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Biomedical subjects

P Marchetti

Publications and source records attributed to P Marchetti.

At least 271 records · Page 15Linked to original sources
PubMedDate not supplied

Biosynthetic human insulin does not modify circulating lipid and apolipoprotein concentrations in type I diabetic patients.

Since insulin modulates key enzymes of lipid metabolism, different biological activities of biosynthetic human insulin (BHI) and conventional insulins might induce different plasma lipid and apolipoprotein patterns in diabetic patients chronically treated with the former or the latter insulin preparation. In this study we have evaluated the effects of 3 months of therapy with BHI on plasma lipid and apolipoprotein concentrations in a group of type I diabetics previously treated with insulin of animal origin and the results have been compared with those from diabetics maintained on conventional insulin therapy. In the latter, no change occurred in the clinical and metabolic parameters. Patients transferred to BHI showed lower HDL-cholesterol and HDL3-cholesterol levels at 30 days from the beginning of BHI treatment, and both parameters returned to, and were maintained the basal values at subsequent controls. Total cholesterol, HDL2-cholesterol, triglycerides, apolipoproteins AI, AII and B remained substantially constant throughout the study. Glycometabolic control, which was evaluated by fasting plasma glucose and glycosylated hemoglobin, exhibited a transient, moderate deterioration at the 30-day control, and returned to basal level in the following weeks. No major change was noted as far as daily insulin dosage and relative body weight were concerned. Thus, long-term BHI treatment of type I diabetics does not cause any major change in plasma lipid and apolipoprotein patterns in comparison with animal insulin therapy, so that the validity of using BHI in the treatment of type I diabetes is confirmed.

Adult↗
PubMedDate not supplied

Metabolic control affects plasma lipid and apolipoprotein levels in women, but not in men, with IDDM.

In order to evaluate if in insulin-dependent diabetes lipid and apolipoprotein levels are differently affected by metabolic control in men and women, we measured the concentrations of fasting plasma glucose, mean plasma glucose, glycosylated hemoglobin, total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides, and apolipoproteins A and B in 94 sex matched patients. Diabetic men and women were strictly comparable as far as age, relative body weight and metabolic control were concerned. In women, total and LDL cholesterol, triglycerides and apolipoprotein A correlated positively with HbA1 but not with fasting and mean plasma glucose. In men, no correlation between metabolic control and lipid and apolipoprotein levels was found. We conclude that, in diabetic women, the degree of metabolic control may affect the concentrations of plasma lipids, thus explaining, at least in part, the increased risk for coronary atherosclerosis in these patients.

Adult↗
PubMedDate not supplied

Free insulin concentrations in immediately extracted plasma samples and their relationships to clinical and metabolic parameters in insulin-treated diabetic patients.

The relationships between free insulin and various clinical and metabolic parameters in insulin-treated diabetic patients are still not clear, possibly because of the technical difficulties in measuring free insulin. Recently, it has been demonstrated that in the presence of insulin antibodies only immediate centrifugation of blood and extraction of insulin antibodies provide an accurate evaluation of in vivo free insulin concentrations. In this study we evaluated the relationships between free and bound insulin levels, insulin antibodies, metabolic control and insulin requirement in 38 insulin-treated diabetic patients, in whom plasma free insulin was assayed in immediately processed samples. The main findings of our study are as follows. Free insulin concentrations ranged from 2.5 to 54 microU/ml; no difference was found between males and females; the unbound hormone level was inversely correlated to fasting plasma glucose (p less than 0.01) and HbA1c (p less than 0.02); a positive correlation was shown between free insulin and daily insulin dose; finally, free insulin concentrations were not correlated with insulin antibody binding.

Adult↗
PubMedDate not supplied

The metabolic effects of cyclosporin and tacrolimus.

The introduction of cyclosporin and, more recently, tacrolimus in the immunosuppression of transplanted patients has lead to prolonged graft survival and increased patients' life expectancy. It has been therefore possible to evaluate the effects of long-term treatment with these drugs and metabolic alterations in patients on cyclosporin or tacrolimus have been reported by several authors. In particular, the use of these drugs is associated with abnormalities of glucose and lipid metabolism. Post-transplant diabetes is more common with tacrolimus, probably due to more marked effects on the pancreatic beta-cells, whereas increased levels of cholesterol and triglycerides are more frequently associated with cyclosporin treatment, even though, in this latter case, steroid treatment seems to play a major role. Comparison and intervention studies must be planned to evaluate the best therapeutical approaches to control these abnormalities and to assess the possibility to further increase graft and patient survival by appropriate treatment of diabetes and hyperlipidemia.

Animals↗
PubMedDate not supplied

Outcome of 118 pancreas transplants with retroperitoneal portal-enteric drainage.

