Biomedical subjects

A V Greco

Publications and source records attributed to A V Greco.

At least 19 recordsLinked to original sources

PubMed1992

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↗

PubMed1992

The beta cell function in NIDDM patients with secondary failure: a three year follow-up of combined oral hypoglycemic and insulin therapy.

Eleven Type 2 (non-insulin-dependent) diabetic patients, islet cell autoantibodies negative, nonobese with secondary failure to oral hypoglycemic agents (OHA) [glyburide (7.5 mg/day) and phenformin (75 mg/day)] and HbA1c 10.2 +/- 0.6% were studied. Insulin receptors on circulating monocytes, glucose utilization at supraphysiological insulin concentrations, and plasma C-peptide after i.v. glucagon were evaluated before and after 2 months of combined therapy with OHA and insulin (Ultratard HM Novo). A significant improvement was demonstrated in HbA1c and glycemia after two months of treatment. Glucose MCR was increased after two months of treatment whilst basal C-peptide was decreased as well as receptor binding to monocytes. After three years of combined therapy, body weight, glycemia and HbA1c did not increase. After three years the C-peptide basal values were significantly increased with respect to values found after 2 months of therapy. These results demonstrate that insulin treatment may restore insulin sensitivity in NIDDM patients resistant to OHA treatment and that after three years there is no exhaustion of B-cell function.

Administration, Oral↗

PubMed1992

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↗

PubMed1992

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↗

PubMed1992

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↗

PubMed1992

[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↗

PubMed1992

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↗

PubMed1992

Effect of propionyl-L-carnitine in the treatment of diabetic angiopathy: controlled double blind trial versus placebo.

Diabetic angiopathy can be treated by medical or surgical means. In the initial stages of the disease (I and II according to Fontaine), pharmacological treatment aims at supplying ischaemic and therefore hypoxic regions with a sufficient quantity of energetic substrates for metabolic needs. A new method of treating peripheral vasculopathy was carried out in this study using propionyl-L-carnitine (PLC), a propionic ester of L-carnitine. The authors evaluated in a double-blind study the efficacy of chronic oral administration of PLC versus placebo. Twenty type II diabetic patients with peripheral angiopathy were enrolled in this study. They were divided into 2 groups of ten patients each. On termination of treatment, the ankle/arm pressure index, measured at rest, showed an improvement in the PLC treated group and a deterioration in the placebo group. The Windsor index, measured at 2, 5 and 10 min after exercise, showed a significant impairment in the PLC treated group with respect to the placebo group. The percent variation in walking distance, measured at various time intervals according to the protocol, showed a marked improvement in the PLC treated group. These results show that PLC significantly improves both walking distance autonomy and symptoms related to peripheral vasculopathy in diabetic patients. Like carnitine, PLC seems to act through a metabolic mechanism which results principally in preventing lactate formation in ischaemic tissue.

Administration, Oral↗

PubMed1991

Pharmacokinetic analysis of azelaic acid disodium salt. A proposed substrate for total parenteral nutrition.

Azelaic acid was the first dicarboxylic acid proposed as an alternative energy substrate in total parenteral nutrition. In this study, the pharmacokinetics of azelaic acid were investigated in 12 healthy volunteers, 7 receiving a constant infusion (10g over 90 min) and 5 a bolus dose (1g). The 24h urinary excretion and plasma concentration in blood samples taken at regular intervals were assayed by gas-liquid chromatography. Experimental data were analysed by a 2-compartment nonlinear model that describes both tubular secretion and cellular uptake in Michaelis-Menten terms. A high value of urinary excretion (mean 76.9% of infused dose) and a mean clearance of 8.42 L/h were found, suggesting the presence of tubular secretion. Estimating the population mean of the pharmacokinetic model parameters gave a maximal cellular uptake of 0.657 g/h. The model predicts that 90% of the maximal uptake should be reached in the plateau phase of a constant infusion of 2.2 g/h. The presence of extensive and rapid losses through urinary excretion, and the low estimated value of the maximal cellular uptake, indicate that azelaic acid is not suitable as an energy substrate for total parenteral nutrition.

Adult↗

PubMed1991

Detection of inner retina dysfunction by steady-state focal electroretinogram pattern and flicker in early IDDM.

The effects of diabetes on the neural retina before the onset of clinically detectable retinopathy can be investigated with electrophysiological methods. Our aim was to detect early retinal dysfunctions in 60 patients with insulin-dependent diabetes mellitus (IDDM) and with a short duration of disease. We used the steady-state focal (9 degrees field size) electroretinogram (ERG) of the macula in response to luminance modulation of a uniform field (flicker ERG) or to counterphase-modulated sinusoidal gratings (pattern ERG). The harmonic analysis of flicker ERG and pattern ERG yielded three main components: a first and a second harmonic to flicker (1F and 2F, respectively) and a second harmonic to pattern (2P). The 1F is believed to be correlated to photoreceptor activity, whereas 2F and 2P represent different subsets of generators in the inner retina. Results of focal ERG in IDDM patients with no or early retinopathy were compared with age-matched control subjects. Mean 2F and 2P amplitudes were significantly reduced in IDDM patients compared with the control group (P = 0.0001 by analysis of variance). 2P but not 2F amplitude was significantly more reduced in patients with retinopathy than in those without retinopathy (P less than 0.05). 2F but not 2P phase abnormalities were observed in some patients. 2F and 2P alterations were slightly correlated with metabolic control (r = 0.22, P = 0.02) and disease duration (r = 0.28, P = 0.003). 1F was not significantly altered in IDDM patients. Our results suggest that early diabetes causes selective neurosensory deficits of inner retina layers, whereas the photoreceptors appear unaffected.

