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Biomedical subjects

A Parra

Publications and source records attributed to A Parra.

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

The higher the dose, the greater the sex differences in escape-avoidance response in mice after acute administration of haloperidol.

Sex differences in the effects of haloperidol in the escape-avoidance response have previously been found in various studies carried out in our laboratory in which mice were used as experimental subjects. Males were more affected than females by the disruptive effects of this neuroleptic of frequent clinical use. In the present work these sex differences were evaluated in a unique training session using several doses of the drug (0.075, 0.25, and 0.75 mg/kg i.p.). The number of avoidances, escapes, nonresponses, crossings during the adaptation period, crossings during intertrial intervals, and response latencies were analyzed. Statistically significant sex differences were found in the number of escapes and nonresponses: males showed fewer escape responses and more nonresponses than females. These sex differences were dose dependent: a positive correlation was obtained between doses of haloperidol and sex differences observed in the number of escapes and nonresponses. The higher the dose, the greater the sex differences. These are related not only to the impairment of motor activity, because no sex differences were found in the number of crossings during the adaptation period and intertrial intervals.

Animals↗
PubMed1998

Sex differences in escape-avoidance response in mice after acute administration of raclopride, clozapine, and SCH 23390.

Sex differences in the effects of haloperidol in the escape-avoidance response in mice have previously been found in various studies carried out in our laboratory. Males were more affected than females by the disruptive effects of this neuroleptic. The work described herein extended the study of these sex differences to raclopride, clozapine, and SCH 23390, using several doses of each drug in acute administration. The results showed dose-dependent sex differences in the deteriorating effects of these dopamine antagonists in the escape-avoidance response. Male mice were more affected by the inhibitory effects of these drugs, showing fewer escape responses and more nonresponses than females. Sex differences were found with all three of the dopamine antagonists studied, indicating, therefore, that these differences do not depend on a unique type of dopaminergic receptor. The results obtained in motor activity, measured by the number of crossings during the adaptation period and the intertrial intervals, suggest that the motor effects are not the origin of these differences. It is concluded that, besides haloperidol, other dopamine antagonists also show sex differences in their behavioral effects in escape-avoidance response in mice, with males being more affected than females by the inhibitory action of these drugs.

Animals↗
PubMed1998

In vivo efficacies of amoxicillin and cefuroxime against penicillin-resistant Streptococcus pneumoniae in a gerbil model of acute otitis media.

The comparative efficacies of amoxicillin and cefuroxime against acute otitis media caused by a penicillin-resistant (MIC, 2 micrograms/ml) Streptococcus pneumoniae strain were assessed in a gerbil model by challenging each ear with 10(7) bacteria through transbullar instillation. Each antibiotic was tested at two doses (5 and 20 mg/kg of body weight) administered at 2, 10, and 18 h postinoculation. Samples were obtained from the middle ear (ME) on days 3 and 7 postinoculation for determination of bacterial counts. Only amoxicillin, at both doses, was able to significantly halt the weight loss in animals, reducing both the number of culture-positive animals and the bacterial concentration in ME samples versus the values for untreated animals. Comparison of the efficacies between the antibiotics, determined by their ability to achieve culture-negative ME specimens, showed that amoxicillin at 5 mg/kg was significantly more active than cefuroxime at the same dose. The use of higher doses of either amoxicillin or cefuroxime did not produce significantly better results than those obtained with the lower dose but caused a greater inflammatory response. The more favorable results obtained with amoxicillin compared with those obtained with cefuroxime could be related to the antimicrobial susceptibility of the pneumococcal strain (MICs and minimum bactericidal concentrations of 1 and 1 microgram/ml and 4 and 4 micrograms/ml for amoxicillin and cefuroxime, respectively) as well as to the better pharmacokinetic parameters obtained with amoxicillin.

Acute Disease↗
PubMed1997

Acute dopaminergic blockade augments the naloxone-induced LH rise in estrogen-treated postmenopausal women.

