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Biomedical subjects

E Ferrannini

Publications and source records attributed to E Ferrannini.

At least 271 records · Page 15Linked to original sources
PubMed1976

Insulin kinetics after portal and peripheral injection of [125I] insulin: II. Experiments in the intact dog.

Insulin metabolism in man is usually investigated by peripheral injection of the hormone, whereas native insulin undergoes hepatic extraction prior to mixing in the general circulation. To quantify this difference, in 10 dogs [125I] insulin was injected into a peripheral vein, and the initial distribution volume (IDV), the metabolic clearance rate (MCR), and the mean transit time (t) were computed from the plasma disappearance curve of the immunoprecipitable activity. The splenic vein was then cannulated under pentobarbital anesthesia, and the parameters were again computed from the peripheral activity after portal introduction of the tracer. The MCR after portal injection [15.1 +/- (SE) 1.1 ml/min per kg] was greater (P is less than 0.001) than the MCR after peripheral administration (13.4 +/- 0.9 ml/min per kg). Also, IDV was larger (P is less than 0.01) after portal injection (167 +/- 12 vs. 138 +/- 10 ml/kg). Mean transit times did not change significantly. Insulin secretion rate (0.29 +/-0.04 mU/min per kg) and body insulin mass (7.03 +/- 1.5 mU/kg) were also measured. An estimate of hepatic extraction was obtained from the difference between the clearance rate values calculated following portal and peripheral injection. Under our experimental conditions, hepatic retention of insulin was found to be 19.6% (range 9.6-36.2%). The method is recommended for investigations in man.

Animals↗
PubMed1976

Evidence for suppressor cell activity associated with depression of contact sensitivity in Pseudomonas aeruginosa infected mice.

Pseudomonas aeruginosa infection depresses contact sensitivity to 2-phenyl-4-ethoximethylene-oxazolone (oxazolone), and enhances the antibody response to sheep erythrocytes (SRBC) in the mouse. Anti-oxazolone antibody titres were found not to be significantly different in infected and uninfected animals; thus, the major circulating classes of antibodies do not seem to be responsibile for the observed depression of skin reactivity. Low dose (20 mg/Kg) cyclophosphamide (CY) pretreatment induced a further potentiation of antibody response to SRBC, and prevented depression of contact sensitivity in infected mice. On the other hand, when infected animals were pretreated with high doses (200 mg/Kg) of CY, antibody production was completely suppressed, whereas contact sensitivity was unaffected. Since CY treatment is known to selectively inhibit B lymphocytes, and since it can abrogate the infection-induced depression of reactivity to oxazolone, it is suggested that suppressor cells, which may have B-cell characteristics, are stimulated during P. aeruginosa infection in the mouse.

Animals↗
PubMed1973

Effect of ischaemia on sensory potentials of normal subjects of different ages.

In 73 normal subjects, from 10 to 82 years of age, maximum orthodromic sensory nerve conduction velocity was measured in the median nerve before and during a 30 minute period of vascular occlusion. During ischaemia progressive slowing in conduction velocity, decrease in amplitude, and increase in duration of the sensory action potential evoked at wrist and elbow by supramaximal stimulation of digit III were observed. However, a statistically significant difference (P<0·05 to P<0·01) between subjects was noted by grouping them by age: the older the subject, the longer the persistence of sensory response and the less marked the slowing in conduction velocity. The mechanism of the phenomenon has been discussed in relation to a similar longer resistance to ischaemia found in peripheral nerves of diabetic and uraemic patients.

Action Potentials↗
PubMedDate not supplied

CD38 autoimmunity: recent advances and relevance to human diabetes.

Human CD38 is a protein which catalyzes the synthesis of nicotinic acid adenine dinucleotide (NAADP+) and the conversion of NAD+ to cADPR. Both cADPR and NAADP+ are powerful intracellular Ca2+ ([Ca2+]i) mobilizers in different cell types. Recently, the presence of CD38 autoantibodies has been found in a significant number (9-15%) of patients with Type 2 or long-standing Type 1 diabetes. These autoantibodies are biologically active, the majority of them (-60%) displaying agonistic properties, i.e., [Ca2+]i mobilization in lymphocytic cell lines and in pancreatic islets. In cultured rat pancreatic islets, the human autoantibodies inhibit glucose-induced insulin release, whereas, in human pancreatic islets CD38 autoantibodies stimulate glucose-mediated insulin secretion. The clinical phenotype of anti-CD38-positive Type 2 diabetes differs from the LADA (latent autoimmune diabetes of adults) phenotype. When accurately matched for age and obesity, only LADA patients with anti-GAD antibodies, but not GAD-negative/ CD38-positive patients, have reduced in vivo beta-cell function in comparison to antibody-negative patients. Transgenic mice overexpressing CD38 show enhanced glucose-induced insulin release, whereas, conversely, CD38 knockout mice display a severe impairment in beta-cell function. Few Japanese diabetic patients carry a missense mutation in the CD38 gene; in Caucasian patients mutations in the CD38 gene have not been found. Collectively, these findings suggest that activation of CD38 represents an alternative signaling pathway for glucose-induced insulin secretion in human beta-cells. More information, however, is necessary to gauge the role of CD38 autoimmunity in the context of the natural history of human Type 1 or Type 2 diabetes.

ADP-ribosyl Cyclase↗
PubMedDate not supplied

Myocardial metabolism in ischemic heart disease: basic principles and application to imaging by positron emission tomography.

