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Biomedical subjects

G Nanni

Publications and source records attributed to G Nanni.

At least 55 records · Page 3Linked to original sources

Kaposi's sarcoma in renal-transplant recipients: experience at the Catholic University in Rome, 1988-1996.

BACKGROUND: The incidence of Kaposi's sarcoma (KS) in patients transplanted at the Organ Transplant Center of Catholic University in Rome appears to have increased in recent years. OBJECTIVE: To describe the clinical characteristics of KS in a group of transplant recipients. METHODS: Over 8 years, a total of 302 renal-transplant recipients were followed. When KS was suspected, histology and staging procedures were performed. RESULTS: Ten cases of KS have been diagnosed (8 males, 2 females; age 46.4 +/- 9.4 years); 4 of them were on triple therapy. All the patients were HIV-1 seronegative. The onset of KS occurred 3 months to 4 years after transplantation (21.1 +/- 17.6 months). The disease was limited to the skin in 6 cases and involved internal organs in the remaining 4. Four patients experienced complete remission of the disease following reduction of the immunosuppressive therapy. CONCLUSION: The high incidence of KS in this population (2.98%), as compared to that reported in other transplant patient groups, suggests that, besides viral infection, genetic predisposition may play a pathogenetic role. However, immunosuppression is the leading factor in transplant patients.

Adult↗

Biliopancreatic diversion: clinical experience.

BACKGROUND: Biliopancreatic diversion (BPD), by ad hoc stomach resection (AHS-BPD) has been accepted as an effective surgical treatment for morbid obesity. METHODS: Between 1.1.1992 and 31.7.1996, 59 patients (54 females, five males, mean age 40.3 years, range 23-61 years) underwent AHS-BPD. Mean preoperative body-weight was 121.2 kg (range 94-160), with a mean body mass index of 48.6 (range 35-64). Three of these patients were converted from a previous vertical banded gastroplasty to AHS-BPD (one patient with stomach preservation). After at least 36 months follow-up, seven patients underwent abdominal dermolipectomy (five with associated incisional hernia repair, one with thigh dermolipectomy). RESULTS: Mean post-operative hospital stay was 13 days (range 10-30 days). Follow-up is currently in progress in all patients. Excess body weight-loss was 78% in 33 patients with 24 months follow-up, with excellent long-term weight loss maintenance. Protein deficiency was the main specific complication, encountered in two patients (3.4%). Mortality was one patient (1.7%), due to pulmonary embolus. CONCLUSIONS: This clinical experience supports the effectiveness and safety of AHS-BPD, despite some criticism. This procedure appears to be suitable for patients with clinically severe obesity who will poorly tolerate food intake restriction but will accept long-term follow-up. Careful preoperative clinical assessment and selection of patients who will be reliable in long-term follow-up are the keys to success with AHS-BPD, both in terms of weight loss and reduction of specific metabolic complications.

Adult↗

Effect of chronic ethanol consumption on glycosylation processes in rat liver microsomes and Golgi apparatus.

Previous studies have demonstrated that acute ethanol intoxication affects various steps of protein glycosylation at the level of rat liver endoplasmic reticulum and Golgi apparatus. The aim of this investigation was to demonstrate whether chronic ethanol intake can induce definitive changes of liver glycoprotein processing. Rats were given ethanol by liquid diet for 8 weeks. At the end of this period the triglyceride levels in liver homogenate and microsomes were significantly higher than in controls. Isolated hepatocytes prelabelled with [3H]Na palmitate and [14C]glucosamine showed a significant storage of the lipid and carbohydrate radioactivity in microsomes and Golgi apparatus and a significant impairment of labelled glycolipoprotein secretion. Changes of the glycosylation steps were observed both in endoplasmic reticulum and in Golgi apparatus: in the former the levels of dolichyl phosphate, which is rate-limiting for the synthesis of glycoprotein, showed a significant reduction; in the latter the activity of the main enzymes responsible for the terminal glycosylation process was significantly decreased. These data suggest that an impairment of glycoprotein maturation may be involved in the pathogenesis of liver injury induced by chronic ethanol intake.

Alcoholism↗

[Lung transplantation: the physiopathological considerations and imaging diagnosis problems].