Adult↗

PubMed1991

Relationship between urinary neopterin excretion and islet cell antibodies in type 1 (insulin-dependent) diabetes.

Neopterin is specifically produced by interferon-activated macrophages, and it may be considered a marker of cellular immunity. In 40 newly diagnosed and 38 longer standing type 1 (insulin-dependent) diabetics the relationship between urinary neopterin levels and islet cell antibodies (ICA) was investigated. Raised urinary neopterin levels were found in 30 ICA positive (mean +/- SD: 729.8 +/- 602.1 mumol/mol creatinine, p = 0.0001) and 10 ICA negative (433.4 +/- 191.2 mumol/mol creatinine, p = 0.0005) diabetics at onset of disease compared with age-matched control subjects (118.1 +/- 33.2 mumol/mol creatinine). No significant difference in urinary neopterin levels was observed between diabetic groups. After the first stages of disease (greater than 5 months from onset), a significant difference (p = 0.0002) in urinary neopterin excretion was found between longer standing ICA positive patients and controls, but not between ICA negative diabetics and controls. In longer standing diabetics, neopterin levels were significantly higher in ICA positive patients than in ICA negative patients (544.6 +/- 341.3 versus 201.7 +/- 180 mumol/mol creatinine, p = 0.0002). No correlation between newly diagnosed or longer standing patients and HbA1c levels was found. Our results suggest that increased neopterin excretion in type 1 diabetes seems to be a sensitive indicator for the activation of cell-mediated immunity even when ICA are undetectable.

Adolescent↗

PubMed1991

Gastric emptying rate and hormonal response in type II diabetics.

Gastric emptying time was measured by ultrasonography in 18 NIDDM patients with and without autonomic neuropathy, evaluated by cardiovascular autonomic tests and in 10 controls before and after a physiologic test meal. Six neuropathic subjects showed gastrointestinal symptoms such as fullness and early satiety. Blood glucose, gastrin and pancreatic polypeptide were evaluated before and up to 200 min after the test meal. The gastric emptying rate was similar in controls (275 +/- 45 min) and in diabetic patients without (260 +/- 49 min) and with autonomic neuropathy (257 +/- 48 min) (p = ns), while diabetic symptomatics showed a significant reduction of gastric emptying rate (420 +/- 19.7 min) (p less than 0.001). Basal serum glucose concentration was similar in all diabetic patients (132 +/- 18 mg/dl, 166 +/- 52 mg/dl, 161 +/- 61 mg/dl, p = ns). A basal value of serum gastrin was similar in all groups while the test meal produced a rise with a peak at 40' significantly higher only in symptomatics (195 +/- 58 pg/ml vs control 107 +/- 88 pg/ml, diabetics without and with autonomic neuropathy: 98 +/- 12 pg/ml and 88 +/- 22 pg/ml respectively; p less than 0.01). Basal and stimulated PP values were similar in all groups. In conclusion ultrasonography is a simple, reliable method to evaluate gastric emptying rate without any interference in the mechanism of digestion and absorption of nutrients. The presence of non specific symptoms, such as nausea and gastric fullness, may indicate an early gastric involvement as supported by sonographic evidence of impaired emptying.

Adult↗

PubMed1990

A glucagon-secretin-like peptide stimulates the intrinsic nervous plexus of guinea pig gallbladder.

The role of vasoactive intestinal peptide (VIP), as a possible neurotransmitter of the intrinsic nerve plexus in the guinea pig gallbladder, was investigated by monitoring spontaneous contractile activity. VIP receptor antagonist (4 Cl-D-Phe6, Leu 17)-VIP did not produce any effect on muscular tone and spontaneous activity, whereas (N-Ac-Tyr1, D-Phe2)-GRF-(1-29)-NH2, (14-GRF analog), which is known to stimulate digestive enzyme secretion by interacting with the VIP-preferring receptors, greatly increased the amplitude and frequency of waves as well as the muscular tone. Since VIP receptor antagonist acts selectively as a competitive antagonist for the action of VIP, we conclude that the gallbladder inhibitory intrinsic plexus neurotransmitter is not VIP, but a member of the glucagon-secretin family of peptides.

Animals↗

PubMed1990

Spatial frequency-selective losses with pattern electroretinogram in type 1 (insulin-dependent) diabetic patients without retinopathy.

