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Biomedical subjects

A V Greco

Publications and source records attributed to A V Greco.

At least 19 recordsLinked to original sources

Lower limb arterio-venous shunts, autonomic neuropathy and diabetic foot.

We have quantitatively assessed the percentage of lower limb arterio-venous (a-v) shunting using a radioisotopic technique and correlated it with autonomic neuropathy evaluated by cardiovascular tests. We have studied three groups of diabetic patients: Group A, 12 non-neuropathic subjects without foot lesions; Group B, 12 neuropathic subjects without foot lesions; Group C, 12 neuropathic subjects with recurrent foot ulcers. Shunting was higher in Group C (10.4 +/- 2.7%) than in Group B (6.8 +/- 2.3%, P less than 0.01) and Group A (3.8 +/- 1.2%, P less than 0.001). Shunts in Group B were higher than in Group A (P less than 0.05). All the tests exploring autonomic function were more impaired in Groups B and C than in Group A, with no difference between Groups B and C. A direct correlation was found between a-v shunting and the following cardiovascular tests: postural hypotension (PH) (r = 0.41, P less than 0.02), sustained handgrip (SH) (r = 0.56, P less than 0.001), deep breathing (DB) (r = 0.40, P less than 0.005) and lying to standing (LS) (r = 0.44, P less than 0.01). A positive correlation was also found between a-v shunts and duration of the disease (r = 0.62, P less than 0.001). Arterio-venous shunting was found to be directly related to autonomic neuropathy even if the higher shunting found in the patients with foot ulcers was not related to a higher degree of autonomic involvement; in addition, this group of patients was characterized by having a more advanced sensory and motor neuropathy. In conclusion, autonomic neuropathy, through its influence on a-v shunts, may play a role in the pathogenesis of diabetic foot, but peripheral neuropathy probably plays a key role in conditioning the development of the overt clinical manifestations of diabetic foot.

Albuminuria

Metabolic effects and disposition of sebacate, an alternate dicarboxylic fuel substrate.

Disodium sebacate is a 10-carbon-atom dicarboxylic acid, proposed as substrate for parenteral nutrition. We investigated its pharmacokinetic profile and thermogenic effect during a short-time infusion (5 h at 10 g/h) in 7 male volunteers. Sebacate in serum and urine was measured by high-performance liquid chromatography. A single-compartment model with two linear elimination routes was fitted. Metabolic measurements (VO2, VCO2, respiratory quotient, metabolic rate) were continuously performed for 8 h (5 h during and 3 h after the infusion) by a canopy indirect calorimeter. The apparent volume of distribution of sebacate was 8.39 +/- 0.69 liters, and the plasma fractional removal rate constant was 0.0086 +/- 0.00077 min-1. The average half-life and plasma clearance were 80.6 min and 72 ml/min, respectively. The increase in metabolic rate, the decrease in respiratory quotient and the changes in ketone body, glucagon and insulin levels during the infusion were not significant. 24-hour catecholamine excretion was within normal limits. Calories administered by sebacate seem to be available for utilization without relevant metabolic side effects.

Adult

Tracer study of metabolism and tissue distribution of sebacic acid in rats.

The present study investigates the metabolic disposition of sebacic acid in rats. Three groups of experimental animals received different doses of disodium sebacate with 25 microCi of 14C-labeled molecule by intravenous injection. In the first group radioactivity plasma elimination curves were examined for two administered doses (80 and 160 mg). In the second group, expired 14CO2, urine tracer and feces tracer were counted after intravenous administration of 160 mg of sebacate. The animals of the third group were sacrificed at different times after intravenous administration of 160 mg of sebacate, and tracer elimination curves were obtained for several organs. The plasma half-life of sebacate is 38.71 min; about 35% of the administered tracer was excreted in the urine as unchanged sebacate; about 25% was eliminated as 14CO2 in expired air. Disposition of sebacate was complete within 4 h of administration. The sebacate half-life is longest in adipose tissue (135 min) and in liver (74 min), sites of likely transformation. In all other organs examined, the sebacate half-life is similar to that in plasma.

Absorption

Nonselective loss of contrast sensitivity in visual system testing in early type I diabetes.

