Biomedical subjects
Antonio Mancini
Publications and source records attributed to Antonio Mancini.
No evidence of in vitro and in vivo porcine endogenous retrovirus infection after plasmapheresis through the AMC-bioartificial liver.
BACKGROUND: Currently a number of bioartificial livers (BAL) based on porcine liver cells have been developed as a treatment to bridge acute liver failure patients to orthotopic liver transplantation or liver regeneration. These xenotransplantation related treatments hold the risk of infection of treated patients by porcine endogenous retrovirus (PERV) released from the porcine cells, as in vitro infection experiments and transplantations in immunocompromised mice have shown that PERV is able to infect human cells. The Academic Medical Center (AMC)-BAL, unlike other BALs, is characterized by direct contact between porcine liver cells and human plasma, and might therefore be permissive for PERV transfer. METHODS: Prior to a clinical phase I trial, human plasma perfused through the AMC-BAL was investigated for PERV DNA and RNA. Moreover productive infectivity was analyzed by exposing the plasma to HEK-293 cells that were subsequently tested for PERV DNA, PERV RNA and reverse transcriptase activity. RESULTS: Although PERV DNA was detected in the perfused plasma, no productive infectivity was detected. Consequently fourteen patients were treated with the AMC-BAL and monitored for PERV transmission. Immediately after treatment the plasma of the patients was positive for PERV DNA, most probably due to porcine liver cell lysis. The PERV DNA was cleared within 2 weeks post-treatment and no PERV RNA was detected. No productive infectivity in human embryonic kidney (HEK)-293 cells exposed to plasma of treated patients was detectable. CONCLUSION: To conclude, no release of infective PERV particles from the AMC-BAL was observed. Therefore we consider the AMC-BAL as safe, however careful surveillance of patients will be continued.
Carbon monoxide improves cardiac energetics and safeguards the heart during reperfusion after cardiopulmonary bypass in pigs.
Ischemia-reperfusion injury, a clinical problem during cardiac surgery, involves worsened adenosine trisphosphate (ATP) generation and damage to the heart. We studied carbon monoxide (CO) pretreatment, proven valuable in rodents but not previously tested in large animals, for its effects on pig hearts subjected to cardiopulmonary bypass with cardioplegic arrest. Hearts of CO-treated pigs showed significantly higher ATP and phosphocreatine levels, less interstitial edema, and apoptosis of cardiomyocytes and required fewer defibrillations after bypass. We conclude that treatment with CO improves the energy status, prevents edema formation and apoptosis, and facilitates recovery in a clinically relevant model of cardiopulmonary bypass surgery.
Coenzyme Q(10) supplementation in infertile men with idiopathic asthenozoospermia: an open, uncontrolled pilot study.
OBJECTIVE: To clarify a potential therapeutic role of coenzyme Q(10) (CoQ(10)) in infertile men with idiopathic asthenozoospermia. DESIGN: Open, uncontrolled pilot study. PATIENT(S): Infertile men with idiopathic asthenozoospermia. INTERVENTION(S): CoQ(10) was administered orally; semen samples were collected at baseline and after 6 months of therapy. MAIN OUTCOME MEASURE (S): Semen kinetic parameters, including computer-assisted sperm data and CoQ(10) and phosphatidylcholine levels. RESULT(S): CoQ(10) levels increased significantly in seminal plasma and in sperm cells after treatment. Phosphatidylcholine levels also increased. A significant increase was also found in sperm cell motility as confirmed by computer-assisted analysis. A positive dependence (using the Cramer's index of association) was evident among the relative variations, baseline and after treatment, of seminal plasma or intracellular CoQ(10) content and computer-determined kinetic parameters. CONCLUSION(S): The exogenous administration of CoQ(10) may play a positive role in the treatment of asthenozoospermia. This is probably the result of its role in mitochondrial bioenergetics and its antioxidant properties.
Effect of gonadotropin-releasing hormone agonist treatment on growth hormone responses in women with polycystic ovary syndrome.
This study supports the importance of regulatory role of the E(2) in growth hormone secretion in women with polycystic ovary syndrome, showing for the first time a different weight-related sensitivity of the growth-hormone axis to hypoestrogenism induced by gonadotropin-releasing hormone agonist.
Total antioxidant capacity in patients with varicoceles.
