75 research outputs found
Signal transduction in cultered cardiomyocytes : alpha1-adrenergic and endothelin receptor mediated responses
Already in ancient times the Greek were aware of the heart in the human body and they gave
it the name kardia, which is still in use in words as cardiac, myocardial, tachycardia and
bradycardia. In those times the importance of the heart was appraised by Aristotle (384-322
B.C.), who thought that the heart was the seat of the soul and centre of man. In 1628,
however, the basis of the modern concepts of the circulation was laid by Harvey (1578-1657)
who described the function of two ventricles of the heart and the whole-body blood
circulation, and who gave the first description of heart failure (Harvey, 1628).
Nowadays, it is known that the function of the systemic circulation is to deliver blood to
all organs of the body in order to provide them with sufficient supply of oxygen and metabolic
substrates. The blood supply to the organs is accomplished primarily by the pump function
of the heart. The rhythmic contractions of the heart underlying this pumping action are elicited
by the electrical signals raised by the specialized cells of the atnum. Thus, the initiation of
contraction is dictated by the cellular organization, subsequently leading to the complex
process termed excitation-contraction coupling occurring within cardiomyocytes. It are the
phasic inward and outward movements of Ca2
+ across the sarcolemma (SL) and the
sarcoplasmic reticulum (SR) and the phasic on and off interactions of Ca'+ with the troponin
C component of the sarcomeres that determine the operation of the contraction-relaxation
cycle. Various regulatory mechanisms control these Ca2
+ movements and interactions,
processes which occur all within the confines of the cell membranes of the cardiomyocytes
Embedding of large specimens in glycol methacrylate: prerequisites for multi-signal detection and high-resolution imaging
Acrylic resin mixtures are commonly used to study microscopic sections of biological specimens, giving the advantage of good morphological preservation. Existing embedding protocols, however, are suitable for tissue blocks, not exceeding 1 mm in thickness. We have developed a protocol to embed larger specimens (up to 2 cm 3) in Technovit 8100. This medium allowed us to perform classic histological (trichrome), silver, as well as immunohistochemical staining, needed for multi-signal detection at high-resolution imaging to reconstruct a three-dimensional interpretation of a serially sectioned muscle. The technique was applied to reconstruct the semitendinosus muscle of a fetal pig, 44 days post conception, featuring connective tissue, intramuscular nerves, blood vessels, and muscle fibre types. For the reconstruction, a technique was used that enabled us to insert high-resolution images of histological details into low-resolution images of the entire muscle. (c) 2005 Wiley-Liss, Inc.Computer Systems, Imagery and Medi
Intracellular signaling and genetic reprogramming during agonist-induced hypertrophy of cardiomyocytes
Eicosapentaenoic acid incorporation in membrane phospholipids modulates receptor-mediated phospholipase C and membrane fluidity in rat ventricular myocytes in culture
The influence of increased incorporation of linoleic acid (18:2n-6) and eicosapentaenoic acid (20:5n-3) in membrane phospholipids on receptor-mediated phospholipase Cβ (PLC-β) activity in cultured rat ventricular myocytes was investigated. For this purpose, cells were grown for 4 days in control, stearic acid (18:0)/oleic acid (18:1n-9), 18:2n-6 and 20:5n-3 enriched media, and subsequently assayed for the basal- and phenylephrine- or endothelin-1-induced total inositol phosphate formation. The various fatty acid treatments resulted in the expected alterations of fatty acid composition of membrane phospholipids. In 18:2n-6-treated cells, the incorporation of this 18:2n-6 in the phospholipids increased from 17.1 mol % in control cells to 38.9 mol %. In 20:5n-3-treated cells, incorporation of 20: 5n-3 and docosapentaenoic acid (22:5n-3) in the phospholipids increased from 0.5 and 2.7 mol % in control cells to 23.2 and 9.7 mol %, respectively. When 20:5n-3-treated cells were stimulated with phenylephrine or endothelin-1, the inositolphosphate production decreased by 33.2% and increased by 43.4%, respectively, as compared to cells grown in control medium. No efffects were seen in 18:2n-6-treated cells. When 18:0/18:1n-9-treated cells were stimulated with endothelin-1, inositolphosphate formation increased by 26.4%, whereas phenylephrine-stimulated inositolphosphate formation was not affected. In saponin-permeabilized cells, that were pre-treated with 20:5n-3, the formation of total inositolphosphates after stimulation with GTPγS, in the presence of Ca2+, was inhibited 19.3%. This suggests that the 20:5n-3 effect on intact cardiomyocytes