Platelet kinetics in Crohn's disease

Summary The pathogenesis of thrombocytosis in Crohn's disease was analized in ten non-treated patients using the⁵¹Cr labelling method. The data obtained were compared to those taken from a control group.Besides platelet survival time, platelet turnover, surface radioactivity, platelet adhesiveness and morphological aspects of bone marrow were investigated.Platelet survival time in patients with Crohn's disease proved to be significantly shortened (p<0.001), whereas platelet turnover appeared augmented. No additional radioactivity is encountered from the organs scanned. The relative platelet adhesiveness is diminished while thrombocytopoesis in bone marrow is augmented.     

Catecholamine elevation in iron deficiency.

Iron-deficient rats have increased blood and urinary catecholamines regardless of whether anemia is or is not present. The catecholamine response in both iron-deficient and control animals is largely temperature dependent, showing little difference at the isothermic temperature of 30 degrees C but a two- to threefold increase in iron-deficient animals over controls at lower temperatures. The iron-deficient rat is unable to maintain body temperature at 4 degrees C and this is independent of anemia or of food intake. When animals are run on the treadmill for 4 h, body temperatures increase but the difference observed at 4 degrees C between iron-deficient and control animals persists. The underlying abnormality in temperature regulation and in catecholamine response disappeared after 6 days of iron therapy.     

Catecholamine metabolite excretion in spina bifida

The urinary excretion of vanilmandelic acid (VMA), homovanillic acid (HVA), and parahydroxyphenylacetic acid (pHPAA) was measured in 55 children with meningomyelocoele selected at random. In 96% of the children the levels of one or other of these compounds was significantly raised above the normal, usually by a factor of about 3. High VMA levels usually meant high HVA levels but the values for pHPAA appeared to be quite independent of the others. These results suggest a disorder of tyrosine metabolism, and the possible implications are discussed.     

Catecholamine metabolism in familial amyloid polyneuropathy

In order to evaluate the involvement of the peripheral autonomic nervous system in the pathogenesis of type 1 familial amyloid polyneuropathy, the urinary excretion rates of catecholamines and serum dopamine-beta-hydroxylase (DB/) activity were examined in 22 patients at various clinical stages. Changes in both indices were closely linked to the progression of the illness; urinary excretion rates of catecholamines were first decreased in patients suffering from moderate autonomic dysfunction, while serum DBH activity was significantly reduced only in patients with far advanced disease. These findings suggested that patients with advanced disease might be suffering from a chronic deficiency of catecholamines in the peripheral sympathetic nerves. Administration of L-dopa, however, failed to improve the clinical manifestations.     

Catecholamine stress responses in arterialized blood

Arterialized and venous blood was compared to determine if the arterialization procedure enhances the detection of stress-related changes in catecholamines. Lipid and hematologic measures were also compared for possible distortion by arterialization. Fifteen men completed two stressors. Indwelling venous catheters were placed retrograde in each hand, and the right hand was warmed to a constant temperature. Blood samples were taken simultaneously from both hands, and plasma catecholamines were determined. Arterialization increased baseline epinephrine; there were no effects of arterialization on catecholamines during stress, nor in lipid or hematologic measures during baseline or stress. Thus, arterialization of blood results in small increases in resting epinephrine levels, but does not obscure lipid measures. More importantly, arterialization of venous blood does not enhance the detection of stress-related changes in catecholamines.     

MR in mouse models of cardiac disease

Transgenic and knockout mice can be used to study the genes and basic mechanisms involved in heart disease, and have therefore assumed a central role in modern cardiac research. MRI and MRS techniques have recently been developed for mice that enable the quantitative or semi-quantitative in vivo assessment of cardiac anatomy, function, perfusion, infarction, Ca(2+) influx, and metabolism. With these techniques, the normal mouse heart has been shown to be well suited as a model of human cardiac disease. The roles of individual genes in normal cardiac physiology have recently been studied by MR, including the role of neuronal nitric oxide synthase in beta-adrenergic stimulation, the roles of the inducible nitric oxide synthase and myoglobin in function, dilation, and energetics, and the role of cardiac troponin I in contractility. Furthermore, with a mouse model of myocardial infarction, the roles of the angiotensin II type 2 receptor, xanthine oxidase inhibitors, blood coagulation factor XIII, and inducible nitric oxide synthase in post-infarct function and remodeling have been further elucidated. Non-invasive in vivo MRI and MRS in mice provide a unique and powerful means for phenotyping genetically engineered mice and can improve our understanding of the roles of specific genes and proteins in cardiac physiology and pathophysiology.     

Matricellular proteins in cardiac adaptation and disease

The term matricellular proteins describes a family of structurally unrelated extracellular macromolecules that, unlike structural matrix proteins, do not play a primary role in tissue architecture, but are induced following injury and modulate cell-cell and cell-matrix interactions. When released to the matrix, matricellular proteins associate with growth factors, cytokines, and other bioactive effectors and bind to cell surface receptors transducing signaling cascades. Matricellular proteins are upregulated in the injured and remodeling heart and play an important role in regulation of inflammatory, reparative, fibrotic and angiogenic pathways. Thrombospondin (TSP)-1, -2, and -4 as well as tenascin-C and -X secreted protein acidic and rich in cysteine (SPARC), osteopontin, periostin, and members of the CCN family (including CCN1 and CCN2/connective tissue growth factor) are involved in a variety of cardiac pathophysiological conditions, including myocardial infarction, cardiac hypertrophy and fibrosis, aging-associated myocardial remodeling, myocarditis, diabetic cardiomyopathy, and valvular disease. This review discusses the properties and characteristics of the matricellular proteins and presents our current knowledge on their role in cardiac adaptation and disease. Understanding the role of matricellular proteins in myocardial pathophysiology and identification of the functional domains responsible for their actions may lead to design of peptides with therapeutic potential for patients with heart disease.     

Effects of 2,3-butanedione monoxime on cross-bridge kinetics in rat cardiac muscle

The effects of 2,3-butanedione monoxime (BDM) on isometric force and myofibrillar adenosine 5′-triphosphatase (ATPase) activity were studied in skinned cardiac trabeculae from the rat. ATP hydrolysis was enzymatically coupled to the breakdown of reduced nicotinamide adeninedinucleotide (NADH). The NADH concentration was monitored photometrically. Measurements were performed at a sarcomere length of 2.1 μm, 20 °C and pH 7.0. Without BDM, isometric force was 45 ± 3 kN/m² and the isometric ATPase activity 0.49 ± 0.04 mM/s (mean ± SEM, n = 31). Force gradually decreased as a function of [BDM] to 2.8 ± 0.4% at 100 mM BDM. ATPase activity was also depressed by BDM, but to a lesser extent than force. BDM therefore has a marked effect on myofibrillar tension cost. The rate of tension redevelopment after unloaded shortening decreased from 29 ± 2 s⁻¹ (n = 10) without BDM to 22 ± 1 s⁻¹ (n = 5) at 20 mM BDM. These results, modelled in a two- and three-state scheme of cross-bridge interaction, indicate that, in cardiac muscle, BDM not only affects cross-bridge formation but, especially at high concentrations (≥ 20 mM), also causes a marked increase in the apparent rate of cross-bridge detachment. Received: 27 October 1995/Received after revision: 24 January 1996/Accepted: 30 April 1996