[Spectrophotometric findings on the amniotic fluid in prolonged pregnancy].
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Amniotic Fluid↗
Biomedical subjects
R Ferrari
Publications and source records attributed to R Ferrari.
Protective effect of propionyl-L-carnitine against ischaemia and reperfusion-damage.
Reperfusion of isolated rabbit heart after 60 min of ischaemia resulted in poor recovery of mechanical function, release of reduced (GSH) and oxidized glutathione (GSSG), reduction of tissue GSH/GSSG ratio and shift of cellular thiol redox state toward oxidation, suggesting the occurrence of oxidative stress. Pretreatment of the isolated heart with propionyl-L-carnitine (10(-7) M) improved the functional recovery of the myocardium, reduced GSH and GSSG release and attenuated the accumulation of tissue GSSG. This effect was specific for propionyl-L-carnitine as L-carnitine and propionic acid did not modify myocardial damage.
Animals↗
Relation between energy metabolism, glycolysis, noradrenaline release and duration of ischemia.
We studied the effect of 12-36 min of global ischemia followed by 36 min of reperfusion in Langendorff perfused rabbit hearts (n = 26). Metabolism was determined in terms of peak and total release of purines (adenosine, inosine, hypoxanthine), lactate and noradrenaline during reperfusion; and myocardial content of nucleotides (ATP, ADP, AMP), glycogen and noradrenaline at the end of reperfusion. An inverse relationship (r = -0.79) existed between duration of ischemia and developed pressure post-ischemia. Early during reperfusion, after 12 min of ischemia, the purine concentration (peak release) increased 100x (p < 0.01), that of lactate and noradrenaline 10x (p < 0.05). Total purine release rose with progression of the ischemic period (30x after 36 min of ischemia; p < 0.01), concomitant with a reduction in nucleotide content. Lactate release was independent from the duration of ischemia, although glycogen had declined by 30% (p < 0.01) after 36 min of ischemia. The acid insoluble glycogen fraction, which presumably contains proglycogen, increased substantially during short-term ischemia. Peak noradrenaline increased 100x, and 200x, (p < 0.05) after 24 and 36 min of ischemia, respectively. Total noradrenaline release due to various periods of ischemia mirrored its peak release. Function recovery was inversely related to total purine and noradrenaline efflux (both r = -0.81); it correlated with tissue nucleotide content (r = 0.84). In conclusion, larger amounts of noradrenaline are released only after a substantial drop in myocardial ATP. During severe ischemia ATP consumption more than limited ATP production by anaerobic glycolysis, is a key factor affecting recovery on subsequent reperfusion. In contrast to lactate efflux, purine and noradrenaline release are useful markers of ischemic and reperfusion damage.
Adenosine↗
Commentary on hibernating myocardium and its clinical relevance.
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Heart↗
Mitochondrial energy production and cation control in myocardial ischaemia and reperfusion.
In the heart mitochondria exert two roles essential for cell survival: ATP synthesis and maintainance of Ca2+ homeostasis. These two processes are driven by the same energy source: the H+ electrochemical gradient (delta microH) which is generated by electron transport along the inner mitochondrial membrane. Under aerobic physiological condition mitochondria do not contribute to the beat to beat regulation of cytosolic Ca2+, although Ca2+ transient in mitochondrial matrix has been described. Increases in mitochondrial Ca2+ of mumolars concentration stimulate the Krebs cycle and NADH redox potential and, therefore, ATP synthesis. Under pathological conditions, however, mitochondrial Ca2+ transport and overload might cause a series of vicious cycles leading to irreversible cell damage. Mitochondrial Ca2+ accumulation causes profound alterations in permeability of the inner membrane to solutes, leading to severe mitochondrial swelling. In addition Ca2+ transport takes precedence over ATP synthesis and inhibits utilization of delta microH for energy production. These processes are important to understand the sequence of the molecular events occurring during myocardial reperfusion after prolonged ischaemia which lead to irreversible cell damage. During ischaemia an alteration of intracellular Ca2+ homeostasis occurs and mitochondria are able to buffer cytosolic Ca2+, suggesting that they retain the Ca2+ transporting capacity. Accordingly, once isolated, even after prolonged ischaemia, the majority of the mitochondria is able to use oxygen for ATP phosphorylation. When isolated after reperfusion, mitochondria are structurally altered, contain large quantities of Ca2+, produce excess of oxygen free radicals, their membrane pores are stimulated and the oxidative phosphorylation capacity is irreversibly disrupted. Most likely, reperfusion provides oxygen to reactivate mitochondrial respiration but also causes large influx of Ca2+ in the cytosol as result of sarcolemmal damage. Mitochondrial Ca2+ transport is therefore stimulated at maximal rates and, as consequence, the equilibrium between ATP synthesis and Ca2+ influx is shifted towards Ca2+ influx with loss of the ability of ATP synthesis.
