Evaluation of the immunomodulatory mechanisms of photochemotherapy in transplantation.
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ADP-ribosyl Cyclase↗
Biomedical subjects
F Mosca
Publications and source records attributed to F Mosca.
C1-inhibitor protects human endothelial cell metabolic activity from prolonged cold storage.
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Adenosine↗
Detection of biliary complications after orthotopic liver transplantation with MR cholangiography.
To assess the diagnostic value of magnetic resonance cholangiography (MRC) when evaluating biliary complications in the follow-up of liver transplant patients. One hundred and thirteen patients prospectively underwent MR imaging and MR cholangiography at 1.5-T unit after orthotopic liver transplantation (OLT). After the acquisition of axial T1- and T2-weighted sequences, MRC involved a coronal, non breath-hold, respiratory-triggered, fat-suppressed, two-dimensional, thin-slab, heavily T2-weighted fast spin-echo sequence, and coronal breath-hold, thick-slab, single-shot T2-weighted sequences. The images and maximum intensity projections were evaluated by two readers in order to determine biliary anatomy and the presence of complications, whose final diagnosis was based on endoscopic retrograde cholangiography (ERC) in 50 patients, percutaneous trans-hepatic cholangiography (PTC) in five, and by integrating clinical follow-up with ultrasound and MR findings in 58 cases. MRC had a sensitivity of 93%, a specificity of 92%, a positive predictive value of 86%, a negative predictive value of 96%, and a global diagnostic accuracy of 93% in detecting all types of biliary complications in OLT patients. MRC is a reliable technique for detecting post-OLT biliary complications. We now restrict the use of ERC to patients for whom therapeutic procedures are advocated or whose MRC results are equivocal.
Adult↗
Modulation of beta2 integrin phenotype, adhesion, chemotaxis, and oxidative burst of neutrophils by cyclosporine.
Cyclosporine (CsA) is an immunosuppressive drug widely used to prevent allograft rejection, but its action on neutrophil function is not well known. Neutrophils play an important role in tissue damage during allograft rejection; chemotactic recruitment, adhesion to endothelial cells and oxidative burst of neutrophils are early events during allograft rejection. The aim of this work was to evaluate the effect of CsA on beta2 integrins' surface expression, adhesion to human umbilical endothelial cells (HUVECs), chemotaxis and oxidative burst by neutrophils. For any neutrophil function studied, data obtained from activated neutrophils exposed to CsA were compared with those derived from untreated controls. Results show that CsA does not block neutrophil chemotaxis and does not reduce surface expression of CD11 complex and HUVECs' adhesion at all concentrations tested (15, 100 and 500 ng/mL) and at incubation times of 1, 2 and 4 h as compared to controls. On the other hand, the drug affects significantly the CD18 phenotype after two hours of treatment at the maximum concentration (500 ng/mL) (P < 0.05; ANOVA) and the oxidative burst after four hours (P < 0.01; ANOVA). This study provides evidence that in addition to the well-known CsA effects on lymphocyte functions, the drug affects some neutrophil functions with dose- and time-dependent modalities.
Antibodies, Monoclonal↗
Animal models of fulminant hepatic failure: need to test liver support devices.
Fulminant hepatic failure is one of the most dramatic entities in clinical medicine, but experimental studies of its pathogenesis, evolution and treatment have, so far been limited by the lack of satisfactory animal models for testing new supportive treatment options. The variable aetiology, complex pathogenetic mechanisms and inconstant clinical evolution of human fulminant hepatic failure make it particularly difficult to establish an "ideal fulminant hepatic failure animal model" suitable for all studies: it is no longer mandatory to develop one single model serving all possible scientific needs, but the use of a specific model for a specific issue is more advisable. The currently available animal models of fulminant hepatic failure are the hepatotoxic, surgical and combined hepatotoxic and surgical models. From a general point of view, surgical models may be particularly appropriate for studying the consequences of hepatic necrosis on cerebral oedema. The anhepatic model is very useful for validating new supportive measures to bridge the period between the onset of fulminant hepatic failure and the time at which a suitable organ becomes available and, despite the many difficulties involved in their development, hepatotoxic models may still be useful for mimicking an acetaminophen overdose. The efficacy and reproducibility of a liver support system can be demonstrated by means of preclinical experimental models that mimic the specific application required in humans as closely as possible.
