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Biomedical subjects

F Cerutti

Publications and source records attributed to F Cerutti.

At least 37 records · Page 2Linked to original sources

Autonomic function and autoantibodies to autonomic nervous structures, glutamic acid decarboxylase and islet tyrosine phosphatase in adolescent patients with IDDM.

Recent studies have linked autoimmunity to nervous tissue structures and diabetic autonomic neuropathy, but data on the early stage of IDDM and on the natural history of this association are not available. For this reason, we investigated autonomic nervous function, and the presence of autoantibodies to sympathetic and parasympathetic nervous structures, to glutamic acid decarboxylase (GAD) and tyrosine phosphatase (IA-2/ICA512) in 85 adolescents with insulin-dependent diabetes mellitus (IDDM) (mean age 14.7+/-1.6 yr, mean duration of diabetes 6.8+/-3.5 yr), and 45 age and sex-matched healthy subjects. Nervous tissues autoantibodies were detected using an indirect immunofluorescent complement-fixation technique, with monkey adrenal gland, rabbit cervical ganglia and vagus nerve as substrates. GAD and IA-2/ICA512 autoantibodies were detected by radioimmunoprecipitation assay. Seven patients (8%) had anti-vagus nerve autoantibodies, 7 other patients (8%) had anti-cervical ganglia autoantibodies, while all controls were negative (P < 0.05). Anti-adrenal medulla antibodies were detected in 16 patients (19%) and in 2 control subjects (P<0.02). None of the patients had autonomic symptoms. When patients were divided according to the presence or absence of autoantibodies, values of the cardiovascular tests (deep breathing, 30:15 ratio, Valsalva ratio) were similar in the two groups and similar to those in healthy subjects. However, when considered together, patients positive for one or more autoantibody showed a trend for lower values of deep breathing test and 30:15 ratio test, compared with healthy control subjects, which failed to reach conventional significance values (P=0.17 and P=0.07, respectively). No correlation was found between cardiovascular parameters and metabolic control or diabetes duration. There was no association between autoimmunity to nervous tissue structures and presence of GAD and IA-2/ICA512 Ab, and no correlation between these two autoantibodies and values of cardiovascular tests. Our data indicate that autonomic dysfunction is not a characteristic of young diabetic patients, but that autoantibodies against autonomic nervous structures are present during the first 1 to 15 yr of diabetes. GAD and tyrosine phosphatase appear to be excluded as target autoantigens within autonomic structures. Follow-up studies are required to evaluate future autonomic dysfunction and symptoms in these patients, and to establish whether the subtle autonomic dysfunction detected and/or the nervous tissue autoantibodies, are predictive of the development of this complication.

Adolescent↗

Insulin secretion and hepatic insulin clearance as determinants of hyperinsulinaemia in normotolerant grossly obese adolescents.

Obesity is characterized by variable degrees of hyperinsulinaemia, which has been attributed to either beta-cell hypersecretion or reduced hepatic insulin extraction, or both. To investigate this controversial issue, a 4-h frequently sampled i.v. glucose tolerance test (glucose dose 12.8 g m(-2)) was performed in 13 normotolerant, grossly obese adolescents (10 F/3 M; 13+/-1 y; body mass index 32+/-0.9; pubertal stage 4-5; obesity duration 7.8+/-3 y) and in a comparable group of 8 healthy, normal-weight subjects. Glucose, insulin and C-peptide time-course were analysed by the minimal model technique, which estimates beta-cell secretion, insulin sensitivity (Si), glucose effectiveness (SG) and hepatic insulin extraction (HE). Despite similar fasting and after load glucose patterns (SG similar in the two groups), obese adolescents showed sustained peripheral hyperinsulinaemia (total insulin area under the concentration curve 67.2+/-10.8 vs 19.1+/-1.2 pmol l(-1) in 240 min; p <0.002) and a 71% reduction in Si (2.02+/-0.33 vs 6.95+/-1.03 x 10(4) min(-1) (microU ml(-1)); p < 0.001). Compared with control subjects, the total amounts of prehepatic insulin secretion and posthepatic insulin delivery were also increased significantly in obese adolescents by 30% and 46%, respectively; HE was reduced by 15% during the first 30 min of the test, but recovered within the normal range during the rest of the test. In conclusion, severely obese adolescents are insulin resistant and their hyperinsulinaemia is primarily caused by beta-cell hypersecretion, whereas the reduction in insulin hepatic extraction is a transient metabolic phenomenon.

Adolescent↗

Levels of natural resistance to Boophilus microplus (Acari: Ixodidae) in Carora breed bulls.

