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Biomedical subjects

R Ferrara

Publications and source records attributed to R Ferrara.

At least 19 recordsLinked to original sources
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↗
PubMed1995

Humoral response to influenza hemagglutinin: oligoclonal spectrotype and failure of thymopentin as immunoadjuvant.

Influenza remains a serious cause of illness and death among certain populations. Influenza vaccines in use at present are of limited effectiveness due to the high variability of the virus, and trials all over the world are in progress to enhance their immunogenicity. Conflicting results, in fact, have been reported about the immune response to influenza vaccination in diverse populations. In this paper we analyzed the antibody response to the hemagglutinin (HA) of the H3N2 A/Shangai 16/89 strain, which was included into the trivalent 1991-92 influenza vaccine, in four groups of subjects: 8 healthy young, 13 human immunodeficiency virus (HIV)-infected and 37 elderly healthy people, 9 of whom were treated with thymopentin (TP-5). Our results show levels of anti-HA IgG before vaccination in HIV-infected and elderly people significantly lower than those of normal young subjects. After vaccination, HIV-infected and elderly healthy people showed a significant increase of specific antibodies, whereas a failure in the specific response in normal young subjects was observed, thus differences among the groups were no longer present. Moreover, the spectrotypic analysis of antibody response, by isoelectric focusing and reverse blotting, showed oligoclonal but polymorphic pattern in the majority of subjects, irrespective of the group, and more frequently lack of expansion of the spectrotype after vaccination, thus demonstrating the lack of the recruitment of antigen-specific B cells. Finally, the treatment with TP-5 did not influence the outcome of the vaccination in the group of elderly people. These results further emphasize the limited immunogenicity of influenza vaccination and the inefficacy of TP-5 as immunoadjuvant, in this model of vaccination.

Adjuvants, Immunologic↗
PubMed1994

[Appendicular mucocele. A report of a case diagnosed preoperatively].

Mucocele of the appendix is an unusual clinical entity. Despite a recognized constellation of findings, the diagnosis is not usually made prior to surgical exploration. A 35 year old man is reported in whom clinical evaluation, including US and CT scans, resulted in the correct preoperative diagnosis confirmed at surgery and leading to appropriate operative decisions.

Adult↗
PubMed1994

[Continence in low resections].

Anorectal function is an important problem after low anterior resection procedure. This paper reports the results from 14 patients undergoing to low resection at Surgical Pathology Institute of the University of Verona. In 12 cases the restoration of the bowel continuity has been obtained by colon-anal anastomosis (Parks Operation) and in 3 cases by colo-rectal anastomosis at the anorectal ring level. The patients have been examined in the preoperative and in the postoperative period by clinical and manometric study. The results confirm that low resection does not involve faecal continence.

Anal Canal↗
PubMed1993

Immunoregulation of autoimmune disorders: the role of intravenous immunoglobulins.

Modified and intact immunoglobulin preparations are available for therapeutic use. The administration of intravenous immunoglobulins (IVI G) gave positive results in Primary Immunodeficiency Syndromes (PIS) (prophylaxis of viral and bacterial diseases), in treatment of secondary immunodeficiencies (hematologic malignancies, bone marrow transplantation), and in some infections. Adverse reactions have been reported during IVIG infusions, but they are rarely serious and do not represent limiting conditions for a short or long term therapy. After the original observation in thrombocytopenic purpura, IVIG have been used as immune modulators in various autoimmune related disorders. Various mechanisms of action are proposed: blockade and down regulation of phagocytic function via Fc receptor, regulation of idiotype-anti idiotype network, suppression of idiotype synthesis, T-B cell interference towards antigen presentation, increase in suppressor lymphocytes, IVIG-cytokine interaction.

Autoimmune Diseases↗
PubMed1992

Suicidal inactivation of human cytochrome P-450 by carbon tetrachloride and halothane in vitro.

A significant loss of human cytochrome P-450 was observed during the anaerobic incubation of NADPH-reduced human liver microsomes obtained from surgical samples, in presence of carbon tetrachloride or halothane. In order to prevent any interference in the classical spectrum of cytochrome P-450 with CO, the method of Johannesen & DePierre (1978) was modified to obtain cytochrome P-450 determination. The enzyme inactivation reaction showed pseudo-first order kinetics and was accompanied by destruction of the haem tetrapyrrolic structure, as indicated by a significant loss of its porphyrin fluorescence. Values of about 200 and 700 were calculated for the partition ratio between metabolic turnover of the substrate and enzyme inactivation during reductive incubation of one of these microsomal preparations with limiting concentrations of CCl4 and halothane, respectively. The results indicate that human liver cytochrome P-450 can be inactivated reductively in vitro by CCl4 and halothane reactive metabolites and suggest that a suicide type of mechanism, similar to that which was recently demonstrated to occur, for both substrates, with rat liver microsomes (Manno et al. 1988a & 1991), may also be involved in the inactivation of the human enzyme(s).

