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P Pozzilli

Publications and source records attributed to P Pozzilli.

At least 145 records · Page 8Linked to original sources
PubMed1992

Immunotherapy with ciamexon in the non obese diabetic (NOD) mouse.

Ciamexon (CMX), a new immunomodulatory compound acting mainly on B-lymphocytes was given orally to 42 NOD mice divided into three sex and litter matched groups (A: 0.3 mg/mouse/day CMX, B: 1.5 mg/mouse/day CMX, C: control) from 7 weeks of age. Animals were followed up for evaluation of diabetes incidence up to 32 weeks of age. There was a tendency for a delayed onset of hyperglycemia in mice of group B up to 26 weeks of age; however no significant difference in the cumulative incidence of diabetes at 32 weeks of age was observed (A: 57.5%, B: 38.5%, C: 38.5%). No differences were found in the number of infiltrated islets in animals culled at 10 weeks of age treated with CMX from 4 weeks of age. We conclude that CMX does not modify the course of insulitis and diabetes incidence in NOD mice although though the appearance of glycosuria was delayed by this treatment.

Adjuvants, Immunologic↗
PubMed1992

Polymorphisms at the GLUT2 (beta-cell/liver) glucose transporter gene and non-insulin-dependent diabetes mellitus (NIDDM): analysis in affected pedigree members.

The precise genetic defects underlying the etiology of non-insulin-dependent diabetes mellitus (NIDDM) have yet to be identified. The beta-cell/liver glucose transporter gene GLUT2 represents a good candidate for the etiology of the disease, being involved in the glucose signalling for beta-cell insulin release. Population association studies of the GLUT2 gene in NIDDM have so far yielded controversial results. In order to determine the possible contribution of this gene to the inheritance of NIDDM, we have employed a new approach, where two polymorphic markers of the GLUT2 locus, detected with the restriction enzyme Taq-1, were examined for linkage with the disease in a group of 22 Italian pedigrees with affected members (n = 50). Departure from independent segregation between markers and disease was analyzed by the Affected-Pedigree-Members (APM) statistical method. Furthermore, association analysis between the Taq-1 RFLPs at the GLUT2 locus and NIDDM was performed in a group of diabetics with a strong family history, comprising the 22 probands and 23 other diabetics with an affected first-degree relative. The results indicate that there was no segregation distortion between the Taq-1 markers of the GLUT2 gene and the disease in the pedigrees examined. Also, no significant difference in genotype distribution, haplotype and allele frequencies was found between diabetics and controls for the two Taq-1 RFLPs. We conclude that genetic variation at the GLUT2 transporter gene is unlikely to contribute in a major way to the inheritance for NIDDM in this Italian population.

Aged↗
PubMed1992

Sib-pair analysis of adenosine deaminase locus in NIDDM.

Recently, linkage between the ADA gene locus and MODY, a subtype of NIDDM, has been reported. The possibility that the region of chromosome 20q containing the ADA locus also may play a role in susceptibility to NIDDM needs to be investigated. Therefore, we examined the linkage between the ADA locus and NIDDM in affected siblings of 50 European white diabetic pedigrees--21 Italian and 29 British. Departure from independent segregation of the disease and an Alu VpA polymorphism within the 5' flanking region of the ADA locus was tested in the affected sib-pairs with the APM statistical method. After DNA amplification by the PCR and PAGE, five alleles were identified in the ALU VpA tract at the ADA locus in the two populations. Allele frequencies did not differ significantly between the two populations (chi 2 = 2.426, P > 0.05 [NS]). Analysis of the 50 diabetic sib sets, and independently of the Italian and British groups of affected sib pairs, revealed no segregation distortion between the marker locus and NIDDM. We conclude that mutations within or around the ADA locus are unlikely to play a major role in the etiology of NIDDM.

Adenosine Deaminase↗
PubMed1992

Secondary aldosteronism documented by plasma renin and aldosterone circadian rhythm in subjects with kidney or heart transplantation.