Acetaminophen↗
Cryptic subtelomeric translocation t(2;16)(q37;q24) segregating in a family with unexplained stillbirths and a dysmorphic, slightly retarded child.
We here describe a submicroscopic translocation affecting the subtelomeric regions of chromosomes 2q and 16q, and segregating in a family with stillbirths, early pregnancy losses, and two dysmorphic and slightly retarded babies. FISH analysis showed a 46,XY,der(2)t(2;16)(q37.3;q24.3) in the propositus, and a balanced t(2;16) in his mother, her conceptus and maternal grandfather. FISH with YACs and BACs made it possible to map the 2q37 breakpoint precisely between the regions covered by y952E1 and y746H1, and the 16q breakpoint between the regions encompassed by bA 309g16 and bA 533d19. The contribution of 2q37.3 monosomy and 16q24.3 trisomy to the proband's phenotype is compared with that in reported patients with similar imbalances of either chromosome.
Chromosomes, Human, Pair 16↗
Very early tracheal extubation without predetermined criteria in a liver transplant recipient population.
This study of all patients undergoing orthotopic liver transplantation (OLT) at our center between January 1997 and December 1999 evaluated the feasibility and safety of very early tracheal extubation without previous selection. Anesthetic management was the same in all cases, and tracheal extubation was performed on the basis of standardized criteria routinely adopted in operating rooms throughout the world, i.e., no residual curarization or anesthetic action, ability to swallow efficiently, and stable hemodynamics. One hundred sixty-nine patients underwent 181 OLTs during the study period. Tracheal extubation was performed within 3 hours of surgery in 115 cases, 8 hours in 19 cases, and 8 to 24 hours in 10 cases. In 36 cases, artificial ventilation was required for more than 24 hours or weaning was not possible. One patient died of primary graft nonfunction within 24 hours and was excluded from the analysis. The feasibility of early extubation was influenced by the amount of intraoperative transfused blood; efficacy of kidney, cardiac, and pulmonary function; and presence of encephalopathy (P <.001). No correlation was found with age or pre-OLT severity of hepatic disease, and the postoperative period was not compromised by early weaning. Very early extubation was feasible and safe in a large number of unselected transplant recipients, thus suggesting that the definition of early tracheal extubation should be changed from 8 to 3 hours after surgery.
Adult↗
Metastatic osteosarcoma involving the colon and ileum.
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Aged↗
Human adult and foetal liver sulphotransferases: inhibition by mefenamic acid and salicylic acid.
1. The aim was to see whether mefenamic acid and salicylic acid had different inhibition profiles for SULT1A1 (substrate: 4-nitrophenol) and SULT1A3 (dopamine) activities and on (-)-salbutamol and minoxidil sulphation rates in the human adult and mid-gestational foetal livers. 2. The activity (pmolmin(-1) mg(-1) of SULT1A1 was 662 +/- 78 (adult) and 246 +/- 159 (foetus; p = 0.003) and that of SULT1A3 was 24 +/- 4 (adult) and 121 +/- 90 (foetus; p = 0.030). The rate (pmol min(-1) mg(-1)) of (-)-salbutamol sulphation was 109 +/- 27 (adult) and 117 +/- 34 (foetus; p = (0.144) and that of minoxidil sulphation was 202 +/- 38 (adult) and 108 +/- 44 (foetus; p = 0.001). 3. With mefenamic acid as an inhibitor, the IC50 (microM) for SULT1A1 was 0.2 +/- 0.004 (adult) and 0.01 +/- 0.002 (foetus; p = 0.001); for SULT1A3 it was 76 +/- 6 (adult) and 77 +/- 13 (foetus; p = 0.889); for the rate of ( )-salbutamol sulphation it was 0.07 +/- 0.005 (adult) and not determinable (foetus) and for minoxidil sulphation it was 1.6 +/- 0.7 (adult) and 0.15 +/- 0.04 (foetus; p = 0.076). 4. With salicylic acid as an inhibitor, the IC50 (microM) for SULT1A1 was 30 +/- 2 (adult) and 25 +/- 1 (foetus; p = 0.011); for SULT1A3 it was 690 +/- 36 (adult) and 570 +/- 16 (foetus; p = 0.229); for the rate of ( )-salbutamol sulphation it was 93 +/- 11 (adult) and 344 +/- 42 (foetus; p = 0.010); with minoxidil as substrate, the IC50 was not determinable. 5. In summary, SULT1A1, SULT1A3 and the sulphotransferases towards (-)-salbutamol and minoxidil had measurable activities in the mid-gestational human foetal liver. Mefenamic acid was a more potent inhibitor than salicylic acid of both human adult and foetal liver SULT1A1 and SULT1A3 activities. Foetal liver SULT1A1 was more susceptible than adult liver SULT1A1 to inhibition by mefenamic acid and salicylic acid. These results are consistent with the view that sulphotransferases develop early in the human foetal liver and drugs may inhibit their activities.