BACKGROUND: We have recently described a technique for retroperitoneal pancreas transplantation (RPTx) with portal-enteric drainage (PED). Further experience with 118 RPTx is detailed herein. METHODS: Between April 2001 and August 2004, 118 patients underwent RPTx with PED among 125 recipients (94.4%) scheduled for this procedure. Surgical complications and patient and graft survivals were recorded prospectively. RESULTS: After a minimum follow-up period of 3 months (mean 27.8 +/- 13.0 months), 18 recipients (15.2%) required relaparotomy because of bleeding (n = 6; 5.1%), allograft pancreatectomy due to either hyperacute/accelerated rejection (n = 3; 2.5%) or vein thrombosis (n = 3; 2.5%), leak from duodenojejunal anastomosis (n = 2; 1.7%), bleeding and vein thrombectomy (n = 1; 0.8%), or small bowel occlusion due to bezoar (n = 1; 0.8%). One patient had a negative relaparotomy and one underwent two relaparotomies. Most patients with hemorrhage (5/7; 71.4%) were recipients of solitary pancreas grafts managed with heparin infusion. No venous thrombi extended into recipient's superior mesenteric vein. Nonocclusive venous thrombosis was diagnosed with duplex ultrasonography and confirmed at computed tomography in seven patients (5.1%). None of these patients lost graft function. Ten patients (8.5%) were diagnosed with peripancreatic fluid collections, all successfully treated by observation (n = 7) or percutaneous drainage (n = 3). Enteric bleeding occurred in eight recipients (6.8%). Overall, 1-year patient and pancreas survival rates were 97.4% and 92.0%, respectively. CONCLUSIONS: We conclude that RPTx with PED is a technical option that may be included in the repertoire of pancreas transplant surgeons.

Anastomosis, Roux-en-Y↗
PubMedDate not supplied

Surveillance and rescue of pancreas grafts.

BACKGROUND: Technical failure rates are higher for pancreas allografts (PA) compared with other solid organs. Posttransplant surveillance and prompt availability of rescue teams with multidisciplinary expertise both contribute to improve this result. We herein report a single institution's experience with posttransplant surveillance and rescue of PA. METHODS: A retrospective survey was performed of a consecutive series of 177 whole organ pancreas transplants in 173 patients. Antithrombotic prophylaxis was used in all recipients and tailored on anticipated individual risk of thrombosis. During the first posttransplant week, all PA were monitored with daily Doppler ultrasonography. Surgical complications were defined as all adverse events requiring relaparotomy during the initial hospital stay or the first 3 posttransplant months. RESULTS: A total of 26 relaparotomies were performed in 25 patients (14.7%). One recipient needed two relaparotomies (0.6%). Graft rescue was attempted in patients without permanent parenchymal damage at repeat surgery and in 12 recipients diagnosed with nonocclusive vascular thrombosis. Overall 25 grafts (96.3%) were rescued and one was lost. One-year recipient and graft survivals in patients with versus without complications potentially leading to allograft loss were 92.6% and 63.0% versus 94.4% and 94.3%, respectively. Excluding complications for which graft rescue was not possible, 1-year graft survival rate increased to 78.7%. CONCLUSIONS: Close posttransplant surveillance can allow rescue of a relevant proportion of PA developing nonocclusive venous thrombosis or other surgical complications. Further improvement awaits better understanding of biological reasons for posttransplant complications jeopardizing PA survival and the development of more effective preventive measures.

Graft Rejection↗
PubMedDate not supplied

Neoral versus prograf in simultaneous pancreas-kidney transplantation with portal venous drainage: three-year results of a single-center, open-label, prospective, randomized pilot study.

BACKGROUND: The preferential use of tacrolimus (Prograf) over cyclosporine microemulsion (Neoral) in simultaneous pancreas-kidney transplantation (SPKTx) is mainly based on historical, retrospective studies. We herein report the 3-year results of a single-center, prospective, randomized comparison of the two calcineurin inhibitors in the setting of mycophenolate mofetil (MMF)-based immunosuppression and portal drainage of pancreas allografts. METHODS: Between May 2001 and August 2004, 47 SPKTx recipients who were stratified by recipient sex, were alternatively assigned to treatment with Neoral (n = 22) or Prograf (n = 25). Concurrent immunosuppression included induction treatment with basiliximab and maintenance with MMF and steroids. RESULTS: After a median follow-up of 24.0 months, all patients remained in the study arm into which they were initially enrolled. No pancreas rejection episode was observed. One acute kidney rejection was recorded in the Neoral arm (4.5%) as compared with 7 (28.0%) including one steroid-resistant episode, in the Prograf arm (P = .03). The cumulative incidence of adverse events was 31.8% (n = 7) in the Neoral arm compared with 92.0% (n = 23) in the Prograf arm (P < .0001). One patient died in each study arm. Patient, pancreas, and kidney survivals overlapped at 1- and 3-years posttransplant, namely all 95.4% for the Neoral arm compared with 95.8%, 91.8%, and 95.8%, respectively, for the Prograf arm (P > .05). CONCLUSIONS: We conclude that in MMF-based immunosuppression there is no convincing evidence that Prograf should be preferred to Neoral in SPKTx.

