Biomedical subjects

A Parra

Publications and source records attributed to A Parra.

At least 37 records · Page 2Linked to original sources

PubMed2001

Decreased dopaminergic tone and increased basal bioactive prolactin in men with human immunodeficiency virus infection.

OBJECTIVE: The aims of the study were: (1) to assess dopaminergic tone in a group of HIV infected men and the bioactivity and the molecular species of their circulating PRL in comparison with healthy men and (2) to search for a correlation between serum PRL and CD4+ T lymphocytes and viral load. DESIGN: In a cross-sectional study the effect of acute dopaminergic blockade with intravenous metoclopramide on serum PRL (both immunoreactive and biologically active), TSH and PRL circulating molecular isoforms was evaluated. PATIENTS: Twenty untreated HIV infected men category C2 or C3, mean (SD) age 26.9 (6.3) years, were compared to 14 clinically healthy HIV-negative men, age 25.4 (2.3) years. MEASUREMENTS: Under fasting conditions and following metoclopramide administration duplicate measurements of serum immunoreactive PRL, bioactive PRL (PRL dependent Nb2 lymphoma cell assay) and immunoreactive TSH were performed. The molecular species of circulating PRL were determined by immunoblot analysis, CD4+ T lymphocytes by flow cytometry and the viral load using a nucleic acid sequence-based amplification assay. RESULTS: In HIV infected men fasting bioactive (but not immunoreactive) PRL was higher (P = 0.03), but the stimulated PRL (both immunoreactive and bioactive) was lower than in healthy men throughout the test (P < or = 0.01). Fasting serum TSH was similar in HIV-infected and healthy men while its response to metoclopramide was absent in the former but not in the latter (P = 0.049). A 23.5-kD PRL was the predominant circulating isoform both in patients and healthy men. Considering HIV-infected and healthy men, CD4+ T lymphocytes correlated negatively with fasting bioactive PRL (P = 0.008) and positively with the area under the PRL (both immunoreactive and bioactive) curves (P < 0.001). The viral load was negatively correlated with the area under the curve of the bioactive/immunoreactive ratio (P = 0.008). CONCLUSIONS: The raised fasting bioactive PRL, the diminished response of both immunoreactive and bioactive PRL and the absent TSH response to metoclopramide in HIV infected men, suggest the existence of a decreased, but not absent dopaminergic tone. A monomeric form of PRL was the predominant circulating species, as in healthy men, and this hormone seems to be associated both with CD4+ T lymphocytes and the viral load.

Adult↗

PubMed2001

Serum prolactin is associated with apoptosis in men with human immunodeficiency virus infection.

We examined the in vivo and in vitro production of prolactin (PRL) in 20 untreated HIV-infected men compared to 14 uninfected men and its association with the cell cycle and apoptosis. Compared to uninfected men, the HIV-infected men had: (i) higher fasting serum bioactive (BIO) PRL; (ii) lower serum immunoreactive (RIA) and BIO-PRL responses to intravenous metoclopramide; (iii) greater BIO-RIA PRL ratio both fasting and during intravenous metoclopramide; (iv) lower percentage of non-stimulated PBMC in the G0/G1 phase, but a higher percentage in the S phase, of the cell cycle with normal response to Concanavalin-A; and (v) higher in vitro production of BIO-PRL by non-stimulated PBMC, which was blocked after Concanavalin-A. Fasting serum BIO-PRL positively correlated with the percent of non-stimulated PBMC in S + G2/M phases. The percentage of apoptotic PBMC negatively correlated with CD4+ T lymphocytes and with the area under the serum RIA-PRL curve, but positively correlated with the area under the curve for the BIO/RIA ratio. These results suggest that in these HIV-infected men: (i) a diminished dopaminergic tone may exist, as an adaptive mechanism attempting to survive; and (ii) BIO-PRL may participate as a cofactor in the stimulation of T-cell proliferation.

Adult↗

PubMed2001

Cerebral blood flow velocity response to magnesium sulfate in patients after subarachnoid hemorrhage.