Adult↗
Differential inhibition of human liver and duodenum sulphotransferase activities by quercetin, a flavonoid present in vegetables, fruit and wine.
1. Quercetin is a natural flavonoid present in vegetables, fruit and wine, and is known to inhibit sulphotransferase. Drugs are often taken orally and the intestinal mucosa is an early site of drug metabolism. The aims of this investigation were to study the inhibition of dopamine, (-)-salbutamol, minoxidil and paracetamol sulphation by quercetin in the duodenal mucosa and liver and to compare the IC50 in these tissues. 2. The rates (pmol min(-1) mg(-1)) of sulphation of 4-nitrophenol were 343+/-92 (liver) and 164+/-22 (duodenum; p = 0.031), of dopamine were 15+/-11 (liver) and 656+/-516 (duodenum; p = 0.049), of (-)-salbutamol 153+/-31 (liver) and 654+/-277 (duodenum; p = 0.018), of minoxidil were 156+/-47 (liver) and 105+/-7 (duodenum; n.s.), and of paracetamol were 229+/-86 (liver) and 328+/-187 (duodenum; n.s.). 3. The IC50 of quercetin for 4-nitrophenol was 48+/-11 nM (liver) and 56+/-1 nM (duodenum, n.s.), for dopamine was 5.7+/-0.7 microM (liver) and 170+/-12 microM (duodenum, p < 0.0001), for (-)-salbutamol was 54+/-4 nM (liver) and 16+/-8 microM (duodenum; p = 0.025), for minoxidil was 134+/-22 nM (liver) and 3+/-0.3 microM (duodenum, p = 0.013), and for paracetamol was 57+/-7 nM (liver) and 35+/-1 microM (duodenum; p = 0.0002). 4. Quercetin inhibited the sulphation of 4-nitrophenol, dopamine, (-)-salbutamol, minoxidil and paracetamol both in liver and duodenum. With dopamine, (-)-salbutamol, minoxidil and paracetamol as substrates, quercetin was a more potent inhibitor in the liver than the duodenum. Such a difference may reflect the different composition of sulphotransferase forms in the liver and duodenum.
Acetaminophen↗
Apoptosis and adaptive responses to oxidative stress in human endothelial cells exposed to cyclosporin A correlate with BCL-2 expression levels.
Treatment of transplanted patients with cyclosporin A (CSA) may cause adverse effects such as nephrotoxicity and hypertension. As CSA is known to induce oxidative stress in several tissues, it may cause vascular problems by triggering oxidative stress in endothelial cells (EC). However, oxidative stress has been reported for acute exposure to CSA concentrations exceeding its clinical range, whereas immunosuppression requires life-long treatment with therapeutic concentrations. We therefore compared the effects of 21 h pharmacological (200 microM) vs. 8 days clinical (0.5-2.5 microM) doses of CSA on cultured human EC. Pharmacological doses of CSA cause a decrease in cell density via apoptosis and a down-regulation of the antiapoptotic protein Bcl-2. However, these effects are independent of CSA-induced oxidative stress. In contrast, therapeutic concentrations of CSA cause Bcl-2 up-regulation and modification of EC morphology, both effects blocked by antioxidants. Therefore, a low level of oxidants may act in EC as second messengers that up-regulate Bcl-2, thus promoting survival of impaired EC. Our data suggest that the oxidative stress induced by clinical concentrations of CSA may be involved in the adverse effects of the drug on the vascular system of transplanted patients via an adaptive response involving Bcl-2 up-regulation rather than an apoptotic process
Apoptosis↗
Th2 cytokines have a partial, direct protective effect on the function and survival of isolated human islets exposed to combined proinflammatory and Th1 cytokines.
