Matrix Metalloproteinase-2 Inhibition in Acute Ischemia-Reperfusion Heart Injury-Cardioprotective Properties of Carvedilol.

Matrix metalloproteinase 2 (MMP-2) is activated in hearts upon ischemia-reperfusion (IR) injury and cleaves sarcomeric proteins. It was shown that carvedilol and nebivolol reduced the activity of different MMPs. Hence, we hypothesized that they could reduce MMPs activation in myocytes, and therefore, protect against cardiac contractile dysfunction related with IR injury.

Analysis of Multiple Risk Factors for Seronegative Rate of Anti-Tick-Borne Encephalitis Virus Immunization in Human Serum.

Tick-borne encephalitis virus (TBEV) infections have been the cause of threatening outbreaks for many years. Apart from several physical and chemical methods to prevent tick bites, active vaccination of people highly exposed to infection is still the most important strategy of prevention. However, in some subjects, the lack of or low response to TBEV antigens is observed.

A drug cocktail for protecting against ischemia-reperfusion injury.

Ischemia followed by reperfusion (I/R) of cardiomyocytes causes release of a large amount of inducible nitric oxide (NO) synthase (iNOS) followed by an increase of asymmetric dimethylarginine (ADMA). ADMA disrupts NO signaling by switching of the NOS activity from NO to the production of reactive oxygen species (ROS). Previously, we have shown that pretreatment of the hearts by co-administration of sub-threshold concentrations of doxycycline, a matrix metalloproteinase (MMPs) inhibitor, ML-7 an inhibitor of myosin light-chain kinase (MLCK) and L-NAME a non-selective NOS inhibitor protects the heart against I/R injury.

Cardioprotective effect of MMP-2-inhibitor-NO-donor hybrid against ischaemia/reperfusion injury.

Hypoxic injury of cardiovascular system is one of the most frequent complications following ischaemia. Heart injury arises from increased degradation of contractile proteins, such as myosin light chains (MLCs) and troponin I by matrix metalloproteinase 2 (MMP-2). The aim of the current research was to study the effects of 5-phenyloxyphenyl-5-aminoalkyl nitrate barbiturate (MMP-2-inhibitor-NO-donor hybrid) on hearts subjected to ischaemia/reperfusion (I/R) injury.

Biocompatible Carbon-Based Coating as Potential Endovascular Material for Stent Surface.

Stainless steel 316L is a material commonly used in cardiovascular medicine. Despite the various methods applied in stent production, the rates of in-stent restenosis and thrombosis remain high. In this study graphene was used to coat the surface of 316L substrate for enhanced bio- and hemocompatibility of the substrate.

Low frequency electromagnetic field decreases ischemia-reperfusion injury of human cardiomyocytes and supports their metabolic function.

Electromagnetic field at extremely low frequencies plays a significant role in the physiological function of human tissues and systems. It is shown that electromagnetic field inhibits production of reactive oxygen species which are involved in heart injury triggered by oxidative stress. We hypothesize that low frequency electromagnetic field protects function of cardiac cells from ischemia-reperfusion injury.

Co-infection with human polyomavirus BK enhances gene expression and replication of human adenovirus.

Immunocompromised patients are susceptible to multiple viral infections. Relevant interactions between co-infecting viruses might result from viral regulatory genes which trans-activate or repress the expression of host cell genes as well as the genes of any co-infecting virus. The aim of the current study was to show that the replication of human adenovirus 5 is enhanced by co-infection with BK polyomavirus and is associated with increased expression of proteins including early region 4 open reading frame 1 and both the large tumor antigen and small tumor antigen.

L-NAME improves doxycycline and ML-7 cardioprotection from oxidative stress.

Matrix metalloproteinase-2 (MMP-2) mediated degradation of myosin light chain 1 (MLC1) and troponin I (TnI) contributes to myocardial ischemia/reperfusion (I/R) injury. Modifications of MLC1 triggered by oxidative stress are mediated by myosin light chain kinase (MLCK), nitric oxide synthase (NOS), and MMP-2. Previous studies have shown that inhibiting both MLCK and MMP-2 protects against I/R injury.

Carvedilol Inhibits Matrix Metalloproteinase-2 Activation in Experimental Autoimmune Myocarditis: Possibilities of Cardioprotective Application.

