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Biomedical subjects

M Capelli

Publications and source records attributed to M Capelli.

At least 73 records · Page 4Linked to original sources

Effects of iloprost (ZK 36374), a prostacyclin derivative, on platelet function after ischaemic exercise in patients with stable angina pectoris.

The effect of a chemically stable prostacyclin analogue (Iloprost) on platelet function was investigated in a controlled study in patients with angiographically confirmed stable angina pectoris after ischaemic exercise. In placebo experiments, ADP platelet aggregation was increased after exercise only when measured in whole blood and not in PRP. While plasma thromboxane B2 levels were unchanged, those of 6-keto PGF1 alpha were significantly although transiently increased after exercise. Iloprost displayed a potent antiaggregating activity in PRP and also reversed platelet hyperaggregation occurring in whole blood determinations after exercise. Plasma thromboxane B2 levels were significantly reduced but occasionally a rebound increase occurred 30 min. after end of the infusion. In contrast plasma level of 6-keto PGF1 alpha did not change after Iloprost and its recorded post-exercise increase was counteracted, thus suggesting a negative feed-back mechanism between Iloprost and natural prostacyclin. The data also suggest that degradation of the analogue is probably accomplished through pathways different from those of PGI2.

6-Ketoprostaglandin F1 alpha↗

Insulin resistance is the main determinant of impaired glucose tolerance in patients with liver cirrhosis.

To clarify the pathogenesis of impaired glucose tolerance in patients with cirrhosis, several factors possibly affecting carbohydrate metabolism were studied in 12 cirrhotic patients with different blood glucose responses to an oral glucose tolerance test. Glucose levels, 120 min after the load, were inversely and significantly related to insulin sensitivity, measured by means of the euglycemic "glucose clamp" technique (r = -0.746). Basal and glucose-induced insulin secretion (insulin and C-peptide levels) only slightly correlated with glucose tolerance, which was not related to functional liver cell mass (galactose elimination), portal-systemic shunting (degree of varices at endoscopy), or maximal glucose-independent insulin secretion (peak C-peptide levels after a glucagon test). Multiple regression analysis identified insulin sensitivity and liver cell mass as the independent variables able to explain most of the variance of 120-min blood glucose (about 84%), and both of them contributed considerably to the regression. While reduced insulin sensitivity is probably the main cause of impaired glucose tolerance, the reduced hepatocellular mass only appears to modulate the degree, and therefore the clinical relevance, of this defect.

Adult↗

Sex hormones in obese premenopausal women and their relationships to body fat mass and distribution, B cell function and diet composition.

We examined sex hormone blood concentrations in a group of 33 obese non-hirsute premenopausal women with normal menses and in 14 age-matched normal-weight controls, and evaluated their relationship with anthropometric parameters, dietary habits and insulin levels. Obese women showed lower than control sex hormone-binding globulin (24.9 +/- 14.6 vs 38.6 +/- 12.5 nmol/l; p less than 0.005) and 5 alpha-dihydrotestosterone (13.7 +/- 5.4 vs 18.2 +/- 4.8 ng/dl; p less than 0.005) values. Despite their consensual behavior, the correlation coefficient between 5 alpha-dihydrotestosterone and sex hormone-binding globulin was not significant in the obese while in controls it was 0.68 (p less than 0.01). This suggests that mechanisms operating to lower the plasma levels of these compounds may be regulated differently in obesity. Body Mass Index, per cent body fat and its distribution showed a highly significant negative correlation with sex-hormone binding-globulin and 5 alpha-dihydrotestosterone values. Insulin levels did not appear to be correlated with sex hormone values. On the contrary, in the obese women we found a highly significant correlation between dietary lipids and sex-hormone-binding-globulin levels (r = -0.54; p less than 0.005) and between dietary carbohydrates and estrone values (r = 0.47; p less than 0.005); all these relationships were independent of body weight. These results confirm that in premenopausal women obesity may be characterized by detectable changes in sex steroid metabolism and suggest a possible causal role not only of the excessive quantity of metabolically active adipose tissue but also of specific dietary factors.

