A prediabetic model in the biobreeding Worcester rat.
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Biomedical subjects
Publications and source records attributed to P Petruzzo.
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BACKGROUND: Iloprost, a prostaglandin I2, is chemically stable and it has been successfully used by intravenous infusion in severe limb ischemia. Usually Iloprost is diluted in 0.9% sodium chloride solution and infused intravenously for six hours each day for 28 days in hospital. METHODS: In the present study after the first three days of infusion with a traditional pump in hospital, a home pump has been utilised for the infusion of Iloprost at home. This device allows the continue infusion of Iloprost at a flow rate of 2 ml/h for six days, then the pump is filled with a new solution. The home pump consists of a protective shell in polycarbonate (10 x 12 cm), 270 ml of volume, inside there is a balloon reservoir (3 membranes) which is filled with Iloprost. The structure of Iloprost does not change into the home pump as evidenced by HPLC studies and its continue infusion allows plasmatic high levels of its active isomers during the 28 days of therapy. In 30 patients, 25 men and 5 women (mean age 61 years) with Fontaine stage IIB (6), III (5) and IV (19) POAD Iloprost has been infused with the home pump. The follow-up period was 1 to 16 months. RESULTS: The results have shown 4 major amputations and 1 death, in 9 patients complete pain relief and ulcer healing, and in 6 patients only improvement in relief of rest pain and ulcers. CONCLUSIONS: All the patients appreciated this system of infusion because they had a normal life; in addition it is less expensive because the patients stay in hospital only 3 days.
Microencapsulation of islets of Langerhans has been proposed in order to prevent immune rejection and possible recurrence of autoimmune disease. This study introduces a fast simple one-step microencapsulation procedure which allows the production of small sized barium-alginate beads. The volume of the microcapsules produced was approximately that of the encapsulated islets. Consequently, the insulin kinetics and the oxygen diffusion were favoured, while the transplanted tissue volume was reduced. Electron microscopy and immunoisolating testing were performed to evaluate the molecular cut-off, the physical and chemical characteristics of these microcapsules. Immunohistochemical staining and perifusion experiments of microencapsulated pancreatic islets showed their viability after the encapsulation procedure as well as in vivo experiments. In fact, microencapsulated porcine islets were implanted intraperitoneally into streptozotocin-diabetic rats. The xenografts reversed the hyperglycemic state and functioned for a period ranging from 9 to 385 days. The low mannuronic acid concentration and the purity grade of the alginate, exerted a combined influence on the capsule biocompatibility as in vivo studies showed.
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Porcine and human pancreatic islets were microencapsulated in an alginate-polylysine biomembrane and put in a chamber of a new vascular prosthesis composed of an inner tubing of Dacron mesh and an outer tubing of expanded polytetrafluorethylene material. The vascular prosthesis was anastomized between the iliac artery and the contralateral vein of diabetic dogs. The recipients did not receive any immunosuppressive therapy. Function of porcine and human islets was monitored by measuring serum glucose levels and human C-peptide concentrations. After transplantation, serum glucose levels were maintained at values lower than 200 mg/dl, and C-peptide concentrations were between 0.8 and 3.2 ng/ml. Injected insulin requirements decreased by 50%-60%. Four to 8 weeks after transplantation, histologic examination showed well-preserved and functioning islets in the majority of intact microcapsules. Fibrin and inflammatory cells were not observed in the chamber. These data suggest long-term survival and function of microencapsulated pancreatic islets in the vascular prosthesis.