OBJECTIVES: To assess the effect of estrogen replacement on the simultaneous blockade of the dopaminergic (DA) and opioidergic neural control of hypothalamic-gonadotropic function in postmenopausal women. METHODS: Twenty healthy postmenopausal women, 48-55 years old were randomly assigned to receive either a 4-h naloxone infusion at 2 mg/h (group 1, n = 7) or a 10 mg i.v. bolus of metoclopramide (group 2, n = 7) or both drugs, simultaneously (group 3, n = 6) before and after 3 weeks of transdermal estradiol (100 microg/day). Blood samples were obtained at 30-min intervals during 4 h and duplicate determinations of serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2) and prolactin (PRL) were performed in all samples. RESULTS: In group 1 only a mild but significant LH rise after but not before estrogen replacement was seen. In group 2 PRL had a greater rise after than before estrogen therapy, without other hormonal changes. In group 3 a greater rise in PRL occurred after than before estrogen administration and serum LH had a sustained rise throughout the test only after estrogen replacement (greater than in group 1). No FSH changes were observed. The after-estradiol PRL response was nearly similar in groups 2 and 3. CONCLUSIONS: Our results indicate that in the untreated postmenopausal women, the dopaminergic system has little and the opioidergic system has no significant input in the control of gonadotropin or prolactin release. However, following estrogen replacement, opioids are involved in the inhibition of LH release and stimulating PRL release, while the dopaminergic system acts to inhibit PRL release and modulates LH release or inhibition, depending on the levels of circulating estrogens.

Dopamine↗
PubMed1997

Differences in the metoclopramide-induced prolactin release related to age at first full-term pregnancy or nulliparity.

To investigate if an association exists in parous women between metoclopramide-induced prolactin (PRL) release and chronological age at first full-term pregnancy and to compare their response to a group of non-parous women, we studied 139 healthy, non-lactating women, aged 15.8-48.2 years, on days 18-22 of their menstrual cycle (except two post-menopausal women). There were 61 parous women divided according to chronological age at first full-term pregnancy: 22 were aged < or = 20.0 years, 25 were aged 20.1-29.9 years and 14 were aged > 30 years. There were also 50 nulliparous women and 28 women who had experienced only first trimester abortions. Three basal blood samples were obtained before oral metoclopramide (10 mg) was administered; subsequently samples were taken at 60, 90 and 120 min. Duplicate serum PRL determinations were performed by radioimmunoanalysis and the area under the curve (AUC) calculated. In parous women, the PRL AUC was positively correlated with chronological age at first full-term pregnancy (P < 0.0001), and it was lower than in nulliparous women or in women with abortions. These data suggest that in parous women a greater dopaminergic tone may exist compared with non-parous women, which seems to decrease gradually as chronological age at first full-term pregnancy increases.

Age Factors↗
PubMed1997

Serum eosinophil peroxidase (EPO) levels in asthmatic patients.

Eosinophil granular proteins are a useful eosinophilic activation marker in asthmatic patients. In this study, the eosinophil peroxidase (EPO) levels were assessed in different stages of bronchial asthma, in 123 patients suffering from asthma, classified as mild (n =49), moderate (n = 49), and severe (n = 25), according to the International Consensus Report of Diagnosis and Treatment of Asthma, as well as in 27 healthy controls, with the aim of evaluating the importance of this protein as a severity marker in bronchial asthma, and its possible correlation with parameters such as anamnesis, respiratory function tests, and peripheral blood eosinophil count, and also with some allergologic diagnostic tests, both in vivo and in vitro. The geometric mean serum level of EPO was 9.3 +/- 11.3 ng/ml (median +/- SD) in controls, 28 +/- 37.8 ng/ml in the asthmatic patients. Depending on the asthma severity, the EPO levels were 25 +/- 30.5; 29 +/- 37.1, and 41 +/- 47.3 ng/ml in mild, moderate, and severe asthmatics, respectively, being the significant differences between the group of patients with mild and severe asthma (P < 0.001). The number of eosinophils (eos) in peripheral blood was 157 +/- 20 eos/mm3 in the controls, 334/35 eos/mm3 in mild asthmatics, 510 +/- 87 eos/mm3 in moderate asthmatics, and 658 +/- 72 eos/mm3 in severe asthmatics, with significant differences between all groups (from P < 0.05 to P < 0.001). Both the serum levels of EPO and the number of eosinophils were greater in patients with active asthma patients with inactive asthma (P < 0.001). Significant negative correlations (P < 0.001) were found between serum levels of EPO and FEV1 (rs = 0.30), MEF25-75 (rs = -0.33) and MEF50 (rs = -0.34), and a good positive correlation (rs = 0.80, P < 0.001) was found between EPO levels and the number of eosinophils in peripheral blood. We also found a significant positive correlation between eosinophil number and clinical score (rs = 0.54, P < 0.001) and between EPO levels and the mentioned score (rs = 0.46, P < 0.001).

