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Biomedical subjects

R Ferrara

Publications and source records attributed to R Ferrara.

At least 55 records · Page 3Linked to original sources
PubMed1998

The role of oxidative imbalance in progression to AIDS: effect of the thiol supplier N-acetylcysteine.

In this study we investigate the redox profile of HIV+ patients at different stages of disease with regard to immunological parameters, i.e., the number of circulating CD4+ and CD8+ lymphocytes. For this purpose, peripheral blood mononuclear cells (PBMCs) obtained from healthy donors, HIV+ patients in the asymptomatic phase, long-term nonProgressors (LTNPs), and AIDS patients have been considered. Cells have been exposed in vitro to the prooxidizing agent menadione, which is able to induce superoxide anion formation, and the susceptibility of the cells to the induced oxidative stress was estimated. Moreover, the possibility that the susceptibility of the cells to oxidative stress might be reduced by preexposing them to the antioxidizing agent N-acetylcysteine (NAC) has also been analyzed. The results obtained can be summarized as follows: (1) treatment with the prooxidant agent is capable of inducing massive morphological alterations in PBMCs. In particular, a significant correlation was found between the decrease in number of CD4+ lymphocytes in patients at different stages of disease and the susceptibility of their PBMCs to oxidative stress; (2) preincubation with NAC was able to preserve partially the ultrastructural characteristics of PBMCs isolated from HIV+ patients. In particular, a direct relationship was found between the efficacy of NAC protection and CD4 counts; (3) evaluation of the plasma index of peroxidation and the number of circulating CD4 lymphocytes indicates the existence of a positive correlation between "systemic" oxidative imbalance and stage of the disease; and (4) cells from LTNPs display either oxidative susceptibility or oxidative markers similar to those of healthy donor cells. Our study suggests that the redox profile of patients may be considered a predictive marker of AIDS progression and that the acute infection and the asymptomatic phase of the disease may represent a useful period in which the combined use of antiretroviral and antioxidant drugs may be beneficial.

Acetylcysteine↗
PubMed1998

A dynamic flux chamber to measure mercury emission from aquatic systems.

A floating flux chamber, built of Plexiglas, has been developed to measure vapour-phase mercury fluxes over aquatic systems. The chamber is connected via Teflon tubes to a semi-automatic sampling device and to a mercury analyzer (battery-powered) to perform the determination of mercury emission in situ. Relatively low chamber blanks have been observed both in laboratory and in field conditions. The low detection limit of the analyzer (0.5 pg of mercury) allows measurements of mercury concentration in a short period of time (10 min). In this way it is possible to follow the real-time temporal trend of mercury emission. Some data obtained with this flux chamber in selected areas of the Mediterranean basin are reported.

Environmental Monitoring↗
PubMed1998

Gastric emptying rates of solid food in relation to body mass index: an ultrasonographic and scintigraphic study.

Gastric emptying can be modified by different physiologic conditions such as aging, menstrual cycle and pregnancy. Few studies in the literature have compared the gastric emptying rate of solid meals in normal subjects of varying size. The purpose of this work is to evaluate the gastric emptying rate of solid meals to determine whether body mass index (BMI) and gastric emptying rate correlate. Both ultrasonographic and scintigraphic techniques have been employed. Twenty-four healthy male subjects, divided into two groups, participated in the study. Our results demonstrate a significant correlation between gastric emptying and BMI. We conclude that variability of BMI must be taken in account when measurements of gastric emptying of solid food are performed.

Adult↗
PubMed1997

C-C chemokines, IL-16, and soluble antiviral factor activity are increased in cloned T cells from subjects with long-term nonprogressive HIV infection.