Magnesium sulfate therapy, standard in preventing seizures in preeclampsia, is under active investigation as a neuroprotective agent. The authors studied the effect of magnesium as a cerebral vasodilator by measuring the cerebral blood flow velocity (CBFV) response to a 5g intravenous bolus of MgSO4 compared with a saline placebo after subarachnoid hemorrhage (SAH). Transcranial Doppler ultrasonography of the middle cerebral artery (MCA) was measured after each infusion. Patients were studied up to three times after SAH at prescribed time intervals. Fourteen patients (11 women, 3 men; mean age 58 years) underwent 29 studies. All patients underwent hypertensive, hypervolemic therapy. Four patients developed cerebral vasospasm. Doubling serum magnesium levels did not affect MCA CBFV but slightly lowered mean arterial blood pressure and systemic vascular resistance. Intravenous magnesium bolus did not reduce elevated CBFV in the subset of SAH patients with clinical vasospasm. The role of magnesium sulfate as a cerebral vasodilator in patients with SAH requires further study.

Adult↗

PubMed2001

Effects of single oral doses of gemifloxacin (320 milligrams) versus trovafloxacin (200 milligrams) on fecal flora in healthy volunteers.

Gemifloxacin and trovafloxacin were administered to 12 volunteers in a randomized crossover trial with a 2-week washout period. Stool samples were collected predose and 1, 2, and 3 days postdose. Both quinolones reduced the number of organisms of the family Enterobacteriaceae and aerobic gram-positive organisms. Escherichia coli reduction was greater with gemifloxacin than with trovafloxacin, with postdose isolation of quinolone-resistant strains for which MICs of trovafloxacin were higher than those of gemifloxacin.

Anti-Infective Agents↗

PubMed2001

Antibacterial properties of gemifloxacin and trovafloxacin in urine ex vivo: phase I study.

Urine bactericidal titers (UBTs) against Escherichia coli ATCC 25922 and Staphylococcus saprophyticus ATCC 1970 were determined after the administration of single oral doses of gemifloxacin at 320 mg and trovafloxacin at 200 mg to healthy volunteers. Gemifloxacin presented significantly lower experimental versus mathematically predicted UBTs over 72 h, due to the effect of urine on the susceptibility of the E. coli strain. Experimental UBTs were significantly higher for gemifloxacin than trovafloxacin against both strains over 72 h.

Administration, Oral↗

PubMed2001

[Isolated ventricular diverticulum in asymptomatic male].

Ventricular diverticulum are small outpouchings, in the cardiac wall, which are mostly described as a part of malformation syndromes. This finding is infrequent in asymptomatic patients with no pathology in the thoraco abdominal line. The case we present shows a diverticulum in the cardiac apex in a male patient with no cardiological clinic manifestations and with an abnormal electrocardiogram. At present, magnetic resonance is the best diagnostic test, for this kind of malformation, and is also the most reliable in the follow-up of these patients.

Cardiomyopathies↗

PubMed2000

Regioselective enzymatic acylations of polyhydroxylated eudesmanes: semisynthesis, theoretical calculations, and biotransformation of cyclic sulfites.

Different lipase enzymes have been tested in order to perform regioselective acetylations on the eudesmane tetrol from vulgarin. High yields (95%) of 1,12-diacetoxy derivative (4) were achieved in 1 h with Candida antarctica lipase (CAL). However, only the 12-acetyl derivative (6) was obtained in similar yield with Mucor miehei (MML) or Candida cylindracea (CCL) lipases. The enzymatic protection at C-1 and C-12 has been used to form eudesmane cyclic-sulfites between C-6 and C-4 atoms. The R/S-sulfur configuration has been assigned by means of the experimental and theoretical (13)C and (1)H NMR chemical shifts. The theoretical shifts were calculated using the GIAO method, with a MM+ geometry optimization followed by a single-point calculation at the B3LYP/6-31G(*) level (B3LYP/6-31G(*)//MM+). Moreover, B3LYP/6-31G(*) geometry optimizations were carried out to test the B3LYP/6-31G(*)//MM+ results, for the deacetylated sulfites (12 and 15). In addition to the delta(C) and delta(H) shifts, the (3)J(HH) coupling constants were also calculated and compared with the experimental values when available. Finally, different reactivities have been checked in both sulfites by biotransformation with Rhizopus nigricans. While the R-sulfite gave 2 alpha- and 11 beta-hydroxylated metabolites, the S-sulfite yielded only regioselective deacetylations. Furthermore, both sulfites showed different reactivities in redox processes.

