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Biomedical subjects

R R-Pena

Publications and source records attributed to R R-Pena.

6 recordsLinked to original sources

Anti-oxidant enzyme activities and expression and oxidative damage in patients with non-immediate reactions to drugs.

Adverse drug reactions with an immunological basis (ADRIB) may involve activation of other concomitant, non-specific mechanisms, amplifying the specific response and contributing to the severity and duration. One concomitant mechanism could be the generation of reactive oxygen species (ROS) and/or their detoxification by anti-oxidants, including anti-oxidant enzymes. We analysed the activity of the anti-oxidant enzymes Cu/Zn-superoxide dismutase (SOD), catalase (CAT) and cellular glutathione peroxidase (GPX), as well as certain markers of oxidative damage (thiobarbituric acid reactive substances (TBARS) and carbonyl content) in peripheral blood mononuclear cells from patients with non-immediate ADRIB using spectrophotometric methods and the anti-oxidant enzymes expression by quantitative real-time reverse transcription-polymerase chain reaction. SOD activity and expression were increased in all types of non-immediate reactions (urticaria, maculopapular exanthema and toxic epidermal necrolysis). Regarding oxidative damage, TBARS were increased in urticaria and maculopapular exanthema, and carbonyl groups in all types of reactions. Our observations indicate that oxidative damage occurs in non-immediate reactions. Carbonyl stress and the inadequacy of the anti-oxidant defences are probable causes.

Adolescent↗

Immediate hypersensitivity reactions to penicillins and other betalactams.

Immediate hypersensitivity reactions to betalactams are IgE mediated and constitute the most frequent allergic reactions mediated by specific immunological mechanisms. IgE responses to benzyl penicillin (BP), the first antibiotic producing the benzyl penicilloyl structure (BPO), are characterized by a quick release of inflammatory mediators, resulting in anaphylactic shock, urticaria and angioedema. With the progressive appearance of other structures, comprising cephalosporins, carbapenems, monobactams and clavulanic acid, IgE selective responses and cross-reactivity reactions were observed. The diagnosis of betalactam hypersensitivity, classically based on skin testing with major and minor determinants of benzyl penicillin or in vitro IgE antibodies to BP, has been modified by the inclusion of different determinants generated from these compounds, for which amoxicillin (AX) is the most relevant, followed by cephalosporins. Some subjects develop positive responses to several betalactams, mostly within the same family, but others develop a selective response. These are relevant for the appropriate selection of antimicrobial drugs in patients who have immediate hypersensitivity to betalactams.

Drug Hypersensitivity↗

Decrease of selective immunoglobulin E response to amoxicillin despite repeated administration of benzylpenicillin and penicillin V.

BACKGROUND: Subjects with IgE responses to betalactams can develop selective or cross-reactive responses after the administration of penicillin derivatives. After the reaction, however, the hapten induces a boosting phenomenon, which may increase the titre and the affinity of the antibody, with the resulting risk of developing allergic reactions to other penicillins. OBJECTIVE: To determine in subjects with selective responses to amoxicillin (AX) and good tolerance to benzylpenicillin (BP) and penicillin V (PV) whether the administration of these compounds induced any change in specificity, measured by either skin or in vitro testing, which could predict the appearance of cross-reactivity. METHODS: Ten subjects with a selective response to AX were followed-up for 2 years with the periodic administration of penicillin G and V (Group A) and compared with another group composed of 10 persons with identical clinical characteristics but without repeated penicillin administration (Group B). Periodic in vitro and in vivo measurements of specific IgE antibodies were performed at 6-month intervals. Patients were randomized to Group A or B according to their order of inclusion. RESULTS: In both groups, skin test reactivity tended to decrease, and although greater in Group A, the difference was not significant compared with Group B. Median RAST values also decreased over time and showed no differences in the exposed group compared with the controls. One patient in Group A became positive to benzylpenicilloyl (BPO), despite becoming negative to AX. CONCLUSION: Subjects with selective IgE responses to side-chain-specific determinants seem to become negative, with no influence from subsequent administration of a closely related penicillin.

Adolescent↗

Anti-transglutaminase IgA ELISA: clinical potential and drawbacks in celiac disease diagnosis.

BACKGROUND: Since the identification of tissue transglutaminase (tTG) as the antigen for the anti-endomysial antibodies (EMA), several antigen-specific immunoassays have been reported for celiac disease (CD) screening. A first objective was to evaluate the suitability for CD screening of three different IgA tTG ELISAs, two of them based on guinea pig liver tTG (gp-tTG) (an in-house ELISA with a partially purified extract and a commercial ELISA with purified gp-tTG antigen) and a third recombinant human tTG (rh-tTG) ELISA. The results are compared with EMA and with the final clinical diagnosis. A second objective was to analyze antibody reactivities in those patients with anti-tTG and EMA discrepancies. METHODS: ELISA and EMA tests were used to measure IgA anti-tTG levels in sera from 259 patients (107 had CD and 72 had Type I diabetes mellitus). RESULTS: The purified gp-tTG ELISA was highly sensitive (97.7%) and specific (98.8%) in the detection of CD, almost equaling EMA. Rh-tTG ELISA did not improved the sensitivity of EMA, but its specificity was slightly superior. Immunoblot analysis with partially purified gp-tTG extract, the antigen most frequently used for anti-tTG detection, showed that the majority of false positives were due to IgA reactivities to contaminant proteins present in the liver antigenic extract. This low specificity was particularly problematic in diabetics. CONCLUSION: Purified tTG ELISAs, either with purified guinea pig liver or recombinant human antigens, can be used as quantitative and observer-independent alternatives to the traditional and time-consuming EMA in the screening of CD.

Blotting, Western↗