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Biomedical subjects

P Piatti

Publications and source records attributed to P Piatti.

11 recordsLinked to original sources
PubMed2000

Familial clustering of arterial blood pressure, HDL cholesterol, and pro-insulin but not of insulin resistance and microalbuminuria in siblings of patients with type 2 diabetes.

OBJECTIVE: To test the hypothesis that selected abnormalities cluster in type 2 diabetic families. Offspring of patients with type 2 diabetes have a 40-60% chance of developing type 2 diabetes and an increased frequency of impaired glucose tolerance (IGT) or unknown diabetes. These offspring also show metabolic abnormalities of type 2 diabetes, such as insulin resistance, high insulin and pro-insulin, low HDL cholesterol levels, arterial hypertension, and microalbuminuria. RESEARCH DESIGN AND METHODS: We studied 87 families including at least one type 2 diabetic patient, i.e., 87 probands and 146 siblings; 60 spouses of probands with no family history of diabetes were compared with siblings. Familial clustering was evaluated by 2 methods: concordance of siblings and probands for a given abnormality (method 1) and intraclass correlation coefficients of values within each family (method 2). RESULTS: At oral glucose tolerance testing, 24 siblings had type 2 diabetes, 31 siblings had IGT, and 14 spouses had IGT (P = 0.0012 vs. siblings). With method 1, familial clustering occurred for microalbuminuria, insulin resistance, arterial hypertension, HDL cholesterol and pro-insulin levels; with method 2, familial clustering was observed for the same variables except for microalbuminuria. With both method 1 and 2, familial clustering for insulin resistance disappeared, whereas familial clustering for arterial blood pressure, HDL cholesterol, and pro-insulin remained after correction for BMI; after further restriction of analysis to probands and to siblings with normal glucose tolerance, familial clustering for pro-insulin was observed only with method 2. CONCLUSIONS: These data indicate that siblings of diabetic patients are at high risk for selected features of type 2 diabetes.

Albuminuria↗
PubMed2000

Detrimental effects of acute heparin administration on ischemic threshold in patients with coronary artery disease.

BACKGROUND: Recent studies have indicated that heparin administration might decrease endothelial nitric oxide production. The aim of this study was to investigate the effect of heparin on ischemic threshold. METHODS: Eighteen patients with a positive exercise test and proven coronary artery disease were submitted to a randomized, placebo-controlled trial using i.v. 0.9% NaCl as placebo and i.v. heparin (5,000 IU bolus + 1,000 IU/h). After both saline and heparin bolus, the infusion was started and, after 10 min, the exercise test was performed. Blood samples for nitric oxide metabolites and free fatty acid determinations were taken before, at peak exercise, and at ECG recovery. RESULTS: As compared to placebo, heparin significantly decreased time to 1 mm ST segment depression (241 +/- 160 vs 303 +/- 175 s, p = 0.003) and prolonged recovery (573 +/- 177 vs 441 +/- 195 s, p = 0.003), while exercise duration was similar. Accordingly, rate-pressure product at 1 mm ST segment depression was lower after heparin, while it was similar at peak exercise. No significant differences were found for plasma nitric oxide metabolite levels. Conversely, free fatty acid levels were higher after heparin throughout the study in all patients. The increase in free fatty acids was not correlated with the difference in rate-pressure product at 1 mm ST segment depression between placebo and heparin (r = 0.34, p = NS). CONCLUSIONS: In patients with stable coronary artery disease, heparin significantly decreased exercise ischemic threshold. The lower rate-pressure product at 1 mm ST segment depression during heparin, compared to placebo, suggests an impairment of coronary blood flow, which does not seem to be mediated by decreased nitric oxide production/release. The increased free fatty acid release, on the other hand, might contribute to the detrimental effect of heparin on exercise-induced ischemia, but the lack of a correlation with changes in ischemic threshold suggests that other, still unknown, factors are involved.

Aged↗
PubMed1999

Endothelial and metabolic characteristics of patients with angina and angiographically normal coronary arteries: comparison with subjects with insulin resistance syndrome and normal controls.