Adenosine Triphosphate↗
Commentary on myocardial stunning and its clinical relevance.
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Humans↗
Effect of D-600 on ischemic and reperfused rabbit myocardium: relation with timing and modality of administration.
In this study we have investigated the possibility that D-600, a phenylalkylamine calcium antagonist, protects the isolated rabbit heart against ischemia and reperfusion-induced damage. D-600 was either subcutaneously injected (2mg/kg, twice daily for 5 to 6 days) in the rabbit before isolation of the heart, or delivered to the isolated hearts in the perfusate (10(-7) M), either at the onset of ischemia and during reperfusion, or only during post-ischemic reperfusion. Ischemia (90 min) was induced by reducing coronary flow from 25 to 1 ml/min, followed by 30 min of reperfusion. Myocardial damage was determined in terms of mechanical function, release of creatine phosphokinase (CPK) and noradrenaline, mitochondrial function, calcium homeostasis, and endogenous stores of ATP and creatine phosphate (CP). Administration of D-600 to the rabbits or to the isolated hearts at the time of ischemia exerted protection. There are four groups of evidence in support of this conclusion: 1) the rise in diastolic pressure during ischemia was diminished with greater recovery of developed pressure during reperfusion; 2) CPK and noradrenaline release during reperfusion were reduced; 3) the oxygen consumption and ATP generating capacities of mitochondria were better maintained; and 4) associated with this preservation of mitochondrial function was the maintenance of near normal calcium homeostasis and of endogenous ATP and CP stores. The two different modalities of administration did not produce substantially different results. When administered to the isolated hearts after the ischemic period, D-600 failed to improve mechanical recovery and release of endogenous substances. However, it reduced mitochondrial calcium overload and improved ATP production. The mechanism of the protective effect of D-600 seems to be multiple: energy-sparing effect, reduction of the toxicity mediated by endogenous catecholamines, and direct inhibition of mitochondrial calcium transport.
Adenosine Triphosphate↗
No evidence of oxygen free radicals-mediated damage during the calcium paradox.
Reperfusion of an isolated mammalian heart with a calcium-containing solution after a brief calcium-free perfusion results in irreversible cell damage: the calcium paradox. We investigated whether the calcium paradox is associated with oxidative damage. We measured the tissue changes of glutathione status and the release of oxidized glutathione from isolated perfused rabbit hearts as indicators of cellular oxidative events. After 10 min of calcium-free perfusion, tissue content of reduced (GSH) and oxidized (GSSG) glutathione, and of protein and non-protein sulfhydryl groups were not significantly different from control values. Restoration of the calcium concentration resulted in an immediate and massive release of GSH and a depletion of tissue content of GSH, GSSG, and non-protein sulfhydryl groups. However, only a minimal release of GSSG into the coronary effluent was observed. In addition, the characteristic features of the calcium paradox were present: development of an irreversible contracture and massive release of creatine kinase. The calcium paradox did not lead to a decrease of the tissue content of protein sulfhydryl groups. These observations indicate that the calcium paradox is not associated with oxidative damage.
Animals↗
Particular outcomes of myocardial ischaemia: stunning and hibernation.
There are several potential outcomes of myocardial ischaemia. When ischaemia is severe and prolonged, irreversible damage occurs and there is no recovery of contractile function. When myocardial ischaemia is less severe but still prolonged, myocytes may remain viable but exhibit depressed contractile function. Under these conditions, reperfusion restores complete contractile performance. This type of ischaemia, leading to a reversible, chronic left ventricular dysfunction, has been termed hibernating myocardium. The difference between this condition and that described before, i.e. prolonged ischaemia, which results in further damage on reperfusion, is, most likely, related to residual coronary flow. In the hibernating myocardium, which is supplied by a narrow coronary artery, blood flow is not low enough to cause progression toward tissue necrosis, but it is low enough to cause intracellular changes and adaptative mechanisms which, in turn, are responsible for the down-regulation of myocardial contractility and for the preservation of viability. The level of underperfusion is sufficient to maintain aerobic metabolism of the quiescent myocardium as demonstrated by the absence of lactate and creatine phosphokinase releases. There are no doubts that revascularization is essential for hibernating myocardium, and the clinical goal to achieve is the possibility of accurately distinguishing viable from infarcted tissue. A third possible outcome of myocardial ischaemia is a post-ischaemic ventricular dysfunction or myocardial stunning. This term describes a transient mechanical dysfunction that persists on reperfusion after a short period of ischaemia, despite the absence of irreversible damage.
Animals↗
Tumor necrosis factor in congestive heart failure: a mechanism of disease for the new millennium?