OBJECTIVE: Psychophysical methods in patients with diabetes mellitus reveal deficits of central or foveal vision. Our aim was to evaluate the contrast-sensitivity thresholds in 24 insulin-dependent (type I) diabetic patients with a short disease duration and without retinopathy, taking into account metabolic control. RESEARCH DESIGN AND METHODS: The control group consisted of age-matched nondiabetic subjects. None had visual or systemic symptoms. Contrast sensitivity measured at eight different spatial frequencies to sinusoidal bar patterns of 0.6-12.2 cycles/deg can detect functional defects in the spatially sensitive retinal ganglion cells or in higher visual pathways. We performed two different temporal types of contrast-sensitivity testing, dynamic (8 Hz) and static (0 Hz). RESULTS: Significant losses with dynamic contrast-sensitivity test at all but the highest spatial frequencies (i.e., 12.2 cycles/deg) were shown, whereas there was significant attenuation of contrast sensitivity at five spatial frequencies (1.0, 1.4, 2.2, 7.1, and 9.6 cycles/deg) in the static mode. Grating losses (less than 2SD of control means) of contrast sensitivity were found in 33.3% (dynamic) and in 72.9% (static) of eyes of diabetic patients. HbA1c values were positively correlated at variable spatial frequencies (1.0, 1.4, and 2.2 cycles/deg for dynamic test and 0.6, 1.0, 1.4, 2.2, 4.8, and 7.1 cycles/deg for static test). CONCLUSIONS: Our results suggest an early, generally nonselective neuronal damage of visual pathways that occurs before the onset of clinically detectable retinopathy. The visual deficit may be related directly to the effects of diabetes; repetitive minor hypoglycemic insults may contribute more than a marked hyperglycemic condition to the mechanisms underlying physiological changes along the optic nerve.

Adult

[Lactic acidosis, hyperamylasemia, and phenformin].

Phenformin is still used in the therapy of non-insulin dependent diabetes in association with sulphonylureas. The controindications to the use of this drug often are not kept in due consideration. It is therefore often possible to observe cases of irreversible lactic acidosis with lethal outcome. In this paper, three cases of lactic acidosis from phenformin administration are reported. Some characteristics of this clinical picture are underscored: accompanying ketoacidosis, hyperamylasemia. On the basis of their observation, the Authors conclude that those diabetic patients who can be treated with diet alone or with diet and sulphonylureas must not be treated with phenformin. Metformin is then proposed as a more flexible and safer drug.

Acidosis, Lactic

Analysis of serum conjugated bile acids by high performance liquid chromatography and mass spectrometry.

A high performance liquid chromatography (HPLC) mass spectrometry (MS) system for the analysis of glycine and taurine conjugated bile acids in human fasting and postprandial sera is described. Following purification on thin layer chromatograms conjugated bile acids were separated in a RP-18 5 microns column with methanol 0.02 M KH2PO4 buffer pH 5.10 as the mobile phase at a flow rate of 1 ml/min and assayed by direct injection MS. The bile acid fractions were assayed by MS. The amounts of conjugated bile acids in the postprandial sera of 15 subjects with normal liver function were significantly higher (p less than 0.05) than in fasting ones and the glycine/taurine ratio was about 1 for both. The method is better suited for a specific research area in experiments requiring a high level of accuracy.

Adult

Effects of insulin on hepatic lipid synthesis in alloxan diabetic rats.

In vitro hepatic synthesis of lipids starting from 1-(14)C-acetate was studied in rats made diabetic by subcutaneous alloxan administration (175 mg/kg b.w.). A second group of diabetic rats was treated with lente insulin. In the alloxan-treated rats, a decrese was observed in hepatic incorporation of 1-(14)C-acetate into phospholipids, triglycerides and esterified cholesterol; there was an increased incorporation into nonesterified fatty acids (NEFA) and free cholesterol. Insulin administration restored lipid synthesis values to normal. On histologic examination, an intranuclear glycogenesis was observed in the hepatocytes of the alloxan-treated rats, along with severe hepatic necrosis; the latter however, only in rats sacrified on the 3rd day. Hepatic steatosis with small, medium and large droplets was present in the insulin-treated rats; signs of cellular degeneration were less evident.

Animals

Glucose, insulin and somatostatin infusion for the determination of insulin resistance in liver cirrhosis.

Twelve patients with liver cirrhosis and ten normal subjects were studied. Using a constant intravneous infusion of glucose, insulin and somatostatin over 2 1/2 hours we determined the stteady state plasma glucose level (SSPG) in order to measure insulin resistance. The results demonstrated that the cirrhotic patients were insulin resistant compared to normals and that plasma glucagon does not account for the insulin resistance in these patients.

Adult

Early insulin and glucagon response to subsequent pulses of arginine, glucose, and tolbutamide in normal man.

To determine the dynamics of insulin and of glucagon secretion in response to several sequential stimuli administered shortly after an arginine pulse (5 g), 20 nonobese, apparently healthy volunteers were given arginine (5 g), glucose (5 g), and tolbutamide (1 g) by rapid intravenous injection. The early insulin and glucagon area 0-8 min was studied. At the intervals and with the dosages used in this study, different stimuli with and without prestimulation with arginine did not lead to changes in early secretion of insulin. There was no exhaustion of the pool of insulin released after multiple sequential pulses. These results suggest a pattern in which stimulation induces a rapid release of insulin and activates the interchange between the stored and labile insulin pool; the 8-min interval is sufficient for the rapid return of the two compartments to a state of equilibrium. Also for glucagon, subsequent different stimuli did not exhaust glucagon release; nevertheless, glucagon is immediately suppressed by a submaximal glucose pulse.