OBJECTIVE: To explore a possible molecular defect linked to infertility, studying total antioxidant capacity (TAC) of seminal plasma in varicocele (VAR). DESIGN: Case-series study. SETTINGS: Volunteers in an academic research environment and out-patients in clinical service. PATIENT(S): Twenty-five VAR patients (9 oligospermic and 16 normospermic) vs 24 non-VAR controls (7 subjects with idiopathic oligospermia and 17 normospermic subjects). INTERVENTION(S): Evaluation of seminal plasma TAC. MAIN OUTCOME MEASURE(S): TAC was measured using myoglobin, as a source of radicals, which interact with a chromogen 2,2'-azinobis(3-ethylbenzothiazoline-6-sulphonate) (ABTS), whose radical cation is spectroscopically detectable. The latency phase (Lag) in the accumulation of ABTS cation is proportional to antioxidant concentration. RESULT(S): Lag showed significantly greater values in the all VAR patients vs non-VAR subjects. Oligospermic-VAR patients showed the greatest values. Lag and sperm motility significantly correlated in VAR normospermic patients. Follicle-stimulating hormone (FSH) showed significant inverse association with Lag in same group. CONCLUSION(S): The augmented Lag values could indicate an ineffective utilization of antioxidants in oligospermic-VAR, while in normo-VAR the direct correlation between TAC and motility suggest a potential protective role toward sperm motility. In the same group, the inverse correlation with FSH suggests that greater FSH levels induce a better utilization of antioxidants by spermatozoa.
Coenzyme Q10: another biochemical alteration linked to infertility in varicocele patients?
Previously we demonstrated that coenzyme Q10 (CoQ10) is present in human seminal fluid and shows a direct correlation with seminal parameters except in patients with varicocele (VAR). We have now evaluated CoQ10 distribution in VAR, versus control subjects, in order to discover metabolic abnormalities within this condition. We studied 32 patients with VAR (11 with oligoasthenozoospermia, 13 with asthenozoospermia, and 8 with normozoospermia), and, as controls, the following groups of subjects, matched with VAR patients according to seminal parameters: 16 patients with idiopathic oligozoospermia, 11 patients with isolated asthenozoospermia, and 14 normal fertile men. CoQ10 was assayed in total seminal fluid, plasma, or cell pellet by high-performance liquid chromatography (HPLC). We found a significantly higher proportion of CoQ10 in seminal plasma in VAR; cellular CoQ10 showed an inverse correlation with sperm concentration and motility in VAR, at variance with controls. As seminal plasma ubiquinone reflects an interchange between intracellular and extracellular compartments, the different distribution in VAR patients could represent a greater sensitivity to peroxidative damage and could suggest reduced utilization for energy, which in turn could cause a defective motility even in patients with a normal cell count. These data suggest a pathophysiological role of CoQ10 in seminal plasma and a possible molecular defect in VAR.
Body composition and energy expenditure: relationship and changes in obese subjects before and after biliopancreatic diversion.
Changes in total and segmental body composition were studied in 101 obese women before and 2, 6, 12, and 24 months after biliopancreatic diversion (BPD) and data 24 months after surgery were matched to 53 control subjects. The patients were studied by anthropometry, indirect calorimetry, and double-emission x-ray absorptiometry (DXA). The combination of calorimetry and body composition analysis allowed estimation of visceral and muscle lean mass. We observed a significant (analysis of variance [ANOVA]: P <.05) progressive reduction of fat and lean body mass (LBM) following BPD, with stabilization of both parameters between 12 and 24 months at levels not different from controls. Fat loss was significant in the arms, legs, and trunk segments. After 24 months, there was no significant difference in segmental fat mass between post-BPD patients and controls. Calorimetric data seem to confirm lean body mass (LBM) reduction. Visceral lean mass (kg) was significantly reduced from 8.1 +/- 2.2 in obese subjects to 6.5 +/- 1.8 in post-BPD patients at 24 months (P <.05); the control value was 7.2 +/- 1.8. Muscular lean mass (kg) was also significantly reduced, from 50.2 +/- 5.8 to 39.8 +/- 5.7 in the same subjects (P <.05), with a control value of 42.5 +/- 5.9. The decrease in muscle and visceral LBM reached control values without significant differences. Viscera/muscle ratio in pre-BPD patients was preserved in post-BPD patients at 24 months, but it was reduced during weight loss. Body composition studies showed a logarithmic relationship between fat and lean mass and a physiological contribution of lean mass to weight loss in the BPD patients. In conclusion, weight loss after BPD was achieved with an appropriate decline of LBM and with all parameters reaching, at stable weight, values similar to weight-matched controls.