Tumor necrosis factor alpha (TNF-alpha), a protein belonging to the family of cytokines, is one of the leading mediators of the immune response to inflammation. Its widespread biological effects are modulated by two circulating binding proteins corresponding to the extracellular domain of the membrane receptors, namely soluble TNF receptors. TNF-alpha was first supposed to be linked with congestive heart failure (CHF) on a cachexia-inducing basis. In patients with advanced CHF, elevated levels of circulating TNF-alpha and soluble TNF receptors have been found. The pathophysiological implications of activation of the TNF system in CHF seem to rely mainly on its effects on the heart and the endothelium. TNF-alpha exerts a negative inotropic effect both directly and indirectly, this latter being mediated by enhancement of nitric oxide production. Moreover, TNF-alpha has been suggested to trigger the apoptotic process in cardiac myocytes. There is consensus on the detrimental role played by TNF-alpha in CHF further supported by the evidence of a temporal association between TNF activation and transition from asymptomatic to symptomatic CHF.
Animals↗
Subunit and region-specific decreases in nicotinic acetylcholine receptor mRNA in the aged rat brain.
We have investigated possible changes in the mRNA levels for several alpha and beta subunits of the nicotinic acetylcholine receptor (nAChR) and the level of binding for nicotinic ligands in 7- to 32-month-old rats. Alpha4 and beta2, and to a lesser extent alpha6 and beta3, mRNA levels showed decreases between 20 and 30% at 29 months of age which in some areas reached 50% at 32 months of age. Alpha7 showed a small increase from 7 to 14 months and then a progressive decrease from 14 to 32 months down to the 7-month levels. 3H-epibatidine binding did not significantly change from 7 to 32 months of age in rat tel- and diencephalon. Binding in the substantia nigra was exceptional in that it showed a significant decrease starting from 23 months of age. 125I-alpha-bungarotoxin binding showed a pattern of change which roughly paralleled that of alpha7 mRNA. These findings show that an alteration in some steps of nAChR biosynthesis takes place during aging, which may be related to functional changes in nicotinic transmission.
Aging↗
Superoxide dismutase: possible therapeutic use in cardiovascular disease.
Superoxide dismutase (SOD) for parenteral administration is in clinical use in several European countries, where it is prescribed principally for treatment of musculoskeletal inflammation, especially osteoarthritis. However, new possibilities for its usefulness are arising from recent progresses of the pathophysiology of several diseases. From the beginning of this decade there has been a virtual explosion of the available informations about the mechanisms and control of free radical-mediated tissue injury. This progress has led us to the threshold of what will probably be broad clinical applications in the next future. Taking into account the mortality and morbidity caused by cardiovascular injury, the most promising application of SOD in human therapy seems to relay in the protection against ischaemia and post-ischaemic reperfusion damage of various organs and tissues but, particularly, of the myocardium. A large body of evidence suggests that myocardial damage following both global or regional ischaemia can be ameliorated by the blockade of free radical mediated injury. SOD has been proposed as a protective agent in various experimental models. The premises of this action, and the available results will be reviewed.
Animals↗
Comparison of two enteric coated microsphere preparations in the treatment of pancreatic exocrine insufficiency caused by cystic fibrosis.
BACKGROUND: Pancreatic exocrine insufficiency is a common condition in patients with cystic fibrosis. Large amounts of pancreatic enzyme supplements are required to reduce malabsorption but patient compliance is not always optimal. AIMS: To compare patients' preference and the efficacy of two enteric coated microsphere preparations in patients with cystic fibrosis. PATIENTS: Patients with pancreatic exocrine insufficiency due to cystic fibrosis. METHODS: Patients were assigned to the crossover treatment with Creon or Pancrease for 1 week and then to the alternative treatment. Patients had to follow a fixed diet (at least 2 g fat/kg) and had to assume 1000 units lipase/g fat. The evaluation parameters were: patients' preference, acceptance of therapy, stool fat excretion, stool weight, gastrointestinal symptoms, and tolerance. RESULTS AND CONCLUSIONS: Of the 33/60 patients who expressed a preference for one of the two treatments, 30 preferred Creon while only 3 patients preferred Pancrease (p<0.001). No difference between the two treatments was observed regarding stool characteristics, gastrointestinal symptoms and tolerance. The mean number of capsules taken daily was reduced by 35% with Creon. The results of this study showed a preference in favour of Creon probably due to the reduction of daily capsule intake of 35%, supporting digestion as well as Pancrease.
Adolescent↗
[Neonatal progeroid syndrome (Wiedemann-Rautenstrauch syndrome): case report and review of the literature].