OBJECTIVES: This study was performed to characterize the endothelial and metabolic alterations of patients with angina and angiographically normal coronary arteries ("cardiac" syndrome X [CSX]) compared with subjects with insulin resistance syndrome ("metabolic" syndrome X [MSX]) and normal controls. BACKGROUND: Previous studies have found high endothelin-1 levels, impaired endothelium-dependent vasodilation and insulin resistance in patients with angina pectoris and angiographically normal coronary arteries. On the other hand, subjects with insulin resistance syndrome have shown high endothelin-1 levels. METHODS: Thirty-five subjects were studied: 13 patients with angina pectoris and angiographically normal coronary arteries (CSX group); 9 subjects with insulin resistance syndrome (MSX group) and 13 normal controls. All subjects received an acute intravenous bolus of insulin (0.1 U/kg) combined with a euglycemic clamp and forearm indirect calorimetry. Endothelin-1 levels, nitrite/nitrate (NOx) levels, end products of nitric oxide metabolism, glucose infusion rates (index of insulin sensitivity) and their incremental areas (deltaAUCs [area under curves]) were measured during this period. RESULTS: Basal endothelin-1 levels were higher in CSX and MSX groups than in normal controls (8.19 +/- 0.46 and 6.97 +/- 0.88 vs. 3.67 +/- 0.99 pg/ml; p < 0.01), while basal NOx levels were significantly higher in MSX group than in CSX and normal controls (36.5 +/- 4.0 vs. 24.2 +/- 3.3 and 26.8 +/- 3.2 mol/liter, p < 0.05). After insulin administration, the deltaAUCs of NOx (p < 0.05) were lower in CSX group than in MSX and normal controls, and the deltaAUCs of endothelin-1 were lower in group CSX than in normal controls. Glucose infusion rate was significantly lower in CSX and MSx groups than in normal controls (p < 0.01), suggesting that in both CSX and MSX groups insulin resistance is present. A positive correlation was found between the deltaAUCs of nitric oxide and the AUCs of glucose infusion rate. CONCLUSIONS: Blunted nitric oxide and endothelin responsiveness to intravenously infused insulin is a typical feature of patients with angina pectoris and angiographically normal coronary arteries and may contribute to the microvascular dysfunction observed in these subjects.

Calorimetry, Indirect↗
PubMed1998

Differential effects of selective beta-adrenergic blockade on insulin sensitivity and release in control subjects and in patients with angina and normal coronary arteries (syndrome X).

AIMS: Betablockers are very effective in patients with angina and angiographically smooth coronary arteries (syndrome X), but may exacerbate the state of insulin resistance that is known to be present in such patients. The aim of the study was to evaluate the effects of short-term treatment with atenolol on carbohydrate metabolism in syndrome X patients, as compared to normal subjects. METHODS AND RESULTS: Seventeen patients (15 females, 55 +/- 8 years, BMI 23.4 +/- 2.7 kg/m2) and 11 controls (5 females, 50 +/- 7 years, BMI 23.1 +/- 2.0 kg/m2) were studied twice by an intravenous glucose tolerance test (IVGTT, 0.5 g/kg) after ten days of both placebo and atenolol (100 mg o.d.), given in random order. Metabolic indices measuring glucose effectiveness and insulin sensitivity were derived from minimal model analysis of the glucose and insulin profiles measured during the IVGTT. Indices of first- and second-phase insulin release were also calculated from the IVGTT insulin response. Atenolol had different metabolic effects on normal subjects and syndrome X patients. Despite the fact that the drug was found to be effective in relieving symptoms of chest pain, it induced a significant (p < 0.05) worsening of insulin resistance in syndrome X patients. No such effect was observed in control subjects. On the other hand, atenolol produced a marked reduction (40%, p < 0.05) of first-phase insulin release in control subjects, but no significant change of the same index in syndrome X patients. CONCLUSION: These results show that betablockers are very effective for controlling symptoms and improving quality of life in syndrome X patients. However, they appear to further impair the ability to dispose glucose. Long-term studies on the net effects of beta-blockade administration for the treatment of such patients are warranted.