Adolescent↗
PubMed1997

[Participation of growth factors in human reproduction].

The Growth Factors (GFs) include a group peptidic molecules, with important trophic, mitotic and cellular differentiation effects in most human tissues. This review encompasses the different types of GFs and their biologic effects on tissues involved in the human reproductive process. The importance of the GF in the embryonic development and the implantation process is also commented. Finally, we assess the participation of the GFs in the pathophysiology of the Polycystic Ovary Syndrome and Endometriosis based on recent investigations. The review permit us appreciate the importance of the GFs as mediators of different hormones (in their secretion and biological effects) and in the regulation of some cellular events. The real value of these GFs in the daily clinical practice is as yet to be established, due to the technical laboratory limitations with respect to their identification and quantification, as well as the lack of more clinical research in humans. The GFs are promising molecules for the treatment of infertiles couples and for the application of the technics of assisted reproduction, in vivo and in vitro.

Endometrium↗
PubMed1996

Granulocyte-macrophage colony-stimulating factor as adjuvant therapy for factor as adjuvant therapy for interferon alpha treatment of chronic hepatitis C.

The safety and efficacy of granulocyte-macrophage colony-stimulating factor (GM-CSF) as adjuvant therapy for interferon alpha (IFN-alpha) treatment has been evaluated in 20 non-cirrhotic patients with chronic hepatitis C virus (HCV) infection. Adjuvant therapy with GM-CSF plus IFN-alpha was associated with less myelosuppression than with IFN-alpha alone (P < .01), although the rate of local adverse reactions increased. GM-CSF adjuvant therapy led to a 50% biochemical response (transaminase values within the normal range at therapy end) and to reductions in HCV RNA concentrations (median HCV RNA reduction of 99%, range 8-100%), which were similarly observed in single IFN-alpha recipients (median HCV RNA reduction of 91%, range 38-100%). However, HCV RNA became undetectable in three biochemical responders to the GM-CSF adjuvant therapy, but in only one biochemical non-responder to IFN-alpha alone. The use of GM-CSF as adjuvant therapy is safe and, although it has not improved the biochemical response, it might potentiate the virologic response to IFN-alpha treatment alone.

Adult↗
PubMed1996

Apparent vs real effects of scopolamine on the learning of an active avoidance task.

The effects of scopolamine hydrobromide (0.5 and 2 mg/ kg) administered intraperitoneally to Balb/c male mice before or after training in active avoidance were explored in four training sessions and in a subsequent test session, free of drug. Animals given scopolamine prior to training performed better than controls, an effect that was reversed in the session free of drug. However, a deeper analysis of the data permits us to interpret this increment in the number of avoidance responses as a consequence of the increase in activity produced by the drug and not as learning. In the animals injected with scopolamine after sessions no effects were observed. In conclusion, the results of the present experiment confirm that scopolamine produces an impairment in the acquisition of an active avoidance task, but also show that this impairment can be easily masked by the facilitating effects of the drug on activity.

Animals↗
PubMed1996

Correlation of in-vitro activity and pharmacokinetic parameters with in-vivo effect of amoxycillin, co-amoxiclav and cefotaxime in a murine model of pneumococcal pneumonia.