The circadian rhythm (CR) of plasma renin activity (PRA), plasma aldosterone (PA), and plasma cortisol (PC) was investigated in 8 patients with kidney transplantation, and in 10 patients with heart transplantation. Ten clinically healthy subjects were studied as controls. The transplanted patients were all under cyclosporine treatment associated with prednisone (PDN). Time-qualified levels of PRA and PA were seen to be higher than normal in both groups of transplanted patients. The analysis of PRA and PA circadian rhythm provided evidence for a systematically higher level of within-day concentrations. The higher level of oscillation suggests the occurrence of a condition of hyperreninemic hyperaldosteronism. The higher levels of PRA and PA 24-h values show no periodicity. The finding suggests the abrogation of the rhythmic function for renin-aldosterone system. The disappearance of PRA-PA circadian rhythm seems to be attributable to a side effect of immunosuppressive therapy.

Adult↗
PubMed1992

[The circadian rhythm of plasma vasoactive intestinal peptide, atrial natriuretic peptide, renin activity, aldosterone and cortisol in heart transplantation. The effects of immunosuppressive therapy].

Vasoactive intestinal peptide (VIP) is released both by neural endings and lymphocytes. Aim of our investigation was to study the effects of immunosuppressive therapy on VIP plasma concentrations. The research has been performed on 10 heart transplanted patients assuming cyclosporine (CYCL) and prednisone (PRED). The circulating T lymphocyte subsets, atrial natriuretic peptide (ANP), plasma renin activity (PRA), plasma aldosterone (PA) and plasma cortisol (PC) have been also assayed. Blood pressure (BP) and heart rate (HR) have been monitored over a 24-hour period to detect whether circulating VIP in heart transplanted patients is influenced by pharmacologically-induced interactions. Seriate samplings along the 24-hour span have been performed. Mean values of ANP, PRA and PA were increased, while VIP, PC and T lymphocyte subsets were decreased in heart transplanted patients as compared to clinically healthy subjects. ANOVA and Cosinor analysis showed, respectively, a statistically significant 24-hour variability and circadian rhythm for all the investigated variables only in normal subjects. BP and HR circadian rhythm in heart transplanted patients suggest that the adrenergic activity regulating the cardiovascular system is restored. This finding argues that the reduction in VIP plasma concentrations is likely due to the decreased lymphocyte production secondary to immunosuppressive therapy, or can also be ascribed to the inhibiting action of high circulating levels of ANP.

Adult↗
PubMed1992

[Strecker vascular prostheses. The median- and long-term results].

Between September 1989 and October 1991, 37 patients were treated with percutaneous transluminal angioplasty (PTA) and the insertion of a Strecker stent. The patients--35 men and 2 women, mean age 61 years, range 41-47--had 39 lesions in 39 arteries--30 iliac arteries, 8 femoral arteries and 1 popliteal artery. The lesions included 19 dissections after PTA (48%), 13 residual stenoses > 30% after PTA (34%), 7 restenoses (18%) and 4 total occlusions (10%). The stents were successfully inserted in 37/39 cases (95%). Complications occurred in 4 patients: 2 acute thromboses (resolved with local infusion of urokinase), 1 distal embolization and 1 pseudoaneurysm. Distal embolization, despite aspiration and local fibrinolysis, required leg amputation after about 1 month. The max follow-up period was 2 years (average 15 months): patency was 97% at 1 and 3 months, 100% at 6 and 12 months, 95% at 18 months and 100% at 24 months. Total patency was 85% at 24 months. Four patients were lost to follow-up, and 1 patient died. Four stents failed: 2 of them at 1 and 3 months, and surgery was performed, and 2 at 18 months. Intimal hyperplasia of minimum grade occurred in 2 vessels. There was no evidence of stent migration. The authors believe that the placement of Strecker stents is a valuable approach to the treatment of PTA complications.

Adult↗
PubMed1992

A radiopharmaceutical for imaging areas of lymphocytic infiltration: 123I-interleukin-2. Labelling procedure and animal studies.

The labelling of interleukin-2 (IL-2) with 123I and its in vivo application for imaging chronic pathological lymphocytic infiltrations are described. The lactoperoxidase/glucoseoxidase technique was the labelling method of choice leading to immunoreactive IL-2 with high specific activity. Labelled IL-2 was injected in diabetes-prone non-obese diabetic (NOD) mice with pancreatic lymphocytic infiltration. As control animals, Balb/c mice were used. As specificity control, monoclonal antibodies AMT13 and UCHT1, bovine serum albumin and alpha-lactalbumin were radioiodinated and injected in mice. Eighteen NOD mice and four control Balb/c mice were used for gamma camera imaging experiments. Fifty-four NOD and 20 Balb/c mice were used for time course single organ counting and autoradiography. Gamma camera images showed that radioactivity accumulated in the pancreatic region from the 10th minute onwards in NOD mice injected with 123I-IL-2 but not in Balb/c mice, or in NOD mice injected with control radiopharmaceuticals. These findings were confirmed by counting the radioactivity present in single organs. Autoradiography of NOD pancreas, after injection of labelled IL-2, showed that radioactivity was specifically associated with infiltrating lymphocytes. In conclusion, this technique is highly specific and easy to perform and we suggest its application in humans for in vivo detection of areas of lymphocytic infiltration.