Boophilus microplus infestation is one of the most serious limitations to cattle industry in tropical regions, even though bovines show natural resistance to ticks. This resistance was evaluated in Cross-bred Carora Bulls (CCB) a tropicalized dairy breed from Venezuela. Seven CCB were experimentally infested with B. microplus larvae, "Mozo" strain, they were considered tick-naive because they had never been infested with ticks. The mean inoculum size applied on each bull was 6,477 larvae. After life cycle was completed adult female body weight (BW), egg mass weight (EW), egg hatching rate (%EH), and reproductive index (RI) were recorded. Results revealed a high variability in the levels of resistance to B. microplus. Thus, one animal showed greater resistance (Dunnett, p < 0.05) for the analyzed parameters in contrast with three non-resistant bulls. The others had moderate resistance. The trait "resistance" should be included together with other traits often used in genetic selection of cattle.

Animals↗

Lamotrigine reduces total postoperative analgesic requirement: a randomized double-blind, placebo-controlled pilot study.

BACKGROUND: Postoperative pain is undertreated. Lamotrigine, a new antiepileptic drug, has analgesic properties in its antisodium and antiglutamatergic effects. It may prevent postoperative pain. This pilot study assessed lamotrigine effects on postoperative pain. METHODS: This was a double-blind, randomized, placebo-controlled pilot study of 30 patients submitted to transurethral prostatectomy under spinal anesthesia and receiving 200 mg of lamotrigine 1 hour before spinal anesthesia. RESULTS: We observed a statistically significant reduction in total analgesic assumption (p < 0.01) and in visual analog scale scores at 2 (p = 0.04), 4 (p < 0.01), and 6 (p = 0.04) hours after operation. CONCLUSIONS: Lamotrigine may be an effective means of reducing postoperative pain.

Adenoma↗

Nonenzymatically glycated albumin (Amadori adducts) enhances nitric oxide synthase activity and gene expression in endothelial cells.

Hyperglycemia is considered to induce diabetic nephropathy through nonenzymatic glycation of proteins. Since hyperfiltration is likely to be the mechanism initiating the glomerular lesions, we investigated the effects of Amadori glucose adducts in serum albumin on the production of vasoactive mediators, including nitric oxide (NO) and eicosanoids, by endothelial cells (EC). Amadori adducts of glycated albumin induced a dose-response increase in NO synthase activity of murine endothelioma cells, up to 16.4 +/- 2.1-fold increase of basal values (P < 0.0001) at concentrations of 35 mg/ml mimicking physiological serum albumin concentration, and 4.6 +/- 0.8-fold increase at 17 mg/ml (P < 0.001). The effect was still detectable with glycated albumin 1.7 mg/ml, which approaches its estimated concentration in diabetic serum (1.6 +/- 0.3-fold increase, P < 0.05) The phenomenon was reproducible in human umbilical vein endothelial cells, though to a lesser extent, and further studies on murine EC were employed. The mRNA encoding for inducible NO synthase was overexpressed in EC incubated with Amadori adducts of glycated albumin in comparison to native albumin. Glycated albumin induced increased mRNA expression and synthesis of TNF-alpha. The stimulatory effect induced by glycated albumin on NO synthase activity was almost completely inhibited by anti TNF alpha antibodies. 3H-thymidine incorporation by EC was significantly inhibited when cells were grown in presence of glycated albumin (P < 0.001), and the phenomenon was abolished by the coincubation of the NO competitive inhibitor L-NAME. The early glycosylation products increased thromboxane production (P < 0.001), while prostaglandin E2 synthesis was unaffected. These data indicate that Amadori products of glycated albumin modulate NO synthase activity and eicosanoid balance in EC. These effects may be relevant to the hemodynamic changes in the early phases of diabetic nephropathy and in the lasting progression to sclerosis.

Albumins↗

Insulin resistance and hyperinsulinemia in homozygous beta-thalassemia.

