Biomedical subjects

R Tapia

Publications and source records attributed to R Tapia.

At least 37 records · Page 2Linked to original sources

PubMed1999

Prevalence and risk of cysticercosis and taeniasis in an urban population of soldiers and their relatives.

To determine markers of Taenia solium transmission and risk factors in an urban community, we studied 1,000 soldiers from a military camp in Mexico City and their relatives. Serum samples were used to detect antigens and antibodies and fecal specimens were examined for Taenia coproantigens and helminth eggs. Prevalences of 12.2% and 5.8% for cysticercosis were found among soldiers and their relatives, respectively. Taeniasis was found in 0.5% and none of the groups, respectively. Relatives of soldiers positive for cysticercosis and taeniasis markers ate more pork from street stores than restaurants or markets compared with relatives of soldiers without these indicators of infection. Also, 12.0% of the relatives of positive soldiers had a history of expelling tapeworm proglottids in the feces in contrast to 3.7% of the family members of the control group. Prevalence values and risk factors in this urban population are similar to those of previous studies performed in rural populations.

Adult↗

PubMed1998

The protein phosphatase inhibitor okadaic acid induces heat shock protein expression and neurodegeneration in rat hippocampus in vivo.

The tumor promoter okadaic acid is a potent and specific inhibitor of protein phosphatases 1 and 2A and therefore it is a useful tool for studying the participation of protein phosphorylation in cellular processes. Since it has been shown that in cultured neurons OKA behaves as a potent neurotoxin, in the present work we have administered different doses of this compound into the dorsal rat hippocampus, in order to assess its neurotoxicity in vivo. Cresyl violet staining of hippocampal sections revealed that as early as 3 h after injection of 300 ng OKA a notable neurodegeneration occurred in the CA1 subfield, the dentate gyrus, and the hilus, particularly in the former. Neuronal death was more evident at 24 h and at this time the extent of damage was dose-dependent. The process of neuronal death was accompanied by a loss of the microtubule-associated protein MAP2, as assessed by immunocytochemistry. Moreover, OKA treatment resulted in a notable expression of the inducible heat shock protein 72 in the surviving neurons of the injected hippocampus and in the corresponding CA1 and hilus of the apparently normal contralateral hippocampus. The expression of the heat shock protein was partially prevented in the injected hippocampus and completely blocked in the contralateral CA1 region, by the systemic previous administration of the NMDA receptor antagonist MK-801. These results suggest that protein hyperphosphorylation due to inhibition of phosphatases in vivo induces neuronal stress and subsequent neurodegeneration.

Animals↗

PubMed1998

Glutamic acid and Alzheimer's disease.

Neurotoxicity mediated by glutamate is thought to play a role in neurological disorders such a stroke, ischemia and slowly progressing neurodegenerative diseases. However, the contribution of excitotoxicity in neuronal death that occurs in Alzheimer's disease is still an open question. This paper briefly reviews the main lines of evidence supporting a participation of excess glutamatergic neurotransmission in the neurodegeneration of selective groups of neurons in this disease.

Alzheimer Disease↗

PubMed1997

Ruthenium red neurotoxicity and interaction with gangliosides in primary cortical cultures.

Ruthenium red (RR) is an inorganic polycationic dye able to exert several effects on the nervous system, including neurodegeneration, both in vivo and in cell cultures. Gangliosides have been shown to protect cultured neurons against several damaging conditions, and it has been postulated that RR can interact with the negative charges of the sialic acid residues of these molecules. In the present work we have tested the effect of the trisialoganglioside GT1b and the monosialoganglioside GM1 on the RR-induced neuronal damage in primary cortical cultures, as well as on the binding of RR to synaptosomes. GT1b at 100-200 microM concentrations partially protected against RR-induced neurodegeneration, as judged by light microscopy and by measurement of the reduction of a tetrazolium salt, while GM1 was ineffective. GT1b, but not GM1, also partly blocked both RR binding and its diminution in the culture medium occurring during incubation. These results suggest that the three negative charges of GT1b enable it to interact with RR and as a consequence the entrance of the dye into the cells is blocked and neurotoxicity is diminished, although other mechanisms of protection cannot be excluded. Endogenous polysialic acid-containing molecules do not seem to be involved in RR effects, since the removal of sialic acid residues by treatment with neuraminidase did not prevent the cell damage.

