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Biomedical subjects

A Valerio

Publications and source records attributed to A Valerio.

At least 73 records · Page 4Linked to original sources
PubMed1992

Leucine and phenylalanine kinetics during mixed meal ingestion: a multiple tracer approach.

To estimate whole body and splanchnic metabolism of dietary amino acids, phenylalanine and leucine kinetics were determined simultaneously in six normal volunteers before and during the constant administration of a complete mixed meal, employing multiple tracers of these amino acids. L-[5,5,5-2H]leucine and L-[2,6-3H]-phenylalanine were infused intravenously; L-[1-13C]leucine and L-[1-14C]phenylalanine were administered orally with the meal. During the meal, steady-state leucine concentration rose from 136 +/- 6 to 190 +/- 14 mumol/l (P less than 0.01), phenylalanine from 44 +/- 4 to 61 +/- 6 mumol/l (P less than 0.01), total leucine rate of appearance (Ra) from 1.29 +/- 0.03 to 1.77 +/- 0.07 (P less than 0.01, +37 +/- 3%), and phenylalanine Ra from 0.73 +/- 0.05 to 0.80 +/- 0.07 mumol.kg-1.min-1 (P less than 0.05, +8 +/- 3%). Splanchnic uptake of dietary phenylalanine was greater (P less than 0.001) than that of leucine (58 +/- 4 vs. 25 +/- 4%, respectively), 44 +/- 3% of circulating leucine derived from the diet vs. 20 +/- 2% of circulating phenylalanine (P less than 0.01). Endogenous leucine and phenylalanine Ra were significantly suppressed (P less than 0.05). In summary: 1) splanchnic uptake of dietary phenylalanine is onefold greater than that of leucine; 2) dietary contribution to systemic phenylalanine Ra is about half of that to leucine Ra; and 3) endogenous appearance of both leucine and phenylalanine after the meal is suppressed. In conclusion, splanchnic metabolism of dietary leucine and phenylalanine differs markedly and can be quantitated in vivo without catheterization.

Adult↗
PubMed1992

Ketone body metabolism in NIDDM. Effect of sulfonylurea treatment.

We assessed the metabolism of the two KBs, AcAc and 3-BOH; the relationships between ketogenesis and FFA inflow rate; and the effect of chronic sulfonylurea treatment in mild NIDDM patients (plasma glucose less than 10 mM). We studied 10 nonobese NIDDM patients in a crossover, randomized, double-blind, placebo-controlled fashion. Each patient was studied 4 times: after a run-in period with placebo, after 3 mo of placebo treatment, after 3 mo of glibenclamide treatments, respectively, and after 3 mo of sulfonylurea treatment during an acute exogenous Intralipid infusion. Ten normal, nondiabetic subjects served as the control group. Glibenclamide treatment decreased plasma FFAs. When these substrates were exogenously increased, plasma FFAs were comparable with placebo and baseline concentrations. In NIDDM patients, baseline and placebo blood total KB concentration was significantly higher than in control subjects (216 +/- 22 and 244 +/- 25, respectively vs. 127 +/- 18 microM; P less than 0.01). Glibenclamide treatment significantly decreased total KBs to 177 +/- 19 microM (P less than 0.05). When FFAs were exogenously increased, total KBs were similar to the placebo and baseline period. In the baseline study, the AcAc/3-BOH ratio was 0.72 +/- 0.06 in control subjects, whereas in NIDDM patients, the ratio was 1.61 +/- 0.13 at baseline (P less than 0.001 vs. control subjects), 1.66 +/- 0.15 during placebo, 1.57 +/- 0.09 during glibenclamide (NS vs. baseline), and 1.51 +/- 0.23 during glibenclamide plus placebo FFAs. Both the AcAc interconversion rate to 3-BOH and the 3-BOH interconversion rate to AcAc were significantly lower in NIDDM patients than in control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

[Thrombolytic therapy in acute myocardial infarct].

The benefits, main pharmacological characteristics, indications, side effects and time limits for use of thrombolytic agents in acute myocardial infarction are reviewed. The authors also point out the strategies to follow in patients after thrombolytic therapy.

Age Factors↗
PubMed1991

Various Ca2+ entry blockers prevent glutamate-induced neurotoxicity.