Acylation↗

PubMed2000

Effects of acute and chronic maprotiline administration on inhibitory avoidance in male mice.

The effects of acute and chronic administration of maprotiline (5, 10 or 20 mg/kg, intraperitoneally) were assessed on inhibitory avoidance in male mice. Acute administration of maprotiline before training did not effect training phase latencies, but impaired performance (i.e. produced shorter latencies) in the test at doses of 5 and 20 mg/kg. When given after training, the drug did not modify test latencies at any of the doses used. Chronic administration for 21 days (interrupted 24 h before training) also shortened latencies in the test but not in training. An experiment on the acute effects of maprotiline on analgesia (determination of flinch and jump thresholds for increasing electric foot shock levels), at the doses stated, was carried out on naive animals. No analgesic effect of the drug was found. Taken together, the results indicate that acute maprotiline produces anterograde amnesia, and tolerance does not appear after 21 days of treatment.

Animals↗

PubMed2000

Predicting how equipotent doses of chlorpromazine, haloperidol, sulpiride, raclopride and clozapine reduce locomotor activity in mice.

Distinguishing the specific effects of neuroleptics on one particular behaviour from its non-specific effects on motility is not easy. In this study, the effects of five neuroleptics on spontaneous motor activity were compared and the ED(50) values of these drugs to impair activity were calculated. Male and female mice were evaluated in an actimeter or in a shuttle-box used as an open field after the administration of chlorpromazine (0.4, 1.2, 3.6 mg/kg), haloperidol (0.1, 0.3, 0.9 mg/kg), raclopride (0.1, 0.3, 0.9 mg/kg), sulpiride (10, 30, 90 mg/kg) and clozapine (0.4, 1.2, 3.6 mg/kg), and two automatic and two observational activity measures were obtained. A very high correlation between automatic and observational measures, absence of sex differences, and a dose-dependent decrease of activity were observed with every compound. The results allow us to make accurate comparisons between these drugs in their potency in reducing spontaneous motor activity.

Animals↗

PubMed2000

Role of Streptococcus pneumoniae and Haemophilus influenzae in the development of acute otitis media and otitis media with effusion in a gerbil model.

The efficacy of amoxicillin/clavulanate and cefuroxime was determined in a gerbil model of otitis media with a mixed Streptococcus pneumoniae plus Haemophilus influenzae middle ear (ME) infection. Results were compared with those obtained in a previous single H. influenzae model. All untreated animals inoculated with the mixed inoculum developed acute otitis media (AOM), whereas 86.7% of those inoculated with H. influenzae developed otitis media with effusion (OME). Antibiotics eradicated H. influenzae from the ME more efficiently in AOM than in OME, and this difference was highly significant (P</=.001) after administration of 5 mg/kg of either drug (amoxicillin/clavulanate, 100% vs. 10%; cefuroxime, 73.3% vs. 10%). Efficacy was predicted by the relation of in vitro susceptibility and ME antibiotic concentration, which was 2.7 times higher in AOM than in OME. In the mixed otitis model, the most efficacious antibiotic was able to prevent AOM, but >80% of animals developed culture-negative OME.

Acute Disease↗

PubMed1999

Transient expression of DNA and RNA in parasitic helminths by using particle bombardment.

Parasitic helminths (worms belonging to several metazoan phyla) cause considerable morbidity and mortality in humans. They are an important veterinary problem, and they result in significant economic losses in animal grazing and agriculture. Experimental studies on parasitic helminths have been limited by a lack of parasite cell lines and methods for molecular genetic analyses. We evaluated particle bombardment (biolistics) as a strategy to introduce and express nucleic acids in these multicellular parasites. By using embryos of the parasitic nematode Ascaris as a model, we developed methods to introduce and express both DNA and RNA during several stages of Ascaris embryogenesis. Biolistic transfection will facilitate experimental strategies in Ascaris embryos complementing other biochemical tools available (e.g., in vitro whole-cell embryo extracts for transcription, RNA processing, and translation). Transfection experiments with adult schistosomes further suggest that the biolistic strategy should be applicable to a variety of other parasitic helminths. The development of these methods provides molecular genetic tools to study gene expression and the biology of a variety of types and developmental stages of important helminth parasites.

Animals↗

PubMed1999

Dose dependency of sex differences in the effects of repeated haloperidol administration in avoidance conditioning in mice.

