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Biomedical subjects

M Rodríguez

Publications and source records attributed to M Rodríguez.

At least 163 records · Page 9Linked to original sources

Susceptibility to Trypanosoma cruzi is modified by a previous non-related infection.

Helminth infections are frequently massive, chronic and strong inductors of Th2-type cytokines. This implies that infection by such parasites could alter the susceptibility to subsequent infections by other pathogens, particularly intracellular parasites. We therefore explored whether a persistent infection, caused by Taenia crassiceps cysticerci, in BALB/c mice could affect susceptibility to a later infection by Trypanosoma cruzi. We found that the presence of the cysticerci indeed modified the immune response and the susceptibility to T. cruzi, and that these modifications depended on the time-course evolution of the initial infection. Coinfection with the protozoan in the early stages of the helminth infection, induced a delay on the onset of parasitaemia, early specific production of IFN-gamma and high specific production of IL-4. A significant increase in susceptibility to T. cruzi was observed only when mice were coinfected in late stages when the helminth load is greater and a Th2 type response against it is predominant. The in vitro specific response to T. cruzi antigens was then characterized by low levels of both IFN-gamma and IL-4. These findings suggest that chronic helminth infections could potentially have a significant influence over the immune response and hence susceptibility to other pathogens.

Animals↗

Arrest of pulsatile luteinizing hormone (LH) secretion during insulin-induced hypoglycemia (IIH): improvement by intrahypothalamic perfusion with glucose.

Insulin-induced hypoglycemia (IIH), as with many other acute stressors, restrains the activity of the reproductive axis, reducing luteinizing hormone (LH) release. In adult ovariectomized, steroid-primed rats, we investigated the effect of IIH and of mediobasal intrahypothalamic perfusion with glucose (200 mg/dl) on pulsatile LH secretion. IIH led to a significant decrease in all pulsatility parameters studied using PC-Pulsar analysis, e.g. pulse amplitude and frequency, maximum and baseline LH levels (p < 0.05 versus control), and LH overall mean release (p < 0.01 versus control). Intrahypothalamic perfusion with glucose normalized LH pulse frequency, improved maximum and baseline levels, and partially ameliorated LH pulse amplitude and overall mean release. Thus, our results show that the glucoprivic cessation of LH release is restored, at least partially, by an adequate glucose supply to the hypothalamus; it is proposed, in view of these and previous results, that different mechanisms in the CNS may be involved in LH suppression observed during IIH.

Animals↗

Control of cytomegalovirus disease in renal transplant patients treated with prednisone, azathioprine and cyclosporine using intensive monitoring and decreased immunosuppression.

BACKGROUND: The aim of this trial was to study the effectiveness of intensive monitoring, together with an early decrease in immunosuppression, in reducing the prevalence of CMV disease in renal transplant recipients treated with prednisone, azathioprine and cyclosporine. METHODS: From 1/95 to 11/97 a prospective, longitudinal study was conducted among 146 consecutive, unselected, renal transplant patients in our unit. Only 96 patients whose immunosuppressive regimens consisted of prednisone, azathioprine and cyclosporine and whose follow-up period was greater than 4 months were included in the study. Preemptive therapy was administered to 27 high-risk patients. CMV antigenemia (CMV-AG) and other virological tests were performed weekly for the first 4 posttransplant months. The immunosuppression was decreased when the first positive CMV-AG was detected. Azathioprine was completely withdrawn when the CMV-AG count was greater than 10 cells per 10(5) PBLs. The cyclosporine dose was gradually decreased in the next 4 weeks, but it was not withdrawn in any patient. The prednisone dose was modified according to the immunosuppressive protocol. RESULTS: 53% (51/96) of the patients had positive CMV-AG on at least one occasion. The dose of azathioprine was decreased after CMV-AG detection in 41/51 (80.4%) patients and it was completely withdrawn in 23 of these (45%). The mean decrease in the dose of azathioprine was 73 +/- 31 (25-175) mg, a mean percentage decrease of 76 +/- 27% (25-100%). The dose of cyclosporine was progressively decreased during the 4 weeks after detection of the first CMV-AG (mean cyclosporine levels: 210 +/- 66, 196 +/- 54 and 164 +/- 36 ng/ml at the time of first CMV-AG detection, 2 and 4 weeks respectively, p < 0.0001, repeated measures analysis of variance). None of the 45 patients without CMV-AG and only 2 of 51 (3.9%) patients with CMV-AG developed symptomatic CMV disease (2% of the total). CMV disease was of moderate intensity in both patients. Only 3/51 (5.8%) patients developed acute rejection after the first CMV-AG detection in the 4 posttransplant months. CONCLUSION: The results of this study suggest that intensive monitoring and an early reduction of immunosuppression, together with preemptive therapy in high-risk patients, is effective in diminishing the prevalence and severity of CMV disease.