In the present study we investigated the effect of different Ca2+ entry blockers on the onset of neuronal damage induced by glutamate, kainate or alpha-amino-3-hydroxy-5-methyl-5-isoxazolo propionate (AMPA) in primary culture of rat cerebellar granule cells. We found that the dihydropyridine derivative, nifedipine used at 100 nM concentration, significantly counteracted the neuronal death induced by 15 min application of 50 microM glutamate. This effect was dependent on the presence of nifedipine before the exposure of granule cells to glutamate and was dose-related (IC50 = 10 nM). The nifedipine response was reproduced by isradipine and by verapamil with IC50 values of 9 and 100 nM, respectively. The activation of voltage sensitive Ca2+ channels elicited by 100 nM Bay K 8644, greatly enhanced glutamate-mediated neurotoxicity. Moreover, 100 nM isradipine was significantly active in blocking the neuronal death produced by 24 h exposure of cerebellar granule cells to 10 microM AMPA or 60 microM kainate. These results reveal a 'preventive' role of the Ca2+ entry blockers on the development of the neurodegeneration induced by overstimulation of various glutamate receptor subtypes.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1990

Age and glucose tolerance in healthy subjects.

An important and still controversial issue is the role played by the aging process itself in the metabolic alterations observed in aged people. We previously reported that a group of normal elderly people exhibited glucose disposal comparable to that of young controls. In the present study we investigated the effect of age on beta-cell secretion, by analyzing C-peptide measurements. Ten elderly men (E, 70 +/- 2 years) with normal oral glucose test and ten young subjects (Y, 27 +/- 1 years) with matching ideal body weight formed the study group. They were studied under highly dynamic conditions by means of a 0.3 g/kg i.v. glucose tolerance test. Fasting glucose and insulin were not different in the two groups (Y: 87 +/- 2 mg/di, E: 88 +/- 3, p greater than 0.1; Y: 50 +/- 7 pM, E: 36 +/- 7, p greater than 0.05). Glucose-insulin data set was analyzed by means of the minimal model of glucose disappearance which provided two parameters for every individual, yielding a quantitative description of glucose utilization: i.e., SI, the index of insulin sensitivity, and SG, the fractional glucose disappearance at basal insulin (glucose effectiveness). Both parameters were unaltered by age (SI = Y: 6.30 +/- 0.41 10(-4)min-1/(microU/ml), E: 7.11 +/- 0.72, p greater than 0.1; SG = Y: 0.020 +/- 0.003 min-1, E: 0.019 +/- 0.002, p greater than 0.1). C-peptide time course in elderly people was systematically lower than in the control group (basal levels: Y: 252 +/- 36 pM, E: 129 +/- 17, p less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1990

Very early nutrition supplementation in burned patients.

We studied some metabolic and hormonal effects of a very early nutrition supplementation in burned patients. The patients were divided into two groups of 10 patients each. Supplementation in the first group, the very early nutritionally supplemented (VENS) group, was started immediately after admission, ie, after 4.4 +/- 0.5 h (mean +/- SEM) from the injury; it was started after 57.7 +/- 2.6 h from the injury in the second group (control group). Hormonal and metabolic indices were recorded every 4 d up to 28 d. In the VENS group, the nitrogen balance became positive in 8.8 +/- 4.1 d whereas it took 24.1 +/- 6.9 d in the control group (p less than 0.05). Urinary catecholamine excretion and plasma glucagon concentrations were lower during the first 2 wk of observation in the VENS group compared with the control group. Insulin concentrations were significantly higher on the fourth and eighth days in VENS patients and plasma cortisol concentrations were similar in both groups.

Adult↗
PubMed1990

Reduced beta-cell secretion and insulin hepatic extraction in healthy elderly subjects.

One factor responsible for the altered carbohydrate metabolism in elderly subjects is impaired insulin release; however, difficulties in directly measuring insulin secretion have limited studies on pancreatic activity and on the contribution of the liver to insulin delivery. This study investigated beta-cell performance and insulin hepatic extraction under dynamic conditions in normal elderly subjects. Two strictly comparable groups of 12 young controls (Y, 27 +/- 1 (SE) years, 73 +/- 3 kg) and 12 elderly men (E, 69 +/- 2 years, 73 +/- 3 kg) were chosen on the basis of normal OGTT and normal insulin sensitivity in order to investigate a "pure" age effect. The subjects underwent a 4-hour frequently sampled intravenous glucose tolerance test (FSIGT) (dose 0.3 g/kg). Although no significant differences were found between the fasting levels of glucose and insulin (respectively: E: 89 +/- 3 mg/dL versus Y: 87 +/- 2, P greater than .1; and E: 5.0 +/- 0.5 microU/mL versus Y: 6.8 +/- 1.0, P greater than .05), basal C-peptide was found to be lower in the old subjects: 0.43 +/- 0.06 ng/mL versus 0.70 +/- 0.11 (P less than .025). The patterns of glucose and insulin during the FSIGT were similar, whereas C-peptide concentration in E was systematically lower, suggesting a reduced insulin secretion. To verify this hypothesis, we analyzed FSIGT data with a mathematical model-based method that provides a noninvasive direct measurement of the time courses of insulin secretion and hepatic extraction.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Impaired renal response to a meat meal in insulin-dependent diabetes: role of glucagon and prostaglandins.