Picotamide is the most interesting compound of 4-OH isophthalic acid. It is effective in vitro and in vivo. Picotamide induces inhibition of platelet aggregation: it is a thromboxane synthetase inhibitor and a thromboxane receptor antagonist. Picotamide causes cyclic endoperoxide accumulation and diverts their metabolism toward PgI2 synthesis in endothelial cells. PGI2 stimulates the adenylate cyclase with cAMP synthesis which makes platelets less sensitive to aggregatory stimulation. Picotamide induces enhancement of fibrinolytic activity, with significant reduction in the level of circulating plasminogen but in the same time it does not affect antithrombin III and FDP levels. In the present study picotamide or placebo were administered in a double blind trial at 600 mg daily for six months to 51 patients effected by diabetic macro and/or microangiopathy. The patients were 38 men and 13 women, the age was between 20 and 80 years (mean age 62.34). Twenty-seven patients were affected by type I diabetes and 24 by type II diabetes. Twenty-three of these patients presented macro-angiopathic lesions, 9 only microangiopathic lesions and 13 both. Twenty-five patients received picotamide and the other 25 an identical placebo for six months. One patient manifested myocardial infarction during the wash-out period and failed to enter the study. The following determinations were carried out: at T0 clinical examination, Doppler ultrasonography, Winsor Index, laboratory parameters; after 90 days (T90) clinical examination and Winsor Index and after 180 days (T180) were repeated photoplethysmography and clinical parameters too. Patients were not only evaluated for the vascular disease of lower extremities, but also for the other complications of diabetes, as retinopathy, nephropathy, cardiac and cerebrovascular disease.(ABSTRACT TRUNCATED AT 250 WORDS)
The purpose of the present study was to investigate the effect of atenolol, a beta 1-selective blocker, along with flunarizine, a calcium antagonist, in the management of Raynaud's disease. Forty patients with Raynaud's disease were randomized into a trial in which atenolol (50 mg daily) was given with flunarizine (10 mg daily). During the trial all patients were subjected to finger photoplethysmography and were given a diary to note daily the number and duration of the crises and presence or absence of pain and paresthesia. The association of atenolol with flunarizine caused an 80% reduction in the number of vasospastic crises, a significant increase (p less than 0.001) in the photoplethysmographic wave amplitude, and complete disappearance of pain and paresthesia. These results were not observed in patients treated with a placebo. Flunarizine reinforces the action of atenolol in causing a decrease in vasoconstriction in patients with Raynaud's disease, as observed previously by us, in that it acts directly on the beta-presynaptic receptors or on the calcium slow channels connected to the beta-receptors. The present study confirms that the principal role in the physiopathologic progression of Raynaud's disease seems to be played by a modification of the beta-presynaptic receptors in the nerve endings of the peripheral vessels.
1. We investigated the hypothesis that the beta 1-adrenoceptor antagonist, betaxolol, can be accumulated by cardiac sympathetic nerve endings and then released together with noradrenaline during accelerans nerve stimulation. 2. Dogs were chronically treated with betaxolol (1 mg kg-1 daily, s.c.) for 7 days. Twenty four hours after the last dose, there was a significant retention of betaxolol in the heart of these dogs treated chronically with the beta 1-adrenoceptor antagonist. However, during in vivo accelerans nerve stimulation, the concentration of betaxolol in the coronary sinus was not modified, whereas the noradrenaline concentration increased significantly. 3. Chronic betaxolol treatment antagonized the tachycardia induced by electrical stimulation of the cardiac accelerator nerves or by intravenous isoprenaline. However, the tachycardia induced by nerve stimulation was not antagonized to a greater extent than that induced by isoprenaline. 4. These findings are discussed in relation to a similar in vivo study in dogs treated with propranolol, in which the drug was found to be released into the coronary circulation during stimulation of the accelerans nerve.