Adult↗

Interrelationships between dietary carbohydrates, B cell function and rate of ketogenesis during underfeeding in obese patients.

Six matched groups of obese patients underwent 3-week selective hypocaloric regimens which consisted of a 240 or 480 kcal/day liquid formula diets for groups 1-4 and an 800 kcal/day conventional diet for groups 5 and 6. Carbohydrate intake ranged from 19 to 112 g/day so that for each energy level two different amounts of carbohydrates were administered. Body weight loss was similar in groups 1-4 and significantly lower in groups 5 and 6. During treatment fasting serum insulin (but not serum C-peptide) levels and the daily urine excretion rate of C-peptide showed quite a similar fall in all groups. Fasting glucagon levels did not change. The rate of ketogenesis which developed during each nutritional treatment was inversely related to the amount of dietary carbohydrates; moreover, a significant correlation was found between percent variation of ketoacids and those of fasting IRI (r = -0.42; p less than 0.01) and glucose (r = -0.52; p less than 0.01) concentrations, but not with those of fasting C-peptide and its daily urine excretion rate. In conclusion, it seems that during underfeeding (1) low- and high-carbohydrate-containing regimens are substantially equipotent stimuli secretagogues of insulin secretion, and (2) carbohydrate (or glucose) availability affects ketogenesis even through noninsulin-mediated mechanisms.

Adult↗

Effects of alpha 1-adrenergic blockade on pulsatile luteinizing hormone, follicle-stimulating hormone, and prolactin secretion in polycystic ovary syndrome.

Central noradrenergic mechanisms may participate in the regulation of pulsatile gonadotropin secretion in women with the polycystic ovary syndrome (PCO). To examine this possibility we measured serum LH, FSH, and PRL concentrations at 10-min intervals and total testosterone and 17 beta-estradiol at 60-min intervals for 8 h basally and during the infusion of the alpha 1-adrenoceptor antagonist thymoxamine (10 micrograms/kg X min) in 10 young women with PCO. Mean and integrated serum LH concentrations as well as LH pulse frequency were not significantly altered (P = NS) during the thymoxamine infusion. However, we found an increase in LH pulse amplitude as both net (P less than 0.002) and percent (P less than 0.002) increment, as well as mean LH peak values (P less than 0.05) during alpha 1-adrenergic blockade. There were no significant changes in pulsatile FSH and PRL secretion or gonadal sex steroids during these experimental conditions. These data suggest that in PCO patients, 1) brain noradrenergic mechanisms do not play a stimulatory role in regulating the frequency of pulsatile LH secretion, 2) central noradrenergic activity inhibits LH pulse amplitude, and 3) PRL and FSH pulsatility are not altered by central noradrenergic blockade.

Adolescent↗

Evidence for a physiological reduction in brain dopamine but not norepinephrine metabolism during the preovulatory phase in normal women.

To investigate the role of brain catecholamine (CA) activity in the mechanisms related to physiological ovulatory function, we used high-performance liquid chromatography with electrochemical detector to measure the levels of urinary dopamine (DA), norepinephrine (NE), epinephrine (E), vanillylmandelic acid (VMA), homovanillic acid (HVA), 3,4-dihydroxyphenylacetic acid (DOPAC), and total 3-methoxy-4-hydroxy-phenylglycol (MHPG) in a group of 12 normal women during both the early follicular and pre-ovulatory phases of the menstrual cycle. The mean (+/- SEM) concentrations of HVA and DOPAC were significantly lower (P less than 0.001) during the pre-ovulatory phase than during the early follicular phase, whereas those of DA, NE, E, VMA and total MHPG were unaltered. A significant negative correlation between urinary HVA and plasma LH (r = -0.70, P less than 0.01) was also found during the pre-ovulatory period, whereas no significant negative correlations were found between urinary HVA and plasma PRL, progesterone and oestradiol. These data show: 1) reduced brain DA activity and 2) unchanged brain NE activity at the time of the midcycle surge in normal women, suggesting a physiological variation of the central DA metabolism in ovulatory function.