A combination of three beta, or C-C, chemokines, as well as IL-16, have been shown to inhibit HIV replication in vitro. Cellular antiviral factor is a more potent agent, and acts on all HIV strains. All are mainly, but not exclusively, produced by CD8+ T cells, both in HIV+ and healthy subjects. We studied the production of these HIV-suppressive factors in patients with HIV infection at different stages of disease. No difference in production by PBMC stimulated with PHA has been observed in asymptomatic HIV+, long-term nonprogressors (LTnP), and AIDS patients. When T cell line supernatants from these three groups were studied, no significant difference was found for C-C chemokines or IL-16 production, and viral suppression. However, T cell clones from LTnP secreted higher levels of all three chemokines, IL-16, and exerted a stronger inhibition on HIV replication. CD8+ clones showed a higher production than CD4+ clones. These clones were able to produce all antiviral factors irrespective of the secretion of type 1 or type 2 cytokines. The antiviral activities were not correlated, implying that viral suppression did not depend solely on C-C chemokines or IL-16. We postulate that all factors are needed to prevent HIV disease progression.

Antiviral Agents↗
PubMed1997

The risk of coronary artery disease after heart transplantation is increased in patients receiving low-dose cyclosporine, regardless of blood cyclosporine levels.

BACKGROUND: Coronary artery disease (CAD) of allografted hearts is the main cause of late mortality after cardiac transplant, but its etiology is still undetermined. HYPOTHESIS: This study was undertaken to evaluate the relevance of several risk factors, including cyclosporine (CsA) dose and blood CsA levels, to the incidence of CAD. METHODS: In 163 heart transplants performed between November 1985 and August 1994 at our Institution, CAD was diagnosed by coronary angiography or at postmortem examination. Patients in whom postmortem examination or coronary angiography was not performed, as well as those < 15 years of age and those who died within 1 month of surgery, were excluded from the study. The following risk factors were analyzed: recipient age, gender, pretransplant diagnosis, donor age, number of human leukocyte antigen (HLA)-AB mismatches, cytomegalovirus serology, mear serum cholesterol and triglyceride levels, the number of treated acute rejections, mean weighted CsA dose (CsA dosew and weighted blood CsA levels (blood CsA levelw). RESULTS: Coronary artery disease was diagnosed in 32 patients (19.6%). A low mean CsA dosew was the only significant predictor for CAD at multivariate analysis (p < 0.01): there was no correlation with blood CsA levelw. In the patients receiving a CsA dosew > 4 mg/kg/day, the 8.9 year probability of their remaining CAD free was 69% [confidence interval (CI) 50-87%] in comparison with 31% (CI 0-65%) in patients receiving a CsA dosew < 4 mg/kg/day. CONCLUSION: In our experience, a low CsA maintenance dose is the main risk factor for CAD, irrespective of blood CsA levels.

Adolescent↗
PubMed1997

Cytochrome P450 inactivation during reductive metabolism of 1,1-dichloro-2,2,2-trifluoroethane (HCFC-123) by phenobarbital- and pyridine-induced rat liver microsomes.

The reductive metabolic activation of 1,1-dichloro-2,2,2-trifluoroethane (HCFC-123), one of the potential substitutes for the ozone-depleting chlorofluorocarbons and a close structural analogue of the hepatotoxic anesthetic halothane, was investigated in vitro. During incubation of liver microsomes from phenobarbital-(PB) or pyridine-induced (PYR) rats with 0-20 mM HCFC-123 under anaerobic conditions, a dose- and time-dependent depletion of added exogenous glutathione was observed, indicating the formation of reactive metabolites. Under similar incubation conditions, except for the absence of glutathione, 1-chloro-2,2,2-trifluoroethane and 1-chloro-2,2-difluoroethene were detected as products of reductive metabolism of HCFC-123, as previously reported for halothane. As shown previously in our laboratory for halothane, under these conditions HCFC- 123 also caused a statistically significant loss of microsomal cytochrome P450 (P450) as indicated by a decrease of the classical absorption spectrum in the presence of CO. Both glutathione depletion and P450 loss were almost completely prevented by previous saturation of the incubation mixture with CO and were partially prevented by the presence of the free-radical scavenger N-t-butyl-alpha-phenylnitrone or the carbene trapping agent 2,3-dimethyl-2-butene, suggesting that both types of intermediates may be involved. The loss of P450 was associated with a quantitatively similar loss of microsomal heme, as measured by the pyridine hemochromogen reaction, with PB but not with PYR microsomes. Finally, both the P4502E1-specific p-nitrophenol hydroxylase activity in PYR microsomes and the P4502B1/2-specific pentoxyresorufin O-depentylase activity in PB microsomes were significantly inhibited (58 and 53%, respectively) by prior incubation with HCFC-123, suggesting that both isoforms are able to catalyze the activation of this halogenated compound. These results indicate that indeed HCFC-123, like its analogue halothane, is activated reductively to reactive metabolites by at least two P450 isoforms, namely P4502E1 and P4502B1/2. These metabolites, probably free radicals and/or carbene species, may attack the enzyme resulting in modification of the heme group and subsequent loss of catalytic activity.

