The burden of clostridium difficile infection in patients with liver cirrhosis

Clostridium Difficile Infection (CDI) has registered a dramatically increasing incidence in the general population over the past decades. Nowadays, Clostridium Difficile is the leading cause of hospital-acquired diarrhea in Europe and North America. Liver cirrhosis is the final stage of any chronic liver disease (CLD). The most common causes are chronic hepatitis C or B and viral co-infections, alcohol misuse, and nonalcoholic fatty liver disease (NAFLD). CLD and cirrhosis are listed among the ten leading causes of death in the US. Cirrhosis due to any etiology disrupts the homeostatic role of the liver in the body. Cirrhosis-associated immune dysfunction (CAID) leads to alterations in both inherited and acquired systemic and local liver immunity. CAID is caused by increased systemic inflammation and immunodeficiency and it is responsible for 30% of mortality rates all over the world. Clostridium Difficile infection frequently affects patients suffering from liver cirrhosis because of the high number of prolonged hospitalizations, regular use of antibiotics for the prevention or treatment of SBP, proton pump inhibitor (PPI) use, and an overall immunocompromised state. Clostridium Difficile is a Gram-positive bacterium responsible for the high morbidity and mortality rates in patients with cirrhosis, with an essential increase in a 30-day mortality

Logic Modeling and the Ridiculome Under the Rug

Logic-derived modeling has been used to map biological networks and to study arbitrary functional interactions, and fine-grained kinetic modeling can accurately predict the detailed behavior of well-characterized molecular systems; at present, however, neither approach comes close to unraveling the full complexity of a cell. The current data revolution offers significant promises and challenges to both approaches - and could bring them together as it has spurred the development of new methods and tools that may help to bridge the many gaps between data, models, and mechanistic understanding. Have you used logic modeling in your research? It would not be surprising if many biologists would answer no to this hypothetical question. And it would not be true. In high school biology we already became familiar with cartoon diagrams that illustrate basic mechanisms of the molecular machinery operating inside cells. These are nothing else but simple logic models. If receptor and ligand are present, then receptor-ligand complexes form; if a receptor-ligand complex exists, then an enzyme gets activated; if the enzyme is active, then a second messenger is being produced; and so on. Such chains of causality are the essence of logic models (Figure 1a). Arbitrary events and mechanisms are abstracted; relationships are simplified and usually involve just two possible conditions and three possible consequences. The presence or absence of one or more molecule, activity, or function, [some icons in the cartoon] will determine whether another one of them will be produced (created, up-regulated, stimulated) [a \u27positive\u27 link] or destroyed (degraded, down-regulated, inhibited) [a \u27negative\u27 link], or be unaffected [there is no link]. The icons and links often do not follow a standardized format, but when we look at such a cartoon diagram, we believe that we \u27understand\u27 how the system works. Because our brain is easily able to process these relationships, these diagrams allow us to answer two fundamental types of questions related to the system: why (are certain things happening)? What if (we make some changes)

Эффекты гипоксического прекондиционирования сосудистoй реактивности in vitro

Laboratorul de Cardiomiopatii şi Miocardite, Institutul de Cardiologie, ChişinăuThe hypoxic precondition was created in rats in order to study its effects on the vascular constriction and relaxation of the isolated aortic rings. The hypoxic precondition led to a significant decrease of the constrictor plateau induced by phenilefrine, norepinephrine, angiotensine II and endotheline-1 in a concentration range of 10-8-10-5 M with an average of 12-33%. This effect results in a stronger blunting (from 15 up to 25%) of the Phe-induced aorta constriction when rings were stimulated by carbacol (10-7-10-5 M). Thus, the hypoxic precondition the endotheliumdependent aortic relaxation, perhaps due to stimulation produced by the synthesis of nitric oxide, a phenomenon closely linked to the diminished plateau of vascular reactivity created by the constricting agents.Гипоксическое прекондиционирование было моделировано на крысах с целью изучения его действия на сосудистую реактивность изолированных колец аорты в условиях воздействия сосудосуживающих и сосудорасширяющих факторов. Гипоксическое прекондиционирование вызвало достоверное снижение в среднем на 12-33% констрикторного плато фенилэфрина, норадреналина, ангиотензина II и эндотелина-1, использованных в диапазоне концентраций 10-8-10-5 M. Данный эффект ассоциировался с более выраженным уменьшением (от 15 до 25%) сокращения колец аорты при стимуляции карбахолом (10-7-10-5 M). Таким образом, гипоксическое прекондиционирование потенцирует эндотелий и зависимое расслабление аорты. Возможно, благодаря стимуляции синтеза окиси азота, феномен тесно связан с уменьшением констрикторного плато, индуцированного сосудосуживающими агентами