could be exerted either on the level of agonist-receptor, receptor-GTP-binding-protein coupling or GTP-binding-protein-PLC-β interaction. Investigation of the time course of saponin-induced permeabilization of the cardiomyocytes, measured by the release of lactate dehydrogenase, unmasked a slight decrease in the rate of permeabilization by 20:5n-3 pretreatment, indicating a protective effect. This led the authors to measure the cholesterol/phospholipid molar ratio, the double bond index of membrane phospholipids, and the membrane fluidity; the latter by using a diphenylhexatriene probe. In 20: 5n-3-pretreated cells, a strong increase in the cholesterol/phospholipid molar ratio (from 0.23 to 0.39), a marked increase in the double bond index (from 1.76 to 2.33), and a slight decrease in fluidity (steady-state anisotropy r(ss) of the diphenylhexatriene probe increased from 0.196 to 0.217) were observed. Thus, treatment of cardiomyocytes for 4 days with 20:5n-3, but not with 18:2n-6, causes alterations of receptor-mediated phospholipase Cβ activity. A causal relationship may exist between the 20:5 n-3-induced alterations of the physicochemical properties in the bilayer and of the agonist-stimulated phosphatidylinositol cycle activity
Fibrinolysis during liver transplantation is enhanced by using solvent/detergent virus-inactivated plasma (ESDEP)
After the introduction of solvent/detergent-treated plasma (ESDEP) in our
hospital, an increased incidence of hyperfibrinolysis was observed (75% vs
29%; P = 0.005) compared with the use of fresh frozen plasma for liver
transplantation. To clarify this increased incidence, intraoperative
plasma samples of patients treated with fresh frozen plasma or ESDEP were
analyzed in a retrospective observational study. During the anhepatic
phase, plasma levels of D-dimer (6.58 vs 1.53 microg/mL; P = 0.02) and
fibrinogen degradation products (60 vs 23 mg/L; P = 0.018) were
significantly higher in patients treated with ESDEP. After reperfusion,
differences increased to 23.5 vs 4.7 microg/mL (D-dimer, P = 0.002) and
161 vs 57 mg/L (fibrinogen degradation products, P = 0.001). The amount of
plasma received per packed red blood cell concentrate, clotting tests, and
levels of individual clotting factors did not show significant differences
between the groups. alpha(2)-Antiplasmin levels, however, were
significantly lower in patients receiving ESDEP during the anhepatic phase
(0.37 vs 0.65 IU/mL; P < 0.001) and after reperfusion (0.27 vs 0.58 IU/mL;
P = 0.001). Analysis of alpha(2)-antiplasmin levels in ESDEP alone showed
a reduction to 0.28 IU/mL (normal >0.95 IU/mL) because of the
solvent/detergent process. Therapeutic consequences for the use of ESDEP
in orthotopic liver transplantation are discussed in view of an increased
incidence of hyperfibrinolysis caused by reduced levels of
alpha(2)-antiplasmin in the solvent/detergent-treated plasma.
IMPLICATIONS: The use of solvent/detergent virus-inactivated plasma is of
increasing importance in the prevention of human immunodeficiency virus
and hepatitis C virus transmission. Since the use of this plasma during
orthotopic liver transplantation has increased, the incidence of
hyperfibrinolysis was observed. Clotting analysis of the patients revealed
small alpha(2)-antiplasmin concentrations because of the solvent/detergent
process
Does Routine Endoscopy or Contrast Swallow Study After Esophagectomy and Gastric Tube Reconstruction Change Patient Management?
Background: Anastomotic leakage is a severe complication after esophagectomy. The objective was to investigate the diagnostic and predictive value of routine contrast swallow study and endoscopy for the detection of anastomotic dehiscence in patients after esophagectomy. Methods: All patients who underwent contrast swallow and/or endoscopy within 7Â days after oesophagectomy for cancer between January 2005 and December 2009 were selected from an institutional database. Results: Some 173 patients underwent endoscopy, and 184 patients underwent a contrast swallow study. The sensitivity of endoscopy for anastomotic leakage requiring intervention is 56Â %, specificity 41Â %, positive predictive value (PPV) 8Â %, and negative predictive value (NPV) 95Â %. The sensitivity of contrast swallow study for detecting leakage requiring intervention in patients without signs of leakage was 20Â %, specificity 20Â %, PPV 3Â %, and NPV 97Â %. Conclusions: In patients without clinical suspicion of leakage, there is no benefit to perform routine examinations
Mesenchymal Stromal Cell-Derived Exosomes Contribute to Epithelial Regeneration in Experimental Inflammatory Bowel Disease
Microscopic imaging and technolog
Mesenchymal stromal cells prevent progression of liver fibrosis in a novel zebrafish embryo model
Cellular mechanisms in basic and clinical gastroenterology and hepatolog
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