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Biomedical subjects

P Pozzilli

Publications and source records attributed to P Pozzilli.

At least 127 records · Page 7Linked to original sources
PubMed1994

New approach for in vivo detection of insulitis in type I diabetes: activated lymphocyte targeting with 123I-labelled interleukin 2.

Insulitis is considered the histopathological hallmark of type I (insulin-dependent) diabetes. In the non-obese diabetic (NOD) mouse, diabetes has never been observed in the absence of insulitis. The in vivo detection of insulitis could be of relevance for early prediction of diabetes. As approximately 15% of islet-infiltrating lymphocytes express interleukin 2 receptors, we have labelled recombinant interleukin 2 with 123I and used this radiopharmaceutical to detect insulitis by gamma camera imaging. We studied 71 prediabetic NOD and 27 normal Balb/c mice. Labelled alpha-lactalbumin was used as the control protein. In the first set of experiments we studied the tissue distribution of radiolabelled interleukin 2 in isolated organs from animals sacrificed at different time points. Higher radioactivity was detected in the pancreas of NOD mice injected with labelled interleukin 2, as compared to NOD mice receiving labelled alpha-lactalbumin (p < 0.003 at 20 min: p < 0.001 at 40 min; p < 0.001 at 60 min) or Balb/c mice injected with labelled interleukin 2 (p < 0.05 at 40 min; p < 0.001 at 60 min). In another set of experiments, gamma camera images have been acquired after injection of 123I-labelled interleukin 2. Radioactivity in the pancreatic region of prediabetic NOD and Balb/c mice showed similar kinetics to those observed by single organ counting, with higher accumulation in the pancreatic region of NOD mice (p < 0.04 after 22-45 min in NOD mice vs Balb/c mice).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Type I diabetes masquerading as type II diabetes. Possible implications for prevention and treatment.

Type I diabetes is probably due to the immune-mediated destruction of islet insulin-secreting beta-cells. This chronic destructive process is associated with both cellular and humoral immune changes in the peripheral blood that can be detected months, even years, before the onset of clinical diabetes. Throughout this prediabetic period, metabolic changes, including altered glucose tolerance and reduced insulin secretion, deteriorate at variable rates toward full-blown diabetes. The ability to predict subsequent clinical diabetes in those nondiabetic individuals with immune and metabolic changes has led to attempts to prevent the disease onset by therapeutic intervention. A small fraction of individuals with immune changes develop clinical diabetes that does not require insulin treatment. The onset of diabetes in these cases is usually in adult life, and because their diabetes is, at least initially, not insulin-dependent, they appear clinically to have type II diabetes. Such patients probably have the same disease process as patients with type I diabetes in that they have similar human leukocyte antigen (HLA) genetic susceptibility as well as autoantibodies to islet antigens. It is proposed that non-insulin-dependent diabetic patients who have markers that characterize individuals at risk of type I diabetes may be suitable candidates for those same therapeutic strategies that seek to prevent progression to insulin-dependence or even to reestablish normal glucose tolerance.

Autoimmunity↗
PubMed1994

Relationship between dairy product consumption and incidence of IDDM in childhood in Italy.

OBJECTIVE: To test the hypothesis that the consumption of dairy products, including fluid cows' milk and cheese, is related to the incidence of insulin-dependent diabetes mellitus (IDDM), we correlated incidence rates in children 0-14 years of age with cows' milk and cheese consumption in nine regions of a single country, Italy. RESEARCH DESIGN AND METHODS: Data on the incidence of IDDM were derived from the only nine Italian regions where primary and secondary sources of ascertainment were available for 1991. Data on fluid cows' milk and cheese consumption in the corresponding year in each region were obtained from the National Institute of Statistics. RESULTS: The correlation between fluid milk consumption and incidence of IDDM in Italy was 0.84 (P < 0.004, Poisson regression analysis). Cheese consumption was not related to IDDM incidence. CONCLUSIONS: The results indicate that there is a relationship, even in a single country, between dairy product consumption and the incidence of IDDM that is confined to fluid milk consumption. Cows' milk may contain a triggering factor for the development of diabetes, but the high incidence of IDDM in Sardinia and in other countries worldwide cannot be explained simply by the quantity of fluid cows' milk consumed.