In the last years, lung transplantation has become a widely accepted treatment for the patients suffering from end-stage chronic lung disease. This study was aimed at investigating the role of diagnostic imaging techniques before and after lung transplantation, in the light of the physiopathological changes occurring in transplanted lungs. Our study included 4 patients (3 men and 1 woman, age range: 33-58 years): 3 of them underwent single lung transplantation and one double lung transplantation. All the operations were successful. Chest radiographs and HRCT showed the main early and late complications that occurred after transplantation. In the early postoperative period, the reperfusion syndrome was observed in 2 patients and acute rejection in the 3 patients submitted to single lung transplantation. In the late postoperative period, chronic rejection occurred in the patient submitted to left lung transplantation. None of our patients presented any infection or such airway complications as bronchial dehiscence or strictures. Both literature data and our personal experience show that preoperative diagnostic imaging allows the assessment of lung conditions, which helps choose the better side for transplantation. Moreover, lung size must be studied to match the donor's lung to the recipient's chest. In the postoperative period, both early and late complications must be investigated, all of them characterized by aspecific radiologic findings. Currently, time plays a major diagnostic role but we hope that more accurate interpretation of radiologic findings will improve the clinical assessment of lung transplant recipients.

Adult↗

Effects of 1,2-dichloroethane intoxication on dolichol levels and glycosyltransferase activities in rat liver microsomes and Golgi apparatus.

Rat intoxication with a single dose of 1,2-dichloroethane (DCE) (50 microliters/100 g b.w) is able to induce a significant modification of protein glycosylation in the liver endoplasmic reticulum and Golgi apparatus. HPLC analysis shows that within 5-60 min after DCE-intoxication, the levels of total dolichol, free dolichol and dolichyl phosphate strongly decreased in the microsomes and Golgi apparatus. Particularly in total microsomes, dolichyl phosphate, which is rate-limiting for the biosynthesis of the N-linked oligosaccharide chains, drops to values significantly lower than in the control group 15 min after DCE poisoning. In the Golgi apparatus, the total dolichol, essential to enhance the fluidity and permeability of these membranes, early and significantly decreases already 5 min after DCE poisoning. Moreover, in the Golgi apparatus galactosyl- and sialyltransferase activities, the main enzymatic activities of terminal protein glycosylation, are significantly reduced, as measured 15 min after DCE intoxication. These data suggest that the impairment of glycoprotein synthesis, maturation and secretion may be involved in the pathogenesis of liver injury induced by acute DCE-intoxication.

Alanine Transaminase↗

Impairment of vitamin A uptake by rat hepatocytes and fat storing cells determined by Monensin--morphological observations.

The action of the Na+/H+ antiport monensin on vitamin A uptake by rat liver has been studied in vivo. The quickfading autofluorescence of vitamin A has been used for the determination of vitamin A uptake by the liver. Pretreatment of rats intraperitoneally with monensin decreases the uptake of vitamin A by hepatocytes and its transfer for storage to fat storing cells. Pretreatment of rats intraperitoneally with vitamin A for a short time, then with monensin, shows that the hepatocytes no longer transfer vitamin A to fat storing cells for storage. These results might indicate that monensin impairs the uptake of vitamin A by the hepatocytes and might also impair the transport of vitamin A from parenchymal to perisinusoidal cells.

Adipocytes↗

[Perisinusoidal stellate cells in a model of experimental liver cirrhosis].

The association of the common bile duct (CBD) ligation followed by CCl4 and progesterone treatment leads to liver cirrhosis in rats in 28 days. The resulting cirrhosis shows mixed aspects: it starts as biliary cirrhosis and goes on to nodular and periportal pseudolobular form of cirrhosis. Because Ito cells are the main source of extracellular matrix components, changing their phenotype from quiescent Ito cells to myofibroblast like cells, the purpose of this study was to evaluate the behaviour of Ito cells by the immunohistochemistry technique of desmin and alpha-SM-actin after these treatments. After CBD ligation alone, positive Ito cells for desmin remarkably proliferate around adenomateous areas; after treatment with CCl4 alone desmin positive stellate cells are more numerous. Desmin positive Ito cells in CBD ligation and CCl4 treatment were even larger than those of the previous lots. Significant differences were not observed after progesterone and for the alpha-SM-actin positive cells.