Animals↗

PubMed1997

Neuronal damage and MAP2 changes induced by the glutamate transport inhibitor dihydrokainate and by kainate in rat hippocampus in vivo.

Neurotoxicity mediated by glutamate is thought to play a role in neurodegenerative disorders, and alterations in cytoskeletal proteins are possibly involved in the mechanisms of neuronal death occurring in Alzheimer's disease. In the present work we studied the neurotoxic effects of the intrahippocampal injections of the glutamate transport inhibitor dihydrokainate as compared to those of kainate, as well as the concomitant changes in the microtubule-associated protein MAP2. Neuronal alterations were assessed at 3, 12, 24, and 48 h by Nissl staining and immunocytochemistry of MAP2. At 3 h, both compounds induced neuronal damage that was correlated with loss of dendritic MAP2 immunoreactivity. Neuronal damage was more evident at 12 h and 24 h after drug injection, and at these times an accumulation of MAP2 in the somata of pyramidal neurons was observed. The effects of dihydrokainate were restricted to the CA1 region and totally prevented by the N-methyl-D-aspartate receptor antagonist (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate (MK-801), but not by the non-NMDA receptor antagonist 2,3-dihydro-6-nitro-7-sulphamoyl-benzo(f)-quinoxaline (NBQX). In contrast, kainate-induced alterations included CA1, CA3, and CA4 subfields, and the changes in CA1 were prevented by NBQX, while MK-801 was ineffective. These results suggest that early MAP2 disruption may be a marker of the excitotoxicity due to activation of different glutamate receptors located in discrete hippocampal regions.

Animals↗

PubMed1997

Ruthenium red as a tool to study calcium channels, neuronal death and the function of neural pathways.

The inorganic polycationic dye ruthenium red (RuR) exerts several effects on the nervous system when added in physiological solutions, both in vivo and in vitro. Part of these effects, including the paralysis observed in mammals after the systemic administration of RuR, can be accounted for by the binding of RuR to nerve ending membranes, which results in inhibition of Ca2+ influx through voltage-sensitive calcium channels and the consequent inhibition of neurotransmitter release. On the other hand, the administration of RuR into the cerebrospinal fluid induces intense convulsive activity, and its microinjection into the substantia nigra reticulata or the hippocampus leads to various motor behavior alterations that can be related to hyperexcitability of the neurons of the injected region. In addition, RuR penetrates the neuronal somata present in the area injected and induces cell destruction, which has been interpreted as an excitotoxic action of the dye. The penetration and the toxicity of RuR were also observed in primary neuronal cultures but did not occur in pure glial cultures, suggesting a selective action on neurons. In the present article the in vitro and in vivo effects of RuR are reviewed and discussed in terms of the usefulness of the dye as an interesting tool to study calcium channels linked to transmitter release, neuronal death mechanisms and the function of neural pathways.

Animals↗

PubMed1997

Glutamate uptake impairment and neuronal damage in young and aged rats in vivo.

The extracellular concentration of glutamate increases during hypoxia/ischemia probably due to deficient uptake. Glutamate might contribute to neuronal damage associated with this disorder and to neurodegeneration during aging. In the present study, we have tested the effect of two inhibitors of glutamate transport, L-trans-pyrrolidine-2,4-dicarboxylate and dihydrokainate, on the extracellular levels of glutamate and on neuronal damage, which was quantitatively studied by image analysis of histological brain sections. Drugs were administered by microdialysis and glutamate concentration was determined by HPLC in the striatum and the hippocampus of 3-month-old and 22-24-month-old rats. In both regions studied, the basal concentration of extracellular glutamate was higher in aged than in young rats. Pyrrolidine dicarboxylate induced a substantial elevation of extracellular glutamate in both regions, and although this increase was almost twofold higher in old than in young animals, no neuronal damage was observed. In contrast, dihydrokainate had a poor effect on glutamate levels, but induced clear neuronal damage in the striatum and the hippocampus in both groups of rats. The present results suggest that age appears not to be a significant factor in the sensitivity of neurons to the toxic effect of extracellular glutamate increase via blockade of its transport system.

