Inflammation and changes in cytokine levels in neurological feline infectious peritonitis.

Feline infectious peritonitis (FIP) is a progressive, fatal, predominantly Arthus-type immune-mediated disease that is triggered when cats are infected with a mutant enteric coronavirus. The disease presents variably with multiple organ failure, seizures, generalized effusion, or shock. Neurological FIP is clinically and pathologically more homogeneous than systemic 'wet' or 'dry' FIP; thus, comparison of cytokine profiles from cats with neurological FIP, wet FIP, and non-FIP neurological disease may provide insight into some baseline characteristics relating to the immunopathogenesis of neurological FIP. This study characterizes inflammation and changes in cytokines in the brain tissue of FIP-affected cats. Cellular infiltrates in cats with FIP included lymphocytes, plasma cells, neutrophils, macrophages, and eosinophils. IL-1 beta, IL-6, IL-12, IL-18, TNF-alpha, macrophage inhibitory protein (MIP)-1 alpha, and RANTES showed no upregulation in the brains of control cats, moderate upregulation in neurological FIP cats, and very high upregulation in generalized FIP cats. Transcription of IFN-gamma appeared upregulated in cats with systemic FIP and slightly downregulated in neurological FIP. In most cytokines tested, variance was extremely high in generalized FIP and much less in neurological FIP. Principal components analysis was performed in order to find the least number of 'components' that would summarize the cytokine profiles in cats with neurological FIP. A large component of the variance (91.7%) was accounted for by levels of IL-6, MIP-1 alpha, and RANTES. These findings provide new insight into the immunopathogenesis of FIP and suggest targets for immune therapy of this disease

The effect of A-PRP-therapy on reparative regeneration of bone tissue with acute bone fractures of the limbs

Objective. To evaluate the effect of A-PRP-therapy on reparative bone regeneration in acute limb bone fractures. Material and Methods. The study consisted of two parts – in the first part we studied the effect of A-PRP-therapy on the model of a comminuted fracture created in the operating room, an experimental study conducted on 40 Mature rabbits of the Flander breed, all animals were divided according to the principle of analogues into 2 groups (20 animals): in the study group – on the 5th day after osteotomy, platelet-rich plasma was injected into the fracture area, in the comparison group – the fusion occurred without the influence of any drugs. The second part presents the results of clinical testing of A-PRP-therapy, analyzed the results of treatment of 16 women with low-energy fractures of the distal radius metaepiphysis. The study group consisted of 6 patients whose surgical treatment was supplemented by A-PRP-therapy on 7, 14 days after surgery. The control group consisted of 10 patients who underwent surgical treatment without A-PRP-therapy.Results. The use of platelet-rich plasma to stimulate reparative osteogenesis in accute fractures reduces the time of fracture consolidation by 9.5 ± 1.1%.Conclusion. Platelet-rich plasma (PRP) to stimulate reparative osteogenesis is an inexpensive, easy to perform and effective alternative to the methods considered. The possibilities of application of this technology in traumatology and orthopedics require further research in order to create protocols for the use of PRP-therapy to stimulate the maturation of bone calluses

Создание новых форм томата с генами устойчивости к грибным болезням на основе маркерной селекции