Animals↗
PubMed1992

Viral infection induces cytokine release by beta islet cells.

Viral infection has been suggested to play a triggering role in the pancreatic beta cell destruction which occurs in insulin-dependent diabetes (IDDM). However, the underlying mechanism of this phenomenon is unknown. In this study a human insulinoma cell line has been infected with measles, mumps and rubella viruses since a temporal association is reported between the clinical onset of IDDM and diseases caused by these viruses. The infection with measles and mumps viruses induced the release of interleukin-1 (IL-1) and interleukin-6 (IL-6) by the cell line as assessed by a bioassay and up-regulated the expression of human leucocyte antigen (HLA) class I and class II antigens as evaluated by cytofluorimetric analysis. Stimulation with rubella virus induced the release of IL-6 only and had no effect on HLA antigen expression. These data show for the first time that IL-1 and IL-6 secretion by an insulinoma cell line may occur after viral infection and suggest that cytokine release and increased expression of HLA molecules by beta cells may act to induce the immune response towards beta cells in IDDM.

Cell Line↗
PubMed1992

[Loco-regional fibrinolysis in peripheral arterial bypasses. Our experience].

Thirty-one patients (29 males and 2 females) with 34 thrombosed grafts were treated by direct intra-arterial infusion of urokinase; the lesions were acute in 27 cases and chronic (2-4 months) in 4. Urokinase was infused in doses of 50,000 UI/h. Angiographic follow-up exams were performed every 12 hours. The infusion was stopped when lumen patency was re-established and there was no significant mural thrombus or peripheral embolus. Treatment usually lasted 4-72 hours (average: 18 hours). The hematological status was controlled by measuring plasma fibrinogen, coagulation time, partial thromboplastin time, prothrombin and antiplasmin time. Initial success rate was 76% (23 patients). Overall 1-year patency was 56% in 23 cases: 85% in the patients with correctable lesions by means of surgery or PTA, and 46% in the patients with non-correctable lesions. After the first period, patency remained high in the patients followed up to 5 years. Our experience confirms that lysis of a thrombosed graft is possible by the local infusion of a low-dose fibrinolytic agent and exhibits high success rate and low complication rate in acute and chronic obstructions.

Aged↗
PubMed1991

Circadian rhythm of T-lymphocyte subsets, cortisol and cyclosporin in kidney-transplanted subjects.

The present study deals with the 24-h changes in circulating lymphocyte subpopulations in eight subjects with kidney grafts established for 2 to 5 years and treated with cyclosporin. The control group consisted of ten age-matched clinically healthy subjects. The chronobiological analysis of time series documented that the circadian rhythm of T-lymphocyte subsets is undetectable in transplanted subjects. Cortisol rhythmicity persists, however, suggesting that the abolition of T-cell rhythmicity is not attributable to a desynchronisation of the adrenal cycle. Even though the therapy was combined with prednisolone, the abrogation of rhythmicity for T-lymphocyte subpopulations seems to be related to the immunosuppressive action of cyclosporin, as the plasma concentrations of the drug show no periodic variations along the 24-h span. Antirejection therapy of kidney-transplanted subjects could be adjusted so that cyclosporin is given at a time that would promote suppression of T-lymphocytes without altering their rhythmic performance.

Adult↗
PubMed1991

Cytokines in sera from insulin-dependent diabetic patients at diagnosis.