Adolescent

GH secretion in open-angle glaucoma.

Open-angle glaucoma is frequently observed in patients with acromegaly suggesting that the somatotropic hormone might facilitate a condition of glaucoma. The open-angle glaucoma patients studied, displayed higher plasma human growth hormone (HGH) levels than control subjects 60 min (30.3 +/- 1.7 against 16.8 +/- 2.7 ng/ml; p less than 0.001) and 90 min (19.0 +/- 1.9 against 9.3 +/- 1.2 ng/ml; p less than 0.001) after intravenous administration of arginine (25 g in 30 min). The authors support the hypothesis that the increased plasma HGH level may interfere with the regulation of ocular pressure by modifying the flow of aqueous humor from the eyeball via changes in the sclero-corneal trabecular meshwork; these changes are also found in diabetic subjects. The interplay between HGH and changes of carbohydrate metabolism (frequently occurring in glaucomatous patients) may be at the root of the variations of intraocular pressure in open-angle glaucoma.

Arginine

The effect of food intake on insulin receptor in man.

Insulin binding to circulating monocytes was studied in 22 normal volunteers before and 1, 3 and 5 h after a 1400 Kcal meal. Results indicate that 3 h after food intake there is an increase in the specific cell binding fraction (P less than 0.001) with a change in receptor affinity. Data emerging from the present study demonstrate that there are rapid changes in insulin receptor properties during the day. These changes probably play a role in the regulation of the hormonal and metabolic pattern in normal subjects.

Adult

Gastrin response to insulin in patients with cirrhosis of the liver.

Fasting gastrinemia in cirrhotics (48.35 +/- 2.77 pg/ml) was higher than in normal controls (32.93 +/- 0.75 pg/ml; P less than 0.001). After insulin-induced hypoglycemia, the mean increase of gastrin above basal level was 42.29 +/- 1.92 pg/ml in controls and 10.85 +/- 5.05 pg/ml in cirrhosis (P less than 0.001). BAO was 2.53 +/- 0.36 mEq/h in controls and 0.42 +/- 0.004 mEq/h in cirrhotics (P less than 0.001). After i.v. insulin, TAO was 8.42 +/- 0.72 mEq/h in controls and 3.06 +/- 0.26 mEq/h in cirrhotics (P less than 0.001). The authors suggest that the lack of an adequate gastrin and acid response to the hypoglycemic stimulus in cirrhotics might be accounted for by a decreased insulin sensitivity.

Adult

Serum gastrin in portal and peripheral veins after arginine in man.

Immunoreactive serum gastrin from portal and peripheral veins was determined in five controls and in five cirrhotic patients with indwelling portal catheters in basal conditions, during and after 30 min arginine infusion, in order to assess whether the human liver is involved in gastrin metabolism. A significant difference was found between portal and peripheral gastrin concentrations in controls at 0, 60 and 90 min; no significant differences were found in cirrhotics. Our findings support the hypothesis of an at least partial breakdown of endogenous gastrin in the human liver.

Adult

Urinary kallikrein excretion and plasma DBH activity in hypertension.

Many factors are to be considered in maintaining normal blood pressure. Authors study the behavior of urinary kallikrein (U.K.) and plasma dopamine-beta-hydroxylase (DBH) activity in various forms of hypertension. The values of U.K. excretion in normals were 20.5 +/- 1.8 E.U./24 h. In essential hypertensive patients (9.4 +/- 2.0 E.U./24 h) U.K. decreased, while in secondary hypertension it was significantly higher (33.8 +/- 3.0 E.U./24 h). Plasma DBH activity in essential hypertensive patients (17.72 +/- 2.33 I.U./ml) was similar to controls (20.22 +/- 1.39 I.U./ml); in secondary hypertension the mean values of plasma DBH were decreased (12.31 +/- 2.55 I.U./ml). No correlation between U.K. and plasma DBH activity was observed in normals and in various forms of hypertensive patients. U.K. seems a more reliable factor than plasma DBH in defining the different types of hypertension.

Adolescent

Insulin receptors during the menstrual cycle in normal women.

Specific binding of 125I-insulin to circulating monocytes from eight normal menstruating women, four postmenopausal women and four men were studied four times during a 28-day period (one sample at 7-day intervals). Data indicate the presence of a higher specific cell binding fraction in the follicular phase compared to the luteal phase due to changes in insulin receptor concentration. No changes were observed in men or postmenopausal women during the same period of time suggesting that sex hormones should be included among the factors influencing insulin receptors.

Adult