3,4-Dihydroxyphenylacetic Acid↗

Investigation of insulin resistance associated with Werner's syndrome.

The tissue sensitivity to insulin and the metabolic clearance rate of insulin were evaluated in a new case of Werner's syndrome, by means of the euglycemic clamp technique using an artificial endocrine pancreas. The possible contribution of pancreatic insulin secretion and of reduced hepatic insulin breakdown to the peripheral hyperinsulinism was also studied by simultaneous determination of C-peptide and insulin levels and by analysis of the C-peptide/insulin molar ratio. The data obtained are consistent with the presence of marked insulin resistance and of reduced metabolic clearance rate of insulin in our patient, confirming what has been observed previously using other techniques. The finding of a reduced C-peptide to insulin ratio during the intravenous glucose tolerance test suggests that hepatic extraction of insulin could also be altered in Werner's syndrome, as found in several hyperinsulinism conditions, therefore contributing to peripheral hyperinsulinism.

Adult↗

Estimation of B-cell function by the urinary excretion rate of C-peptide in diabetic patients: comparison with C-peptide response to glucagon and to a mixed meal.

This study examined the relationship between the C-peptide response to intravenous glucagon and mixed meal stimulation and the 24 h urinary excretion rate of C-peptide and its urinary excretion during the glucagon test in nine control subjects, eighteen Type 1 (insulin-dependent) and twenty-two Type 2 (non-insulin-dependent) diabetic patients. Compared to controls (61.0 +/- 7.1 micrograms), the 24-h urine excretion rate of C-peptide was 8.2 +/- 3.1 micrograms (p less than 0.001) in Type 1 and 89.8 +/- 12.9 micrograms (p = NS) in Type 2 diabetic patients. C-peptide urinary excretion rate during the glucagon test was 6.92 +/- 1.11 micrograms, 0.42 +/- 0.10 microgram (p less than 0.001) and 6.47 +/- 1.13 micrograms (p = NS) respectively. Fasting serum C-peptide values were 1.53 +/- 0.16 ng/ml in controls, 0.42 +/- 0.09 ng/ml in Type 1 (p less than 0.0001) and 2.08 +/- 0.22 ng/ml in Type 2 diabetics (p = NS); C-peptide areas under the curve after glucagon stimulation were, respectively, 241.6 +/- 20.3 ng/ml, 29.2 +/- 5.9 ng/ml (p less than 0.0001) and 170.9 +/- 17.9 ng/ml (p less than 0.03) and after the meal test they were 204.7 +/- 15.6, 68.7 +/- 19.8 ng/ml (p less than 0.0001) and 265.5 +/- 32.9 ng/ml (p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Somatomedin-C levels related to gestational age, birth weight and day of life.

Capillary blood samples on filter paper were assayed by means of an RIA method (Kit Nichols Institute USA) from 1096 newborns divided into full term, preterm and small-for-date infants. The somatomedin-C (Sm-C) mean value, which did not differ in the three groups, was 0.15 +/- 0.09 IU/ml. One hundred and ten (10%) showed Sm-C disc values less than or equal to 0.075 IU/ml, the minimum value measurable by our method. The day of life and birth weight had a significant influence on Sm-C levels. Gestational age did not have any significant effect. No significant interaction was found among the parameters considered. All the groups presented a progressive increase of Sm-C. Unlike preterm and small-for-date infants, in full term infants the latter increase seemed already to be evident from 5th day of life and reached higher levels from the 7th day of life onwards. In conclusion, Sm-C rates were reduced in the neonatal phase of life, but showed a tendency to rise later.

Age Factors↗

Effects of obesity on gonadotropin secretion in patients with polycystic ovarian disease.