Aims: Acute myocarditis is a potentially lethal inflammatory heart disease that frequently precedes the development of dilated cardiomyopathy and subsequent heart failure. At present, there is no effective standardized therapy for acute myocarditis, besides the optimal care of heart failure and arrhythmias in accordance with evidence-based guidelines and specific etiology-driven therapy for infectious myocarditis. Carvedilol has been shown to be cardioprotective by reducing cardiac pro-inflammatory cytokines present in oxidative stress in certain heart diseases.

Multidrug prevention or therapy of ischemia-reperfusion injury of the heart-Mini-review.

Restoration of blood flow to myocardium previously subjected to ischemia leads to ischemia/reperfusion injury due to oxidative stress. An increased production of toxic peroxynitrite, an enhanced phosphorylation and nitration/nitrosylation of myocyte contractile proteins and overactivation of matrix metalloproteinases -are only one of the several causes of heart damage. Multifactorial basis of ischemia/reperfusion injury demands the use of multiple pharmacological agents, inhibiting several pathways of cardiac injury.

Diagnostic usefulness of sCD163, procalcitonin and neopterin for sepsis risk assessment in critically ill patients.

Background: Sepsis is one of the most common causes of hospitalization and it is characterized by a high mortality rate in spite of the great progress in diagnosis and treatment achieved in recent years. Early diagnosis of sepsis is one of the most important elements of effective treatment. The clinical symptoms are not specific and biomarkers are considered to be useful tools in sepsis diagnostics.

An efficient method for isolation of representative and contamination-free population of blood platelets for proteomic studies.

To date, there has been no ideal method for blood platelet isolation which allows one to obtain a preparation devoid of contaminations, reflecting the activation status and morphological features of circulating platelets. To address these requirements, we have developed a method which combines the continuous density gradient centrifugation with washing from PGI-supplemented platelet-rich plasma (PRP). We have assessed the degree of erythrocyte and leukocyte contamination, recovery of platelets, morphological features, activation status, and reactivity of isolated platelets.

Subthreshold nitric oxide synthase inhibition improves synergistic effects of subthreshold MMP-2/MLCK-mediated cardiomyocyte protection from hypoxic injury.

Injury of myocardium during ischaemia/reperfusion (I/R) is a complex and multifactorial process involving uncontrolled protein phosphorylation, nitration/nitrosylation by increased production of nitric oxide and accelerated contractile protein degradation by matrix metalloproteinase-2 (MMP-2). It has been shown that simultaneous inhibition of MMP-2 with doxycycline (Doxy) and myosin light chain kinase (MLCK) with ML-7 at subthreshold concentrations protects the heart from contractile dysfunction triggered by I/R in a synergistic manner. In this study, we showed that additional co-administration of nitric oxide synthase (NOS) inhibitor (1400W or L-NAME) in subthreshold concentrations improves this synergistic protection in the model of hypoxia-reoxygenation (H-R)-induced contractile dysfunction of cardiomyocytes.

Lyme Borreliosis--the Utility of Improved Real-Time PCR Assay in the Detection of Borrelia burgdorferi Infections.

Background: Infections of Borrelia burgdorferi sensu lato reveal clinical manifestations affecting numerous organs and tissues. The standard diagnostic procedure of these infections is quite simple if a positive history of tick exposure or typical erythema migrans appears. Lack of unequivocal clinical symptoms creates the necessity for further evaluation with laboratory tests.

An infection of human adenovirus 31 affects the differentiation of preadipocytes into fat cells, its metabolic profile and fat accumulation.

The primary issue undertaken in this study was to test the hypothesis that preadipocytes would have intrinsically elevated propensity to differentiate into mature adipocytes due to HAdV31 infection. To prove that, the metabolic and molecular mechanisms responsible for HAdV31-induced adipogenesis were examined. 3T3L1 cells (mouse embryonic fibroblast, adipose like cell line) were used as a surrogate model to analyze an increased proliferation, differentiation, and maturation of preadipocytes infected with human adenovirus.

Low Frequency Electromagnetic Field Conditioning Protects against I/R Injury and Contractile Dysfunction in the Isolated Rat Heart.

Low frequency electromagnetic field (LF-EMF) decreases the formation of reactive oxygen species, which are key mediators of ischemia/reperfusion (I/R) injury. Therefore, we hypothesized that the LF-EMF protects contractility of hearts subjected to I/R injury. Isolated rat hearts were subjected to 20 min of global no-flow ischemia, followed by 30 min reperfusion, in the presence or absence of LF-EMF.