Aging↗

PubMed1997

[Assessment of neurotoxic effects of methyl bromide in exposed workers].

BACKGROUND: Methyl bromide is an aliphatic hydrocarbon derivative used as a pesticide that causes skin, kidney, respiratory, liver and neurological damage. AIM: To assess the neurological and psychiatric damage caused by methyl bromide in exposed workers of seed and fruit export industries in a rural area near Santiago. SUBJECTS AND METHODS: We studied prospectively 15 male middle age workers before and after a fumigation period with methyl bromide, that lasted two to four weeks. According to the initial assessment, 5 of these subjects had a chronic exposure to the chemical. As controls, 10 non exposed workers matched for age, sex and working conditions were studied in two occasions. The evaluation included the WHO Neuro Behavior Core Test Battery, dynamometric and vibrator assessment of peripheral nerve function, the Nothingham test for psychological functioning and Titmus test for visual acuity. Methyl bromide levels were measured in blood and urine. RESULTS: Blood methyl bromide levels increased from 13.3 to 30 mg/dl after exposure. Symptoms that appeared with a higher frequency in exposed workers were insomnia, headache, paresthesiae, mood changes and loss of memory and concentration. In these subjects, the threshold for the Vibraton test increased from 2.4 to 2.85 sec, dynamometry showed a strength reduction in the right side from 51.4 to 47.2 kg and there was an increase in the score for negative auto-perception in the Nothingham test from 11.2 to 13.6. No deterioration in these tests were observed in unexposed workers. CONCLUSIONS: Acute and chronic methyl bromide exposure causes important psychological and neurological derangement.

Adult↗

PubMed1997

[National survey of the infrastructure of research centers in advanced biotechnology and molecular epidemiology in Mexico].

An International Molecular Epidemiology Task Force group (IMETAF) was established in 1993, where the Mexican group include as their objectives: the evaluation of the main public health problems that could be improvement through molecular epidemiology; the analysis of the interaction between molecular biology and epidemiology; development of international nets of collaboration and the establishment of surveys toward the prevention and control of some diseases. As part of a general strategy the Mexican scientific committee developed the first national infrastructure survey of the centers of biotechnology and molecular epidemiology. This survey obtained data trough a questionnaire of the general characteristics the development of the molecular epidemiology, the main tools of surveys, equipment, material and reagents, the personnel trained in biotechnology, epidemiology and public health, the needs of training, the national and international nets, how to develop molecular epidemiology and areas to be considered. The results give a general idea of the possibilities to develop the field in Mexico. More than 50% are currently working in this theme. The majority in infectious diseases. The centers have the equipment, material reagents and human resources well trained to incorporate the molecular epidemiology in their usual work. They reported the need of technology transfer to develop collaborations and courses, symposia or congresses. We conclude that Mexico has the capability and the infrastructure to develop molecular epidemiology. A survey is needed on animals.

Academies and Institutes↗

PubMed1996

Inhibition of glutamate uptake induces progressive accumulation of extracellular glutamate and neuronal damage in rat cortical cultures.

It is known that neurons exposed to high concentrations of glutamate degenerate and die. The clearance of this amino acid from the extracellular space depends on their active transport by Na(+)-dependent high-affinity carriers. In the present study we tested whether inhibition of glutamate transport in mixed glial/neuronal cortical cultures induces accumulation of extracellular glutamate and whether such increase results in cell damage. Three inhibitors of glutamate transport were used: L-trans-pyrrolidine-2,4-dicarboxylate (PDC), DL-threo-beta-hydroxyaspartate (THA), and dihydrokainate (DHK). Cell damage was assessed by light microscopy observations, reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, and leakage of lactate dehydrogenase. PDC induced a significant concentration- and time-dependent neuronal damage, whereas pure glial cultures were not affected. A good correlation was found between this damage and elevations of glutamate concentration in the medium. These effects of PDC were similar in glutamine-free medium and in medium supplemented with glutamine. THA induced identical cell damage and elevations of extracellular glutamate to those produced by PDC, while DHK did not affect at all any of these parameters. PDC- and THA-induced toxicity was protected by the N-methyl-D-aspartate receptor antagonist (+)-5-methyl-10,11-dihydro-5H-dibenzo-(a,d)cyclohepten-5,10-imine maleate but not by the non-N-methyl-D-aspartate receptor antagonist 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(f)quinoxaline.