Bridging a patient with acute liver failure to liver transplantation by the AMC-bioartificial liver.
Recently a phase I clinical trial has been started in Italy to bridge patients with acute liver failure (ALF) to orthotopic liver transplantation (OLT) by the AMC-bioartificial liver (AMC-BAL). The AMC-BAL is charged with 10 x 10(9) viable primary porcine hepatocytes isolated from a specified pathogen-free (SPF) pig. Here we report a patient with ALF due to acute HBV infection. This patient was treated for 35 h by two AMC-BAL treatments and was bridged to OLT. There was improvement of biochemical and clinical parameters during the treatment. No severe adverse events were observed during treatment and follow-up of 15 months after hospital discharge. Possible porcine endogenous retrovirus (PERV) activity could not be detected in the patient's blood or blood cells up to 12 months after treatment.
Effect of the opioid blockade on the feeding-induced growth hormone response to growth hormone-releasing hormone in women with polycystic ovary syndrome.
OBJECTIVE: To investigate the effect of naloxone, an opioid receptor antagonist, on the release of growth hormone (GH) induced by the growth hormone-releasing hormone (GHRH) in normal-weight and obese women with PCOS in relation to feeding. DESIGN: Prospective clinical study. SETTING: Academic research center. PATIENT(S): Seventeen women with PCOS (10 who were normal weight and 7 who were obese) and 14 control women (7 who were normal weight and 7 who were obese). INTERVENTION(S): A GHRH test (50 microg i.v.) and, on a different day, a GHRH test during a naloxone infusion (1.6 mg/h) during fasting. The same tests were repeated after a standard meal. MAIN OUTCOME MEASURE(S): GH response to GHRH (expressed as the area under the curve [AUC]) in different experimental conditions. RESULT(S): All normal-weight women showed a significantly higher AUC-GH compared with obese women in the fasting state. Normal-weight controls had a decrease in GH response to GHRH after feeding, and naloxone did not reverse the decrease. In obese controls, feeding increased the GH response but naloxone induced a decrease in the AUC. In fasting, normal-weight women with PCOS, naloxone significantly decreased the AUC-GH; in these patients, food intake induced an inhibition of GH response to GHRH, reversed by naloxone infusion. In obese PCOS patients, GH levels did not increase significantly after GHRH stimulation, either in the fasting state or after a meal, and naloxone did not affect these responses. CONCLUSION(S): Factors other than obesity and insulin may be involved in disruption of GH secretion in women with PCOS.
Seminal antioxidant capacity in pre- and postoperative varicocele.
In order to explore the impact of surgical treatment on antioxidant defense system in varicocele (VAR), we evaluated seminal total antioxidant capacity (TAC) in 25 patients affected by VAR, in 14 patients studied 10-24 months after varicocelectomy (post-VAR) and separated into normo- and oligospermic groups, and in 24 non-VAR control patients with seminal parameters matched to patients with VAR in the oligo- and normospermic groups (7 subjects with idiopathic oligospermia and 17 normal fertile subjects). TAC was measured in seminal plasma with the system H(2)O(2)-metamyoglobin as a source of radicals, which interact with a chromogen 2,2',-azinobis (3-ethylbenzothiazoline-6-sulphonate) (ABTS), generating a radical cation spectroscopically detectable. The presence of antioxidants induces a lag time in the production of ABTS cation proportional to the concentration of antioxidant compounds. When whole groups of patients were analyzed, lag values were significantly higher in VAR vs non-VAR controls (mean +/- SEM, 106.6 +/- 8.8 seconds vs 78.7 +/- 8.8 seconds) but were not modified by surgery (mean +/- SEM, 105.8 +/- 8.6 seconds). In groups separated according to seminal parameters, oligospermic VAR presented significantly higher lag values than oligospermic controls. Finally, when exploring a possible association of TAC with seminal parameters, we found a significant correlation between lag and sperm motility only in patients with VAR who were in the normospermic group (r = 0.65, P <.01). This correlation was not yet manifest post-VAR. In conclusion, surgical treatment does not seem to modify absolute values of TAC but influences its fine regulation and relationships with sperm motility.