Animals↗
PubMed1992

Simultaneous measurement of gastric emptying of digestible and indigestible solids in healthy humans.

Gastric emptying of digestible and indigestible solids has been simultaneously evaluated in healthy humans. Gastric emptying of indigestible solids occurs simultaneously during the emptying of digestible solids. The knowledge of the mechanism responsible for gastric emptying of both digestible and indigestible solids may contribute to improve physiologic insight in this field and to develop further clinical applications.

Adult↗
PubMed1991

Ultrasonographic study of the Wirsung duct caliber after meal.

The pancreatic duct or at least parts of this structure can be demonstrated today by sonography in 50-82% according to various authors. We have measured the caliber of the sonographically visualized pancreatic duct in 20 normal subjects after physiological stimulation with meal. The mean caliber of the duct markedly increased after meal. During dilatation a longer segment of duct is more clearly visualized. It is possible to document an increase of caliber of Wirsung duct "in vivo" as an evident sign of pancreatic secretion.

Adult↗
PubMed1991

Uterine motility and cervical ripening in second trimester elective abortion by two different PGE analogues.

The clinical effects were studied of two different PGE analogues on the uterine motility and cervical ripening of eighty pregnant women asking for a second trimester elective abortion for fetal abnormalities. Forty women received vaginal suppositories each containing 1 milligram of 16, 16-dimethyl-trans-s2-PGE1 (Gemeprost) every 3 hours (5 mg max). Intramuscular injections of 500 micrograms of 16-phenoxy-w 17, 18, 19, 20 tetranor PGE2 methyl-sulphonylamide (Sulprostone) were administered every four hours (2000 mcg max.) to the remaining forty patients. Thirty-three Gemeprost treated patients (82.5%) and 34 Sulprostone treated patients (85%) experienced a complete abortion in the mean of 12.92 +/- 6.95 hours and 11.88 +/- 6.8 hours respectively. The histological and ultrastructural findings of cervical ripening were similar in both groups, while the tocographic patterns showed different characteristics. Side effects occurred in 16 Sulprostone (40%), but only in 9 (22.5%) Gemeprost treated patients, demonstrating that Gemeprost, although equally effective, is better tolerated.

Abortion, Induced↗
PubMed1989

Cisapride and gastric emptying of a solid meal in dyspeptic diabetics without autonomic neuropathy and in healthy volunteers.

Gastric emptying was studied in 10 insulin-treated, long-standing, diabetic out-patients with upper gastrointestinal, dyspeptic symptoms. Autonomic neuropathy, mucosal lesions and chloropeptic hyposecretion were excluded. Gastric emptying of a labelled solid meal (99mTc-sulphur colloid-infiltrated chicken liver) was clearly delayed by comparison with normal subjects: the mean gastric emptying half-time was almost 5-times longer (245.6 vs 52.5 min), and the gastric emptying rate at 120 min was 75% slower. Cisapride 10 mg i.v. significantly accelerated both parameters, and placebo had no effect upon them. In conclusion, gastroparesis may be present in diabetics without autonomic neuropathy, and cisapride may improve gastric emptying in such patients.

Adult↗
PubMed1989

Mercury levels in total suspended matter and in plankton of the Mediterranean basin.

Mercury levels in total suspended matter (TSM) and in plankton of sea water from some Mediterranean areas have been determined. The mercury concentration in TSM collected with a filter of 0.45 micron pore size ranges from 0.1 to 2.4 ng l-1 and from 0.1 to 4.7 ng mg-1, dry wt. These levels are 3-10 times higher than those observed in plankton (0.08-0.29 ng mg-1 dry wt.) collected with a 200 microns net mesh size. The larger amounts of mercury in TSM than in the matter collected by the plankton nets are probably due to the high abundance of smaller sized particles selected by the filter.

Animals↗
PubMed1989

[Gastric emptying of solids in patients with nonorganic dyspepsia].

The purpose of this work was to evaluate gastric emptying of a solid meal in 20 patients with functional dyspepsia and in 20 healthy controls. Gastric emptying time (T 1/2 = 188.45 +/- 93.79; p less than 0.001 - E.I. = 0.43 +/- 0.16; p less than 0.001) was significantly delayed in patients with functional dyspepsia compared with controls. The conclusion is drawn that either antral motor activity or antral-pyloric-duodenal motor activity is impaired in such patients.

Adult↗