[Diagnostic utility of RHD-gene detection in maternal plasma in the prophylaxis of feto-maternal Rh-incompatibility].

Objectives: The aim of the study was analytical validation of prenatal noninvasive fetal RHD detection in maternal plasma and the preliminary assessment of its clinical utility Introduction of this noninvasive test into routine diagnostic use is important for more rational and safe immunoprophylaxis.

Material And Methods: RHD gene was detected using real-time PCR. Primers and probes complementary to sequence on exons 7 and 10 were chosen.

Is there any link between visceral obesity and adenovirus infections in the Polish population?

Background: Obesity is a chronic disease of multiple etiologies. Alongside the traditionally recognized causes of obesity, such as genetic inheritance and behaviour/environmental factors, in recent years adenoviral infections have been considered as a possible cause of obesity. Although numerous studies involving animals confirmed a strong relation between adenoviral infection and increased predisposition to obesity, an association of AdVs with human obesity has not been established conclusively.

Adenovirus type 9 enhances differentiation and decreases cytokine release from preadipocytes.

The hypothesis was that preadipocytes would have intrinsically elevated propensity to differentiate into mature adipocytes due to AdV9 infection. To test this hypothesis, the metabolic and molecular mechanisms responsible for AdV9-induced adipogenesis were examined. An association between anti-AdV9 antibodies and human obesity was also identified.

Inhibition of MMP-2 expression affects metabolic enzyme expression levels: proteomic analysis of rat cardiomyocytes.

Unlabelled: In this study we examined the effect of inhibition of MMP-2 expression, using siRNA, on the cardiomyocyte proteome. Isolated cardiomyocytes were transfected with MMP-2 siRNA and incubated for 24h. Control cardiomyocytes from the same heart were transfected with scrambled siRNA following the same protocol.

CD117 (c-kit) expression on CD34+ cells participates in the cytogenetic response to imatinib in patients with chronic myeloid leukemia in the first chronic phase.

Background: Chronic myeloid leukemia (CML) biology seemed to be perfectly explored especially at the beginning of the tyrosine kinase inhibitors era. Later years with imatinib and second-generation tyrosine kinase inhibitors showed a variety of resistance mechanisms and it became obvious that the bcr-abl chimeric gene is not the only enemy to fight. Some studies assumed the decreased rate of programmed cell death (apoptotic) to be the primary mechanism by which BCR-ABL affects expansion of the leukemic clone in CML.

Lack of adenovirus DNA in mediastinal adipose tissue of obese/overweight adults with cardiovascular disorders?

Mediastinal adipose tissue can be found on the anterior surface of pericardial sac below the remnants of the thymus. On the basis of previous studies describing adenoviruses (AdVs) as a causative factor of obesity, the causative relation between the presence of AdVs and an increased accumulation of mediastinal adipose tissue was studied. The study included 25 obese/overweight subjects with cardiac disorders.

Matrix metalloproteinases and the activity of their tissue inhibitors in patients with ST-elevation myocardial infarction treated with primary angioplasty.

Background: Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) play a role in heart remodelling after acutemyocardial infarction (MI). Their activity is connected with outcome and heart failure development. There is little data on MMP and TIMP activity changes in the setting of ST elevation MI (STEMI) treated with primary percutaneous coronary intervention (pPCI).

The decrease in prolidase activity in myeloproliferative neoplasms.

Background: The development of bone marrow fibrosis is a severe complication in hematological diseases. The progress of bone marrow myelofibrosis is evaluated by a trephine examination and may be characterized by the biochemical markers of collagen turnover determination.

Objectives: Investigation of serum prolidase activity and biochemical markers of collagen metabolism in order to establish its role in the development of bone marrow fibrosis.

Effect of the myosin light chain kinase inhibitor ML-7 on the proteome of hearts subjected to ischemia-reperfusion injury.

In the development of ischemia/reperfusion (I/R) injury, the role of the myosin light chain (MLC) phosphorylation has been given increased consideration. ML-7, a MLC kinase inhibitor, has been shown to protect cardiac function from I/R, however the exact mechanism remains unclear. Isolated rat hearts were perfused under aerobic conditions (controls) or subjected to I/R in the presence or absence of ML-7.