Insulin resistance and hyperinsulinemia have been reported in homozygous beta-thalassemia before the development of diabetes. However, insulin sensitivity (SI) has never been studied in normoinsulinemic patients. Furthermore, whether hyperinsulinemia is due to increased beta-cell secretion or to decreased hepatic insulin extraction is poorly understood. We estimated SI, beta-cell secretion, and hepatic insulin extraction using the minimal model analysis of a frequently sampled intravenous glucose tolerance test (2.8 g/m2) in two groups of nondiabetic pubertal patients with homozygous beta-thalassemia (seven hyperinsulinemic and seven normoinsulinemic patients) and seven control subjects matched for age, body mass index, and pubertal stage. In both thalassemic groups, SI was reduced by approximately 40% (3.52 +/- 0.57 and 3.74 +/- 0.66 v 6.89 +/- 1.02 10(-4).min-1 [microU/mL], P = .011) and was inversely correlated with iron overload (r = -.707, P = .006). All parameters of beta-cell secretion were not significantly different in patients and controls. On the other hand, basal posthepatic insulin delivery (BDR) was more than doubled in hyperinsulinemic patients with respect to normoinsulinemic patients or controls (15.1 +/- 2.4 v 6.1 +/- 1.1 and 7.5 +/- 2.3 pmol/L.min-1, P = .012), and the same was true for total posthepatic insulin delivery ([TID] 6.3 +/- 1.0 v 2.9 +/- 0.5 and 2.9 +/- 0.7 pmol/L.240 min-1, P = .015). Hepatic insulin extraction was significantly lower in hyperinsulinemic patients than in normoinsulinemic patients or controls (49.3% +/- 9.4% v 73.0% +/- 3.7% and 77.4% +/- 3.9%, P = .011), and in patients it was inversely correlated with iron overload (r = -.829, P = .0001). In conclusion, insulin resistance is present even in normoinsulinemic patients, beta-cell responsiveness to glucose is normal, and hyperinsulinemia is mainly due to decreased hepatic insulin extraction. In nondiabetic thalassemic patients, these defects are possibly related to iron overload.

Adolescent↗

Evaluation of left ventricular diastolic function in insulin dependent diabetic children by M-mode and Doppler echocardiography.

To evaluate the presence of diabetic cardiomyopathy, we measured various parameters of left ventricular systolic and diastolic function by means of M-mode and Doppler echocardiography in 50 IDDM children (mean age 13 +/- 3 years; mean IDDM duration 5.9 +/- 4.1 years) free of cardiovascular symptoms. As compared to age-matched healthy control subjects, diabetic children evidenced a significant increase in mean values of pressure half time (PHT), an index of the early diastolic phase (53.7 +/- 10.2 msec vs 44.5 +/- 9, p < 0.002). When the patients were subdivided on the basis of IDDM duration, metabolic control and the presence of retinal microangiopathic abnormalities, those with longer IDDM duration and poor glycemic balance had higher PHT values. These data indicate that an early diastolic dysfunction, expressed by reduced left ventricular compliance, can be found in children with Type 1 diabetes mellitus of relatively short duration. Doppler echocardiography is a reliable non-invasive means to assess early impairment of cardiac function in IDDM patients.

Adolescent↗

The insulin signal and its effects on the pyruvate dehydrogenase complex in circulating lymphocytes of obese children.

1. Studies have shown that in circulating lymphocytes pyruvate dehydrogenase (PDH) is responsive to insulin. 2. To improve existing knowledge on how insulin influences PDH behaviour, situations in which cell responsiveness to insulin is impaired could be of interest. 3. PDH behaviour in circulating lymphocytes from obese children, with high plasma insulin levels and normal glucose tolerance, was examined. 4. Masking and unmasking processes of insulin receptors on the plasma membrane appear to modulate the enzyme response to insulin.

Adolescent↗

Screening of diabetic children for coeliac disease with antigliadin antibodies and HLA typing.

IgA and IgG antigliadin antibodies were measured in 498 patients with insulin dependent diabetes mellitus and no history of intestinal malabsorption. Thirty patients had abnormal concentrations of antigliadin antibodies; 22 of these had an intestinal biopsy carried out and 16 of the 22 had subtotal villous atrophy suggestive of coeliac disease (prevalence 3.2%). There were no significant differences between patients with coeliac disease and diabetes and diabetic patients with normal IgA antigliadin antibodies in any of the nutritional variables measured, duration of diabetes, and mean insulin requirement. The mean age of onset of diabetes and attainment of expected height for age were both significantly lower in the patients with both diseases. Typing HLA classes I and II was done in 242 patients. The incidence of HLA-B8, DR3, and DQW2, which are commonly associated with both the diseases, is increased when both are present.

Adolescent↗

[The use of propofol in combination with fentanyl or buprenorphine in long-duration anesthesia].

Fifty patients of both sexes, aged between 37 and 60 years old and belonging to ASA classes I, II, III and IV, underwent urological surgery lasting more than two hours under general anesthesia using a continuous infusion of propofol, N2O/O2, vecuronium bromide 0.02% infusion. Patients were divided into two groups of 25, group A and group B, according to whether they received fentanyl or buprenorphine as an analgesic. Propofol and fentanyl consumption in group A were 5.43 +/- 0.7 mg/kg/hour and 10.53 +/- 1.7 micrograms/kg respectively, whereas those of propofol and buprenorphine in group B were 5.71 +/- 1.08 mg/kg/hour and 6.05 +/- 0.06 micrograms/kg; there was a statistically non-significant difference for propofol consumption (p greater than 0.005). During the induction and maintenance phases of anesthesia, hemodynamic parameters decreased significantly (p less than 0.001) in comparison to starting values in both groups, but no statistically significant differences were observed. Buprenorphine prolonged reawakening from anesthesia by a few minutes but at the same time extended postoperative analgesia by several hours, thus improving the overall quality of the immediate postoperative period. The most frequent side effect (32% in group A and 52% in group B) was sinusal bradycardia.