Relevance. The presented studies are aimed at obtaining new forms of tomato with a complex of genes for resistance to fungal diseases in combination with a standard type of bush and dark coloring of fruits based on marker-mediated selection.Methodology. The biological objects of the study are varieties and hybrid forms of tomato from the collection of the Michurinsky SAU. Molecular genetic analysis was performed using the following methods. DNA extraction was carried out from young leaves using a kit for isolation of NC Sample NC manufactured by Agrodiagnostika LLC according to the manufacturer's protocol. Fermentas production kits were used for PCR. Identification of the cladosporosis resistance gene was Cf-19 performed using the DNA marker R7. The presence of a fusarious wilting resistance gene was determined by a I-2/5 marker. The amplification results were visualized by agarose gel electrophoresis.Results. During the research, a collection of varieties and hybrid forms of tomato of the Michurinsky GAU was analyzed in order to identify genes for resistance to cladosporiosis Cf-19 and fusarium wilt I-2. A total of 52 genotypes were analyzed. It was found that most samples (41 samples) are characterized by a heterozygous state of the Cf-19 gene. All indeterminant and semi-determinant forms had both alleles. Of the 23 determinant forms presented in the collection, 10 had only one allele corresponding to recessive homozygote. Among all analyzed tomato genotypes, no dominant homozygous forms were noted. The study of the collection revealed several alleles of the I-2 gene. In total, four fragments corresponding to various alleles were amplified. A total of 50 resistant genotypes have been identified in the collection. Two alleys of the I-2 gene (633/693 bp) were identified in 42 tomato samples. Four varieties are homozygous in one allele (633 bp), which determines resistance. Three varieties have a second resistance allele (566 bp). One genotype has only an allele defining susceptibility (693 bp). On the basis of molecular analysis, as well as an assessment of the type of bush and fetal color, initial forms were selected with subsequent hybridization. 67 hybrid tomato plants were obtained. Evaluation of the presence of resistance genes showed that most of the resulting hybrids are resistant to cladosporiosis and fuzariosis. This is due to the presence of dominant alleles of Cf-19 and I-2 genes in a heterozygous state. Among the resulting hybrids, plants with a bark type of bush were identified. A total of 13 such plants were obtained.Conclusion. Thus, the work carried out allowed to obtain hybrid forms of tomato combine the signs of resistance to two pathogens of fungal diseases and the stem type of the bush. These forms are planned to be used in further selection work.Цель. Исследования направлены на получение новых форм томата с комплексом генов устойчивости к грибным болезням в сочетании со штамбовым типом куста и темной окраской плодов на основе маркер-опосредованной селекции.Методы. Объект исследований – сорта и гибридные формы томата из коллекции Мичуринского ГАУ. Молекулярно-генетический анализ проводили с использованием следующих методов. Экстрагирование ДНК осуществляли из молодых листьев с применением набора для выделения НК «Проба НК» производства ООО «Агродиагностика» согласно протоколу производителя. Для проведения ПЦР использованы наборы производства компании Fermentas. Идентификацию гена устойчивости к кладоспоризу Cf-19 проводили с использованием ДНК-маркера Р7. Наличие гена устойчивости к фузариозному увяданию определяли с помощью маркера I-2/5. Визуализацию результатов амплификации осуществляли с помощью электрофореза в агарозном геле.Результаты. При проведении исследований была проанализирована коллекция сортов и гибридных форм томата Мичуринского ГАУ с целью идентификации генов устойчивости к кладоспориозу Cf-19 и фузариозному увяданию I-2. Всего проанализировано 52 генотипа. Установлено, что для большинства образцов (41 образец) характерно гетерозиготное состояние гена Cf-19. Все индетерминантные и полудетерминантные формы имели оба аллеля. Из 23 представленных в коллекции детерминантных форм у 10 отмечен только один аллель, соответствующий рецессивной гомозиготе. Среди всех анализируемых генотипов томата не отмечено доминантных гомозиготных форм. Изучение коллекции позволило выявить нескольких аллелей гена I-2. Всего амплифицировано четыре фрагмента, соответствующих различным аллелям. Всего устойчивых генотипов в коллекции выделено 50. У 42 образцов томата идентифицированы два аллея гена I-2 (633/693 п.н). Четыре сорта гомозиготны по одному аллелю (633 п.н.), обуславливающему устойчивость. Три сорта имеют второй аллель (566 п.н.) устойчивости. Один генотип имеет только аллель определяющий восприимчивость (693 п.н.).На основании молекулярного анализа, а также оценки типа куста и окраски плода был проведен отбор исходных форм с последующей гибридизацией. Получено 67 гибридных растений томата. Оценка наличия генов устойчивости показала, что большинство полученных гибридов являются устойчивыми к кладоспориозу и фузариозу. Это обусловлено наличием доминантных аллелей генов Cf-19 и I-2 в гетерозиготном состоянии. Среди полученных гибридов выделены растения со штамбовым типом куста. Всего таких растений получено 13. Проведенная работа позволила получить гибридные формы томата, сочетающие признаки устойчивости к двум возбудителям грибных болезней и штамбовый тип куста. Эти формы планируется использовать в дальнейшей селекционной работе

Interleukin-6 Induces Gr-1+CD11b+ Myeloid Cells to Suppress CD8+ T Cell-Mediated Liver Injury in Mice

Agonist antibodies against CD137 (4-1BB) on T lymphocytes are used to increase host anti-tumor immunity, but often leading to severe liver injury in treated mice or in patients during clinical trials. Interleukin-6 (IL-6) has been reported to protect hepatocyte death, but the role of IL-6 in protecting chronic T cell-induced liver diseases is not clearly defined due to lack of relevant animal models. We aimed to define the role of IL-6 in CD8+ T cell-mediated liver injury induced by a CD137 agonistic mAb (clone 2A) in mice.We expressed IL-6 in the liver by hydrodynamic gene delivery in mice treated with 2A or control mAb and studied how IL-6 treatment affected host immunity and T cell-mediated liver injury. We found that ectopic IL-6 expression in the liver elevated intrahepatic leukocyte infiltration but prevented CD8+ T cell-mediated liver injury. In IL-6 treated mice, CD8+ T cells proliferation and IFN-γ expression were inhibited in the liver. We discovered that IL-6 increased accumulation of Gr-1+CD11b+ myeloid derived suppressor cells (MDSCs) in the liver and spleen. These MDSCs had the ability to inhibit T cells proliferation and activation. Finally, we showed that the MDSCs were sufficient and essential for IL-6-mediated protection of anti-CD137 mAb-induced liver injury.We concluded that IL-6 induced Gr-1+CD11b+ MDSCs in the liver to inhibit T cell-mediated liver injury. The findings have defined a novel mechanism of IL-6 in protecting liver from CD8+ T cell-mediated injury

