Monocyte participation in connective tissue repair

Zusammenfassung Monocyten des strömenden Blutes könnenin vitro die morphologischen und funktionellen (Hydroxyprolinbildung) Kriterien von Fibrocyten erwerben. Die quantitative Bedeutung dieses Phänomens für den reparativen Bindegewebsaufbau wurde mit folgender Versuchsanordnung geprüft: Vergleichbare Inokulate von Monocyten (enthalten in der Leucocytenhaut des zentrifugierten Blutes) und von Fibrocyten (aus subcutanem Bindegewebe) von Kaninchen verschiedenen Geschlechts, wurden in Millipore-Kammern eingeschlossen und für 14–21 Tage in das Abdomen eines Kaninchens implantiert. Die Auszählung des Sex-Chromatins in den fibrocytären Kernen am Ende der Züchtungsperiode ergibt, dass ca. 50% monocytären Ursprunges sind. Es wird gefolgert, dass dieses Phänomen bei der eigentlichen Wundheilung noch bedeutungsvoller sein dürfte, da der Zustrom teilungsfähiger Monocyten in einem Wundgebiet kontinuierlich vor sich geht und nicht auf ein initiales Inokulum beschränkt ist.     

Early functional differentiation of heart muscle cells

Zusammenfassung Von embryonalen Hühnerherzen wurdenin vivo Membranpotentiale verschiedenen Regimes registriert. Bereits auf sehr frühen Entwicklungsstadien (37 h) wird eine Differenzierung in Schrittmachergasern und spätere Vertrikelfasern gefunden.

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Aided by a grant from the Italian Consiglio Nazionale delle Ricerche.     

AMP deaminase, 5'-nucleotidase and adenosine deaminase in rat myocardial tissue in myocardial infarction and hypothermia

AMP deaminase, 5'-nucleotidase and adenosine deaminase have been estimated in skeletal muscle and myocardial tissue in normal rats and in rats subjected to experimental myocardial infarction or hypothermia. A difference in the enzyme distribution was found between the right and left ventricles in the normal rat. A decrease in the activity of 5'-nucleotidase and an increase in the activity of adenosine deaminase were observed in infarcted myocardial tissue. The activity of all 3 enzymes was found to be depressed in the myocardium in rats subjected to hypothermia. These results are discussed in relation to adenosine production and its beneficial effects.     

Correlation between functional and morphological heart changes due to isoproterenol

Zusammenfassung Intravenös verabreichtes Vasopressin (Hypophysen-Hinterlappen-Extrakt) verursacht hypoxisch-ischaemische EKG-Veränderungen an mit Isoproterenol vorbehandelten Ratten (wesentlich kleinere Dosen als bei Normaltieren). Dieser Vasopressin-Test erlaubt den Nachweis einer herzschädigenden Wirkung von Isoproterenol bereits mit Dosen, die noch zu keiner histologisch erkennbaren Veränderung (Nekrose) des Myokardiums führten.     

The role of neuropeptides in adverse myocardial remodeling and heart failure

In addition to traditional neurotransmitters of the sympathetic and parasympathetic nervous systems, the heart also contains numerous neuropeptides. These neuropeptides not only modulate the effects of neurotransmitters, but also have independent effects on cardiac function. While in most cases the physiological actions of these neuropeptides are well defined, their contributions to cardiac pathology are less appreciated. Some neuropeptides are cardioprotective, some promote adverse cardiac remodeling and heart failure, and in the case of others their functions are unclear. Some have both cardioprotective and adverse effects depending on the specific cardiac pathology and progression of that pathology. In this review, we briefly describe the actions of several neuropeptides on normal cardiac physiology, before describing in more detail their role in adverse cardiac remodeling and heart failure. It is our goal to bring more focus toward understanding the contribution of neuropeptides to the pathogenesis of heart failure, and to consider them as potential therapeutic targets.     

Connective tissue degradation and distensibility characteristics of the non-living heart

Zusammenfassung Isolierte Hasenherzen wurden im Inkubator in 3 Gruppen von Enzymgemengen behandelt, ihre Ausdehnungscharakteristika durch Druckvolumen-Messungen bestimmt. Von den verwendeten Enzymen Collagenase, Elastase und Trypsin, erzeugte nur Collagenase einen Wechsel in der Ausdehnung.     

MicroRNAs in myocardial ischemia: identifying new targets and tools for treating heart disease. New frontiers for miR-medicine

MicroRNAs (miRNAs) are natural, single-stranded, small RNA molecules which subtly control gene expression. Several studies indicate that specific miRNAs can regulate heart function both in development and disease. Despite prevention programs and new therapeutic agents, cardiovascular disease remains the main cause of death in developed countries. The elevated number of heart failure episodes is mostly due to myocardial infarction (MI). An increasing number of studies have been carried out reporting changes in miRNAs gene expression and exploring their role in MI and heart failure. In this review, we furnish a critical analysis of where the frontier of knowledge has arrived in the fields of basic and translational research on miRNAs in cardiac ischemia. We first summarize the basal information on miRNA biology and regulation, especially concentrating on the feedback loops which control cardiac-enriched miRNAs. A focus on the role of miRNAs in the pathogenesis of myocardial ischemia and in the attenuation of injury is presented. Particular attention is given to cardiomyocyte death (apoptosis and necrosis), fibrosis, neovascularization, and heart failure. Then, we address the potential of miR-diagnosis (miRNAs as disease biomarkers) and miR-drugs (miRNAs as therapeutic targets) for cardiac ischemia and heart failure. Finally, we evaluate the use of miRNAs in the emerging field of regenerative medicine.     