Animals↗

Impairment of lipoglycoprotein metabolism in rat liver cells induced by 1,2-dichloroethane.

BACKGROUND: 1,2-Dichloroethane (DCE) is a volatile liquid readily absorbed through dermal, digestive, or inhalatory routes. After inhalation or oral administration to rats, death occurs within a narrow range of concentrations (six hour LC50 = 5100 mg/m3). Exposure to single high doses of DCE resulted in adverse effects on the central nervous system, liver, kidneys, adrenals, and lungs. The liver showed fatty changes and hepatocellular necrosis with haemorrhage. These injuries are probably related to changes in several cell functions and constituents. Therefore, it was decided to investigate whether DCE was capable of impairing the secretion of hepatocellular lipoglycoproteins acting both at the level of the Golgi apparatus and endoplasmic reticulum. METHODS: Isolated hepatocytes of Wistar rats were prelabelled with two precursors of lipoglycoproteins 3H-Na-palmitate and 14C-glucosamine, and then exposed to concentrations of DCE from mean (SD) 4.4 (0.03) to 6.5 (0.02) mM for different durations ranging from five to 60 minutes. To measure lipid and sugar bound radioactivity, a preliminary separation of cell homogenate, cytosol, total microsomes, Golgi apparatus, and lipoglycoproteins secreted into cell suspension medium was carried out. RESULTS: After five minutes of exposure, DCE did not induce obvious changes in cell viability or lactic dehydrogenase leakage, but a significant (p < 0.01) depletion of reduced glutathione content was seen (40.10 (4.3) nM/10(6) cells). Furthermore, the cells poisoned by DCE started to show noticeable accumulation of 3H-Na-palmitate in the Golgi apparatus after five minutes (5103 (223) dpm/10(6) cells) and in the microsomes after 15 minutes (85,470 (7190) dpm/10(6) cells). There was a simultaneous significant increase in 14C-glucosamine content in the Golgi apparatus (690 (55) dpm/10(6) cells) and the microsomes (15,975 (2035) dpm/10(6) cells). The specific radioactivity of lipid and sugar moieties incorporated in secreted lipoglycoproteins was already significantly reduced after only five minutes of exposure (480 (57) dpm/10(6) cells for lipids, and 315 (45) dpm/10(6) cells for sugars). CONCLUSIONS: Overall, DCE, like other haloalkanes, produces a block of secretion of hepatocellular lipoglycoproteins as early as five minutes after poisoning. The simultaneous percentage increases into Golgi apparatus and microsomes of lipid and sugar bound radioactivity suggest that lipid retention at the sites of processing of lipoglycoproteins would probably play an important part in the early stages of cellular accumulation of fat after exposure to DCE.

Animals↗

Normalization of Insulin Sensitivity in the Obese Patient after Stable Weight Reduction with Biliopancreatic Diversion.

Insulin resistance is a common feature in obese patients. To evaluate the modifications in insulin sensitivity after a bariatric operation such as Bilio-pancreatic diversion (BPD), three groups of subjects (14 normal controls (N); seven ex-obese patients (X) with at least 2 years at weight-stable conditions after BPD surgery; and eight morbidly obese patients (0)) were studied with intravenous (IVGTT) and oral (OGTT) glucose tolerance tests. The ratio of the area under the curve (AUC) for glucose over that of insulin was used as a measure of insulin sensitivity. All the following tests were conducted as Bonferroni-corrected pairwise t-tests, in case overall ANOVA was significant. No significant difference was found between N and X subjects, while obese patients showed a reduced AUCg/AUCI ratio with respect to the normal controls (O vs N: 0.01164 +/- 0.00039 vs 0.02392 +/- 0.0039, p < 0.05). IVGTT, AUCS: significant differences were found in each case: N vs X: 0.0591 +/- 0.0075 vs 0.1402 +/- 0.0399, p < 0.05; N vs 0:0.0591 +/- 0.0075 vs 0.0223 +/- 0.0031, p < 0.01; X vs 0:0.1402 +/- 0.0399 vs 0.0223 +/- 0.0031, p < 0.05. IVGTT-derived data were also analyzed using the minimal model of glucose kinetics; with this method, glucose effectiveness was significantly different between normal subject and obese subjects (0.0248 +/- 0.00288 Vs 0.00906 +/- 0.00135 per min, p < 0.001). The insulin sensitivity index was not significantly different between normal and ex-obese subjects, while both of these groups were significantly different from obese patients (N vs 0: 12.04 x 10&sup5; +/- 2.61 x 10&sup5; vs 3.29 x 10&sup5; +/- 0.61 x 10&sup5;, p < 0.066; X vs 0: 16.42 x 10&sup5; +/- 4.23 x 10&sup5; vs 3.29 x 10(1)+/- 0.61 x 10&sup5; per min per pM, p < 0.02). In conclusion, the present study indicates that, after a body weight reduction operation capable of almost re-establishing ideal body weight like BPD, obese individuals with a family history of obesity show a normalization of insulin response to glucose load.