The human heart in the fasting state extracts FFA, glucose, lactate, pyruvate, and ketone bodies from the systemic circulation. Of these substrates, FFA utilization accounts for the greater part of oxygen consumption and energy production. The oxidative use of lipid (FFA) and carbohydrate (glucose and lactate) fuels is reciprocally regulated through the operation of Randle's cycle. Feeding, by increasing both insulin and glucose concentration, shifts myocardial metabolism towards preferential carbohydrate usage, both for oxidative energy generation and for glycogen synthesis. During conditions of reduced oxygen supply, the oxidation of all substrates is decreased while anaerobic metabolism is activated. In patients with coronary artery disease and stable angina pectoris, lactate release in the CS can be demonstrated during pacing stress. However, this occurs in only 50% of patients, and no relationship can be demonstrated between lactate production and the severity of ischemia. In patients with chronic angina, a significant release of alanine in the CS and an increased myocardial uptake of glutamate could be demonstrated at rest and following pacing. These two phenomena result from increased transamination of excess pyruvate to alanine with glutamate serving as NH2 donor. In addition, release of citrate (a known inhibitor of glycolysis) in the CS can be demonstrated following pacing in patients with stable angina. The introduction of PET has made it possible to study regional myocardial perfusion and metabolism in humans noninvasively. Two basically different patterns of myocardial glucose utilization have been observed in patients with coronary artery disease studied at rest using 18F-flurodeoxyglucose. In patients with stable angina on exercise but studied at rest, regional myocar- dial glucose utilization was homogeneously low and comparable with that of a group of normals. In contrast, in patients with unstable angina, myocardial glucose utilization at rest was increased even in the absence of symptoms and ECG signs of acute ischemia. In patients with stable angina, a prolonged increase in glucose uptake could be demonstrated in the post-ischemic myocardium in the absence of perfusion abnormalities, and a state of chronic metabolic ischemia is proposed. PET imaging has also allowed prospective differentiation between viable and nonviable segmental function in patients with recent myocardial infarction and in those undergoing coronary artery surgery; in both cases viable segments have relatively maintained glucose uptakes, whereas nonviable segments have depressed glucose uptakes.

Angina Pectoris↗
PubMedDate not supplied

Parental history of diabetes is associated with increased cardiovascular risk factors.

Serum insulin concentrations are higher in persons with a positive parental history of diabetes than in persons without such a history. Since hyperinsulinemia is associated with both an increased prevalence of hypertension and an atherogenic pattern of serum lipids and lipoproteins, we hypothesized that among nondiabetic persons, a parental history of diabetes would be associated with an atherogenic pattern of cardiovascular risk factors. In the San Antonio Heart Study, a population-based study of cardiovascular disease and diabetes, we examined 549 nondiabetic persons with a parental history of diabetes and 1167 nondiabetic persons without such a history. Compared to persons without a parental history of diabetes, those with such a history had a more atherogenic pattern of cardiovascular risk factors, including higher body mass index, higher systolic and diastolic blood pressures, higher serum insulin and triglyceride concentrations, and lower levels of high density lipoprotein cholesterol. After adjustment for serum insulin concentration, body mass index, and waist-to-hip ratio, the differences in lipids, lipoproteins, and blood pressure between the two parental history groups were no longer statistically significant. Since persons with a parental history of diabetes are more likely to be prediabetics, the present results suggest that prediabetics have an increased risk of coronary heart disease even before they become diabetic. This phenomenon may help explain why the duration of clinical diabetes is only weakly associated with the risk of coronary heart disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Anthropometry↗
PubMedDate not supplied

Inadvertent catheterization of the internal thoracic vein mimicking pulmonary embolism: a case report.

Although aberrant locations are typical complications of central venous catheterization, the right internal thoracic vein (mammary vein) is an exceptional one. A case of this unusual aberrant location occurring after right internal jugular venous cannulation for total parenteral nutrition, is described. This aberrant position caused signs and symptoms resembling pulmonary embolism. This is the first known description of the symptoms induced by the infusion of parenteral solution into the right internal thoracic vein.

Adult↗
PubMedDate not supplied

Conventional electromyography in myotonic dystrophy.

In 31 subjects of 23 different families with unequivocal signs and symptoms of myotonic dystrophy EMG was performed with conventional technique on brachial biceps, extensor digitorum communis and tibialis anterior muscles. In 14 of these patients motor and orthodromic sensory conduction velocities were measured in median nerve as well. During full muscular effort, an interference pattern of low amplitude was seen in most of the explored muscles, while "after discharge" of different duration was present in 57-83% of the patients. At weak effort, mean potential duration was nearly always significantly reduced if polyphasic potentials were not included in the calculation; polyphasic potentials, however, exceeded the limits of normal incidence and their duration was longer than that of motor unit potentials of simple shape. At rest, spontaneous activity of short duration and positive sharp waves occurred in about 50% of the patients, but rarely in more than two places. Bursts of myotonic or pseudomyotonic discharges occurred either spontaneously or mechanically in all subjects. Conduction velocity along motor, or sensory, peripheral nerve fibres was constantly within normal values. Results were discussed in relation to the hypothesis of a primary neuronal pathogenesis of muscle wasting, and the conclusion was that nerve changes are to be considered as a collateral disorder dependent on the pleiotropic action of the gene.

Adolescent↗
PubMedDate not supplied

Sympathetic activation and muscle spindle.

An adrenergic central control on fusimotor activity has been demonstrated since 1954. At peripheral level, a muscle spindle autonomic innervation is not clearly demonstrated in man, but several data seem to suggest a direct autonomic innervation of muscle spindle in cats and rabbits. Data obtained in patients with peripheral adrenergic denervation (Idiopathic Orthostatic Hypotension) suggest a prevalent control of central adrenergic pathways on muscle spindle sensitivity.

Blood Pressure↗