Gap Junctions and Epileptic Seizures – Two Sides of the Same Coin?

Electrical synapses (gap junctions) play a pivotal role in the synchronization of neuronal ensembles which also makes them likely agonists of pathological brain activity. Although large body of experimental data and theoretical considerations indicate that coupling neurons by electrical synapses promotes synchronous activity (and thus is potentially epileptogenic), some recent evidence questions the hypothesis of gap junctions being among purely epileptogenic factors. In particular, an expression of inter-neuronal gap junctions is often found to be higher after the experimentally induced seizures than before. Here we used a computational modeling approach to address the role of neuronal gap junctions in shaping the stability of a network to perturbations that are often associated with the onset of epileptic seizures. We show that under some circumstances, the addition of gap junctions can increase the dynamical stability of a network and thus suppress the collective electrical activity associated with seizures. This implies that the experimentally observed post-seizure additions of gap junctions could serve to prevent further escalations, suggesting furthermore that they are a consequence of an adaptive response of the neuronal network to the pathological activity. However, if the seizures are strong and persistent, our model predicts the existence of a critical tipping point after which additional gap junctions no longer suppress but strongly facilitate the escalation of epileptic seizures. Our results thus reveal a complex role of electrical coupling in relation to epileptiform events. Which dynamic scenario (seizure suppression or seizure escalation) is ultimately adopted by the network depends critically on the strength and duration of seizures, in turn emphasizing the importance of temporal and causal aspects when linking gap junctions with epilepsy

Возможные пути совершенствования системы охраны здоровья мужского персонала предприятий атомной промышленности

Oncological morbidity among the male workers of the Siberian Group of Chemical Enterprises (SGCE) in 1970—2005 was studied. Increased related risk (in comparison with the standard) of malignant neoplasms of resiratory and digestive tract, urinary ways and genitals was found. On the basis of the received results proposals on perfection of system of health protection of the man's personnel of the enterprises of nuclear branch are made.Исследована заболеваемость злокачественными новообразованиями (ЗНО) мужского персонала Сибирского химического комбината (СХК) (г. Северск). Установлено, что работники отдельных производств СХК имеют достоверно более высокий (по сравнению со стандартом) риск возникновения ЗНО пищеварения и дыхания, а также мочевых путей и половых органов. На основании полученных результатов сформулированы предложения по совершенствованию системы охраны здоровья мужского персонала предприятий атомной отрасли

Solubility of Rock in Steam Atmospheres of Planets

Extensive experimental studies show that all major rock-forming elements (e.g., Si, Mg, Fe, Ca, Al, Na, K) dissolve in steam to a greater or lesser extent. We use these results to compute chemical equilibrium abundances of rocky-element-bearing gases in steam atmospheres equilibrated with silicate magma oceans. Rocky elements partition into steam atmospheres as volatile hydroxide gases (e.g., Si(OH)4, Mg(OH)2, Fe(OH)2, Ni(OH)2, Al(OH)3, Ca(OH)2, NaOH, KOH) and via reaction with HF and HCl as volatile halide gases (e.g., NaCl, KCl, CaFOH, CaClOH, FAl(OH)2) in much larger amounts than expected from their vapor pressures over volatile-free solid or molten rock at high temperatures expected for steam atmospheres on the early Earth and hot rocky exoplanets. We quantitatively compute the extent of fractional vaporization by defining gas/magma distribution coefficients and show that Earth's subsolar Si/Mg ratio may be due to loss of a primordial steam atmosphere. We conclude that hot rocky exoplanets that are undergoing or have undergone escape of steam-bearing atmospheres may experience fractional vaporization and loss of Si, Mg, Fe, Ni, Al, Ca, Na, and K. This loss can modify their bulk composition, density, heat balance, and interior structure

Rapid and Sensitive Detection of Yersinia pestis Using Amplification of Plague Diagnostic Bacteriophages Monitored by Real-Time PCR