Journal Article↗

[Primary carcinoid of the umbilicus. Description of the 1st case].

A 78-year old male came to our observation presenting and enlargement of bilateral inguinal lymph nodes and a tumor of the mesogastric abdominal wall. Three years before the patient had been operated on for a primary tumor of the umbilicus with concomitant longstanding diarrhea. No histological examination was performed at that time. We performed a lymph node biopsy which demonstrated carcinoid metastasis. We went on to perform radical resection of the abdominal wall, regional lymphadenectomy and right hemicolectomy for malignant villous adenoma of the right colon. The abdominal defect was repaired by using Goretex mesh. Cyclic adjuvant alpha-interferon therapy was continued for more than 1 year, followed by long term therapy with longastatin. Twenty months after the operation the patient is in good clinical conditions and disease-free. On the basis of literature review our case appears to be the first primary carcinoid of the umbilicus.

Abdominal Muscles↗

[Perisinusoidal stellate cells or Ito cells and their role in hepatic fibrosis].

In this review on stellate cells, discovered by Kupffer more than 100 years ago, morphological and ultrastructural aspects, origin and differentiation are described through also a comparative analysis in some animal species. Many methods used from different laboratories for isolation, identification and in vitro culture of these heterogeneous cells are reported and discussed regarding advantages and disadvantages. The normal Ito cells functions, that are metabolism and storage of vitamin A, extracellular matrix (ECM) synthesis under cytokines control, and sinusoidal tonus through its reversible contraction are discussed. Then an update description is reported about fibrogenesis and all the factors involved in liver fibrosis, from cytokines to the adhesion molecules. Stellate cells being the main source of ECM in chronic liver injury, can play different and primary roles by shifting its functions toward fibrosis. The role of metalloproteinases and their inhibitors on the balance of the ECM synthesis and degradation are also evaluated. When liver is injured, Ito cells became activated and change their phenotype from fat-storing cells to cells to cell devoid of retonoid droplets. They express the smooth muscle-like features, including a-SM-actin. The role of vitamin A in liver fibrosis is not yet clear: current data and hypothesis about this topic are discussed. Contractile behaviour of the perisinusoidal stellate cells seems also important in influencing portal blood pressure during fibrosis and cirrhosis. Diagnostic methods for hepatic fibrosis and Ito cells activation are also briefly reported. The review is supplied with more than three hundred references updated to August 1994.

Cell Differentiation↗

[The choice of substrates in total parenteral nutrition].

This review contains a full outline on the choice of substrates in total parenteral nutrition (NPT). The basic properties of "conventional" substrates (glucose, long chain triglyceride-containing fat, common amino acid mixtures) are used to outline the general principles for NPT support in normal conditions and in stress (surgical and nonsurgical trauma, sepsis). Without taking into account factors which are not strictly metabolic (vascular access, local availability of products, costs), particular attention is then paid to "non-conventional" substrates and substrate mixtures, including some under study, with specific reference to properties and features which may motivate their choice.

Amino Acids↗

[Changes in lipoglycoprotein metabolism in toxic fatty liver].