Cytokines are known to play an important role in autoimmunity and have been suggested to be involved in the pathogenesis of insulin-dependent diabetes (IDDM). In the present study we have measured IL-1, IL-2, IL-4, IL-6, interferon-gamma (IFN-gamma) and tumour necrosis factor (TNF) (using both immunoassays and bioassays) in sera from 50 patients affected by IDDM at the time of clinical diagnosis and 51 age and sex matched controls. Detectable levels of IL-1, IL-2, IL-6 and IFN-gamma were found in the serum of a small percentage of subjects and were not significantly different between patients and controls. IL-4 was detectable in a higher number of both patients and controls and circulating TNF-alpha (greater than 1 U/ml) was found in a percentage of patients (24%) significantly higher than controls (P less than 0.01). Raised levels of TNF-alpha were detectable using an immunoenzymatic assay whereas TNF bioactivity in these samples was negligible. We conclude that the presence of immunoreactive TNF-alpha in the patient's sera may reflect an increased localized production of this cytokine at pancreatic level. However, the measurement in serum of other cytokines does not add information on the role that they may play in the pathogenesis of IDDM.

Cytokines↗
PubMed1991

Parathyroiditis in the non-obese diabetic mouse--a new finding.

Autoimmune reactions to parathyroid cells have been observed in human autoimmune polyendocrinopathy, but such findings have not been described in animal models of polyendocrine autoimmunity. We report here three cases of lymphocytic infiltrations in 12 parathyroid glands identified in a total of 18 thyroid glands studied in the non-obese diabetic (NOD) mouse. The majority of parathyroid-infiltrating lymphocytes possessed the helper/inducer phenotype as defined by the L3T4 monoclonal antibody. Parathyroiditis was accompanied by lymphocytic thyroiditis only on one occasion, whereas in other cases of thyroiditis, lymphocytic infiltration of the parathyroid was undetectable. We conclude that parathyroiditis in the NOD mouse is part of the wide spectrum of autoimmunity observed in this animal model of diabetes.

Animals↗
PubMed1991

Temporal interrelationships between circadian rhythms of vasoactive intestinal peptide and T lymphocyte subpopulations.

Recent investigations documented an immunosuppressive action of VIP. Previous studies demonstrated that T lymphocytes exhibit a circadian rhythm (CR). This investigation was, thus, performed with the aim of detecting the relationships intercurrent between the 24-h patterns of VIP and T lymphocyte subsets. The hypothesis was formulated that circulating VIP may play a role in controlling the CR of T cells. The research was carried out on 10 clinically healthy subjects, tested six times during the 24-h span by assaying circulating levels of VIP and total T (OKT3), T helper (OKT4), and T suppressor/cytotoxic (OKT8) lymphocytes. Time data series were analyzed by Cosinor method. All investigated variables were seen to be characterized by a statistically significant CR. While the acrophase of VIP CR was found to be located at 18.20, the crest of OKT3, OKT4, OKT8 CR was seen to occur at 03.04, 02.16 and 02.56, respectively. The phase shift was found to be significant, suggesting that VIP and T lymphocytes physiologically fluctuate with a phase angle during their nyctohemeral cyclicity. The finding can be regarded as an indirect evidence of a negative VIPergic chronoregulation of CR of T lymphocytes.

Adult↗
PubMed1991

[Circadian rhythm of the renin-angiotensin-aldosterone system in subjects with kidney and heart transplants].

The present investigation evaluates the circadian rhythm of renin-angiotensin-aldosterone system (RAAS) in subjects with kidney (KTS) or heart (HTS) transplantation undergoing conventional therapy with prednisone and cyclosporine. RAAS circadian rhythmicity has been compared with the circadian cycle of cortisol as a marker rhythm. The chronobiological exploration has been performed by measuring the circulating levels of plasma renin activity (PRA), plasma aldosterone (PA), and serum angiotensin-converting-enzyme (SACE) and plasma cortisol (PC) in serial samplings collected six times over a 24-h span. Time-qualified levels of plasma cyclosporine (CYCL) have been established. The control group consisted of 10 normal subjects matching in age and sex. Individual data series were analysed by the Cosinor method. The chronobiometric estimates demonstrate the lack of a circadian rhythmicity for PRA, PA and SACE in KTS and HTS. The PC circadian rhythm is demonstrable in KTS, but not in HTS. The abolition of the RAAS circadian rhythm in both KTS and HTS seems to be attributable to the effects exerted by CYCL. The disappearance of the PC circadian rhythm may be due to the prednisone therapy that is administered twice a day in HTS but not in KTS. The asynchronous effects of this drug lead us to suggest that antirejection therapy may be optimized by administering prednisone and cyclosporine according to a chronomodulated scheme.

Adult↗