Воздействие гипоксического прекондиционирования на некоторые показатели оксидативного стресса

Department of Interventional Cardiology, Institute of CardiologyThe circulating levels of lipid peroxidation products such as lipid hydroperoxides and malonic dialdehyde as well as of several antioxidants such as catalase, glutationreductase and ceruloplasmin have been found in the blood of 74 patients with arterial hypertension who underwent antihypertensive treatment and had experienced hypoxic precondition. Likewise the expression and quantity of thioredoxin were found in human umbilical endothelial cells exposed to progressive hypoxia using laser confocal microscopy and the Western Blot exam. Compared to samples obtained from patients who received only antihypertensive treatment the hypoxic precondition led to a greater increase of antioxidants levels and to a deeper decline of products of oxidative stress. Hypoxic precondition increased almost 7-fold the expression and quantity of the endotheliocyte thioredoxin. Содержание в крови продуктов перекисного окисления липидов (гидроперекиси липидов и малоновый диальдегид), а также некоторых антиоксидантов (каталаза, глутатионредуктаза и церулоплазмин) было определено у 74 пациентов с артериальной гипертензией, подверженных гипоксическому прекондиционированию на фоне антигипертензивной терапии. Также были исследованы экспрессия и количество тиоредоксина в эндотелиальных клетках пупочной вены человека с помощью лазерной конфокальной микроскопии и экзамена Western Blot. По сравнению с полученными данными у пациентов, получивших только антигипертензивное лечение, гипоксическое прекондиционирование способствовало более выраженному увеличению уровня антиоксидантов и более значительному снижению продуктов гидроперекиси липидов. Гипоксическое прекондиционирование привело к 7-ми кратному повышению экспрессии и количества тиоредоксина в эндотелиальных клетках

Оксидативный стресс в сердечно-сосудистой патологии

Oxidative stress is recognized as a universal feature of many diseases, including cardiovascular disorders. In this article, the main pathogenic mechanisms of oxidative stress regarding heart failure and arterial hypertension evolution are underlined. The role of free oxygen radicals in myocardial hypertrophy development as well as their importance in extracellular matrix reorganization are emphasized. Likewise, the molecular and cellular substrate of crosslink between oxidative stress and cell apoptosis and inflammation are estimated. The contribution of oxidative stress on arterial hypertension evolution is basically observed through targeting of vascular endothelium especially concerning nitric oxide depletion, inflammatory response, and compromising of vascular endothelium dependent reactivity. Thus, activation of grow and transcription factors, cytokines, caspases and matrix metalloproteinases are most important mechanisms in oxidative stress induced heart failure, while the vascular endothelium and nitric oxide synthesis impairment are basically involved in arterial hypertension evolution.Оксидативный стресс признан универсальным механизмом многих заболеваний, включительно сердечно-сосудистых нарушений. В настоящем обзоре рассмотрены основные механизмы оксидативного стресса в развитии сердечной недостаточности и артериальной гипертензии. Выделена роль свободных радикалов кислорода в генезе гипертрофии миокарда, а также реорганизации межклеточной матрицы. В том числе обобщён клеточный и молекулярный субстраты взаимосвязи оксидативного стресса, апоптоза и воспаления. Участие оксидативного стресса в развитии артериальной гипертензии подчёркнуто в основном соотносительно сосудистому эндотелию, выделяя значимость снижения продукции окиси азота, воспалительного процесса и нарушения эндотелий зависимой сосудистой реактивности. Активирование оксидативным стрессом факторов роста и транскрипции, цитокинов, каспаз и матричных металлопротеиназ является основным механизмом сердечной недостаточности, а нарушение сосудистого эндотелия и синтеза окиси азота вовлечено, главным образом, в развитии артериальной гипертензии