Under in vitro conditions, 3H-betaxolol was accumulated in rat atrial slices, reaching a tissue-medium ratio of 12.3 +/- 1.8 ml/g. This process was temperature-dependent, but ouabain-resistant. 3H-Betaxolol accumulated in atrial slices was subsequently released by electrical stimulation. The electrically-evoked release of 3H-betaxolol was abolished in the absence of calcium, and reduced in the presence of bretylium 10 microM. After surgical sympathetic denervation by stellate ganglionectomy there was a marked reduction in the endogenous content of noradrenaline and in the retention of 3H-noradrenaline in atrial slices. The concomitant decrease in the amount of 3H-noradrenaline released by electrical stimulation following denervation was modest, although statistically significant. Following sympathetic denervation, the tissue retention of 3H-betaxolol was not significantly affected, but the release of 3H-betaxolol by electrical stimulation was considerably reduced. After pretreatment with reserpine the amount of radioactivity released by electrical stimulation from slices labelled with 3H-betaxolol or 3H-noradrenaline was markedly reduced. The tissue retention of 3H-noradrenaline was reduced to a larger extent than that of 3H-betaxolol following the administration of reserpine. The simultaneous release of noradrenaline and betaxolol by nerve stimulation observed under our experimental conditions may represent a mechanism through which betaxolol can reach selectively the postsynaptic beta 1-adrenoceptors and reinforce beta-adrenoceptor blockade in the heart.
This report concerns the results of a study carried out to show the presence of presynaptic Beta adrenergic receptor supersensitivity in RD patients and the possibility to prevent or at least decrease this supersensitivity with Beta-blocker treatment. It is shown that the paradoxical vasoconstriction response to ISP infusion can be prevented in RD patients by the acute administration of Beta-blocker, such as Atenolol or DL Propranolol. Moreover, chronic treatment with the correct Beta-blocker was seen to prevent angiospastic crisis in these patients.
Recent studies have shown that a membrane p-glycoprotein, encoded by MDR1 gene, is involved in the transport of free cholesterol from the plasma membrane to endoplasmic reticulum, the site of cholesterol esterification by acyl-CoA:cholesterol acyltransferase (ACAT). Moreover, results deriving from our previous studies have shown that the rate of cell proliferation was positively correlated with cholesteryl ester levels as well as with ACAT and MDR1 gene expression. In this study, lipid content and the expression of the genes involved in cholesterol metabolism such as hydroxy-methylglutaryl coenzyme A reductase (HMGCoA-R), low-density lipoprotein receptor (LDL-R), ACAT and MDR1 have been investigated in control and atherosclerotic arteries. The results have shown that the levels of cholesteryl ester increase with the age of cadaveric donors in arteries prone to atherosclerosis (abdominal aorta, superficial femoral artery) and become predominant in advanced atherosclerotic lesions. The mRNA levels of ACAT and MDR1 showed the same age correlation, reaching the highest values in atherosclerotic specimens. These results suggest that MDR1 may be involved in the accumulation of intracellular cholesterol ester levels found in atherosclerotic lesions. Moreover, the levels of HMGCoA-R, LDL-R and ACAT gene expressions progressively increased with the age of cadaveric donors; conversely, in atherosclerotic specimens, the mRNA levels of HMGCoA-R and LDL-R drastically decreased while ACAT gene expression reached its maximum. These findings suggest a reactivation of normal homeostatic regulation of cholesterol in advanced and complicated lesions.
Results of clinical islet transplantation remain disappointing despite the advances in islet technology. Availability of human organs and control of rejection by adequate immunosuppressive therapy remain the unsolved problems. Transplantation of xenogeneic tissue enclosed in immuno-separating membranes without immunosuppressive drugs may be a solution. In the present study porcine pancreatic islets were isolated by semiautomated method and purified utilizing discontinuous Euroficoll gradients on IBM 2991 cell separator. The porcine pancreatic islets were encapsulated with a new one-step method utilizing a home-made droplet generator. Each microcapsule contained one or two islets and microcapsule diameter was approximately that of the islets. This condition allows an optimal diffusion of insulin, glucose, nutrients and oxygen. Consequently, perifusion experiments with encapsulated porcine islets revealed a typical biphasic pattern of insulin release as it was seen in unencapsulated controls. Human erythrocytes were encapsulated and incubated with serum containing hemolysins and complement. These experiments showed that the encapsulated erythrocytes were protected against the hemolytic activity of Ig G and complement fractions. In conclusion, this encapsulation procedure allows the production of a very thin barium alginate membrane around the islets with very little increase of the total volume of transplanted tissue.