Animals↗
PubMed1997

Clinical trials in rheumatoid arthritis: methodological suggestions for assessing radiographs arising from the GRISAR Study. Gruppo Reumatologi Italiani Studio Artrite Reumatoide.

OBJECTIVES: The three x ray assessors of the GRISAR study (blinded to treatment) gave consensual erosion and damage scores to the baseline and 12 month radiographs of 284 rheumatoid arthritis (RA) patients using three different methods: single readings (blinded as to patient and chronological sequence of the x rays), paired readings (blinded as to sequence), and chronologically ordered paired readings. The aim was to evaluate which of these reading procedures is the most appropriate for clinical trials. METHODS: The progression of the scores obtained using each procedure was compared by means of descriptive statistics, principal components analysis, and intra-patient correlation coefficients of pairs of methods. Bootstrap estimates of the variance of the difference in the means of two equally sized random samples were calculated to evaluate the power of the statistical analysis performed to assess the possible treatment effect for both paired and chronological reading methods. RESULTS: (a) The standard deviations of the paired and chronological readings were similar, but that of the single readings was higher. (b) The knowledge that two x rays were of the same patient accounted for a sizeable proportion of the between method variability. (c) Agreement was satisfactory between the paired and chronological methods for both scores but, between them and the single readings, it was modest for erosions and poor for damage. (d) The bootstrap estimate of the variance of the difference was smaller for the paired than the chronological method, possibly giving it greater power to test treatment effect. CONCLUSIONS: These results suggested that paired readings were the most suitable for evaluating the progression of joint damage in the GRISAR study.

Arthritis, Rheumatoid↗
PubMed1997

On-line predilution hemofiltration versus ultrapure high-flux hemodialysis: a multicenter prospective study in 23 patients. Sardinian Collaborative Study Group of On-Line Hemofiltration.

The aims of the present prospective multicenter study were to assess the clinical tolerance and well being, the correlation between nPCr and Kt/V and the pretreatment beta 2-microglobulin level in patients sequentially treated with high-flux dialysis with ultrapure bicarbonate hemodialysis (HD; phase 1) and predilution hemofiltration (HF) with on-line prepared bicarbonate substitution fluid (phase II). The same monitor (Gambro AK 100 ULTRA) and membrane (polyamide) were used. Twenty-three patients, all in a stable clinical condition, entered the study. The treatment was targeted to an equilibrated Kt/V (eqKt/V) of 1.4 for HD and 1.0 for HF. No mortality or relevant morbidity were observed. The number of hypotensive episodes was 1.78 +/- 2.8 per patient and month during HD vs. 1.17 +/- 3.1 during HF (p = 0.003) and the number of the hypertensive episodes 1.28 +/- 2.8 during HD vs. 0.42 +/- 0.8 during HF (p = 0.04). Incidences of arrhythmia, muscular cramps and headache were significantly less frequent during HF. Interdialytic cramps, arthralgia and fatigue were also significantly less frequent during the HF period. The average beta 2-microglobulin level was 27.1 +/- 14.7 mg/dl at the start of the study, 22.9 +/- 4.9 mg/dl at the beginning of phase II and 22.4 +/- 4 mg/dl at the end of phase II (p = 0.01 compared to the start). A significant linear correlation between the normalized protein catabolic rate and eqKt/V was obtained faster during HD than during HF (45 vs. 120 days) indicating that HF affects the nutritional status with mechanisms different from HD. The present study is in agreement with the hypothesis that HF gives and adequate nutritional status with improved clinical stability and well being at a lower Kt/V compared to HD. Both therapies were efficient in controlling the pretreatment beta 2-microglobulin level.