Ischemic myocardial injury in cultured heart cells: In situ lysosomal damage

Summary Primary cultures of rat myocardial cells which were subjected to oxygen and glucose deprivation, 2 conditions associated with ischemia, were evaluated for alterations in lysosomal integrity. A photometric technique measured changes in latent acid phosphatase activity and lysosomal membrane permeability.Acknowledgments: The authors thank Dora Fernandez for skillful technical assistance. Research was supported by a grant from the National Heart, Lung, and Blood Institute, HL 18647.     

Currents through ionic channels in multicellular cardiac tissue and single heart cells

Ionic channels are elementary excitable elements in the cell membranes of heart and other tissues. They produce and transduce electrical signals. After decades of trouble with quantitative interpretation of voltage-clamp data from multicellular heart tissue, due to its morphological complexness and methodological limitations, cardiac electrophysiologists have developed new techniques for better control of membrane potential and of the ionic and metabolic environment on both sides of the plasma membrane, by the use of single heart cells. Direct recordings of the behavior of single ionic channels have become possible by using the patch-clamp technique, which was developed simultaneously. Biochemists have made excellent progress in purifying and characterizing ionic channel proteins, and there has been initial success in reconstituting some partially purified channels into lipid bilayers, where their function can be studied.     

Genome-wide association study to identify SNPs conferring risk of myocardial infarction and their functional analyses

Myocardial infarction might result from the interactions of multiple genetic and environmental factors, none of which can cause disease solely by each of themselves. Although molecular biological studies revealed that a number of proteins are possibly involved in its pathogenesis, little, if any genetic findings have been reported so far. To reveal genetic backgrounds of myocardial infarction, we performed a large-scale, case-control association study using 92,788 gene-based single-nucleotide polymorphism (SNP) markers. We have identified functional SNPs within the lymphotoxin-α gene (LTA) located on chromosome 6p21 that conferred susceptibility to myocardial infarction. Furthermore, we could identify galectin-2 protein as a binding partner of LTA protein. The association study further revealed that a functional SNP in LGALS2 encoding galectin-2, which led to altered secretion of LTA, also indicated a risk of myocardial infarction. A combined strategy of genetic and molecularcellular biological approaches may be useful in clarifying pathogenesis of common diseases.Received 7 March 2005; received after revision 22 April 2005; accepted 25 April 2005     

Inhibition of local connective tissue repair in the neoplastic response to water soluble carcinogens administered subcutaneously

Zusammenfassung Nach subkutaner Injektion einiger sogenannter wasserlöslicher Karzinogene (N-Methyl-N-Nitrosoharnstoff, Nitroquinolin-N-Oxyd und Butyryl-ethylenimin) erfolgt eine lokale Nekrose der subkutanen Gewebe mit verzögerter Regenerierung des Bindegewebes.     

Cephalopod myocardial receptors: Pharmacological studies on the isolated heart ofSepia officinalis (L.)

Summary This paper presents a synopsis of the information available about the pharmacological action of various substances on the cephalopod heart, with special emphasis on the central heart ofSepia officinalis. Threshold concentrations, EC₅₀ values and maximum effective concentrations have been experimentally determined. Studies with various transmitter substances, analogous compounds and antagonists have led to the following picture: Acetylcholine is the natural inhibitory transmitter substance; it acts via receptors with nicotinic properties which can be blocked by d-tubocurarine and -bungarotoxin. The probable excitatory transmitter system is represented by a noradrenergic innervation. Noradrenaline has a positive inotropic and a positive chronotropic action on in vitro heart preparations. A positive inotropic response can also be evoked by serotonin (5-HT); this effect is not due to stimulation of the catecholamine receptor, as is shown by cross-over experiments with specific blocking agents. Furthermore, a peptidergic receptor system has been described which reacts with the molluscan cardioactive peptide FMRF amide most effectively. It is assumed that cardioactive peptides may reach the central heart in the circulating blood; the sites of synthesis and release are still unknown. Possibly the NSV-layer of the vena cava is involved in hormonal cardiovascular regulation processes.     

Induced pluripotent stem cells for cardiac repair

Myocardial stem cell therapies are emerging as novel therapeutic paradigms for myocardial repair, but are hampered by the lack of sources for autologous human cardiomyocytes. An exciting development in the field of cardiovascular regenerative medicine is the ability to reprogram adult somatic cells into pluripotent stem cell lines (induced pluripotent stem cells, iPSCs) and to coax their differentiation into functional cardiomyocytes. This technology holds great promise for the emerging disciplines of personalized and regenerative medicine, because of the ability to derive patient-specific iPSCs that could potentially elude the immune system. The current review describes the latest techniques of generating iPSCs as well as the methods used to direct their differentiation towards the cardiac lineage. We then detail the unique potential as well as the possible hurdles on the road to clinical utilizing of the iPSCs derived cardiomyocytes in the emerging field of cardiovascular regenerative medicine.