Adult↗

Influence of comorbidity and severity on the clinical outcome of bacteremic pneumococcal pneumonia treated with beta-lactam monotherapy.

The influence of the severity of pneumonia and comorbidity factors, as predictors of clinical outcome, was assessed in patients with microbiologically documented pneumococcal bacteremic pneumonia treated with penicillin or third generation cephalosporin monotherapy in a 5-year retrospective study. Among 288 patients admitted to three Spanish hospitals with bacteremic pneumococcal pneumonia, 65 (23%) were included. Twenty-four were treated with penicillins and 41 with a third-generation cephalosporin. Twenty-seven patients (42%) had severe pneumonia and 41 (63%) had a comorbidity index >1. Twenty-one patients (32%) were infected with penicillin-resistant strains. Four cases (2 with penicillin-resistant strains; 3 treated with cephalosporins) were clinical failures. Four cases (3 with penicillin-resistant strains; 2 treated with cephalosporins) died, i.e. 6% mortality rate. The only factor that influenced empirical treatment election was HIV-positive condition. Clinical outcome was not influenced by treatment election, penicillin susceptibility of the infecting pneumococci, patient basal conditions or severity of pneumonia, but the latter was associated with mortality and length of hospitalization.

Adolescent↗

Nematocide activity of 6,7-diarylpteridines in three experimental models.

The in vitro nematocide activity of seventeen 6,7-diarylpteridines has been tested using three different experimental models, Caenorhabditis elegans, Nippostrongylus brasiliensis and Heligmosomoides polygyrus. The method of evaluation of inhibition in the secretion of acetylcholinesterase by H. polygyrus seems to be the most indicated to avoid false positives. The in vivo activities, against Trichinella spiralis, of the most in vitro active pteridines have been assayed. All pteridine derivatives bearing 6,7-di-p-bromophenyl substituents have shown in vitro nematocide activities in the three experimental models used. Amongst all the pteridines tested in vivo, only 2,4-pteridinedithione derivatives exhibited moderate activity.

Animals↗

Highly heterogeneous families of Ty1/copia retrotransposons in the Lycopersicon chilense genome.

We have used the degenerated oligonucleotide primers-PCR (DOP-PCR) technique to determine the presence of Ty1/copia-related retrotransposons in the wild species of tomato, Lycopersicon chilense. Using degenerated oligonucleotides corresponding to highly conserved domains in the Ty1/copia retrotransposons, fragments of roughly 300 bp were obtained by PCR amplification. These were cloned in a plasmid vector and the nucleotide sequence determined for 20 clones, 19 of which showed sequence homology to retrotransposon-related sequences. Comparison of the deduced amino-acid sequence of these clones with those reported for other retrotransposons has allowed their classification into four distinct families: TLC1-TLC4. The level of amino-acid sequence similarity between these elements extends from 66.7% (between TLC1 and TLC2) to 42.6% (between TLC2 and TLC3). Altogether, the four families comprise about 0.17% of the L. chilense genome. RT-PCR analysis shows that the four TLC families are transcriptionally active, suggesting a mechanism for the generation of the observed diversity between the L. chilense retrotransposons.