Aged↗
PubMed1997

Long conservation organs in heart transplantation: postoperative results and long-term follow-up in fourteen patients.

Between 1988 and 1995, 14 heart transplantations were performed after a long preservation period (10 to 13 hours). The transplantation procedure (Shumway) was standard, and our results were achieved through the implementation of a very strict reperfusion technique that included low pressure and low cardiopulmonary bypass output for the first 10 minutes. Three patients died during the postoperative period, and the survival rate was 75% at 1 year and 71% at 5 years. The results obtained with hearts stored for such long periods are comparable to the results obtained with hearts stored for less than 4 hours.

Adolescent↗
PubMed1997

Radiographic changes in the feet of patients with early rheumatoid arthritis. GRISAR (Gruppo Reumatologi Italiani Studio Artrite Reumatoide)

OBJECTIVE: To assess the value of radiographs of the feet of patients with early rheumatoid arthritis (RA) in the evaluation of RA classification and outcome. METHODS: Within a multicenter therapeutic trial, baseline and 12 month radiographs of the hands, wrists, and feet of 284 patients with early RA (< or = 4 years; mean 1.4; median 0.6) were scored according to a modified Larsen-Dale method by an independent radiological reading committee, blinded to the treatment, clinical, and laboratory data. RESULTS: Thirty-two patients (11%) had only foot erosions at baseline. Twelve month progression in the eroded joint count was more frequent in the patients with foot erosions than in those without (63% CI 55 divided by 71 vs 42% CI 35 divided by 50). CONCLUSION: Foot radiographs facilitate the identification of patients with early erosive RA. Foot involvement is indicative of more aggressive disease. Assessment of foot radiographs allows the most adequate therapeutic strategy to be adopted.

Adolescent↗
PubMed1996

Ultrasound demonstration of gallbladder wall thickening as a method to differentiate cirrhotic ascites from other ascites.

RATIONALE AND OBJECTIVES: Gallbladder wall thickness was measured by ultrasound in 16 patients with ascites caused by liver cirrhosis and in 16 noncirrhotic patients with ascites. This study was performed to evaluate if gallbladder wall thickening could differentiate cirrhotic ascites from ascites due to other causes. METHODS: Gallbladder thickness was measured by duplex ultrasound in 16 cirrhotic patients with ascites and in 16 noncirrhotic patients with ascites. Measurements of portal vein flow and serum albumin also were performed. RESULTS: Gallbladder wall thickness was 0.76 +/- 0.21 cm in cirrhotic patients and 0.24 +/- 0.09 in noncirrhotic patients (P < 0.001, Student's t test for unpaired data). Gallbladder wall thickening was significantly more frequent in patients with cirrhotic ascites than in patients with noncirrhotic ascites (P < 0.001, chi-square test). CONCLUSIONS: The authors feel that the ultrasound finding of gallbladder wall thickening in patients with ascites is highly predictive of liver cirrhosis diagnosis.

Aged↗
PubMed1996

Reductive activation of 1,1-dichloro-1-fluoroethane (HCFC-141b) by phenobarbital- and pyridine-induced rat liver microsomal cytochrome P450.