Adolescent↗
PubMed1994

Combination of nicotinamide and steroid versus nicotinamide in recent-onset IDDM. The IMDIAB II Study.

OBJECTIVE: The aim of this study was to compare the effect of nicotinamide (NCT) alone or in combination with a cortisone-like substance, deflazacort (DFL), on the integrated parameters of metabolic control in patients with the recent-onset of insulin-dependent diabetes mellitus (IDDM). RESEARCH DESIGN AND METHODS: Thirty-six patients who were diagnosed with diabetes between 5 and 35 years of age entered a randomized, double-blind, 1-year prospective study. Group A (n = 18) received NCT for 1 year (25 mg.kg-1.day-1) plus DFL for 3 months (0.6 mg.kg-1.day-1 in the first month, 0.3 mg.kg-1.day-1 in the other 2 months). Group B (n = 18) received NCT for 1 year (25 mg.kg-1.day-1) plus placebo for the first 3 months. All patients were treated with intensified insulin therapy. RESULTS: At 3 months after diagnosis, the insulin dose was significantly higher in group A compared with group B (P < 0.03) with similar HbA1 levels. Basal and stimulated C-peptide levels in group A of both adults and children were significantly higher compared with patients of group B (P < 0.05 and P < 0.03, respectively). At the end of a 1-year follow-up, basal C-peptide did not differ between the two groups, although stimulated C-peptide was still significantly higher in patients of group A compared with group B (P < 0.05). Finally, insulin requirement did not differ between the two groups. CONCLUSIONS: A short-term course of DFL therapy at diagnosis in addition to NCT slightly increases glucagon-stimulated but not basal beta-cell function after 1 year.

Adolescent↗
PubMed1994

[The magnetic resonance imaging of abdominal aortic aneurysms].

The diagnostic role of Magnetic Resonance Imaging (MRI) was investigated in the study of abdominal aortic aneurysms and compared with that of Computed Tomography (CT) and digital subtraction angiography (DSA). Magnetic Resonance angiography (MRA) was performed on 21 patients with radiologically proved abdominal aortic aneurysms, using a superconductive 1.5 T magnet (GE, Signa Advantage); the 2D TOF technique with gradient-echo sequences was used (SPGR: FA 45-60 degrees, TR/TE 33/7, ST 2 mm, 1 nex, 256 x 128 matrix, inferior presaturation and flow compensation). The images acquired on the axial plane were reconstructed according to MIP and rotated on the z-axis from +90 degrees to -90 degrees. In all cases SE 2D T1- and T2-weighted sequences were acquired on the axial plane. Twelve patients were examined with MRI, CT and DSA; 3 with MRI and CT; 2 with MRI and DSA and finally 4 with MRI only. The radiologic studies were then reviewed blind and the results of the different methods compared. In all cases MRI yielded similar information to CT and DSA as to aneurysm extent and size, vessel involvement, status of visceral, iliac and common femoral arteries and finally the conditions of perianeurysmatic tissues. The authors conclude that MRI is a useful and accurate technique for the preoperative examination of abdominal aortic aneurysm patients.

Adult↗
PubMed1993

IDDM and rainfall.

Explore the source record for details and available documents.

Diabetes Mellitus, Type 1↗
PubMed1993

Tolbutamide reduces the incidence of diabetes mellitus, but not insulitis, in the non-obese-diabetic mouse.