Amino Acid Sequence↗

Relationship of specific EEG frequencies at specific brain areas with performance.

This study shows that incorrect responses are preceded by different EEG characteristics than correct responses, and that these differences appear in specific brain regions that participate in each particular task. EEGs were recorded in children during three different tasks: color discrimination (CDT), verbal working memory (VWM), and word categorization task (WCT). EEG segments previous to the presentation of the stimulus were analysed. Incorrect responses were preceded by lower EEG power values at 7.8 Hz in posterior temporal and right parietal leads in CDT, 8.59 and 9.36 Hz in frontal areas in VWM, and 10.72 Hz in the left hemisphere in WCT. In the former task > 1.56 Hz power in frontal areas prior to an incorrect response was also observed.

Alpha Rhythm↗

Design of a new multiparticulate system for potential site-specific and controlled drug delivery to the colonic region.

A multiparticulate dosage form consisting of a hydrophobic core coated with a pH-dependent polymer is proposed for colonic specific delivery of drugs. Different approaches for colon-specific drug delivery have been studied over the last decade, including prodrugs, polymeric coating using pH-sensitive or bacterial degradable polymers and matrices. In this work, we present a new multiparticulate system to deliver active molecules to the colonic region, which combines pH-dependent and controlled drug release properties. This system was constituted by drug loaded cellulose acetate butyrate (CAB) microspheres coated by an enteric polymer (Eudragit(R) S). Both, CAB cores and pH-sensitive microcapsules, were prepared by the emulsion-solvent evaporation technique in an oily phase. Ondansetron (OS) and budesonide (BDS), two interesting drugs with a potentially new application for the local treatment of intestinal disorders, were efficiently microencapsulated in CAB microspheres at different polymer concentrations (6 and 8%). These hydrophobic cores (about 60 and 110 micrometer in size, respectively) were then microencapsulated with Eudragit(R) S, resulting in multinucleated structures, except in the case of BDS-CAB microspheres prepared at 8% CAB concentration, in which more mononucleated microcapsules were obtained. The in vitro drug release studies of pH-sensitive microcapsules containing the hydrophobic cores showed that no drug was released below pH 7. After that, CAB microspheres efficiently controlled the release of BDS, the release behavior being affected by the different polymer concentration used in their preparation. However, OS-CAB microspheres did not maintain their controlled-release properties once the enteric polymer dissolved. The extraction of the drug by the Eudragit(R) solvent during the second microencapsulation process was in this case the cause for the failure of the controlling release mechanism.

Capsules↗

Unsupervised classification of neural spikes with a hybrid multilayer artificial neural network.

The understanding of the brain structure and function and its computational style is one of the biggest challenges both in Neuroscience and Neural Computation. In order to reach this and to test the predictions of neural network modeling, it is necessary to observe the activity of neural populations. In this paper we propose a hybrid modular computational system for the spike classification of multiunits recordings. It works with no knowledge about the waveform, and it consists of two moduli: a Preprocessing (Segmentation) module, which performs the detection and centering of spike vectors using programmed computation; and a Processing (Classification) module, which implements the general approach of neural classification: feature extraction, clustering and discrimination, by means of a hybrid unsupervised multilayer artificial neural network (HUMANN). The operations of this artificial neural network on the spike vectors are: (i) compression with a Sanger Layer from 70 points vector to five principal component vector; (ii) their waveform is analyzed by a Kohonen layer; (iii) the electrical noise and overlapping spikes are rejected by a previously unreported artificial neural network named Tolerance layer; and (iv) finally the spikes are labeled into spike classes by a Labeling layer. Each layer of the system has a specific unsupervised learning rule that progressively modifies itself until the performance of the layer has been automatically optimized. The procedure showed a high sensitivity and specificity also when working with signals containing four spike types.

Animals↗

The bovine IFN-omega 1 is biologically active and secreted at high levels in the yeast Pichia pastoris.

