muramidase and Cardiomyopathies

Topics: Amyloidosis; Apolipoproteins A; Cardiomyopathies; Dialysis; Fibrinogen; Humans; Kidney Diseases; Liver Diseases; Muramidase; Organ Transplantation; Prealbumin

We report the first protein selective Spiegelmers of diagnostic relevance by rational identification of a target epitope and reverse screening of Spiegelmer candidates following the selection procedure. Application of the presented approach resulted in isolation of cardiac troponin I selective Spiegelmers with low nanomolar dissociation constant and functionality in serum.

Topics: Aptamers, Peptide; Biomarkers; Cardiomyopathies; Epitopes; Humans; Indicators and Reagents; Kinetics; Muramidase; Protein Binding; Troponin I

Since early intervention using corticosteroids improves prognosis in some patients with cardiac sarcoidosis, early and accurate diagnosis of this clinical condition is important. However, it is still not easy to evaluate the activity of cardiac sarcoidosis in clinical practice. The aim of this study was to determine whether high-sensitive cardiac troponin T (hscTnT) is useful as an additional parameter to standard assessment in patients with cardiac sarcoidosis. Twelve patients who were diagnosed as having cardiac sarcoidosis at our institution were retrospectively studied. Evaluation of patients included clinical examinations, electrocardiography, echocardiography, 67-gallium-citrate (Ga) scintigraphy, 18F-fluoro2-deoxyglucose positron emission tomography (18F-FDG PET) and laboratory data including hs-cTnT, angiotensin-converting enzyme (ACE), lysozyme and B-type natriuretic peptide (BNP). The activity of cardiac sarcoidosis was judged mainly by using 18F-FDG PET. Localized uptake of 18F-FDG, which was considered to be active cardiac sarcoidosis, was seen in 8 patients. Based on the findings of 18F-FDG PET, hs-cTnT was considered to be a reliable parameter: sensitivity and specificity were 87.5% and 75.0%, respectively. The positive predictive value (PPV) and negative predictive value (NPV) were 87.5% and 75.0%, respectively. On the other hand, these values in lysozyme and BNP markers were not as high as those in hs-cTnT. Although an ACE marker and Ga-67 scintigraphy showed specificity and PPV of 100%, both sensitivity and NPV were less than 50%. Furthermore, hs-cTnT levels decreased after steroid therapy in some patients. Hs-cTnT seems to be a useful marker for evaluating the activity of cardiac sarcoidosis.

Topics: Aged; Biomarkers; Cardiomyopathies; Echocardiography; Electrocardiography; Female; Fluorodeoxyglucose F18; Glucocorticoids; Humans; Male; Middle Aged; Muramidase; Natriuretic Peptide, Brain; Peptidyl-Dipeptidase A; Positron-Emission Tomography; Predictive Value of Tests; Retrospective Studies; Sarcoidosis; Sensitivity and Specificity; Stroke Volume; Troponin T; Ventricular Function, Left

Cardiovascular dysfunction in septic shock (SS) is ascribed to the release of inflammatory mediators. Norepinephrine (NE) is often administered to treat low MAP in SS. We recently found that lysozyme c (Lzm-S) released from leukocytes was a mediator of myocardial depression in an Escherichia coil model of SS in dogs. This effect can be blocked in an in vitro preparation by chitobiose, a competitive inhibitor of Lzm-S. In the present study, we examined whether chitobiose treatment can reverse myocardial depression and obviate NE requirements in two respective canine E. coli preparations. In a 6-h study, we administered chitobiose after 3.5 h of E. coli bacteremia and compared stroke work (SW) and MAP at 6 h with a sepsis control group. In a 12-h study, we determined whether chitobiose treatment can reduce the need for NE requirements during 12 h of bacteremia. In the latter study, either chitobiose or NE was given when MAP decreased approximately 20% from the presepsis value in respective groups. In anesthetized, mechanically ventilated dogs, we monitored hemodynamic parameters during continuous E. coli infusion. In the 6-h study, chitobiose improved SW and MAP at the 6-h period as compared with the nontreated sepsis group. In the 12-h study, SW and MAP increased after chitobiose without the necessity of NE administration. These results suggest that inhibitors of Lzm-S such as chitobiose may improve myocardial depression and reduce the need for NE requirements in SS.