The neonatal progeroid syndrome represents a complex of symptoms with unknown cause and pathogenesis. At 37 weeks of uncomplicated pregnancy a boy of non-consanguineous turkish parents was delivered by section. The weight of 1740 g and the length of 43 cm were striking, the circumference of the head was still within normal range. Further on the patient showed the diagnostic criteria of Wiedemann-Rautenstrauch syndrome: Beside growth failure and nearly absence of subcutaneous fat, old-looking face with hydrocephalic appearance, prominent scalp veins and sparse scalp hair, large hands and feet with long fingers and toes were found. Neonatal teeth didn't exist. But neonatal teeth are not always present in this syndrome. Among 19 published cases they were also not described in 6 cases (31.6%). Cataract was not found. A skin biopsy taken at the age of four months revealed an extremely thin dermis with pronounced rarefication of elastic material by light microscopy. On the electron microscopical level, no qualitative morphological aberrations or signs of degeneration were found, but normal although very small elastic fibres. With increasing age the appearance was nearly unchanged. In spite of high-caloric nutrition the increase of weight was not sufficient. The clinical symptoms of this patients were compared with the 19 already published cases of Wiedemann-Rautenstrauch syndrome. This shall be a contribution to the exact description of that extremely rare syndrome. We hope to facilitate, that hereby the differential diagnosis in difficult cases will be more easy. Because of heterogeneity it has to discuss if the Wiedemann-Rautenstrauch syndrome really represents a separate genetic entity within the group of premature aging syndromes.
Biopsy↗
[Follow-up of Spielmeyer-Vogt disease over 21 years].
Spielmeyer-Vogt-disease (juvenile neuronal ceroid-lipofuscinosis, Batten's disease) is one of a group of severe inherited neurodegenerative disorders called neuronal ceroid-lipofuscinosis, being characterized by accumulation of ceroid-lipofuscin within different organs of the body. A patient is described who developed visual, intellectual and motor deterioration as well as recurrent seizures during an observation period of 21 years. At the age of ten years vacuoles and "fingerprint-profiles" in lymphocytes and "fingerprint-profiles" beside "curvilinear bodies" in dermal cells lead to the diagnosis juvenile neuronal ceroid-lipofuscinosis. Clinical assessment of vision, intellect, language, motor function and epilepsy established a scoring system. The practicability of this scoring system is documented by the particularly poor clinical course of the disease over 21 years in our patient. Since there is no causal therapy the continuous care by the pediatrician for the whole family is of great importance.
Adolescent↗
Compensation and a psychiatric model of chronic pain.
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Attitude of Health Personnel↗
Effect of prenalterol on contractility, relaxation, and filling phase in coronary artery disease patients with previous myocardial infarction.
Twelve postmyocardial infarction patients, with angiographically proven asynergic areas, but without overt cardiac failure, were treated with prenalterol intravenously, (a new cardioselective inotropic agent) at a dose of 30 micrograms/kg. The aim of this study was to test the usefulness and safety of this new drug in postmyocardial infarction patients, monitoring systolic and diastolic acute hemodynamic changes. Significant improvement in cardiac contractility was demonstrated by the increase of ejection fraction (+23%), stroke volume index (+22%), cardiac output (+41%), positive dp/dt (+82%), and Vmaxd (+39%). Left ventricular systolic, mean aortic, and mean right atrial pressure remained unchanged; a slight decrease in end-diastolic volume index (-2%) occurred. A significant increase in heart rate (from 66 +/- 7 to 85 +/- 14 beats/min), without electrocardiographic changes or subjective complaints of angina pectoris, was observed. Segmental wall motion analysis showed an improved systolic shortening in normal (from 34 to 44%) and in asynergic areas (from 10 to 18%), whereas no changes were observed in dyskinetic areas. The relaxation and filling phase also improved, as tested by negative dp/dt (+39%), time constant of relaxation (-36%), and by indices of ventricular compliance. Side effects consisted of a slight feeling of tension in two patients and a short episode of ventricular tachycardia (5 beats) in another patients. No episode of angina pectoris was observed. These results, with special emphasis on lack of exacerbation of pre-existing ischemia (although obtained in patients without evident heart failure), suggest the potential usefulness of prenalterol in acute cardiac failure, as well as postmyocardial infarction low-output syndrome.
Adrenergic beta-Agonists↗
Exacerbation of chronic hepatitis D during interferon alpha administration.
Acute and severe impairment of liver function with jaundice and ascites occurred in two out of seven patients with chronic hepatitis D during interferon alpha administration (10 MU three times a week). Both of them were young women with histological diagnoses of moderate to severe chronic hepatitis and cirrhosis with no signs of portal hypertension. Only a slow and partial recovery was observed after interferon withdrawal. Autoantibodies against basal cell layer tested positive in these two patients. In the remaining five patients with hepatitis D who did not experience liver impairment during interferon administration, basal cell layer antibodies were found only in one case. We conclude that severe decompensation of liver cirrhosis related to hepatitis D may occur during interferon administration. Positivity of basal cell layer antibodies may be associated with the risk of developing such an adverse event but our data are not sufficient to prove this association.
Adult↗