The gene coding for bIFN-omega 1 was isolated from bovine genomic DNA by polymerase chain reaction (PCR). Recombinant bIFN-omega 1 was expressed in the yeast Pichia pastoris and high levels of the recombinant protein (0.4 mg ml-1) were secreted to the culture media. The obtained bIFN-omega 1 showed a cross-species antiviral activity on four mammalian cell lines of calf, pig, hamster and human origin, but this activity was absent on Madin-Darby canine kidney (MDCK) cells. A delivery carrier was developed to permit a better release of bIFN-omega 1. When compared with a control group, an increase in 6 days in the corpus luteum lifespan was obtained in cyclic ewes following three interferon (IFN) intrauterine administrations on days 9, 10 and 11 post-estrus. In summary, these results demonstrated for the first time that biologically active recombinant bIFN-omega 1 was highly secreted by P. pastoris showing antiviral activity in different cell lines and an antiluteolytic effect in cyclic ewes, with no detrimental effects on the animals.

Amino Acid Sequence↗

Diagnosis of herpetic keratoconjunctivitis by nested polymerase chain reaction in human tear film.

A study was performed to evaluate nested PCR (nPCR) versus viral cultures as method and tear film versus corneal scrapings as specimen in the diagnosis of viral keratoconjunctivitis. Tear film specimens were taken from both eyes and corneal scrapings from the affected eye only in 17 patients with suspected viral keratoconjunctivitis. In 15 of the 17 patients the viral agent of the infection could be detected: 11 patients had herpes simplex virus type 1, two varicella-zoster virus, one both herpes simplex virus type 1 and varicella-zoster virus, and one adenovirus. Overall there was no significant difference between the detection rate for corneal scrapings (85%) and tear film (75%). In both types of specimens nPCR showed a higher detection rate than viral cultures (corneal scrapings: 87.5% vs 31.25%; tear film: 75% vs 12.5%; P 0.05). For the diagnosis of keratoconjunctivitis nPCR is superior to viral culture and tear film is an adequate sample that is easier to collect, causing the patient less discomfort.

Adenovirus Infections, Human↗

The manganese superoxide dismutase from the penicillin producer Penicillium chrysogenum.

The antioxidant enzyme superoxide dismutase has been studied in order to define mechanisms for the influence of oxygen on penicillin production. Manganese-containing SOD activity was purified from penicillin-producing cultures of the filamentous fungus Penicillium chrysogenum and reverse genetics was used to identify full-length cDNA and genomic clones. Sequence analysis revealed a 630-bp ORF containing three exons and two introns with fungal consensus splice-site junctions. The deduced amino-acid sequence (210 amino acids; 23.13 kDa) includes conserved residues required for enzymatic activity and metal binding, and shares significant similarity with Mn- and Fe-containing superoxide dismutases. The sod gene is present as a single copy in the genome of different P. chrysogenum strains and its expression level is not correlated with penicillin-G productivity.

Amino Acid Sequence↗

Field studies and cost-effectiveness analysis of vaccination with Gavac against the cattle tick Boophilus microplus.

The control of tick infestations and the transmission of tick-borne diseases remains a challenge for the cattle industry in tropical and subtropical areas of the world. Traditional control methods have been only partially successful and the parasites continue to result in significant losses for the cattle industry. Recently, vaccines containing the recombinant Boophilus microplus gut antigen Bm86 have been developed. These vaccines have been shown to control tick infestations in the field. However, extensive field studies investigating the efficacy and cost-effectiveness of vaccination have not been reported and are needed to appraise the effect of this new approach for tick control. Here is reported the results of the application of Gavac in a field trial including more than 260,000 animals in Cuba. In this study the correlation between the antibody response to vaccination and the effect on ticks fertility is determined. Physiological status of the animals was found to affect the primary response to vaccination but not the antibody titers after revaccination. A cost-effectiveness analysis showed a 60% reduction in the number acaricide treatments, together with the control of tick infestations and transmission of babesiosis, which resulted in savings of $23.4 animal-1 year-1. These results clearly demonstrate the advantage of vaccination and support the application of Gavac for tick control.