To investigate the interrelationships between body weight and gonadotropin secretion of polycystic ovarian disease (PCO), basal hormonal pattern and responses of gonadotropins and 17 beta estradiol (E2) to 25 micrograms (bolus) and 175 micrograms (4-h infusion) of synthetic luteinizing hormone-releasing hormone (LHRH) were studied in two age-matched groups of 18 obese (OB-PCO) and 18 normal-weight (NO-PCO) women suffering from the syndrome. Unlike other hormone levels, plasma LH and the LH/FSH ratio values were significantly higher (p less than 0.001) in NO-PCO than in OB-PCO females. Moreover, LH response to both stimuli was significantly greater in NO-PCO with respect to OB-PCO. No differences were found in FSH response, whereas E2 response was significantly higher (p less than 0.05) in the NO-PCO group during the continuous infusion test. These results emphasize the role of body weight in the development of PCO in obese females.

Adolescent↗

Effects of polyunsaturated fatty acids and prostaglandin synthesis on renal function.

The effects of polyunsaturated fatty acids (phosphatidylcholine) on renal function in healthy subjects and in patients with chronic renal failure, with liver cirrhosis, and with heart failure were studied. The drug was administered at 3.5 mg/kg i.v. (Linoleic acid 1.24 mg/kg). In all cases, the administration of the drug caused an increased excretion of sodium and especially of water with a reduction in basal urinary hypertonicity. The polyuria was caused by the higher glomerular filtration rate not being counterbalanced by an increase in tubular water reabsorption. The water reabsorption was mostly anisosmotic. The presence of urinary hypertonicity excluded an inhibition of ADH secretion by this drug. The sodium excretion was probably caused by an increase of the glomerular filtration rate whereas no significant changes in the tubular reabsorption of sodium were seen. We found a significant (p 0.05) increase in PGE2 urinary excretion after phosphatidylcholine administration. Lysine - acetylsalicylate injection after phosphatidylcholine, in other trials in the same patients, prevented the effects previously reported. Therefore we suggest that the effects of this drug are mediated by an increased availability of renal prostaglandins.

Aspirin↗

Relationships between growth factors (somatomedin-C and growth hormone) and body development, metabolic control, and retinal changes in children and adolescents with IDDM.

We used the radioimmunoassay (RIA) method to determine somatomedin-C (SmC) basal values in 59 diabetic children and adolescents (20 prepubertal and 39 pubertal subjects; age range 2.75-20.16 yr; duration of diabetes 0.08-15.83 yr) and in 274 control subjects. In comparing diabetic subjects with controls, we considered only those 50 diabetic subjects who were age matched with the controls, i.e., those not over 16 yr chronological age. SmC basal levels in pubertal diabetic patients were no different from those of pubertal age-matched control children, whereas in prepubertal diabetic patients SmC was significantly lower than in the respective control children (P less than .001). No correlation was found between the z score for SmC (i.e., the number of standard deviations each SmC level is from the age- and sex-normalized mean) and duration of disease, velocity standard deviation score, severity of fluoroangiographic retinal changes, basal C-peptide values and HbA1 levels. No differences were encountered in mean SmC and SmC z-score values in the separate groups of poorly, fairly, and well-controlled diabetic children, in the groups with and without residual pancreatic activity, and in the group with and without retinal changes. In 16 of the pubertal diabetics and in 15 pubertal controls, serum glucose, growth hormone (GH), and SmC concentrations were determined during the night. The integrated nocturnal secretion of SmC was no different in diabetics than in controls, whereas the integrated nocturnal secretion of GH was significantly (P less than .025) higher in diabetics than in controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Effects of somatostatin on plasma ammonia and amino acid profile during fasting and after protein feeding in cirrhotic patients.