In an attempt to determine the susceptibility breakpoints for amoxycillin, co-amoxiclav and cefotaxime in pneumococcal pneumonia, a neutropenic mouse model was established and tested with two strains having different susceptibility to penicillins and cefotaxime. With a penicillin-sensitive strain (MIC/MBC = 0.01/0.01 mg/L) the minimum dosage tested achieving significant cure was 2 mg/kg for amoxycillin, co-amoxiclav and cefotaxime. For the penicillin-insensitive strain (MIC/MBC = 1/2 mg/L), the minimum dosage tested giving significant cure was 50 mg/kg for amoxycillin and co-amoxiclav but 100 mg/kg for cefotaxime. Our results support the belief that MICs of amoxycillin, co-amoxiclav and cefotaxime for pneumococcal strains of < or = 0.5 or < or = 1 mg/L can be considered as clinically relevant susceptibility breakpoints.

Amoxicillin↗
PubMed1996

Development of experimental pneumonia by infection with penicillin-insensitive Streptococcus pneumoniae in guinea pigs and their treatment with amoxicillin, cefotaxime, and meropenem.

Acute respiratory infection with penicillin-insensitive Streptococcus pneumoniae (MIC and MBC, 1 and 2 micrograms/ml, respectively) was established in guinea pigs. Intratracheal instillation of 0.5 ml of an overnight culture of S. pneumoniae concentrated 25 times (approximately 3 x 10(9) CFU) induced a bacteremic and fatal pneumonia in > 85% of untreated animals within 46 h, with a mean +/- standard deviation bacterial count of 8.83 +/- 1.11 log10 CFU in lung homogenates. This model was used to evaluate the efficacies of two doses each of amoxicillin, cefotaxime, and meropenem given 1 h after bacterial inoculation. The antibiotics were given at 8-h intervals for up to a total of four injections. The dose of 50 mg of any antibiotic per kg of body weight gave 66.6% survival, compared with 5.05% survival for untreated control animals (P < 0.001). A dose of 200 mg/kg gave a survival rate of 77.8% for meropenem and 83.3% for amoxicillin and cefotaxime, while survival for untreated controls was 11.1% (P < 0.001). Although antibiotic treatment decreased mortality compared with that in untreated controls, the antibiotics contributed to a high early (less than 9 h after bacterial inoculation) mortality, being 53.5% compared with only 6.06% for the untreated controls (P < 0.001). Quantitative cultures of the lungs of animals that died during the 46-h observation period or that were killed after this time showed a significant reduction in the numbers of organisms among treated animals compared with numbers among the control animals (P < 0.001). The described model is an appropriate system for evaluating antibiotic efficacy in invasive pulmonary infection caused by penicillin-insensitive S. pneumoniae.

Amoxicillin↗
PubMed1996

[Clinical usefulness of Multitest in the evaluation of cellular immunity].

The aim of this work was to assess cellular immunity using the Multitest CMI and relate its results with lymphocyte counts and lymphocyte subpopulations determined using monoclonal antibodies against CD4 and CD8 and fluorescence microscopy. We studied 51 patients (31 male), 20 infected with HIV, 18 recurring infections, 5 with cancer, 2 with tuberculosis and 6 with miscellaneous diagnoses. According to Multitest results, patients were classified as normal, hypoergic or anergic. Twenty five percent of patients were normal, 65% hypoergic and 10% anergic. Eighty percent of anergic patients were infected with HIV. No differences in total lymphocyte count were observed between the three groups. CD4 lymphocyte count was lower in anergic patients when compared with the other two groups. All patients with CD4 counts below 200 cells/mm3 were anergic. It is concluded that Multitest CMI is useful for the assessment of cellular immunity and complements the determination of lymphocyte subpopulations.

Adult↗
PubMed1995

Attenuation of sucrose consumption in mice by chronic mild stress and its restoration by imipramine.