Neurosensory abnormalities have been implicated in the first stages of diabetic retinopathy. The activity of retinal ganglion cells in 24 Type 1 (insulin-dependent) diabetic patients with short disease duration without retinopathy on fluorescein angiography was investigated by using a pattern electroretinogram in response to sinusoidal gratings of different spatial frequencies (0.6, 1.0, 1.4, 2.2 4.8 cycles/deg), counterphase modulated at 8 Hz. The pattern electroretinogram reflects, at least in part, the activity of subsets of generators (i.e. ganglion cells) which show spatial selectivity. Mean pattern electroretinogram amplitude was significantly reduced in patients at lower and intermediate, but not at higher spatial frequencies compared with 40 age-matched control subjects. At 1.4 cycles/deg the pattern electroretinogram amplitude was significantly correlated (r = 0.59) with age at onset (p = 0.002) and duration of disease (p = 0.002). Our results suggest that in Type 1 diabetic patients without retinopathy, there is an early sensory deficit of specific inner retina neurons which respond preferentially to gratings of medium and large size.

Diabetes Mellitus, Type 1↗

PubMed1990

Serum and biliary lipid pattern in rabbits feeding a diet enriched with unsaturated fatty acids.

Adult male New Zealand white rabbits were fed for 3 months a stock diet supplemented with 6% (w/w) soybean oil heated at 240 degrees C for 60 min. After the first month of treatment a significant increase in total lipid content of serum was observed mainly due to the cholesterol ester fraction. Simultaneously, grossly induced atherosclerosis and marked liver damage were histologically and clinically demonstrated. Lipid peroxide values, performed by thiobarbituric acid test in lipid extracts from liver, aorta and bile showed a significant increase as compared to controls. Lipoperoxidation rate increased with the duration of feeding. Parallel to this there was a marked reduction in the activities of glutathione peroxidase, superoxide dismutase and catalase in liver and aorta, all enzymes involved in the mechanism of detoxification of lipid peroxides. The results are in agreement with the hypothesis that lipid peroxidation can play a significant role in the pathogenesis of atherosclerosis.

Animals↗

PubMed1990

Free fatty acids stimulate mucin hypersecretion by rabbit gall-bladder epithelium in vitro.

1. Mucin, a high-molecular-weight glycoprotein secreted by the gall-bladder and biliary duct epithelium, is a well-known nucleation-prompting factor in experimental and human gall-stone disease. 2. Free fatty acids when incubated in vitro (micellar suspension with 1 mmol/l Tween 40) with rabbit gall-bladders can promote abundant mucus secretion. 3. The hexosamine content of rabbit gall-bladder walls, measured by gas-liquid chromatography, was significantly higher in gall-bladders incubated with fatty acids than in control tissues. 4. The biochemical data were supported by ultrastructural findings showing numerous droplets with a translucent content in the perinuclear cytoplasm. Exocytosis was also seen in treated gall-bladders, confirming the secretory nature of the vesicles. 5. These results suggest that free fatty acids, which appear in high amounts when bile lecithins are hydrolysed by phospholipase, play an active role in the gall-stone formation.

Acetylgalactosamine↗

PubMed1990

Ultrasound-Doppler diagnosis of Budd-Chiari syndrome.

We report a case of apparently idiopathic Budd-Chiari syndrome, diagnosed by ultrasound and Doppler sonography, in a patient with latent myeloproliferative disease. This case proves that Doppler sonography shows in the hepatic veins a flow pattern suggestive of partial thrombotic obstruction. Moreover, we suggest that the search for a latent myeloproliferative disorder, by means of the spontaneous erythroid colonies formation in culture of bone marrow or blood mononuclear cells, should be routinely included in the diagnostic evaluation of each case of hepatic vein thrombosis without other recognizable causes.

Blood Flow Velocity↗

PubMed1990

Evidence for early impairment of macular function with pattern ERG in type I diabetic patients.

The electroretinogram (ERG) elicited by alternating gratings at constant mean luminance (pattern ERG) is a focal response reflecting the activity of the directly stimulated retinal area. In addition, pattern ERG is related, unlike the flash ERG, to ganglion cell activity. Therefore, this technique may be used to evaluate the integrity of inner retinal layers in the macular region. In this study, the steady-state pattern ERG, in response to alternating gratings (1.7 cycles/deg spatial frequency; 9 degrees field size) temporally modulated at 8 Hz, was recorded in 42 type I (insulin-dependent) diabetic patients with zero to four microaneurysms on fluorescein angiography and a duration of disease less than 11 yr. No patient had concomitant ocular or systemic complications. Mean pattern-ERG amplitude was significantly reduced in patients compared with age-matched control subjects (analysis of variance, F = 25.6, P less than 0.0001). Significant differences were observed between control and diabetic subjects without retinopathy (Scheffé F test, P less than 0.0001), between control and retinopathic subjects (Scheffé F test, P less than 0.0001), and between diabetic patients without retinopathy and those with early retinopathy (Scheffé F test, P less than 0.02). Pattern-ERG amplitude was inversely correlated with duration of diabetes (r = 0.22, P less than 0.05). Our results suggest a macular dysfunction in early diabetes resulting from metabolic and/or vascular injuries in the neurosensory retina.

Adolescent↗