BACKGROUND: A number of agents that produce liver injury also cause the accumulation of an abnormal amount of fat, predominantly triglycerides (TGs) in the parenchymal cells. Fatty liver (FL) is the result of an hepatocyte imbalance between the rate of synthesis and output of TGs into the plasma. TGs are not secreted as such, but combined with a glycoprotein moiety, and particularly with the very low density lipoproteins (VLDLs). This fraction is involved in the transport of hepatic TGs to extrahepatic tissues. FL can be induced by either acute or chronic administration of ethanol (EtOH), and/or several haloalkanes (carbon tetrachloride, CCl4; 1.2-dichloroethane, DCE; 1.1.2.2-tetrachloroethane, TTCE), both in laboratory animals and in man. Since the pathogenesis of this disease is a crucial problem, as yet undefined, the purpose of this article is to summarize the studies which have unraveled some of the mechanisms involved in FL, particularly the role played by impaired lipoglycoproteins (LGP) metabolism in rat liver. DISCUSSION: An important element in the pathogenesis of EtOH- and haloalkanes-induced FL is the impairment of hepatic secretion of VLDLs, which occurs soon after poisoning. Various steps of the secretory pathway are probably involved in the expression of such damage. The intoxication of rats with these xenobiotics leads to an early impairment of the hepatocyte system responsible for terminal glycosylation and maturation of LGP at the level of three different subfractions (F1, F2 and F3) of purified Golgi apparatus (GA). The earliest functional change is a block of LGP transit through the GA cisternae and vesicles, both in isolated hepatocyte model and in the whole animal. The glycosylation of LGP is a multistep process which starts in the rough endoplasmic reticulum (RER), and comes to its end in the GA. Dolichols (Dol) are a family of long-chain polyisoprenoid alcohols, present either as neutral free-Dol and dolichyl-phosphate (Dol-P). The latter acts as a glycosyl carrier across the RER membranes in the initial steps of LGP biosynthesis. Nearly all the other reactions occur in GA, where free-Dol have a role either in terminal LGP processing or in their secretion into the blood stream. Several investigations indicated that both EtOH and haloalkanes (CCl4, DCE, and TTCE) may selectively and precociously impair the total microsomes (TM) and GA pool of Dol, particularly in F1. Lipid peroxidation appears to be the fundamental mechanism involved. CONCLUSIONS: Such results, obtained in several works, point out a key role played in FL by selective impairment of MT and GA processes which provide for the synthesis, maturation and release of hepatic LGP.

Animals↗

Acetaldehyde-induced impairment of protein glycosylation in liver Golgi apparatus.

The effects of acute ethanol intoxication on the glycoprotein metabolism of rat liver Golgi apparatus have been investigated. A marked reduction of the galactosyltransferase and sialyltransferase activities was observed in Golgi membranes 6 h after ethanol administration (6g/Kg body wt) together with the retention of glycoproteins in the hepatocyte. Methylpyrazole, an inhibitor of alcohol dehydrogenase, administrated "in vivo" (10 mg/Kg body wt) prevented the ethanol-induced inhibition of both the transferase activities. Acetaldehyde formed "in vitro" unstable and stable adducts with Golgi membrane proteins and with purified galactosyltransferase. These results suggest that the impairment of glycoprotein metabolism at the level of liver Golgi apparatus may be mediated, at least in part, through the acetaldehyde formation during ethanol oxidation.

Acetaldehyde↗

[The drug treatment of postoperative pain].

The study, conducted on 40 patients with pain resulting from "minor" general surgery, for the purpose of evaluating the efficacy and tolerability of ST-679 (administered in a single oral dose of 1200 mg in 20 patients) and to compare them with those of paracetamol (administered in a single oral dose of 1000 mg in 20 patients), demonstrated that the new drug was active on all recorded parameters and superior to the reference drug. The evaluation of the evolution of pain, performed using the Scott-Huskisson visual analog scale, evidenced that the maximum analgesic efficacy of ST-679 is reached after 1 hour and 15 minutes from assumption and remains unaltered until the final observation (6 hours). The paracetamol registers maximum analgesic efficacy after 30 minutes, but does not remain constant for the entire observation period. All the other parameters evaluated (variation in pain intensity, peak of analgesic activity and total remission of pain) are significantly favorable to ST-679. The tolerability of ST-679 was very good and better than the reference drug.

Acetaminophen↗