Administration, Oral↗
PubMed1996

[Functional aspects of the fetal urinary apparatus in relation to growth].

The normal and regular development of the fetal renal function is related to fetal growth and to the correct development of the fetal lung. Besides, the fetal kidneys plays an important role in the regulation of the hydro-electrolytic balance and in the modulation of the fetal arterial pressure. The postnatal renal failure is one of the most dangerous factors which may occur in the very small preterm babies (birth weight below 1000 g) and their therapeutical answer depends on the degree of kidney maturation. The knowledge of the kidney maturation process is one of the actual controversies in perinatal medicine. The development of the renal nephron and of the excretory system continues until 32-36 weeks of gestation, their maturation process ends only some months after birth. At 9 weeks of gestation the embryonic kidney may be seen in a transvaginal ultrasonographic scanning; the calico-pelvic system is visible from the 11th week of gestation and the bladder may be seen by ultrasound from the 12 weeks' gestation. The fetal glomerular ultrafiltration process starts at the 10-11 week of gestation and the most important factors that improve the volume of glomerular ultrafiltrate is the total renal mass which is related to the number of functional nephron units. The Doppler velocimetry performed on the fetal renal artery has shown that the fetal renal blood flow increases with the increase of the renal volume and gestational age and it depends on the cardiac output. In the renal artery the resistance to blood flow decreases with gestational age. During fetal hypoxia there is a reduction of the amniotic fluid production; this phenomenon is related to the redistribution of the fetal blood flow with a decrease of the perfusion of peripheric organs (as the kidney) and an increase of the perfusion of brain, heart, liver and adrenals. The hypoxic fetal kidney is ischemic; moreover, the urine production rate is diminished and the humoral response of the kidney increase the fetal arterial pressure which maintains the haemodynamic compensation to hypoxia. When this situation is prolonged, there is possibly renal failure. The fetal renal ultrasonographic examination can give important information about the maturity degree of the fetal kidney and the evaluation of Doppler velocimetry on renal artery and the evaluation of the amniotic fluid allow the monitoring of fetal hypoxia. In future the Doppler velocimetry of intrarenal arteries and the biochemical evaluation of the amniotic fluid may a real evaluation of the fetal renal function.

Adult↗
PubMed1995

Antigenic variants in a plaque-isolate of foot-and-mouth disease virus: implications for vaccine production.

The occurrence of many subtypes within a serotype of foot-and-mouth disease virus (FMDV) makes it difficult to control the disease by vaccination. Although inactivated vaccines are used successfully in many countries, the appearance in the field of antigenic variants against which the vaccines do not confer protection is a constant problem in vaccine manufacture. We had found previously a mixture of antigenic variants in a field isolate of serotype A12. In this report we demonstrate the presence of two variants in a plaque-isolate from this mixture. The second variant was detected only when the growth conditions were altered. Our observation points to the problems which may be encountered in the large scale growth of a virus for vaccine production.

Amino Acid Sequence↗
PubMed1995

Structure and immunogenicity of experimental foot-and-mouth disease and poliomyelitis vaccines.