The renal response to 100 g/1.73 m2 protein load in the form of a meat meal was studied in 19 normal subjects and 35 normoalbuminuric insulin-dependent diabetic patients (IDDs) under conditions of sustained euglycemia. The area under the glomerular filtration rate (GFR) curve rose above base line by 1,904 +/- 292 in normals and 502 +/- 237 ml/1.73 m2 in IDDs (P less than 0.01). The meat meal induced a greater increment in the area under the glucagon curve in normals (14,930 +/- 186 pg.ml-1.min-1) than in IDDs (7,227 +/- 67, P less than 0.01); similarly urinary excretion of prostaglandin E2 and 6-ketoprostaglandin F1 alpha rose by 119 and 98%, respectively, in normals but only by 2% (P less than 0.01 vs. normals) and 10% (P less than 0.01 vs. normals) in IDDs. The fractional albumin clearance rose by 102 and 251% in normals and IDDs, respectively. In five normal subjects indomethacin administration abolished the GFR, glucagon, prostaglandin, and albuminuric response to meat ingestion. Glucagon replacement under indomethacin treatment failed to restore these responses. In five diabetic patients, selected for having a flat glucagon and GFR response to a meat meal, replacement of glucagon to postprandial levels increased urinary vasodilatory prostaglandins and restored a normal GFR response. Thus in normal subjects renal vasodilatory prostaglandins appear to be the final effector of the renal hemodynamic and albuminuric response to a meat meal. The prostaglandin increase is likely to be mediated under physiological conditions by a glucagon rise, which, however, has no effect per se on renal hemodynamics.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Potassium channels involved in the transduction mechanism of dopamine D2 receptors in rat lactotrophs.

1. Radioactive rubidium (86Rb+) efflux was used to measure potassium (K+) permeability in a study designed to asses both the presence and the sensitivity to ions and drugs of the K+ channels in the plasma membrane of rat lactotrophs. 2. Rb+ efflux from Rb+-pre-loaded lactotrophs into nominally calcium-free solution containing 5 mM-K+ was linear from 1 to 60 s, with a calculated rate of about 0.1%/s. Raising K+ concentrations to depolarize the cells stimulated the Rb+ efflux (0.2%/s), which was already significant after 1 s of exposure of the cell to 100 mM-K+. This component of Rb+ efflux has been designated component V (sensitive to voltage and Ca2+ independent). 3. Addition of Ca2+ to 5 mM-K+ solution had no effect on resting Rb+ efflux (0.1%/s), but did further stimulate Rb+ efflux into K+-rich solutions. This component, which has been designated component C, was completely inhibited by 0.5 mM-cadmium. These data fit the view that the increase in intracellular Ca2+ concentration during depolarization opens certain (Ca2+-activated) K+ channels. 4. K+ efflux was differently affected by K+ channel blockers. Tetraethylammonium (TEA) inhibited both V and C components while 4-aminopyridine (4-AP) inhibited the component V without modifying the C component of Rb+ efflux. 5. Dopamine appears to affect both types of Rb+ efflux components. Dopamine increased the efflux of Rb+ in a nominally Ca2+-free medium containing 5 mM-K+ (component V). This effect was statistically significant 15 s after exposure of the cells to 10 nM-dopamine. Increasing the concentrations of K+ to gradually depolarize the cells enhanced the rate of increase of Rb+ efflux induced by dopamine, being evident in the initial 2-5 s of incubations. Dopamine also increased Rb+ efflux in a 5 mM-K+ solution containing 1 mM-Ca2+ (component C). This effect was rapid (2-5 s) and inhibited by 0.5 mM-cadmium. The combined action of dopamine on both component C and V caused the cells to be less sensitive to depolarizing concentrations of K+. The increase in Rb+ efflux and the enhancement of prolactin release induced by high concentrations of K+ were, indeed, prevented by exposure of the cells to 10 nM-dopamine. 6. The effects of dopamine on either component V or component C were pharmacologically characterized as D2 receptor mediated, being mimicked by selective D2 receptor agonists (quinpirole and RU 24213) and stereospecifically blocked by the D2 receptor antagonist sulpiride.(ABSTRACT TRUNCATED AT 400 WORDS)

4-Aminopyridine↗
PubMed1988

Dopamine D2 receptor stimulation inhibits inositol phosphate generating system in rat striatal slices.