Animals↗

PubMed1996

Protection by NMDA receptor antagonists against seizures induced by intracerebral administration of 4-aminopyridine.

The effects of NMDA receptor antagonists on the convulsant action of the administration of 4-aminopyridine in the rat lateral cerebral ventricle (i.c.v. injection) and motor cerebral cortex (i.cx. injection) were studied. 4-Aminopyridine administration in both regions induced various preconvulsive symptoms, such as salivation, tremors, chewing and rearing, followed by continuous clonic convulsions and, only after i.c.v. injection, running fits and generalized tonic convulsions. This behavioral pattern appeared 5-9 min after administration of 4-aminopyridine and persisted for 100-150 min. 4-Aminopyridine also generated epileptiform electroencephalographic (EEG) discharges characterized by isolated spikes, poly-spikes and spike-wave complexes, which began some seconds after administration of the drug and were present for more than 2 h. The NMDA receptor antagonists (+/-)-3-(2-carboxy-piperazin-4-yl)-propyl-1-phosphonic acid (CPP), (+/-)-2-amino-7-phosphono-heptanoic acid (AP7) and (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine hydrogen maleate (MK-801) clearly protected against some of the behavioral alterations induced by i.c.v. 4-aminopyridine, particularly the tonic convulsions, but were less effective against those produced by i.cx. 4-aminopyridine. These antagonists also delayed the appearance of EEG epileptiform discharges, reduced its amplitude, frequency and duration, and blocked their propagation to other cortical regions after i.cx. 4-aminopyridine. These results, together with previous data showing that 4-aminopyridine stimulates the release of glutamate in vivo, suggest that an excessive glutamatergic neurotransmission involving NMDA receptors is implicated in 4-amino-pyridine-induced seizures.

2-Amino-5-phosphonovalerate↗

PubMed1996

Preferential stimulation of glutamate release by 4-aminopyridine in rat striatum in vivo.

The potassium channel blocker 4-aminopyridine (4-AP) is a potent convulsant drug which, in vitro, stimulates the release of neurotransmitter amino acids. We have studied the effect of 4-AP in vivo on the extracellular concentration of amino acids in rat striatum, by means of microdialysis and HPLC. Perfusion with 4-AP in the awake animal produced intense motor alterations, including barrel turning and running fits. Therefore, most microdialysis experiments were carried out in anesthetized rats. Perfusion with 20-75 mM 4-AP for 12.5 min resulted in a massive increase in extracellular glutamate (up to 20-fold), smaller increases in aspartate and taurine (up to 10-fold) and slight increments in glutamine, alanine, glycine and GABA. In contrast, perfusion with 100 mM K+ produced, mainly, an increment in taurine (7-fold) and modest increases in glutamate and aspartate (100-300%), as well as a notable decrease in glutamine. Tetraethylammonium (TEA, 120 mM) perfusion induced taurine and glutamate elevations similar to those after high K+, but glutamine was not affected. In unanesthetized rats, perfusion with 40 mM 4-AP induced changes in extracellular amino acids similar to those observed under anesthesia. In these animals neither high K+ nor TEA affected significantly the motor behavior. The results suggest that an enhancement of glutamatergic synaptic transmission, rather than a general depolarizing action, is an important factor in the neuronal hyperexcitability induced by 4-AP, which is consistent with the previously demonstrated inhibition of its convulsant effect by glutamate receptor antagonists.

4-Aminopyridine↗

PubMed1996

Release and uptake of glutamate as related to excitotoxicity.