1. During anaerobic reductive incubation of liver microsomes, from either the pyridine- or phenobarbital-treated rat, with 1,1-dichloro-1-fluoroethane (HCFC-141b) in the presence of a NADPH-regenerating system, a time- and dose-dependent formation of reactive metabolites was detected as indicated by a depletion of added exogenous glutathione. 2. A statistically significant, dose-dependent loss of both cytochrome P450 and microsomal haem was also observed under these experimental conditions. Furthermore, a statistically significant decrease of p-nitrophenol hydroxylase and pentoxyresorufin O-depentylase activity was measured in microsomes from the pyridine- and phenobarbital-induced rat, respectively indicating that both P4502E1 and P4502B undergo substrate-dependent inactivation. 3. Both reactive metabolite formation and P450 inactivation were almost completely inhibited by previous bubbling of the incubation mixture with carbon monoxide, indicating that interaction of the substrate with a free and reduced P450 haem iron is required for substrate bioactivation and enzyme loss. 4. The presence in the incubation mixture of the spin-trap N-t-butyl-alpha-phenylnitrone (PBN) and the carbene trap 2,3-dimethyl-2-butene (DMB) largely prevented both glutathione depletion and P450 loss. This suggests that free radical and carbene intermediates formed by the metabolic activation of the substrate are involved in the inactivation of P450 and the loss of its prosthetic haem group.

Alkenes↗
PubMed1995

Suicidal inactivation of haemoproteins by reductive metabolites of halomethanes: a structure-activity relationship study.

Human haemoglobin (Hb), methaemalbumin (MHA) or rat liver microsomal cytochrome P-450 (P-450) were incubated anaerobically at microM concentrations with 1 mM carbon tetrachloride (CCl4), trichlorobromomethane (CCl3Br), chloroform (CHCl3) or methylene chloride (CH2Cl2) in presence of 1 mM sodium dithionite as the reducing agent. At the end of a 5-min incubation, haem was measured by various methods, i.e. binding spectrum with CO, pyridine-haemochromogen haem assay and porphyrin fluorescence, and compared for the four analogues. Statistically significant losses were observed, with all three haemo-protein systems, for CCi3Br, CCl4 and CHCl3, but not CH2Cl2. For Hb, the loss was greater with CCl3Br (haem assay, 63%; porphyrin fluorescence, 48%; CO binding, 24%) than with CCl4 (haem assay, 31%) or CHCl3 (haem assay, 13%). On the other hand, with MHA, CCl4 gave a dramatic loss (haem assay, 88%; porphyrin fluorescence, 83%; CO binding, 67%), which was greater than that observed with CCl3Br (haem assay, 49%; porphyrin fluorescence, 38%; CO binding, 25%). No loss was found with CHCl3. Finally, with microsomes, the inactivation was larger with CCl4 (CO binding, 58%; haem assay, 50%; porphyrin fluorescence, 33%) than with CCl3Br (CO binding, 33%; haem assay, 10%) or CHCl3 (haem assay, 9%; CO binding, 6%). In a separate set of similar experiments, an ion-pairing reverse phase HPLC method showed the formation of substrate-dependent hae-derived products during incubation of CCl3Br with Hb or microsomes, and of CCl4 with Hb. A correlation between potential for free radical formation (CCl3Br > CCl4 > CHCl3 > CH2Cl2) and extent of haem inactivation was observed with all methods for Hb, but not for microsomal P-450 or MHA. The results indicate that these halomethanes may be activated differently by different haemoproteins and suggest that their potential ability to undergo reductive metabolism may not be the only critical factor involved in P-450 haem inactivation by these chemicals.

Animals↗
PubMed1995

Reductive activation of halothane by human haemoglobin results in the modification of the prosthetic haem.