Sex differences in the effects of haloperidol in active avoidance conditioning 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 here broadens the study of these sex differences to higher doses of haloperidol (0.1 and 0.2 mg/kg) using a repeated administration schedule (5 days). The results did not show sex differences in the deteriorating effects of this dopamine antagonist in the escape-avoidance response, but a tendency in the number of nonresponses was observed in the same direction as former results: male animals were more sensitive than females to the inhibitory effect of the low dose of haloperidol. It is concluded that the appearance of sex differences in the effects of haloperidol on active avoidance conditioning is a dose-dependent phenomenon.

Animals↗

PubMed1999

Sex differences in the effects of neuroleptics on escape-avoidance behavior in mice: a review.

The literature of the effects of dopamine antagonists on escape-avoidance, focusing on data obtained in our laboratory with male and female mice, is reviewed. The acute administration of haloperidol, raclopride, clozapine, and SCH 23390 impaired escape-avoidance behavior more in males than in females, and the subchronic administration of haloperidol had a similar effect. This appeared to be a reliable phenomenon, because it was observed in both kinds of administration, in two mouse strains, and with several drugs and doses. The observed results were dose dependent, although the dose-effect relationship was not the same in all drugs. The sex differences in escape avoidance did not seem related to sex differences in the well-known deteriorating effects of these drugs on motor activity. In addition, an analysis of all our studies showed that there were no sex differences in the variability of responses, reinforcing the idea that female subjects should be included in these types of studies.

Animals↗

PubMed1999

Impaired metoclopramide-induced pituitary prolactin release in men with human immunodeficiency virus infection.

To investigate whether metoclopramide-induced prolactin release is impaired in HIV-infected men, we studied 10 clinically healthy HIV-negative adult men (group 1) and 10 consecutive HIV-positive adult men (group 2) with anti-HIV antibodies confirmed by Western blot analysis and a CD4 cell count from 13 to 570x10(6)/L. After a 10- to 12-hour overnight fast, three basal blood samples were obtained at 15-minute intervals (-30, -15, and 0 minutes) and thereafter at 15, 30, 60, 90, 120, 180, and 240 minutes after a 10-mg intravenous bolus of metoclopramide. Duplicate serum prolactin concentrations were measured in each sample with commercially available radioimmunoassay kits. No significant differences between groups were observed in basal prolactin levels. Group 2 had lower serum prolactin concentrations than group 1 throughout the test (P< or =.002). The area under the prolactin curve (mean +/- SD) was also lower in group 2 than in group 1 (7156+/-1433 ng/mL/240 min vs. 12430+/-2454 ng/mL/240 min, P<.0001), and the area under the prolactin curve had a significant correlation with the CD4 cell counts (r = 0.7912, P<.001). These findings suggest that the hypothalamic dopaminergic tone, although present, was clearly diminished in these HIV-positive men regardless of their clinical stage.

Adult↗

PubMed1999

The uncoupled couple? Prolactin and CD4 lymphocytes in HIV infection.

The possible role of prolactin (PRL) in human immunodeficiency virus (HIV) infection is unknown, despite the modulatory role of this hormone in humoral and cell-mediated immune responses. Recent studies have evidenced: (a) intralymphocyte synthesis of dopamine (DA) which down-regulates their own proliferation and differentiation; (b) decreased DA but increased PRL concentrations in cerebrospinal fluid of HIV-infected men; and (c) diminished hypothalamic DA tone in HIV-infected men. The present hypothesis proposes that, in HIV-infected men, a diminished generalized DA tone exists to stimulate human lymphocyte proliferation and differentiation at a maximum possible rate by: (1) decreasing the inhibitory influence of intralymphocyte DA; and (2) maintaining pituitary and extrapituitary (i.e. lymphocyte) PRL synthesis and release as high as possible. If this hypothesis is correct, it may have a potentially important therapeutic implication: the possibility to rebuild the battered immune system in HIV-infected patients from inside the body in a physiologic manner by the parenteral administration of recombinant human PRL.

CD4-Positive T-Lymphocytes↗

PubMed1999

Antimicrobial treatment of an experimental otitis media caused by a beta-lactamase positive isolate of Haemophilus influenzae.