It has been established that neurons exposed to high concentrations of glutamate or other excitatory amino acids degenerate and die. Neuronal damage appears to be due to the activation of different types of glutamate receptors, among which the ionotropic N-methyl-D-aspartate (NMDA) type seems particularly involved, since its channel is permeable to Ca2+ and an increase in the cytoplasmic concentration of this cation promotes a chain of events leading to cell death. The mechanism of such glutamate receptor-mediated neurodegeneration has been defined as excitotoxicity, and several pieces of evidence suggest that this mechanism might contribute to the neuronal death associated with certain neurological disorders, such as ischemia, cerebral trauma and some chronic neurodegenerative diseases. A relevant question is whether the origin of endogenous extracellular glutamate is important for the induction of excitotoxicity. An excess of glutamate release, or a deficiency in its clearance from the synaptic cleft, which depends mainly on its transport by high affinity carriers, are potential sources for the accumulation of extracellular glutamate. In the present article some experimental results from our laboratory, aimed at obtaining information on this question, are reviewed. These experiments include the use of 4-aminopyridine, a convulsant drug that enhances the release of glutamate, and of some inhibitors of glutamate transport, in vivo and in neuronal cell cultures. The results obtained indicate that an increase of endogenous extracellular glutamate due to these procedures is not sufficient to induce neuronal death, at least under the experimental conditions used.

4-Aminopyridine↗

PubMed1995

beta-Amyloid peptide fragment 25-35 potentiates the calcium-dependent release of excitatory amino acids from depolarized hippocampal slices.

beta-Amyloid protein (beta AP) has been frequently associated with the neuropathology of Alzheimer's disease (AD), although the mechanisms by which it can induce neurodegeneration are still unknown. Some studies in hippocampal cultured neurons suggest that beta AP, particularly its fragment 25-35, may induce neural growth or render neurons more vulnerable to excitotoxic insults by a mechanism involving intracellular Ca2+ dyshomeostasis. We have studied the effect of fragment 25-35 on the release of endogenous amino acids from hippocampal slices of young adult (3-3.5-month-old) and aged (23-25-month-old) rats, under basal, K(+)-depolarization, and post-depolarization conditions, in the presence and absence of Ca2+. In both young and aged tissue, the basal release of amino acids was not affected by the peptide. By contrast, 1-hr preincubation of slices from young animals with 10 microM 25-35 fragment resulted in a 140% increase of glutamate and aspartate release stimulated by K+ depolarization, compared with the control-stimulated release. These effects were strictly dependent on external Ca2+. Neither the K(+)-stimulated release of gamma-amino butyric acid (GABA) nor the release of glycine, glutamine, taurine, or alanine, which was not stimulated by high K+, were affected. Substance P and a scrambled sequence of the 25-35 fragment were without any effect per se, but substance P blocked the stimulatory effect of fragment 25-35 on glutamate and aspartate release. In slices from aged rats the basal release of glutamate was significantly higher (260%) than that in young tissue, and the K(+)-induced release of both aspartate and glutamate was also higher.(ABSTRACT TRUNCATED AT 250 WORDS)

Alzheimer Disease↗

PubMed1995

Selective neurotoxicity of ruthenium red in primary cultures.

The inorganic dye ruthenium red (RuR) has been shown to be neurotoxic in vivo when injected intracerebrally. In this work the toxicity of RuR was compared in primary cultures of rat cortical neurons, cerebellar granule neurons and cerebellar astroglia. Microscopic examination of the cultures revealed that RuR penetrates the somata of both types of neurons used and produces vacuolization and loss and fragmentation of neurites. In contrast, no RuR was seen inside cultured astrocytes and no morphological signs of damage were observed in these cells. RuR toxicity was also assessed by immunocytochemistry of alpha-tubulin and by biochemical measurement of the reduction of (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) by the cultured cells. The morphological alterations in the neurons were closely correlated with loss of tubulin immunoreactivity and particularly with a notable decrement in the ability to reduce MTT. Using the latter parameter, it was found that neuronal damage was independent of the age of the cultures, augmented progressively with time of incubation with RuR, from 8 to 24 h, and showed a clear dose-response curve from 20 to 100 microM RuR. Astrocytes showed only a slight decrease in MTT reduction after 24 h of incubation with 100 microM RuR. It is concluded that RuR seems to be toxic for neurons but not for astroglia, and that this selectivity is probably related to the ability of the neurons to internalize the dye. The possible mechanisms of RuR penetration and neuronal damage are discussed.