Previous studies on the transduction mechanisms triggered by dopamine receptor stimulation have established that both D1 and D2 subtypes of dopamine receptors are linked to the adenylate cyclase system, the former in a stimulatory and the latter in an inhibitory manner. The present report provides the first evidence that stimulation of D2 receptors in rat brain tissue affects the turnover of polyphosphoinositides, as revealed by changes of the content of inositol phosphates. We found that the basal level of [3H]inositol trisphosphate, [3H]inositol bisphosphate and [3H]inositol monophosphate decreased following the stimulation of the D2 receptor. The rank order of potency was quinpirole (IC50 5 nM) greater than lisuride (IC50 8 nM) greater than RU 24213 (IC50 50 nM) greater than dopamine (IC50 200 nM). In contrast, selective D1 receptor stimulation by fenoldopam did not alter the inositol monophosphate, inositol bisphosphate and inositol trisphosphate content. The quinpirole effect was prevented by selective D2 antagonists, such as domperidone and L-sulpiride (both 5 microM) while it was unaffected by the selective D1 antagonist SCH 23390 (100 nM) and by the pharmacologically inactive D-isomer of sulpiride. Our data indicate that the activation of striatal D2 receptors leads to the inhibition of inositol phosphate production.

Animals↗
PubMed1988

Modifications of brain electrical activity after activation of the benzodiazepine receptor types in rats and rabbits.

The present study reports a comparative electroencephalographic (EEG) study of drugs belonging to different chemical classes which share the property to bind at benzodiazepine (BDZ) recognition sites. The EEG patterns are recorded from the neocortex of rats and rabbits as well as from dorsal hippocampus and red nucleus in rabbits after intravenous administration of diazepam (0.1-10 mg/kg), clonazepam (0.02-2.5 mg/kg), zopiclone (0.3-3 mg/kg), flunitrazepam (0.03-2.5 mg/kg), CGS 9896 (0.1-3 mg/kg), zolpidem (0.1-3 mg/kg) and Cl 218,872 (0.1-10 mg/kg). The most relevant differences are observed at the level of the neocortex. All drugs induced appearance of 7-12 Hz spindle bursts. On the contrary, the presence of 15-30 Hz waves (defined beta-like activity) mainly occurs after diazepam, clonazepam and zopiclone. Scarce beta-like activity is present after CGS 9896, zolpidem and Cl 218,872. According to the selectivity of these drugs for the various types of BDZ receptor, one can speculate that activation of BDZ2 is relevant for the appearance of the beta-like activity. Flunitrazepam, diazepam, and zolpidem increase the amplitude of the red nucleus waves. Such an effect is less marked after zopiclone and CGS 9896, whereas is almost absent after clonazepam and Cl 218,872. A reduction of the frequency is observed after flunitrazepam, diazepam, clonazepam, CGS 9896 and zolpidem, whereas it is almost absent after zopiclone and Cl 218,872. Finally, all drugs induce a reduction of the amplitude of the hippocampal theta rhythms, whereas after diazepam, flunitrazepam, zolpidem and CGS 9896 a slowing of the record also occurs.

Animals↗
PubMed1988

Electroencephalographic changes after short-term exposure to agonists of benzodiazepine receptors in the rat.

Naive rats receiving IV diazepam (10 mg/kg), flunitrazepam (2.5 mg/kg) and clonazepam (2 mg/kg) show electroencephalographic (EEG) changes consisting of lengthening of the spindle bursts (7-12 Hz; 200-300 microV) and appearance of 15-30 Hz waves (beta-like activity). These EEG manifestations are associated with signs of behavioral sedation (crouched, eyes open and myorelaxation) and stimulation (gnawing, running, ear twitches and sometimes wet-dog shakes), respectively. Bursts of 2-4 Hz waves can be occasionally observed associated with either marked sedation (lying down, eyes closed and presence of righting reflex) or sleep (stretched in the side with absence of righting reflex). Measurements of the periods spent by the animals in the two EEG patterns within the first hour after intravenous injection show the large preponderance of the spindle bursts over the beta-like activity. After the triazolopyridazine Cl 218,872 (10 mg/kg) the beta-like activity is almost absent, and in no case loss of the righting reflex can be observed. These agonists of BDZ receptors have been injected at the above reported doses for 5 days, once-a-day. At the 5th day, animals receiving diazepam exhibit a preponderance of the EEG and behavioral activation within the first hour after injection. Rats receiving flunitrazepam show a significant increase of the periods of stimulation and a slight decrease of the periods of sedation. These phenomena of "habituation" are absent in animals treated with clonazepam and Cl 218,872.