The functional state of beta cells may influence the rate of their destruction in Type 1 (insulin-dependent) diabetes mellitus. We examined the effect of diazoxide, which inhibits insulin secretion, or tolbutamide, which stimulates insulin secretion, upon the incidence of diabetes in the non-obese-diabetic (NOD) mouse. Female mice were treated from 3-30 weeks of age with diet containing diazoxide 250 mg.kg-1 or tolbutamide 125 mg.kg-1. The cumulative incidence of diabetes at 35 weeks was similar in the diazoxide (16 of 24) and control (18 of 24) groups, but reduced in the tolbutamide group (10 of 23, p < 0.04 vs control group). In a second experiment, treatment was started from 9 weeks of age, by which time insulitis is already present. The cumulative incidence of diabetes at 35 weeks was 16 of 24 in controls, 15 of 24 on diazoxide and 11 of 24 on tolbutamide (p = NS vs control). A third experiment compared the effect of treatment from 3 weeks with control diet or diet containing tolbutamide 125 mg.kg-1 or 500 mg.kg-1. Diabetes was reduced by tolbutamide treatment, with a cumulative incidence of 25 of 31 in controls, 18 of 30 on tolbutamide 125 mg.kg-1 (p < 0.04) and 14 of 32 on 500 mg.kg-1 (p < 0.002), although the difference between the two treatment groups failed to reach statistical significance. A fourth experiment showed that treatment from 3-12 weeks with diazoxide 1000 mg.kg-1 increased the extent of insulitis compared with controls and animals treated with tolbutamide 500 mg.kg-1.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1993

NOD mouse colonies around the world--recent facts and figures.

Non-obese diabetic (NOD) mice are commonly used in autoimmune research. However, the diversity of these mice in developing autoimmune disease under different conditions prompted a group of researchers to compile a questionnaire on this subject. Here Paolo Pozzilli and colleagues comment on the results of this survey.

Age Factors↗
PubMed1993

The effect of a heparin analogue, ITF-5005, on diabetes incidence and insulitis in the non-obese diabetic mouse.

It has been suggested that heparin and its analogues may have a suppressive effect on the immune response by interfering with T-lymphocyte heparinase activity, thus altering the ability of T-lymphocytes to penetrate the extracellular matrix and migrate to target tissues. We have investigated whether a heparin analogue (ITF-5005) can alter lymphocytic infiltration of the endocrine pancreas (insulitis) and/or diabetes incidence in the non-obese diabetic (NOD) mouse. Sixty-four NOD mice were divided at weaning and injected subcutaneously five times per week with either 18, 36 or 72 micrograms/kg body weight of ITF-5005 or saline as a control. At 12 weeks of age, the animals were culled and their pancreata sectioned, stained and assessed 'blind' for insulitis and insulin containing cells. Insulitis was similar in all groups as was the proportion of insulin-containing cells. To determine the effect on diabetes incidence, two groups of mice were injected with either saline or 140 micrograms/kg body weight of ITF-5005 from weaning until 30 weeks of age. No difference was found in overall diabetes incidence; however, disease onset was significantly accelerated in the treated group. We conclude that ITF-5005, at the doses employed, has no effect on insulitis or the proportion of treated group. We conclude that ITF-5005, at the doses employed, has no effect on insulitis or the proportion of insulin-containing cells found in the pancreas, but that it can accelerate the course of diabetes in the NOD mouse.

Animals↗
PubMed1993

Intervention therapies for insulin-dependent diabetes.

Treatment of insulin-dependent diabetes remains problematic since there continues to be high rates of morbidity and mortality among affected patients. Good outcomes are most likely to be more common among patients who maintain endogenous insulin reserves for the longest time following diagnosis. The disease process can now be identified in its early, pre-symptomatic stages and thus, the time has come for the investigation of preventive therapies through multicenter clinical trials. A wide variety of strategies are available and their choice should be dependent on the pathogenic stage of disease at which treatment is initiated. This stage-specific approach to prevention is discussed with a particular focus on those therapies that will soon be tested in clinical trials.

Animals↗
PubMed1993

[Comparison of Gunther, Filcard and LGM definitive caval filters. Our experience].

