Діагностика цитолітичного синдрому у хворих на туберкульоз легень

Introduction. The liver is one of the most important organs of the human body, performing a number of important functions. Among the common liver diseases, infiltrative pathologies we distinguished: fatty degeneration, lymphomas, amyloidosis, sarcoidosis and tuberculosis. Characterizing liver disease, the manifestations of disorders are divided into syndromes that help to diagnose a particular disease of the liver and determine its causes. In particular – the cytolytic syndrome (CS).The aim of the study – to examine the CS markers in the case of liver dysfunction in patients with newly diagnosed lung tuberculosis prior to treatment and after two months of therapy with first-line anti-tuberculosis drugs.Methods of the research. Two groups of people were examined: the 1st control group of practically healthy donors – 34 people; and the 2nd – patients with newly diagnosed pulmonary tuberculosis prior to treatment and after two months of therapy with first-line anti-tuberculosis drugs (31 people). All patients underwent standard biochemical blood tests, ultrasound of the liver in dynamics. The spectrum of biochemical blood test parameters included determination of alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH) and γ-glutamyltranspeptidase (GGTP).Results and Discussion. The obtained data testifying to occurrence of CS in newly diagnosed tuberculosis patients before the start of treatment are confirmed by the tendency to increase the levels of AST and GGTP. Especially such changes are observed after intensive therapy with antituberculous drugs. There are likely changes in such markers as ALT, LDH and GGTP.Conclusions. It is established that tuberculous intoxication can affect the functional state of the liver. After prolonged treatment of patients with pulmonary tuberculosis, an increase in the indices of such markers of cytolysis as ALT, LDH and GGTP is observed. Disturbance of liver function during therapy may be due to the hepatotoxic effect of anti-tuberculosis drugs, which necessitates the appointment for patients hepatoprotectors.Вступление. Печень является одним из важнейших органов тела человека и выполняет ряд важнейших функций. Среди распространенных заболеваний печени выделяют инфильтративные патологии: жировую дистрофию, лимфомы, амилоидоз, саркоидоз и туберкулез. Характеризуя болезни печени, проявления расстройств принято разделять на синдромы, которые помогают диагностировать то или иное заболевание этого органа и определить его причины. В частности, выделяют цитолитический синдром (ЦС).Цель исследования – изучить маркеры ЦС при нарушении функции печени у больных с впервые диагностированным туберкулезом легких до лечения и через два месяца терапии противотуберкулезными препаратами первого ряда.Методы исследования. Было обследовано две группы лиц: 1-я (контрольная) – практически здоровые доноры (34 человека); 2-я – больные с впервые диагностированным туберкулезом легких до лечения и через два месяца терапии противотуберкулезными препаратами первого ряда (31 человек). Всем пациентам проводили стандартные биохимические исследования крови, УЗИ печени в динамике. Спектр показателей биохимического исследования крови включал определение аланинаминотрансферазы (АлАТ), аспартатаминотрансферазы (АсАТ), лактатдегидрогеназы (ЛДГ) и γ-глутамилтранспептидазы (ГГТП).Результаты и обсуждение. Полученные данные, свидетельствующие о возникновении ЦС у больных с впервые диагностированным туберкулезом до начала лечения, подтверждаются тенденцией к увеличению уровней АсАТ и ГГТП. Особенно такие изменения наблюдали после интенсивной терапии противотуберкулезными препаратами. Отмечали вероятные изменения таких маркеров, как АлАТ, ЛДГ и ГГТП.Выводы. Установлено, что туберкулезная интоксикация может влиять на функциональное состояние печени. После длительного лечения больных туберкулезом легких отмечают увеличение показателей таких маркеров цитолиза, как АлАТ, ЛДГ и ГГТП. Нарушения функции печени во время терапии могут быть вызваны гепатотоксическим действием противотуберкулезных препаратов, что обусловливает необходимость назначения больным гепатопротекторов.Вступ. Печінка є одним із найважливіших органів тіла людини і виконує низку надзвичайно важливих функцій. Серед поширених захворювань печінки виділяють інфільтративні патології: жирову дистрофію, лімфоми, амілоїдоз, саркоїдоз і туберкульоз. Характеризуючи хвороби печінки, прояви розладів прийнято розділяти на синдроми, які допомагають діагностувати те чи інше захворювання цього органа та визначити його причини. Зокрема, виділяють цитолітичний синдром (ЦС).Мета дослідження – вивчити маркери ЦС при порушенні функції печінки у хворих на вперше діагностований туберкульоз легень до лікування і через два місяці терапії протитуберкульозними препаратами першого ряду.Методи дослідження. Було обстежено дві групи осіб: 1-ша контрольна – практично здорові донори – (34 особи); 2-га – хворі на вперше діагностований туберкульоз легень до лікування і через два місяці терапії протитуберкульозними препаратами першого ряду (31 особа). Усім пацієнтам проводили стандартні біохімічні дослідження крові, УЗД печінки в динаміці. Спектр показників біохімічного дослідження крові включав визначення аланінамінотрансферази (АлАТ), аспартатамінотрансферази (АсАТ), лактатдегідрогенази (ЛДГ) та γ-глутамілтранспептидази (ГГТП).Результати й обговорення. Отримані дані, які свідчили про виникнення ЦС у хворих на вперше діагностований туберкульоз до початку лікування, підтверджувалися тенденцією до збільшення рівнів АсАТ і ГГТП. Особливо такі зміни спостерігали після інтенсивної терапії протитуберкульозними препаратами. Відмічали вірогідні зміни таких маркерів, як АлАТ, ЛДГ і ГГТП.Висновки. Встановлено, що туберкульозна інтоксикація може впливати на функціональний стан печінки. Після тривалого лікування хворих на туберкульоз легень відмічають збільшення показників таких маркерів цитолізу, як АлАТ, ЛДГ і ГГТП. Порушення функції печінки під час терапії можуть бути спричинені гепатотоксичною дією протитуберкульозних препаратів, що зумовлює необхідність призначення хворим гепатопротекторів.