Animals↗

PubMed1995

Motor alterations and neuronal damage induced by intracerebral administration of Ruthenium red: effect of NMDA receptor antagonists and other anticonvulsant drugs.

The effects of the intracerebroventricular (icv) and the intrahippocampal (ih) microinjection of the inorganic dye Ruthenium red (RuR) on motor activity, and the protective action of excitatory amino acid receptor antagonists and of GABAergic drugs, were studied in the rat. When administered icv, RuR produced intense tonic-clonic convulsions which were refractory to N-methyl-D-aspartate (NMDA) receptor antagonists and to diphenylhydantoin, whereas aminooxyacetic acid (AOA) and valproate only partially protected against seizure activity. The most notable motor effect of the ih RuR administration was the appearance of intense wet-dog shakes (WDS) behavior, which was remarkably attenuated by the icv or intraperitoneal (ip) administration of the NMDA receptor antagonists (+/-)-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP), CGP-37849, and MK-801, but not by their ih coinjection with RuR. Systemic AOA and valproate were also effective in reducing the number of WDS, whereas the non-NMDA receptor antagonist CNQX was ineffective. Light and electron microscopic observations of the RuR-injected brains revealed that the dye was highly concentrated in neuronal somas located in or near the injected areas. In the case of the CA1 region, remarkable damage of the pyramidal neurons was manifested by vacuolization, and 5-9 d after the injection notable cell loss and disruption of the CA1 cell layer organization was apparent. The results indicate that RuR penetrates selectively neuronal bodies and damage them, and suggest that the resulting motor alterations involve hyperactivity of glutamatergic neurotransmission.

Animals↗

PubMed1995

Prevalence of antibodies against Entamoeba histolytica in Mexico measured by ELISA.

The prevalence of antibodies against Entamoeba histolytica was studied in the Mexican population using an immunoenzyme assay in solid phase (ELISA) and semiautomatic equipment. The antigen was a mixture of membrane proteins obtained by Triton X-100 extraction from an axenic culture of Entamoeba histolytica HM1-IMSS. The method was standardized by comparing serum samples from amoebic liver abscess patients with healthy volunteers. From the 60,538 samples supplied by the National Seroepidemiology Survey, antibodies were found in 4.49% (4.32-4.65% at 95% confidence limit). More significant titres occurred in the central region of the country. The ratio female to male was 1.25:1. The population living in metropolitan areas had probably been infected at a younger age than those living in the country. Important differences were found in the seroprevalence obtained by ELISA compared with a study which used indirect haemagglutination (IHA) in the same sample frame.

Adolescent↗

PubMed1995

Neurotoxic effect of intranigral injection of 1-methyl-4-phenylpyridinium on GABA-containing neurons and its relation to circling behavior.

The ionic species 1-methyl-4-phenylpyridinium (MPP+) seems to be the metabolite responsible for the damage to dopaminergic neurons occurring after administration of the parkinsonian drug 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. In the present study we show that the unilateral stereotaxic microinjection of MPP+ into the substantia nigra pars reticulata in rats produces immediately intense and long-lasting (up to 96 h) contralateral turning behavior in a dose-dependent manner. This behavioral effect was correlated with a dose- and time-dependent decrease (up to 90%) of glutamate decarboxylase activity and with a notable loss of neurons in the injected nigra reticulata. GABA levels in the injected nigra were also decreased, whereas the dopamine concentration in the ipsilateral striatum was not affected at 24 h, when maximal behavioral effects were observed. The circling behavior was prevented by the dopamine carrier blocker nomifensine only during the first 2 h, whereas the dopamine receptor antagonist haloperidol was ineffective. The results indicate that MPP+ is toxic for inhibitory GABAergic neurons in the nigra pars reticulata and, furthermore, suggest that disruption of the function of these GABAergic neurons may be involved in the abnormal motor behavior produced by the injection of MPP+ in the substantia nigra.

1-Methyl-4-phenylpyridinium↗