The authors report their experience with 30 caval filters placed throughout 3 years, and compare it with the data from the literature. In 8 patients (26.5%) Gunther filters were used, in 16 cases (53.5%) Filcard filters (4 DF-01 and 12 DF-04) and finally the last 6 patients (20%) were treated with LGM filters. In 18 cases (60%) the filters were positioned through right common femoral vein, whereas in the remaining 12 patients (40%) they were placed through the right internal jugular vein. Early complications were 1 mispositioning (3.3%) with a LGM filter, 2 incomplete opening (6.6%) of Filcard DF-01 filters, 3 significant tiltings (10%) with Filcard DF-04 filters. One patient (3.3%) died one week after the placement of a Gunther filter. The radiologic follow-up, which included controls with conventional radiology, US, cavography, MR and CT revealed no later complications. All the filters exhibited both advantages and disadvantages. Although all the filters commonly in use are effective to prevent pulmonary embolism, further experience is necessary to find out the "ideal" filter.

Adult↗
PubMed1992

Polymorphisms at the GLUT1 (HepG2) and GLUT4 (muscle/adipocyte) glucose transporter genes and non-insulin-dependent diabetes mellitus (NIDDM).

In order to determine the possible contribution of the GLUT1 (HepG2) glucose transporter gene to the inheritance of non-insulin-dependent diabetes mellitus (NIDDM), two restriction fragment length polymorphisms (RFLPs) and the related haplotypes at this locus were studied in 48 Italian diabetic patients and 58 normal subjects. Genotype frequencies for the XbaI polymorphism were significantly different between patients and controls (XbaI: chi 2 = 9.80, df = 2, P less than 0.0079). A significant difference was also found in the allele frequencies between NIDDM patients and controls (chi 2 = 9.39, df = 1, P less than 0.0022), whereas no differences were found for the StuI RFLP. No linkage disequilibrium was detected between the XbaI and StuI RFLPs in this sample. The analysis of the four haplotype frequencies (X1S1, X1S2, X2S1, X2S2) revealed a significant difference between diabetic patients and controls (chi 2 = 14.26, df = 3, P less than 0.002). By comparing single haplotype frequencies, a significant difference between the two groups was found for the X1S1 and X2S2 haplotypes. A two-allele RFLP at the GLUT4 (muscle/adipocyte) glucose transporter gene, detected with the restriction enzyme KpnI, was also examined; no differences were found between patients and controls for this RFLP. The finding of an association between polymorphic markers at the GLUT1 transporter and NIDDM suggests that this locus may contribute to the inherited susceptibility to the disease in this Italian population.

Adipose Tissue↗
PubMed1992

Early T-cell defects in pre-type 1 diabetes.

Alterations of lymphocyte subsets have been recently reported in pre-type 1 diabetes but the relation with other immunological markers, in particular islet cell antibodies (ICA), is still unknown. In the present study, we have investigated prospectively changes of lymphocyte subsets in 86 first-degree relatives of patients affected by type 1 diabetes and correlated such modifications with ICA titres. Among individuals with persistent ICA, 8 had ICA titres of more than 20 JDF units, 14 had ICA titres between 5 and 20 JDF units and 64 had ICA titres between 0 and 5 JDF units. First-degree relatives with ICA titres of more than 20 JDF units had significantly decreased proportions of CD3 cells. This reduction was predominantly in the CD4 subset, giving rise to a decreased CD4/CD8 lymphocyte ratio. Those with ICA titres between 5 and 20 JDF units showed abnormalities in both CD3 and CD4 lymphocytes, but not in CD4/CD8 lymphocyte ratio. Further characterization of the CD4 cell subset was performed using three other monoclonal antibodies, CD45RO (UCHL1), CD45RA and CD29, phenotyping memory T-cells, the inducer cells of suppressor function and helper-inducer cells, respectively. The proportions of total CD45RO and CD45RA were not significantly different among first-degree relative with distinct ICA titres in a cross-sectional study, whereas a trend towards a reduced proportion of CD4/CD45RA cells was observed. The longitudinal study demonstrated that individuals potentially susceptible to the development of type 1 diabetes and who possess high titres of ICA have impairment of CD4/CD8 lymphocyte ratio, mainly due to a reduction in the CD4 subset.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