Chronic exposure to mild unpredictable stressors (CMS) has previously been found to reduce the consumption of palatable, sweet solutions in rats. In the present study, the utility of this procedure was assessed in mice. Male AP mice subjected to CMS showed reduced consumption of a 2% or 4% sucrose solution. This effect was reversed by chronic (3 weeks) treatment with the tricyclic antidepressant imipramine (20 mg/kg per day). These results extend previous reports of a generalized decrease in sensitivity to reward (anhedonia) in rats caused by CMS and the efficacy of antidepressant treatment in this paradigm. Chronic unpredictable mild stress in mice appears to provide a realistic animal model of depression.

Analysis of Variance↗
PubMed1995

A computerized procedure for developing and administering time perception protocols: application to a sample of adults and adolescents.

The principal goals of this work are: (a) To describe an integrated computerized procedure for designing, administering, and recording time perception experiments (more specifically, reaction time and time estimation) on human subjects; (b) To present the results of applying this procedure to the study of fourteen normal adolescents and fourteen normal adults. Individualized time perception protocols can be designed with this menu-driven highly interactive computer-program. Such protocols can then be used for testing experimental subjects. The programs run on any IBM-compatible computer, and the resulting test data are stored in ASCII format. As an example of the use of this procedure, reaction time with five regular and irregular preparatory intervals (PIs), and time estimation of 10 s with and without feedback was measured on normal adolescents and adults. For short PIs the adolescents had reaction times (RTs) similar to adults, but significant longer RTs than adults for long PIs. In the case of time estimation no differences between the two groups were observed; however, both groups underestimated time when no feedback was provided; that is, they thought that less time had elapsed than really had.

Adolescent↗
PubMed1995

Synthesis of enantio-manoyl oxides: modifiers of the activity of adenylatecyclase enzyme.

Cyclization of methyl ent-8 alpha-hydroxylabd-13(16),14-dien-18-oate with m-chloroperbenzoic acid gave methyl (13S)-ent-16-hydroxy-8 alpha,13-epoxylabd-14-en-18-oate and its epimer at C-13. Biotransformation of the former (which exhibits antileishmania activity) with Rhizopus nigricans cultures produced the methyl (13S)-ent-11 beta,16-dihydroxy-8 alpha,13-epoxilabd-14-en-18-oate (carbomanoyl, which inhibits the activity of the adenylatecyclase enzyme), methyl (13S)-ent-3 beta,16-dihydroxy-8 alpha,13-epoxilabd-14-en-18-oate, methyl (13S)-ent-3 beta,11 beta,16-trihydroxy-8 alpha,13-epoxilabd-14-en-18-oate and the (14S)-ent-3 beta-hydroxy-14,15-epoxy derivative that cyclized spontaneously to a spiran compound. Biotransformation of methyl (13S)-ent-16-hydroxy-3-oxo-8 alpha,13-epoxilabd-14-en-18-oate with R. nigricans produced ent-11 beta-hydroxylation, reduction of the keto group at C-3 (to give 3S-alcohol) and 14(S),15-epoxidation, which also rearranged to a spiro compound.

Adenylyl Cyclase Inhibitors↗
PubMed1995

Gender differences in the effects of haloperidol on avoidance conditioning in mice.

Gender differences in the effects of haloperidol (0.075 mg/kg per day for 5 days) on avoidance conditioning were evaluated. We also studied performance of the subjects free of the drug and the acute effects of haloperidol in animals trained without drug 48 h after the last haloperidol administration. Latencies of escape and avoidance responses, number of nonresponses, escapes, avoidances, crossings during the adaptation period, crossings during intertrial intervals, and total crossings per minute were analyzed. This dosage impaired conditioning of the male animals but did not attain the same effects on females. Haloperidol did not deteriorate performance of the task when it had been learned previously without drug. The results confirm the existence of gender differences in haloperidol effects on avoidance conditioning in mice and suggest that these differences are related to the learning process and not only to the impairment of motor behavior characteristic of neuroleptic drugs.

Animals↗