A gerbil model of otitis media induced by a beta-lactamase producing and non-serotypeable isolate of Haemophilus influenzae was used to assess the in-vivo efficacy of co-amoxiclav and cefuroxime at low (5 mg/kg) and high (20 mg/kg) doses. The MIC of the antibiotics tested against the pathogen was 1 mg/L (1/0.5 mg/L for co-amoxiclav). The organism was inoculated (+/-10(6) cfu) by transbullar challenge directly in the middle ear and antibiotic treatment was commenced 2 h post-inoculation and continued at 8 h intervals for three doses. Only high dose co-amoxiclav significantly reduced the number of culture-positive specimens as compared with untreated animals or with other treatment groups (91.7% as compared with 36.7% for high dose cefuroxime). The results obtained in any treatment group were related to middle ear antibiotic level/MIC. Antibiotic concentrations in the middle ear 90 min after administration were about 10% of serum levels at 15 min, probably related to a slight inflammatory response. Only after high dose co-amoxiclav did the concentration in the middle ear exceed the MIC by a factor of four. In otitis media with effusion, if indicated, antibiotics active in vitro should be administered in high doses and, to avoid side effects, probably in short courses.

Amoxicillin-Potassium Clavulanate Combination↗

PubMed1999

The after breakfast 50-g, 1-hour glucose challenge test in urban Mexican pregnant women: its sensitivity and specificity evaluated by three diagnostic criteria for gestational diabetes mellitus.

BACKGROUND: To study the sensitivity and specificity of the 50-g, 1-hour gestational glucose challenge test performed 1 to 2 hours after a non-standardized home breakfast in urban Mexican women by using three different gestational diabetes mellitus diagnostic criteria. METHODS: Four hundred and forty-five consecutive women of 24-28 weeks gestation were studied. The glucose challenge test was performed in the fed state and a week later a fasting 100-g, 3-hours oral glucose tolerance test was carried out in all of them. Duplicate serum glucose concentrations were determined by a glucose-oxidase method. Sensitivity and specificity were calculated using three different diagnostic criteria for gestational diabetes mellitus. RESULTS: The glucose challenge test performed as indicated, with a cutoff of 7.8 mmol/L, had 88-89% sensitivity and 85-87% specificity when using as diagnostic criteria those proposed by the National Diabetes Data Group and by Carpenter & Coustan; by using Sacks et al. criteria, the values were 82% and 88%, respectively. Considering only pregnant women > or = 25 years of age, the sensitivity increased to 92% with the National Diabetes Data Group criteria. Pregnant women < 25 years of age had significantly lower blood glucose values than those with age > or = 25 years during the glucose tolerance test. CONCLUSIONS: For the general group the sensitivity of the glucose challenge test performed 1 to 2 hours after breakfast was similar, based on the National Diabetes Data Group and the Carpenter & Coustan's diagnostic criteria for gestational diabetes mellitus. However, when pregnant women > or = 25 years of age were considered, the use of the former criteria yielded a slightly better sensitivity.

Adult↗

PubMed1998

HLA associations with multiple sclerosis in the Canary Islands.

The study of small island populations has proved informative with respect to the epidemiology and genetics of many complex traits including multiple sclerosis. The class II major histocompatibility antigen DR15 is associated with multiple sclerosis in all groups except Sardinians, where the primary association is with DR4. We compared HLA-DR and -DQ allele frequencies in a representative sample of patients with multiple sclerosis from the Canary Islands with appropriate controls. There was a significant association with DR15 (patients 21/53: 40%: controls 11/55; 20%: chi2=4.09; pc=0.04; relative risk [RR]=1.98). DRB1*1501-DRB5*0101 was present in 17/53 (32%) patients in whom sub-types could be identified compared with 6/55 (11%) controls (chi2=7.21; pc=< 0.01; RR=2.94). All DR15 positive controls carried the DQA1*0102, DQB1*0602 haplotype whereas this was only present in 26/30 patients, suggesting that the primary association is with HLA-DR and not -DQ. We also found a significant increase in HLA-DR4 (16/53 [30%] in patients compared with 7/55 [13%] in controls; pc=0.05). This study contributes a new point on the immunogenetic map of multiple sclerosis in Europe, confirming the primary DR15 association with multiple sclerosis in a previously unstudied population but again highlighting the importance of DR4 in Mediterranean peoples.

Alleles↗