Studies in rodents have suggested that Th2 and Th3 cytokines can be effective in reducing proinflammatory and Th1 cytokine-induced islet damage. Whether this is the case with human islets and might be due to a direct action of Th2 and Th3 cytokines is not known. In the present study, we evaluated whether Th2 (500 U/ml IL-4 plus 100 U/ml IL-10) or Th3 (5 ng/ml TGF-1beta) cytokines may prevent the derangements induced on isolated human islets by prolonged (12 or 72 h) exposure to combined proinflammatory (50 U/ml IL-1beta, 1000 U/ml TNF alpha) and Th1 (1000 U/ml interferon gamma) cytokines. Compared with control islets, cells preincubated for 12 or 72 h with proinflammatory and Th1 cytokines showed a significant decrease of glucose-stimulated insulin secretion and a significant increase of nitrites production. The addition of IL-4 plus IL-10 or TGF-1beta in the medium prevented these cytostatic effects in the 12-h incubation experiments, but not after the 72-h exposure period. IL-1beta, interferon gamma, and TNF alpha caused no major change in either islet cell survival or Bcl-2 and Bax mRNA expression after a 12-h incubation; however, a marked increase in the amount of dead cells, with a major decrease of Bcl-2 mRNA expression, was observed after 72 h. The presence of Th2, but not of Th3, cytokines significantly reduced beta-cell death, without any major effect on Bcl-2 and Bax mRNA expression. These results suggest that Th2 and (at lower extent) Th3 cytokines may have a partial, direct protective effect on isolated human islets exposed to the cytostatic and cytotoxic action of proinflammatory and Th1 cytokines.
Glucose↗
Elevated hydroperoxide levels and antioxidant patterns in Papillon-Lefèvre syndrome.
BACKGROUND: Since it has been found that reactive oxygen species seem to be involved in the pathogenesis of both periodontitis and hyperkeratotic syndromes, we studied a group of patients belonging to 3 generations of a family with different degrees of severity of Papillon-Lefèvre syndrome (PLS) to ascertain whether altered concentrations of the most important hydrophobic and hydrophilic plasma antioxidants as well as products of oxidative damage are present in PLS. METHODS: Coenzyme Q (CoQ), vitamin E, glutathione (GSH), and uric acid were evaluated by high-performance liquid chromatography (HPLC) (supplied with electrochemical detector) techniques and hydroperoxides by a spectrophotometric method. RESULTS: GSH and uric acid were in the range of reference values; CoQ was very low in both the child of the third generation and his mother, and these 2 subjects had the highest hydroperoxide levels. The child also had extremely low values of vitamin E. In general, all family members showed abnormally high hydroperoxide levels, with the exception of those members who are phenotypically healthy. CONCLUSIONS: Since the subjects with the lowest hydroperoxide contents are phenotypically healthy, whereas the affected individuals presented lower antioxidant levels and very high hydroperoxide concentrations, it has been suggested that a specific antioxidant therapy could be a promising approach in treating some PLS subjects. Moreover, unexpected manifestations of heterozygosity in the child of the third generation were also detected.
Adult↗
Personality change as defensive responses of patients evaluated for liver transplant.