The complex medical-surgical treatment in septical states

Clinica 2 Chirurgie „Constantin Ţîbîrnă”, Catedra 2 Chirurgie USMF „N.Testemiţanu”, Chişinău, Republica Moldova, Al XI-lea Congres al Asociației Chirurgilor „Nicolae Anestiadi” din Republica Moldova și cea de-a XXXIII-a Reuniune a Chirurgilor din Moldova „Iacomi-Răzeșu” 27-30 septembrie 2011Introducere: Conform concepţiilor moderne, sepsisul reprezintă o reacţie sistemică către agresia microbiană cu expulzia incontrolabilă a mediatorilor inflamaţiei şi dereglări grave de microcirculaţie, asociate hipoxiei tisulare. Astfel este argumentată utilizarea metodelor noi de inactivare a metaboliţilor proinflamatorii şi sistarea stresului oxidativ cu corijarea hipoxiei hemocirculatorii sistemice. Scopul studiului a constituit estimarea posibilităţilor aplicării ozonoterapiei sistemice în tratamentul complex medico-chirurgical la bolnavii cu stări septice. Material şi metode: Studiul dat include analiza retrospectivă a rezultatelor tratamentului la 382 bolnavi cu sepsis chirurgical (bărbaţi-199, femei-183, vîrsta medie-47+/-3,1 ani), trataţi în Clinicele Chirurgie şi ATI ale SCM “Sfînta Treime” în perioada aa.2005-2010. Diagnosticul de sepsis a fost stabilit conform criteriilor Bone R. Obligatoriu s-a recurs la examenul bacteriologic cu aprecierea antibioticogramei, în baza căreea s-a elaborat o schemă optimă de conduită în tratamentul antimicrobian.. Ozonoterapia sistemică s-a efectuat la 84 pacienţi prin perfuzii de Sol NaCl 0,9%-400,0 ml saturată cu ozon, cu o concentraţie a O3 în limite de 800-1200 mkg/l în amestecul ozonat-oxigenat. Rezultate: Hemocultura pozitivă a fost stabilită în 132 (34,5%) cazuri. Monoinfecţia - în 36. cazuri, inclusiv bacili Gram negativi-28 (77%); Gram pozitivi -8 (23%). La 96 bolnavi a fost identificată poliinfecţie. Durata medie de spitalizare a constituit 21+/-1,7 zile. Însănătoşirea a survenit în 317 (83%) cazuri. Au decedat 65 pacienţi, ce atestă o letalitate de 17.%. În lotul pacienţilor la care s-a aplicat ozonoterapia sistemică letalitatea a constituit 12 pacienţi (14,2%). Concluzii: Rezultatele obţinute demonstrează persistenţa dominaţiei sepsisului Gram negativ. Ozonoterapia sistemică în stările septice micşorează mortalitatea spitalicească.Introduction: According to modern concepts, sepsis is a systemic response to microbial aggression with uncontrollable expulsion of mediators of inflammation and disorders of microcirculation serious, associated with tissue hypoxia. So appear to be motivated the using of new methods for inactivation of proinflammatory metabolites and oxidative stress with correction and stopping of systemic hemocirculating hypoxia. Aim: The purpose of the study was estimation of possibility of systemic ozone therapy in the complex medical and surgical treatment in patients with sepsis. Material and methods: This study includes retrospective analysis of treatment results from 382 patients with surgical sepsis (men-199, female 183, average age, 47 + / -3.1 years) treated in the clinics of surgery and ATI SCM “Sfînta Treime”from aa.2005-2010. The diagnosis of sepsis was established according to criteria R. Bone with obligatory using of antibioticogramme. Bazed on bacterial appreciation, was have performed the scheme to prepare optimal conduct for antimicrobial treatment. Ozone therapy was performed in 84 patients by systematiically infusion of Sol. NaCl 0.9% -400.0 ml, saturated with ozone at a concentration of O3 in the range of 800-1200 mkg / l ozone-oxygen in the mixture. Results: Positive blood culture was established in 132 (34.5%) cases. Monoinfection was stabilited in 36. cases, including Gram-negative bacilli- 28 (77%), Gram positive -8 (23%). 96 patients were identified poliinfection. Average length of stay was 21 + / -1.7 days. Recovery occurred in 317 (83%) cases. Diedet 65 patients (17%). In the group of patients who received systemic Ozone therapy lethality was 12 patients (14.2%). Conclusions: The results demonstrate the domination of Gram-negative sepsis. The application of systemic Ozone therapy decreased hospital mortality in septic states