The effects of somatostatin on fasting and absorptive plasma ammonia and amino acids were studied in 12 cirrhotic patients. They received a 6 h intravenous infusion of somatostatin (500 micrograms/h) or saline, starting 90 min before protein feeding. During the fasting period somatostatin significantly reduced plasma ammonia (-18%) and total tryptophan (-39%), increased plasma leucine (+19%), isoleucine (+17%), glutamine (+22%), glycine (+13%), arginine (+14%) and lysine (+12%), and prevented the significant fall of phenylalanine (-8%), tyrosine (-6%), alanine (-8%) and threonine (-9%) seen with saline. The percent changes in ammonia and glutamine concentrations were inversely correlated (r = -80; p less than 0.001) After protein ingestion, somatostatin slowed the maximal plasma increase in ammonia and alpha-nitrogens by at least two hours, but their total 5 h plasma response was not reduced, and even, in some instances, significantly increased (valine, leucine, glutamine, alanine and serine) with respect to saline. The results suggest that in fasting cirrhotics somatostatin reduces plasma ammonia, probably through an impaired intestinal ammoniogenesis from circulating precursors, and inhibits the disposal of branched chain, aromatic (except tryptophan) and gluconeogenic amino acids. Furthermore, it delays, but does not reduce, the plasma increase in nitrogen after protein ingestion.

Adult↗

Pancreatic beta-cell function in cirrhotic patients with and without overt diabetes. C-peptide response to glucagon and to meal.

To study the role of pancreatic beta-cell function in glucose intolerance and frank diabetes that sometimes develops in cirrhosis, the C-peptide response to a bolus IV injection of 1 mg of glucagon was measured in nine controls and in two groups of patients with cirrhosis. The first group comprised nine subjects with normal or high-normal fasting plasma glucose and no glycosuria; five of them had impaired glucose tolerance. The second group consisted of eight cirrhotics in whom frank diabetes had developed six to 48 months after the diagnosis of cirrhosis. They were characterized by fasting plasma glucose greater than 140 mg/dL and permanent glycosuria. No differences in the degree of liver impairment or portal-systemic shunting were observed between the two groups. Plasma glucose response to glucagon was similarly reduced in cirrhotic subjects. Basal C-peptide was high normal in patients with cirrhosis, and significantly increased in nondiabetic subjects. By contrast peak C-peptide levels and total C-peptide responses to glucagon were low normal in cirrhotics and significantly reduced in patients with cirrhosis and diabetes. In 14 patients the C-peptide response to a standard meal was also measured. It was significantly reduced in patients with cirrhosis and diabetes (six cases), as compared to cirrhotic subjects without diabetes. Peak C-peptide after IV glucagon significantly correlated with peak C-peptide after the meal (r = .927), or total C-peptide response to meal (r = .871). Impaired insulin secretion may add to insulin resistance in patients with liver cirrhosis, leading to the development of frank diabetes, characterized by fasting hyperglycemia and glycosuria.

Adult↗

Differences in somatomedin-C between short-normal subjects and those of normal height.

We evaluated basal somatomedin-C (SmC) levels in 98 subjects 2 to 16.6 years of age, with height less than 3rd centile (Tanner), and in 274 healthy controls 2 to 15.8 years, with height greater than 10th centile. Growth-retarded subjects were defined as short-normal when they had normal GH release (greater than 8 ng/ml) in at least one of three tests: arginine, L-dopa, and sleep. In control subjects, there was a significant positive correlation between SmC levels and chronologic age, bone age, and pubertal stage (pubic hair, breast or testicular volume). The same correlations were present in short-normal subjects, but SmC levels were significantly lower than in normal children. The percentage of subjects with very low SmC values (less than or equal to 0.25 IU/ml in those older than 6 years, and less than 0.1 IU/ml in those younger than 6 years) was higher in the short-normal group of children older than 6 years. In growth-retarded subjects, SmC values were significantly higher (P less than 0.005) in subjects with normal GH response in at least one of the two pharmacologic tests, compared with those with normal GH response only during sleep. We conclude that short-normal subjects have, on average, low SmC values, which might indicate insufficient GH release. Therefore, current criteria to define GH deficiency and children needing treatment may be too restrictive.

Adolescent↗