BACKGROUND: Yersinia pestis, the agent of plague, has caused many millions of human deaths and still poses a serious threat to global public health. Timely and reliable detection of such a dangerous pathogen is of critical importance. Lysis by specific bacteriophages remains an essential method of Y. pestis detection and plague diagnostics. METHODOLOGY/PRINCIPAL FINDINGS: The objective of this work was to develop an alternative to conventional phage lysis tests--a rapid and highly sensitive method of indirect detection of live Y. pestis cells based on quantitative real-time PCR (qPCR) monitoring of amplification of reporter Y. pestis-specific bacteriophages. Plague diagnostic phages phiA1122 and L-413C were shown to be highly effective diagnostic tools for the detection and identification of Y. pestis by using qPCR with primers specific for phage DNA. The template DNA extraction step that usually precedes qPCR was omitted. phiA1122-specific qPCR enabled the detection of an initial bacterial concentration of 10(3) CFU/ml (equivalent to as few as one Y. pestis cell per 1-microl sample) in four hours. L-413C-mediated detection of Y. pestis was less sensitive (up to 100 bacteria per sample) but more specific, and thus we propose parallel qPCR for the two phages as a rapid and reliable method of Y. pestis identification. Importantly, phiA1122 propagated in simulated clinical blood specimens containing EDTA and its titer rise was detected by both a standard plating test and qPCR. CONCLUSIONS/SIGNIFICANCE: Thus, we developed a novel assay for detection and identification of Y. pestis using amplification of specific phages monitored by qPCR. The method is simple, rapid, highly sensitive, and specific and allows the detection of only live bacteria

Final 5-year findings from the phase 3 HELIOS study of ibrutinib plus bendamustine and rituximab in patients with relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma

We report final analysis outcomes from the phase 3 HELIOS study (NCT01611090). Patients with relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma without deletion 17p (n = 578) were randomized 1:1 to 420 mg daily ibrutinib or placebo plus <= 6 cycles of bendamustine plus rituximab (BR), followed by ibrutinib or placebo alone. Median follow-up was 63.7 months. Median investigator-assessed progression-free survival was longer with ibrutinib plus BR (65.1 months) than placebo plus BR (14.3 months; hazard ratio [HR] 0.229 [95% confidence interval (CI) 0.183-0.286];p < .0001). Despite crossover of 63.3% of patients from the placebo plus BR arm to ibrutinib treatment upon disease progression, ibrutinib plus BR versus placebo plus BR demonstrated an overall survival benefit (HR 0.611 [95% CI 0.455-0.822];p = .0010; median not reached in either arm). Long-term follow-up data confirm the survival benefit of ibrutinib plus BR over BR alone. Safety profiles were consistent with those known for ibrutinib and BR

Differential utilization of ketone bodies by neurons and glioma cell lines: a rationale for ketogenic diet as experimental glioma therapy

Background: Even in the presence of oxygen, malignant cells often highly depend on glycolysis for energy generation, a phenomenon known as the Warburg effect. One strategy targeting this metabolic phenotype is glucose restriction by administration of a high-fat, low-carbohydrate (ketogenic) diet. Under these conditions, ketone bodies are generated serving as an important energy source at least for non-transformed cells. Methods: To investigate whether a ketogenic diet might selectively impair energy metabolism in tumor cells, we characterized in vitro effects of the principle ketone body 3-hydroxybutyrate in rat hippocampal neurons and five glioma cell lines. In vivo, a non-calorie-restricted ketogenic diet was examined in an orthotopic xenograft glioma mouse model. Results: The ketone body metabolizing enzymes 3-hydroxybutyrate dehydrogenase 1 and 2 (BDH1 and 2), 3-oxoacid-CoA transferase 1 (OXCT1) and acetyl-CoA acetyltransferase 1 (ACAT1) were expressed at the mRNA and protein level in all glioma cell lines. However, no activation of the hypoxia-inducible factor-1alpha (HIF-1alpha) pathway was observed in glioma cells, consistent with the absence of substantial 3-hydroxybutyrate metabolism and subsequent accumulation of succinate. Further, 3-hydroxybutyrate rescued hippocampal neurons from glucose withdrawal-induced cell death but did not protect glioma cell lines. In hypoxia, mRNA expression of OXCT1, ACAT1, BDH1 and 2 was downregulated. In vivo, the ketogenic diet led to a robust increase of blood 3-hydroxybutyrate, but did not alter blood glucose levels or improve survival. Conclusion: In summary, glioma cells are incapable of compensating for glucose restriction by metabolizing ketone bodies in vitro, suggesting a potential disadvantage of tumor cells compared to normal cells under a carbohydrate-restricted ketogenic diet. Further investigations are necessary to identify co-treatment modalities, e.g. glycolysis inhibitors or antiangiogenic agents that efficiently target non-oxidative pathways