Patients affected by endstage liver disease and awaiting liver transplant suffer very stressful conditions. The aim of this study was to evaluate the person ality and behavioral responses of a group of liver transplant candidates, 95 men (M age 50 yr.) and of a group of 18 normal men (M age 49 yr.). The 16 Personality Factor Questionnaire of Cattell, and the PSY Inventory for Behavioral Assessment were administered to assess personality and behavior. On the 16PF Questionnaire, patients had significantly different mean scores from normal subjects on Scale B- (low mental capacity), G (conformity), N (shrewdness), and Q1- (conservatism). They also showed a somewhat lower but not a statistically significant mean on Scale E (submissiveness). In addition, on the four second-order factors of the 16PF (Anxiety, Control, Pathemia, and Extraversion) patients had a significantly higher mean on Control. With respect to PSY Inventors factors, patients showed impairment in energy, sleep, sexual disturbances, and obsessive behaviors. It appears these patients with endstage liver disease, who were evaluated for liver transplant, showed psychological regressive functioning, i.e., high control and dependency on medical staff, submissiveness, which are interpretable as defensive responses to upcoming transplant.
Adult↗
[Pancreatic pseudocysts. Our experience with 21 cases treated surgically].
Twenty-one consecutive patients with pancreatic pseudocyst have been reviewed. Nine cases have been treated with internal drainage, 9 with external drainage, while 3 patients have undergone distal pancreatectomy. No mortality was associated to the surgical treatment, while morbidity was of 9.5% due to pancreatic fistulas. Based on their own experience and literature review the Authors describe clinical, diagnostic and therapeutic features of the disease and point out the good results of cistojejunostomy with Roux-en-Y loop.
Adult↗
Benign paroxysmal positional vertigo, incidence and treatment.
Benign paroxysmal positional vertigo is characterized by acute vertigo that is accentuated by movements of the head. It can be identified by the presence of nystagmus triggered by certain head positions. Over a 1-year period, among 1,902 cases of different types of equilibrium disorders, there were 98 cases of BPPV including 63 BPPV ofthe posterior canal, 21 of the lateral canal, 13 combined (HC + PC) and one case affecting the anterior canal. Most of the cases were idiopathic. Treatment was based on the Semont maneuver for BPPV-PC. BPPV-HC was treated with the Vannucchi maneuver and a personal method. The one case of BPPV-AC was treated with a modified Semont maneuver. Satisfactory therapeutic results were noted in all cases. Cases with a long-term follow-up showed a high percentage of elimination of relapse after 24 months.
Adult↗
[Blood coagulation monitoring during liver transplantation: Sonoclot analysis and laboratory tests].
BACKGROUND: Aim of this paper is to validate blood coagulation data obtained using the Sonoclot thromboelastographic analyser (Sienco Inc., Morrison, USA) by means of standard laboratory tests during orthotopic liver transplantation (OLT). METHODS DESIGN: comparative study between laboratory data and Sonoclot analysis on simultaneously collected blood samples. SETTING: National Health System Liver Transplantation Center. PATIENTS: fifty-one patients, both males and females, affected by terminal hepatic disease submitted to OLT were enrolled in the study. DATA COLLECTION: simultaneous blood samples were collected during the pre-anhepatic, anhepatic and post-reperfusion phases of OLT; coagulation status was assessed by means of either standard Laboratory tests (INR, aPTT, Fibrinogen, PLT, D-Dimer) and Sonoclot analyser data (SonACT, Rate, Time to Peak, Downward Deflection); a statistical analysis was performed (Pearson s chi(2) test). RESULTS: A statistically significative correlation between the analysed data was found. The Sonoclot analyser was useful in identifying platelets dysfunction and was more sensitive to detect fibrinolysis. CONCLUSIONS: The Sonoclot thromboelastographic analyser is a reliable device for monitoring coagulation during OLT.
Adult↗
Combined percutaneous and surgical approach to a postnephrectomy arteriovenous fistula.
The case of a patient with long-standing severe heart failure that was ultimately found to be secondary to a large communication between the right renal artery stump and the inferior vena cava is reported. The occurrence of an arteriovenous fistula should be suspected in patients who underwent previous nephrectomy since early diagnosis would avoid relevant cardiac complications and the demise of a patient suffering from a disease that may be corrected surgically or percutaneously. We describe a combined approach that allowed the percutaneous decompression of the inferior vena cava and relief of the volume overload to the heart prior to the surgical ligation of the arteriovenous fistula. This approach should be considered a valuable option for treating long-standing high output postnephrectomy arteriovenous fistulas.
Aged↗