The metabolic activation of halothane by human haemoglobin (Hb) under reducing conditions in vitro is reported. Absolute spectra of sodium dithionite-reduced Hb, recorded during its anaerobic incubation in the presence of the substrate, showed decreasing concentrations of reduced Hb (Hb2+) with time. The loss of Hb2+ was accompanied, although only to some extent, by a concurrent oxidation to methaemoglobin (Hb3+), suggesting that electron transfer from Hb to the substrate had occurred. Reductive halothane metabolism was observed under these conditions as indicated by a dose-dependent inorganic fluoride (F-) production, which was, however, lower than that observed with heated Hb or a water soluble haem preparation (methaemalbumin). A rapid, partial loss of Hb was found upon addition of the substrate to the incubation mixture, as indicated by a decrease of the typical peak at 418 nm in the absolute spectra recorded in the presence of carbon monoxide (CO). This effect was associated with a loss of the Hb prosthetic group, haem, as shown by a decrease of the pyridine-haemochromogen reaction. Both effects were time and dose dependent. The inhibition of the Hb inactivation reaction by adding exogenous CO or the spin trapping agent N-t-butyl-alpha-phenylnitrone (PBN) to the incubation mixture beforehand indicated that (a) a reduced and free haem iron is required by Hb to activate halothane, and (b) the formation of free radical reactive metabolites of halothane is likely to be responsible for Hb inactivation. The mechanism of the reaction may involve the attack of these metabolites on the haem group of Hb, as indicated by the detection, with a reverse-phase ion-pairing HPLC system, of two Hb-derived products showing a typical haem-like absorption spectrum. The present results resemble those obtained recently with carbon tetrachloride (Ferrara et al., Alternatives to Laboratory Animals 21: 57-64, 1993) and suggest a common mechanism of activation of the two polyhalogenated alkanes by Hb.

Biotransformation↗
PubMed1995

HIV-specific lymphoproliferative responses in asymptomatic HIV-infected individuals.

In vitro lymphoproliferative responses to HIV-1 recombinant antigens (gp160, p24, and Rev protein) were studied in 83 patients with asymptomatic HIV-1 infection (CDC groups II and III) and circulating CD4 lymphocyte numbers > 400/mm3. Significant response to at least one of the three antigens was detected in 52.4% of the subjects, but the responses were weak, and concordance of the response to the three antigens was rare, the frequency of individuals responding to each antigen not exceeding 22.4%. Increasing frequencies of response were observed when recall antigens (tetanus toxoid and Candida albicans glycomannoprotein) (65.5%) and anti-CD3 MoAb (76.6%) were used as stimuli. Although a significant association between lymphocyte response to p24, but not gp160, and steadiness of CD4 lymphocyte numbers before the assay was observed, no predictive value for lack of CD4 cell decrease was confirmed for either antigen, and fluctuation of the responses to HIV antigens was seen during subsequent follow up. The panel of T cell assays used could be regarded as appropriate for monitoring both HIV-specific responses and T lymphocyte function during immunotherapy with soluble HIV antigens.

Adolescent↗
PubMed1995

Urinary and synovial pyridinium crosslink concentrations in patients with rheumatoid arthritis and osteoarthritis.

OBJECTIVES: To assess urinary and synovial concentrations of hydroxypyridinium crosslinks of collagen in patients with rheumatoid arthritis (RA) and osteoarthritis (OA) and to evaluate whether a combined measurement in the two compartments could give additional information about the origin of these compounds in joint diseases. METHODS: Concentrations of hydroxypyridinoline (HP) and lysylpyridinoline (LP) were measured by high pressure liquid chromatography in urinary and synovial samples collected from 20 patients with RA and 20 patients with knee OA. Full laboratory and clinical assessments were performed. RESULTS: Urinary concentrations of both HP and LP were significantly greater in RA than in OA. Urinary HP in RA correlated with the number of swollen joints corrected for Lansbury index and with erythrocyte sedimentation rate and C reactive protein. In synovial fluid from both groups, only relatively small amounts of HP were measured, while bone type I collagen specific LP was below the limit of detection in all samples. In RA patients, but not in OA patients, there was a strong correlation between urinary and synovial concentrations of HP (r = 0.75). CONCLUSIONS: The results underline the relationship between urinary HP and disease extent and activity in RA. The findings in synovial fluid support the hypothesis of an extraskeletal origin of HP in chronic joint diseases in which cartilage and synovial turnover may be increased.

Amino Acids↗