Search for eta-mesic 4He in the dd->3He n pi0 and dd->3He p pi- reactions with the WASA-at-COSY facility

The search for 4He-eta bound states was performed with the WASA-at-COSY facility via the measurement of the excitation function for the dd->3He n pi0 and dd->3He p pi- processes. The beam momentum was varied continuously between 2.127 GeV/c and 2.422 GeV/c, corresponding to the excess energy for the dd->4He eta reaction ranging from Q=-70 MeV to Q=30 MeV. The luminosity was determined based on the dd->3He n reaction and quasi-free proton-proton scattering via dd->pp n_spectator n_spectator reactions. The excitation functions determined independently for the measured reactions do not reveal a structure which could be interpreted as a narrow mesic nucleus. Therefore, the upper limits of the total cross sections for the bound state production and decay in dd->(4He-eta)_bound->3He n pi0 and dd->(4He-eta)_bound->3He p pi- processes were determined taking into account the isospin relation between both the channels considered. The results of the analysis depend on the assumptions of the N* momentum distribution in the anticipated mesic-4He. Assuming as in the previous works, that this is identical with the distribution of nucleons bound with 20 MeV in 4He, we determined that (for the mesic bound state width in the range from 5 MeV to 50 MeV) the upper limits at 90% confidence level are about 3 nb and about 6 nb for npi0 and ppi- channels, respectively. However, based on the recent theoretical findings of the N*(1535) momentum distribution in the N*-3He nucleus bound by 3.6 MeV, we find that the WASA-at-COSY detector acceptance decreases and hence the corresponding upper limits are 5 nb and 10 nb for npi0 and ppi- channels respectively.Comment: This article will be submitted to JHE

Search for the eta-mesic 4He with WASA-at-COSY detector

An exclusive measurement of the excitation function for the dd->3Heppi- reaction was performed at the Cooler Synchrotron COSY-Juelich with the WASA-at-COSY detection system. The data were taken during a slow acceleration of the beam from 2.185 GeV/c to 2.400 GeV/c crossing the kinematic threshold for the eta meson production in the dd->4He-eta reaction at 2.336 GeV/c. The corresponding excess energy with respect to the 4He-eta system varied from -51.4MeV to 22MeV. The integrated luminosity in the experiment was determined using the dd->3Hen reaction. The shape of the excitation function for the dd->3Heppi- was examined. No signal of the 4He-eta bound state was observed. An upper limit for the cross-section for the bound state formation and decay in the process dd->(4He-eta)bound->3Heppi- was determined on the 90% confidence level and it varies from 20nb to 27nb for the bound state width ranging from 5MeV to 35MeV, respectively.Comment: 8 pages, 9 figure

Cross section ratio and angular distributions of the reaction p + d -> 3He + eta at 48.8 MeV and 59.8 MeV excess energy

We present new data for angular distributions and on the cross section ratio of the p + d -> 3He + eta reaction at excess energies of Q = 48.8 MeV and Q = 59.8 MeV. The data have been obtained at the WASA-at-COSY experiment (Forschungszentrum J\"ulich) using a proton beam and a deuterium pellet target. While the shape of obtained angular distributions show only a slow variation with the energy, the new results indicate a distinct and unexpected total cross section fluctuation between Q = 20 MeV and Q = 60 MeV, which might indicate the variation of the production mechanism within this energy interval.Comment: 9 pages, 9 figure

ABC Effect in Basic Double-Pionic Fusion --- Observation of a new resonance?