Animals↗
PubMed1988

A superfusion method for the study of calcium fluxes from pituitary cells.

This paper describes a superfusion technique that allows the study of calcium fluxes from a preparation of anterior pituitary cells. There is easy reproducibility, high sensitivity, controlled conditions that closely resemble those in vivo, possibility to operate sequential treatments on the same sample. These are some of the advantages of this method. An interesting application consists of the possibility of simultaneous measurement of calcium fluxes and hormone release.

Animals↗
PubMed1988

Insulin sensitivity and beta-cell responsivity are not decreased in elderly subjects with normal OGTT.

Glucose intolerance has been observed often in elderly subjects, but it is not yet clear whether this impaired metabolic state is due to the aging process itself or is secondary to the appearance of other age-related variables. This study attempts to elucidate the effect of age in itself on factors controlling glucose tolerance. Several metabolic parameters were measured in 10 young male controls (23-29 yr) and 17 nonhospitalized, healthy, nonobese, old (60-80 yr) male subjects. Insulin binding to circulating cells was performed along with the intravenous glucose tolerance test, and the data were analyzed by the minimal model method. This approach yields the following measures: tissue insulin sensitivity (SI), fractional glucose disappearance at basal insulin (glucose effectiveness, SG), and first (phi 1) and second (phi 2) phase beta-cell responsiveness to glucose. Insulin-binding capacity to monocytes and erythrocytes was respectively 6.03% +/- 0.57% and 5.96% +/- 0.53% (elderly), 5.97% +/- 0.39% and 5.36% +/- 0.57% (young); SI was 6.20 +/- 0.59 X 10(4) min-1/(microU/mL) (elderly) and 6.35 +/- 0.30 (young); SG was 0.016 +/- 0.002 min-1 (elderly) and 0.019 +/- 0.003 (young); phi 1 was 1.84 +/- 0.29 min-1 (microU/mL)/(mg/dL) (elderly) and 3.37 +/- 0.84 (young); phi 2 was 13.80 +/- 1.78 X 10(4) min-2 (microU/mL)/(mg/dL) (elderly) and 9.59 +/- 2.65 (young). These results show no change with aging of tissue insulin sensitivity and an intact beta-cell activity, suggesting that age per se does not contribute to the deterioration of glucose tolerance when the effect of other age-related variables, eg, obesity and physical inactivity, is precluded.

Adult↗
PubMed1988

Reduced in vivo biological activity of in vitro glycosylated insulin.

We evaluated the in vivo biological activity of in vitro extensively glycosylated insulin (GI) with the euglycemic-hyperinsulinemic glucose-clamp technique in postabsorptive nondiabetic subjects. Insulin-mediated glucose disposal was approximately 30% lower (P less than .03) with GI (9.2 +/- 1.2 mg.kg-1.min-1, mean +/- SE) than with the nonglycosylated hormone (12.6 +/- 0.7 mg.kg-1.min-1) at comparable plasma insulin concentrations (approximately 90 microU/ml). Binding of GI to a specific receptor on circulating cells (erythrocytes and monocytes) was normal. We conclude that in vitro extensive glycosylation of insulin reduces its biological activity in vivo, as reflected by insulin-mediated glucose disposal, probably at a postreceptor level.

Adult↗
PubMed1987

Ketone bodies increase glomerular filtration rate in normal man and in patients with type 1 (insulin-dependent) diabetes mellitus.

The purpose of this study was to investigate whether the administration of acetoacetic and hydrochloric acids in a group of control and Type 1 (insulin-dependent) diabetic patients influenced renal haemodynamics. Renal plasma flow increased from 657 +/- 88 to 762 +/- 81 ml X min-1. 1.73 m-2 in diabetic patients (p less than 0.01) and from 590 +/- 71 to 691 +/- 135 in control subjects (p less than 0.01). Glomerular filtration rate increased from 135 +/- 9 to 180 +/- 8 ml X min-1. 1.73 m-2 in diabetic patients (p less than 0.001) and from 117 +/- 8 to 145 +/- 7 in control subjects (p less than 0.01). Similar effects on renal haemodynamics, even if less pronounced, were observed with low dose acetoacetic but not with hydrochloric acid infusion. Total protein, beta 2-microglobulin but not albumin excretion rates were increased by acetoacetic acid. We conclude that an acute increase in blood concentration of ketone bodies within the range found in diabetic patients with poor metabolic control increases renal plasma flow and glomerular filtration rate both in control subjects and diabetic patients and causes a tubular proteinuria.

Acetoacetates↗