0.001). p21, an important regulator of cell senescence, was induced ∼3 fold in HCT116 PTTG1−/− cells upon doxorubicin or Trichostatin A treatment. Binding of Sp1, p53 and p300 to the p21 promoter was enhanced in PTTG1−/− cells after treatment, suggesting transcriptional regulation of p21. p21 knock down abrogated the observed senescent effects of these drugs, indicating that PTTG1 likely suppresses p21 to regulate drug-induced senescence. PTTG1 also regulated SW620 colon cancer cells response to doxorubicin and TSA mediated by p21. Subcutaneously xenografted PTTG1−/− HCT116 cells developed smaller tumors and exhibited enhanced responses to doxorubicin. PTTG1−/− tumor tissue derived from excised tumors exhibited increased doxorubicin-induced senescence. As senescence is a determinant of cell responses to anti-neoplastic treatments, these findings suggest PTTG1 as a tumor cell marker to predict anti-neoplastic treatment outcomes

MODERN TRENDS OF THE SPREADING LEPTOSPIROSIS OVERSEAS

In this study the increased number of the imported cases from endemic countries or occurring of the disease in earlier unknown natural leptospirosis foci in the world among participants of various extreme competitions, hostilities and travelers was revealed at analysis of the epidemiological leptospirosis situation. New human risk groups subjected to infection were determined

Results of experimental infection of vaccinated and non-vaccinated ducklings with duck hepatitis virus

Duck virus hepatitis, a highly contagious disease occurring in ducklings, is currently reported in all countries with duck breeding industry. This infection is included in the list of notifiable diseases of the World Organization for Animal Health, restrictive measures are established and the regionalization of the country’s territory is carried out in case of its occurrence. Timely vaccination of parent flocks in order to obtain immune offspring takes a priority place in the system of anti-epidemic measures. Due to active development of duck breeding industry and increasing number of backyard farms, the need for high-quality and effective prevention tools for this infectious disease is growing. To date, one domestic native vaccine produced by FGBI «ARRIAH» and registered in the Russian Federation is available in native form and is intended for parenteral use. In order to extend the vaccine’s shelf life and for storage and transportation convenience, a live freeze-dried vaccine against duck virus hepatitis is being developed. The paper presents results of studying the pathogenesis of duck virus hepatitis and evaluating the efficacy and safety of the vaccine under development. Pathomorphological studies carried out post experimental infection indicate that duck hepatitis virus induces pathogenic effect not only in birds’ digestive organs (the liver, in particular) but also causes degenerative changes in central and peripheral immune organs: in cloacal bursa, thymus and third eyelid gland, that may be manifested as deficiency of B- and T-cell immunity and requires further studies. It has been shown that in case of immunization of 3-day-old ducklings, the experimental vaccine induces antibody-mediated immune response, no harmful effect is produced on poultry if a tenfold dose is admin­istered which indicates its safety, and the vaccine ensures protection against infection with a control virulent strain of hepatitis virus

Improvement and Standardization of Laboratory Diagnostics Procedures as Concerns Particularly Dangerous, “Emerging”, and “Reemerging” Infectious Diseases

Represented are the data on the key stages of laboratory diagnostics practices standardization as regards particularly dangerous infectious diseases and on the improvement of the normative-regulatory framework on the procedure for organization and carrying out laboratory diagnostics in accordance with three-level system. Worked out are the principles, scheme of indication and identification of pathogenic biological agents of emerging, previously unknown, and atypical microorganisms using modern computerized systems and high-tech equipment

Epidemiological Situation on Tick-Borne Viral Encephalitis in the Territory of the Russian Federation in 2012 and Prognosis for 2013

Analyzed are the epidemiological situation and preventive measures against tick-borne encephalitis in the territory of the Russian Federation in 2012. Short-term forecast for 2013 is made based on the population morbidity rate in the federal districts of Russia in 2007–2012

IDENTIFICATION AND STUDY OF LEPTOSPIROSIS FOCUS IN IRKUTSK REGION

Due to examination of animal breeding workers at the Irkutsk Region a case of human leptospirosis was identified. at the cattle farm of Tugutuy settlement. Due to epizootological-epidemiological study a mixed, leptospirosis focus in Ekhirit-Bulagat district was established, the agent circulation among commensal and wild, small mammals was demonstrated. Continuous pathogenic Leptospira DNA detection during the second, half of 2011, as well as the positive tularemia laboratory results require further study of the focus

Results of Monitoring over the West Nile Fever Pathogen in the Territory of the Russian Federation in 2017. Forecast of Epidemic Situation Development in Russia in 2018

In Europe, in the epidemic season 2017, the incidence of West Nile fever did not exceed the index of the previous season. In the US and Canada, there was an increase in the incidence of cases. West Nile fever morbidity rates in the Russian Federation and in separate constituent entities were below the average long-term index and had the lowest value for the period since 2008. 41.6 % of WNF cases were imported to Russia from the distant countries. Analysis of the monitoring results indicated the circulation of WNF virus markers in carriers of the pathogen in 6 constituent entities of the Russian Federation, and the presence of IgG antibodies in healthy population cohorts in 24 RF entities. According to molecular-genetic typing of WNF virus samples from mosquito Culex modestus from the Volgograd Region, WNF virus genotype II was established. Forecasting of epidemiological situation development for the year 2018 does not rule out the possibility of local increase in WNF incidence in certain regions of Russia

Lineage-Specific Restraint of Pituitary Gonadotroph Cell Adenoma Growth

Although pituitary adenomas are usually benign, unique trophic mechanisms restraining cell proliferation are unclear. As GH-secreting adenomas are associated with p53/p21-dependent senescence, we tested mechanisms constraining non-functioning pituitary adenoma growth. Thirty six gonadotroph-derived non-functioning pituitary adenomas all exhibited DNA damage, but undetectable p21 expression. However, these adenomas all expressed p16, and >90% abundantly expressed cytoplasmic clusterin associated with induction of the Cdk inhibitor p15 in 70% of gonadotroph and in 26% of somatotroph lineage adenomas (p = 0.006). Murine LβT2 and αT3 gonadotroph pituitary cells, and αGSU.PTTG transgenic mice with targeted gonadotroph cell adenomas also abundantly expressed clusterin and exhibited features of oncogene-induced senescence as evidenced by C/EBPβ and C/EBPδ induction. In turn, C/EBPs activated the clusterin promoter ∼5 fold, and elevated clusterin subsequently elicited p15 and p16 expression, acting to arrest murine gonadotroph cell proliferation. In contrast, specific clusterin suppression by RNAis enhanced gonadotroph proliferation. FOXL2, a tissue-specific gonadotroph lineage factor, also induced the clusterin promoter ∼3 fold in αT3 pituitary cells. As nine of 12 pituitary carcinomas were devoid of clusterin expression, this protein may limit proliferation of benign adenomatous pituitary cells. These results point to lineage-specific pathways restricting uncontrolled murine and human pituitary gonadotroph adenoma cell growth