We report on a high-statistics measurement of the basic double pionic fusion reaction $pn \to d\pi^0\pi^0$ over the energy region of the so-called ABC effect, a pronounced low-mass enhancement in the $\pi\pi$-invariant mass spectrum. The measurements were performed with the WASA detector setup at COSY. The data reveal the ABC effect to be associated with a Lorentzian shaped energy dependence in the integral cross section. The observables are consistent with a resonance with $I(J^P) =0(3^+)$ in both $pn$ and $\Delta\Delta$ systems. Necessary further tests of the resonance interpretation are discussed

Intrinsic NLRP3 inflammasome activity is critical for normal adaptive immunity via regulation of IFN-γ in CD4+ T cells

The NLRP3 inflammasome controls interleukin-1b maturation in antigen-presenting cells, but a direct role for NLRP3 in human adaptive immune cells has not been described.We found that the NLRP3 inflammasome assembles in human CD4+ Tcells and initiates caspase-1–dependent interleukin-1b secretion, thereby promoting interferon-g production and T helper 1 (TH1) differentiation in an autocrine fashion. NLRP3 assembly requires intracellular C5 activation and stimulation of C5a receptor 1 (C5aR1), which is negatively regulated by surface-expressed C5aR2. Aberrant NLRP3 activity in Tcells affects inflammatory responses in human autoinflammatory disease and in mouse models of inflammation and infection. Our results demonstrate that NLRP3 inflammasome activity is not confined to “innate immune cells” but is an integral component of normal adaptive TH1 responses

Isospin violating dark matter in Stückelberg portal scenarios

Journal of High Energy Physics 2015.4 (2015): 175 reproduced by permission of Scuola Internazionale Superiore di Studi Avanzati (SISSA)Hidden sector scenarios in which dark matter (DM) interacts with the Standard Model matter fields through the exchange of massive Z′ bosons are well motivated by certain string theory constructions. In this work, we thoroughly study the phenomenological aspects of such scenarios and find that they present a clear and testable consequence for direct DM searches. We show that such string motivated Stückelberg portals naturally lead to isospin violating interactions of DM particles with nuclei. We find that the relations between the DM coupling to neutrons and protons for both, spin-independent (fn/fp) and spin-dependent (an/ap) interactions, are very flexible depending on the charges of the quarks under the extra U(1) gauge groups. We show that within this construction these ratios are generically different from ±1 (i.e. different couplings to protons and neutrons) leading to a potentially measurable distinction from other popular portals. Finally, we incorporate bounds from searches for dijet and dilepton resonances at the LHC as well as LUX bounds on the elastic scattering of DM off nucleons to determine the experimentally allowed values of fn/fp and an/apThe authors are grateful to D. G. Cerdeño, L. Ibañez, F. Kahlhoefer and G. Shiu for useful comments. V.M.L. and M.P. would like to thank the support of the European Union under the ERC Advanced Grant SPLE under contract ERC-2012-ADG-20120216-320421, the support of the Consolider-Ingenio 2010 programme under grant MULTIDARK CSD2009-00064, the Spanish MICINN under Grant No. FPA2012-34694, the Spanish MINECO “Centro de excelencia Severo Ochoa Program” under Grant No. SEV-2012-0249, and the Community of Madrid under Grant No. HEPHACOS S2009/ESP-1473. P.S. would like to thank DESY, the University of Hamburg, and the Hong Kong IAS for kind hospitality during the completion of this work. He acknowledges support from the DOE grant DEFG-02-95ER40896 and the HKRGC grant HKUST4/CRF/13G, 604231, as well as the Collaborative Research Center SFB676 of the DFG at the University of Hambur

Carboxypeptidase-M is regulated by lipids and CSFs in macrophages and dendritic cells and expressed selectively in tissue granulomas and foam cells

Granulomatous inflammations, characterized by the presence of activated macrophages (MAs) forming epithelioid cell (EPC) clusters, are usually easy to recognize. However, in ambiguous cases the use of a MA marker that expresses selectively in EPCs may be needed. Here, we report that carboxypeptidase-M (CPM), a MA-differentiation marker, is preferentially induced in EPCs of all granuloma types studied, but not in resting MAs. As CPM is not expressed constitutively in MAs, this allows utilization of CPM-immunohistochemistry in diagnostics of minute granuloma detection when dense non-granulomatous MAs are also present. Despite this rule, hardly any detectable CPM was found in advanced/active tubercle caseous disease, albeit in early tuberculosis granuloma, MAs still expressed CPM. Indeed, in vitro both the CPM-protein and -mRNA became downregulated when MAs were infected with live mycobacteria. In vitro, MA-CPM transcript is neither induced remarkably by interferon-γ, known to cause classical MA activation, nor by IL-4, an alternative MA activator. Instead, CPM is selectively expressed in lipid-laden MAs, including the foam cells of atherosclerotic plaques, xanthomatous lesions and lipid pneumonias. By using serum, rich in lipids, and low-density lipoprotein (LDL) or VLDL, CPM upregulation could be reproduced in vitro in monocyte-derived MAs both at transcriptional and protein levels, and the increase is repressed under lipid-depleted conditions. The microarray analyses support the notion that CPM induction correlates with a robust progressive increase in CPM gene expression during monocyte to MA maturation and dendritic cell (DC) differentiation mediated by granulocyte–MA-colony-stimulating factor+IL-4. M-CSF alone also induced CPM. These results collectively indicate that CPM upregulation in MAs is preferentially associated with increased lipid uptake, and exposure to CSF, features of EPCs, also. Therefore, CPM-immunohistochemistry is useful for granuloma and foam MA detections in tissue sections. Furthermore, the present data offer CPM for the first time to be a novel marker and cellular player in lipid uptake and/or metabolism of MAs by promoting foam cell formation