Antibodies, Monoclonal↗
PubMedDate not supplied

Solid-phase synthesis of indolizidine and quinolizidine derivatives.

An efficient method for the construction of simple indolizidine and quinolizidine derivatives on solid support has been developed. An intramolecular tandem Michael reaction initiated by the nucleophilic attack of a suitably placed amino group on the tethered Wittig condensation products between 4- or 5-aminoaldehydes attached to a trityl chloride resin and 4-[(4-methylphenyl)sulfonyl]-1-(triphenylphosphoranylidene)-2-b utanon e is the key step.

Drug Design↗
PubMedDate not supplied

Beta- and alpha-cell dysfunction in type 2 diabetes.

Insulin resistance is a common pathogenetic feature of type 2 diabetes. However, hyperglycemia would not develop if a concomitant defect in insulin secretion were not present. Impaired insulin secretion results from functional and survival defects of the beta-cell. The functional defects can be demonstrated early in the natural history of diabetes and they are hallmarked by abnormal pulsatility of basal insulin secretion and loss of first-phase insulin release in response to a glucose challenge. Moreover, a significant reduction of the beta-cell mass is apparent at the time of the diagnosis of diabetes. The progressive increase in glucose levels, that seems to characterize the natural history of type 2 diabetes, has been claimed to be largely due to progressive reduction of function and mass of beta-cells. Although a genetic predisposition is likely to account for impaired insulin secretion, chronic exposure to hyperglycemia and high circulating FFA is likely to contribute to both functional and survival defects. The disturbance in the endocrine activity of the pancreas is not limited to insulin, since a concomitant increase in fasting plasma glucagon and impaired suppression after the ingestion of an oral glucose load are often observed. This alteration becomes prominent after the ingestion of a mixed meal, when plasma glucagon remains much higher in the diabetic patient as compared to normal individuals. The disproportionate changes in the plasma concentration of the two pancreatic hormones is clearly evident when the insulin:glucagon molar ratio is considered. It is the latter that mainly affects hepatic glucose production. Because of the reduction of the insulin:glucagon molar ratio basal endogenous glucose concentration will be higher causing fasting hyperglycemia, while the hepatic glucose output will not be efficiently suppressed after the ingestion of a meal, contributing to excessive post-prandial glucose rise. Correcting beta- and alpha-cell dysfunction becomes, therefore, an attractive and rational therapeutic approach, particularly in the light of new treatments that may directly act on these pathogenetic mechanisms of type 2 diabetes.

Diabetes Mellitus, Type 2↗
PubMedDate not supplied

Short-term weekly neoadjuvant chemotherapy in the treatment of locally advanced cervical cancer.

Twenty patients with locally advanced cervical cancer (FIGO stage Ib-IIa "bulky"/IIb) were treated with three courses of weekly PVB (day 1: cisplatin, 50 mg/m2; vincristin, 1 mg/m2; bleomycin, 30 IU over 24-hr) in a neoadjuvant setting. Toxicity was generally mild (no grade 3-4 toxicity was observed), and the treatment was well tolerated without reduction of programmed dose intensity. Fourteen patients (70%) experienced a clinical response and underwent surgery within 20 days after the third course of chemotherapy. Six patients (30%) with stable disease were treated with salvage radiotherapy. Two of the 14 responders experienced a pathologic complete response (14.2%); microscopic disease was detected in one patient with clinical complete response. Pelvic node metastases were found in 4/14 patients (28.5%) and microscopic parametrium involvement in 3/14 (21.4%). All 14 patients had free margins of resection. A short-term weekly platinum-based chemotherapy is highly effective, has little toxicity, and allows a prompt salvage therapy for nonresponding patients.

Adult↗
PubMedDate not supplied

Endothelial cell anergy is mediated by bFGF through the sustained activation of p38-MAPK and NF-kappaB inhibition.

Tumors escape from immune surveillance by, among other mechanisms, the down- regulation of endothelial adhesion molecules, such as ICAM-1, and by unresponsiveness to inflammatory signals, a process mediated by angiogenic factors that is called endothelial cell anergy. Here we present the cell biological regulation of these processes. The angiogenic basic fibroblast growth factor (bFGF/FGF-2) was found to inhibit tumor necrosis factor-alpha (TNF-alpha)- induced elevation of ICAM-1, at transcriptional level. Furthermore, we found that bFGF inhibits the TNF-mediated activation of NF-kappaB by blocking phosphorylation and degradation of IkappaBalpha. We also found that bFGF induces hyperphosphorylation of p38 MAPK on endothelial cells, whereas inhibition of such kinase abrogates the effect of bFGF on the TNF-mediated activation of NF-kappaB. Thus, we suggest that bFGF acts as an inhibitor of leukocyte adhesion in tumor vessels by decreasing the ICAM-1 expression through the sustained activation of p38-MAPK and via inhibition of NF-kappaB.

Cell Line↗