Topics: Animals; Bacteremia; Cardiomyopathies; Disaccharides; Dogs; Enzyme Inhibitors; Escherichia coli; Escherichia coli Infections; Humans; Inflammation Mediators; Male; Muramidase; Norepinephrine; Shock, Septic; Stroke Volume; Time Factors; Vasoconstrictor Agents

In sepsis, reversible myocardial depression has been ascribed to the release of mediators of inflammation. We previously found that lysozyme released from leukocytes from the spleen and other organs mediated myocardial depression in an Escherichia coli model of septic shock in dogs. We hypothesize that lysozyme binds to or cleaves a cardiac surface membrane N-glycoprotein to cause depression. The objectives of the present study were: 1) to determine whether the binding of lysozyme is reversible; 2) to assess the N-glycan structure to which lysozyme binds; 3) to examine whether nonenzymatic proteins, termed lectins, with a binding specificity similar to that of lysozyme could also cause depression; and 4) to assess whether the membrane to which lysozyme binds is affected by the enzymes protease type XIV and collagenase A, that are used to prepare single cell myocyte experiments.. We measured isometric contraction in a right ventricular trabecular preparation.. We found that lysozyme binds in a reversible manner to the Man beta(1-4) GlcNAc beta(1-4)GlcNAc moiety in the tri-mannosyl core structure of high mannose/hybrid and tri-antennary carbohydrate classes where GlcNAc is N-acetylglucosamine and Man is mannose. Lectins with a specificity similar to that of lysozyme also caused depression, and lysozyme's depressant activity was eliminated by protease type XIV and collagenase A.. These results indicate that lysozyme reversibly binds to a membrane glycoprotein to cause myocardial depression in sepsis. We further localize its binding site to a variant of the chitotriose structure in the tri-mannosyl core of the membrane glycoprotein.

Topics: Animals; Binding Sites; Cardiomyopathies; Dogs; Lectins; Membrane Glycoproteins; Muramidase; Myocardial Contraction; Oligosaccharides; Shock, Septic

Cardiac involvement is the major determinant of morbidity and mortality in patients with sarcoidosis, but clinical evaluation of the disease activity is occasionally difficult in cardiac sarcoidosis. The present study examined whether serum levels of interleukin-10 (IL-10) could reflect the disease activity of patients with cardiac sarcoidosis. Serum IL-10 levels were measured using an enzyme-linked immunosorbent assay, and compared with clinical manifestation, levels of angiotensin-converting enzyme (ACE), levels of lysozyme and accumulation of gallium-67 citrate. Sera were collected from 8 patients with cardiac sarcoidosis (CS group), 22 patients with miscellaneous heart diseases except for sarcoidosis (MHD group), and 8 healthy control subjects (HC group). Serum IL-10 levels of the CS group were significantly higher than those of the 2 control groups. Before steroid therapy, the levels of IL-10 in the CS group showed a significantly positive correlation with levels of ACE (r=0.868, p<0.05) and lysozyme (r=0.890, p<0.05). In 5 patients who were analyzed before and after steroid therapy, the levels of IL-10 tended to correlate with a decrease of an abnormal accumulation in gallium-67 citrate. Serum IL-10 levels may play a role in evaluation of the disease activity in patients with cardiac sarcoidosis.

Topics: Adult; Aged; Cardiomyopathies; Enzyme-Linked Immunosorbent Assay; Female; Humans; Interleukin-10; Male; Middle Aged; Muramidase; Renin; Sarcoidosis