Adult↗

Erythrocyte Na,Li countertransport and arterial pressure in diabetic adolescents.

The aim of this study was to analyze Na,Li countertransport in erythrocytes from adolescents with insulin dependent diabetes mellitus (IDDM) and to see if those with elevated values present distinct clinical features, in particular as regards arterial pressure and urinary albumin excretion (UAE). Twenty-nine adolescents with IDDM (17 males, 12 females, mean age 15 +/- 0.6 years, mean diabetes duration 11.4 +/- 0.7 years) and fifteen healthy age-matched control subjects (8 males, 7 females, age 14.5 +/- 1 years) were investigated. Diabetic adolescents had a RBC Na,Li countertransport activity higher than age matched normal controls; geometric mean 283 (95% limits 259-340) vs. 193 (169-252) mumol/l RBC/h; p less than 0.01. Seven out of 29 subjects had values higher than the 95th percentile of normal subjects (Counter +). Both systolic and diastolic arterial pressures were significantly higher in Counter + than in Counter - patients. No significant differences were found as regards age, body mass index, diabetes duration, HbA1c, fructosamine, serum potassium, triglycerides, creatinine clearance and UAE. The logarithm of systolic pressure was independently positively correlated with ln Na,Li countertransport (r = 0.38; p less than 0.05), ln [Nai] (r = 0.38; p less than 0.05), and ln body mass index (r = 0.5; p less than 0.01) in diabetic patients. The main finding of this study is that diabetic adolescents with a high erythrocyte Na,Li countertransport rate have an arterial pressure significantly higher than patients with normal Na,Li countertransport fluxes.

Adolescent↗

[Erythrocyte sodium-lithium countertransport in diabetic adolescents].

Aim of this study is to evaluate whether among type I diabetic adolescents (IDDM) the erythrocyte Na-Li countertransport (CNT Na-Li) is correlated with arterial pressure and tubular sodium reabsorption. We have studied 16 IDDM adolescents (age 15 +/- 0.5 year) et 15 normal subjects (age 14.5 +/- 1 year). CNT Na-Li, creatinine and lithium clearances (as markers of glomerular filtration rate and proximal tubular sodium reabsorption) have been measured in all subjects and nocturnal urinary albumin excretion rate (UAER) was measured in IDDM adolescents. CNT Na-Li was 308 +/- 26 mumol Li/l RBC/h in IDDM adolescents and 211 +/- 74 mumol Li/l RBC/h in controls (p less than 0.01). The fractional excretion of lithium (FELi) was significantly reduced in IDDM adolescents compared to normal subjects (12 +/- 2 vs 19 +/- 2%; p less than 0.01). Among the IDDM adolescents, 5 had the CNT Na-Li higher than the 95th percentile of controls (greater than 360 mumol Li/l GR/h); their systolic arterial pressure was significantly higher than in diabetics with normal CNT Na-Li (126 +/- 2 vs 116 +/- 2; p = 0.03), while there were no differences for diabetes duration, glycemic control, serum potassium, creatinine clearance, FELi and UAER. The relationship between CNT Na-Li and arterial pressure in IDDM adolescents deserves further studies.

Adolescent↗

The behaviour of pyruvate dehydrogenase in circulating lymphocytes from diabetic children.

The basal and total pyruvate dehydrogenase activities were assayed in circulating lymphocytes from children with juvenile diabetes at diagnosis and after five days of insulin therapy and from control subjects. In untreated diabetic children, basal and total pyruvate dehydrogenase activities were deeply decreased and both showed very similar values; whereas, in control subjects basal activity was about 30% lower than total activity. In diabetic patients treated with insulin (in vivo situation), both basal and total activity levels were equal or even higher than those of the control subjects. The incubation of lymphocytes from diabetic patients with insulin (5 microU/ml) (in vitro situation) stimulates, but less than in vivo, the basal and total pyruvate dehydrogenase activities.

Blood Glucose↗

Course of retinopathy in children and adolescents with insulin-dependent diabetes mellitus: a ten-year study.

The prevalence and development of retinal changes were longitudinally documented from 1978 to 1987 in 112 insulin-dependent diabetic children by means of fluorescein angiography and fundus photography. At the end of the study period, 43 patients (38.4%) developed retinal changes, most of which were classified as minimal. Age, diabetes duration, puberty and long-term metabolic control were found to be independent factors affecting the development of retinopathy.

Age Factors↗