The physico-chemical properties and immunogenicity of experimental vaccines against foot-and-mouth disease (FMD) and poliomyelitis, prepared by treatment of the viruses with N-acetylethyleneimine (AEI), formaldehyde or neutral red, have been studied. None of these reagents affects the rate of sedimentation of the particles or their reaction with antibody against the major immunogenic sites. FMD vaccines prepared by inactivation with AEI or neutral red, behaved like the untreated virus, in that they were disrupted on lowering the pH below 7. The RNA of the AEI-inactivated virus was degraded into slowly sedimenting molecules. Unlike AEI-inactivated virus, from which all the RNA could be extracted with phenol-SDS, the recovery from the neutral red inactivated virus was variable and was sometimes as low as 40%; this RNA gave a heterogenous profile in sucrose gradients. The capsid proteins in the AEI preparation migrated in SDS-PAGE to the same positions as those of untreated virus, but in the neutral red preparation there was evidence of cross-linking. In contrast, the formaldehyde-inactivated vaccine was stable below pH 7 and the RNA could not be released by extraction with phenol-SDS at pH 5, because the capsid proteins had become cross-linked and/or linked to the RNA. As with foot-and-mouth disease virus (FMDV), poliovirus which had been inactivated with formaldehyde did not release its RNA on extraction with phenol-SDS and the capsid proteins were also cross-linked. Surprisingly, although AEI cleaved the viral RNA slowly in situ, the virus was no longer infectious after 6 h. Neutral red did not reduce the infectivity of the virus. All of the preparations gave similar levels of neutralizing antibody after a single inoculation. The high levels obtained with the formaldehyde-inactivated vaccines have implications for the processing of fixed particles by the antigen-presenting cells.

Animals↗
PubMed1995

Myocardial glucose uptake evaluated by positron emission tomography and fluorodeoxyglucose during hyperglycemic clamp in IDDM patients. Role of free fatty acid and insulin levels.

Myocardial and whole-body glucose metabolism was assessed in 19 insulin-dependent diabetes mellitus (IDDM) patients. A hyperglycemic clamp was performed 1) in the absence of insulin at free fatty acid (FFA) levels of 1.0 mmol/l (test 1); 2) in the absence of insulin at low FFA levels (0.1 mmol/l) by means of a lipid-lowering drug, acipimox (test 2); 3) during insulin infusion to achieve systemic levels of 400 pmol/l and FFA levels of 0.1 mmol/l (test 3); and 4) at the insulin levels of test 3 but increasing FFA to 1.0 mmol/l by means of heparin and intralipid infusion (test 4). Myocardial glucose uptake was measured by positron emission tomography (PET) and 2-[18F]fluoro-2-deoxy-D-glucose. Whole-body glucose uptake was measured in the four conditions by the glucose infusion rate during the PET scanning period. Myocardial glucose uptakes were 40.3 +/- 18.0, 395.5 +/- 139.6, 852.2 +/- 99.1, and 1,388.4 +/- 199.1 mumol.kg tissue-1.min-1 (mean +/- SD) and whole-body glucose uptakes were 10.1 +/- 2.3, 10.1 +/- 3.4, 42.8 +/- 5.8, and 30.5 +/- 5.6 mumol.kg body wt-1.min-1 during tests 1, 2, 3, and 4, respectively. Thus, in IDDM patients without coronary artery disease under the condition of hyperglycemia, an increase of myocardial glucose uptake was obtained either by lowering of FFA levels during hypoinsulinemia or by an increase in FFA levels during hyperinsulinemia. In both conditions no significant changes of whole-body glucose uptake were demonstrated.

Adult↗
PubMed1991

Enhancement of the immune response elicited with foot-and-mouth disease virus vaccines by an extract of the Mycobacterium sp. wall.

The immunomodulating effect of an extract of the cell wall of Mycobacterium sp. (WSF, Vetrepharm Inc., London, Canada) in foot-and-mouth disease virus inactivated vaccines was tested in a murine model. The duration of immunity, protection, stimulation of immunocompetent cells acting on the long-lasting secondary response and possible tissue damage were examined. The incorporation of 10 micrograms WSF into aqueous and oil vaccines induced a high and long-lasting specific antibody response. The neutralizing titres of these antibodies were significantly higher than those observed in animals immunized with vaccines lacking WSF and conferred protection for at least 7 months. The data collected in repopulation assays indicate that WSF participates in the activation of immune cell populations involved in long-lasting memory. This results in an efficient B-cell secondary response even in the absence of T cells, lasting at least 5 months. No adverse reactions were detected. The enhancement effect of WSF on the immune response to foot and mouth disease vaccines observed in the murine model indicates the possibility of its inclusion in aqueous vaccines to be tested in cattle.

Adjuvants, Immunologic↗