Animals↗

Effect of particulation on the immunogenic and protective properties of the recombinant Bm86 antigen expressed in Pichia pastoris.

The recombinant Bm86 tick antigen expressed in Pichia pastoris is obtained in a highly particulated form, as a distinguish feature of this expression system. This particulated protein, the active principle of the recombinant vaccine Gavac against the cattle tick, have shown high immunogenic and protective properties, probably associated with its own characteristics. To evaluate the effects of particulation on the properties of Bm86, three groups of calves were immunized with particulated or non-particulated recombinant Bm86 and the anti-Bm86 antibody response determined. Animals were challenged with a controlled tick infestation and the protective capacities of both proteins assessed. Humoral immune response and protection in cattle vaccinated with the particulated antigen were higher. These experiments suggested that particulation of the Bm86 expressed in P. pastoris is an important feature for the protective properties of the antigen in vaccine preparations.

Animals↗

Protection against Boophilus annulatus infestations in cattle vaccinated with the B. microplus Bm86-containing vaccine Gavac. off.

Tick infestations by Boophilus spp. constitute a major problem for the cattle industry in tropical and subtropical areas of the world. The use of traditional control methods has been only partially successful and tick infestations remain a serious problem. Recently, the gut antigen Bm86 was isolated from B. microplus. Recombinant preparations of this antigen have been used in vaccines for the control of B. microplus infestations. However, in several regions of the world, B. microplus coexists with other Boophilus species, mainly B. annulatus and B. decoloratus. Therefore, there is a need for the simultaneous control of infestations by different Boophilus species. To test the capacity of the P. pastoris-derived Bm86 antigen preparation (Gavac, Heber Biotec S.A., Havana) to control B. annulatus infestations, controlled experiments were conducted in Mexico and Iran. Cattle were vaccinated with Gavac or not vaccinated and then artificially infested with B. annulatus larvae. The results showed for the first time a high protection efficacy (> 99.9%) of Gavac in the control of B. annulatus infestations. These results support the application of Bm86-containing vaccines for the control of Boophilus spp. infestations.

Animals↗

Effects of ethylcholine mustard azirinium ion (AF64A) on the choline acetyltransferase and nitric oxide synthase activities in mesopontine cholinergic neurons of the rat.

The choline analogue, ethylcholine mustard azirinium ion (AF64A), has been proposed as a selective neurotoxin that produces degeneration of central cholinergic neurons. However, the mechanisms of action and the specificity or non-specificity of this toxin are still undefined. In this study, we have investigated the effects of AF64A, in comparison with kainic acid, on cholinergic neurons of the mesopontine formation (pedunculopontine and laterodorsal tegmental nuclei), a neuronal population also expressing nitric oxide synthase, the enzyme responsible for the synthesis of nitric oxide. We used choline acetyltransferase immunohistochemistry as a marker of acetylcholine activity, and nitric oxide synthase immunohistochemistry and NADPH-diaphorase histochemistry as markers of nitric oxide synthase activity. Our results show that the injection of low doses of AF64A produces: (1) an area of cavitation in the injection site of pedunculopontine tegmental nucleus (local non-specific effect), and (2) a transient decrease in choline acetyltransferase immunoreactivity in choline acetyltransferase-nitric oxide synthase neurons in both the ipsilateral laterodorsal tegmental nucleus and the perilesional area of the pedunculopontine tegmental nucleus, while their morphology and nitric oxide synthase immunoreactivity remain unaltered (post-diffusion specific effect). These findings indicate that the loss of choline-related enzymatic activity is not necessarily associated with degeneration of cholinergic neurons, and that the recovery of choline acetyltransferase immunoreactivity may arise from neurons whose activity is diminished during the first postinjection weeks. Taking into account that AF64A is a suitable tool to develop a reversible model of neurological disorders related to cholinergic deficit, further efforts should be directed toward elimination of its local non-specific effect.

Animals↗