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L Rocha

Publications and source records attributed to L Rocha.

At least 37 records · Page 2Linked to original sources
PubMed1999

Gabapentin modifies extracellular opioid peptide content in amygdala: a microdialysis study.

Opioid peptide release was monitored in the amygdala and hippocampus of freely moving rats following a single oral administration of gabapentin using microdialysis. Extracellular opioid peptide levels were elevated above basal levels in the amygdala within the first 60 (54%) and 90 min (68%) after gabapentin administration. Levels returned to basal conditions 120 min following the treatment. No significant changes were detected in the hippocampus. The majority of immunoreactive material recovered from the amygdala following gabapentin administration was identified as Leu-enkephalin and Met-enkephalin by high performance liquid chromatography (HPLC) analysis. It is proposed that the enhanced opioid peptide release in the amygdala induced by gabapentin might be involved with the antiepileptic effects as well as with some adverse events produced by this drug.

Acetates↗
PubMed1999

Opioid peptide systems following a subconvulsant dose of pentylenetetrazol in rats.

The development of epilepsy and a progressive increase in susceptibility to seizures may involve changes in inhibitory and excitatory systems from the beginning of the process. The present study was focused to analyze the opioid peptide changes induced by a chemical sub-convulsant stimulation. Experiments were carried out to determine opioid peptide release, mu receptor binding and proenkephalin expression in rat brain, as well as nociceptive responses, following the administration of a sub-convulsant dose of pentylenetetrazol (PTZ) (30 mg/kg, i.p.). Membrane binding experiments revealed reduced number of mu binding sites (Bmax) in cortex and amygdala, but not in striatum and hippocampus, an effect that was evident only 24 h, but not 28 days, after PTZ treatment. In situ hybridization experiments suggested a significant enhancement of proenkephalin mRNA expression in specific brain regions 24 h after PTZ treatment. Microdialysis combined with a universal opioid peptide radioimmunoassay revealed extracellular opioid peptide levels to be elevated in the amygdala (137%) 90 min after PTZ administration. Evaluation of nociceptive responses using the Randall-Selitto test showed an analgesic effect short term (30-90 min) after PTZ injection. Collectively, these data provide evidence for a significant activation of opioid peptide systems as a consequence of the administration of a sub-convulsant dose of PTZ. These neurochemical changes may play an important role in the progression of epileptogenesis.

Animals↗
PubMed1999

N-acetyltransferase (NAT2) genotype and susceptibility of sporadic Alzheimer's disease.

The importance of environmental aggression and individual susceptibility to develop Alzheimer's Disease (AD) has been suggested by epidemiological studies on both typical familial and sporadic AD cases. In order to elucidate functions that can influence the susceptibility to AD pathogenesis, we genotyped a group of 53 sporadic late-onset AD patients, matched control individuals and a larger randomly selected non-demented population for the N-acetyltransferase (NAT2). We determined the relative frequencies of individual allele combinations that define a broad range of acetylator phenotypes. Inter-individual variability in the cytotoxic and genotoxic responses to a wide diversity of environmental chemicals is known to result from the polymorphism of NAT2 as well as other drug-metabolizing-enzyme genes. The results presented are the first to demonstrate a significant difference in the NAT2 genotype profiles of sporadic AD patients compared with the healthy population. A lower frequency of the recessive alleles NAT2*6 (chi-squared 1 d.f. = 12.56, P < 0.0004) and NAT2*5B (chi-squared 1 d.f. = 6.72, P < 0.01) was found among the AD population compared with control individuals, which was concomitant with a significantly higher number of NAT2*4 fully active allele homozygotes and heterozygotes (chi-squared 1 d.f. = 5.69, P = 0.017). The most notable observation was the absence of NAT2*5B/NAT2*6 heterozygotes among cases while being present in 22.5% of control individuals (chi-squared 1 d.f. = 13.08, P = 0.0003). These observations indicate that NAT2 is a potential low-penetrance gene in AD pathogenesis, determining an individual susceptibility trait predisposing to this degenerative disease.

Alzheimer Disease↗
PubMed1998

In vivo administration of c-Fos antisense oligonucleotides accelerates amygdala kindling.

Repeated subconvulsive electrical stimulation of the amygdala leads to generalized seizures and provides an experimental model of epileptogenesis. Following electrical kindling stimulation the expression of c-Fos is rapidly induced. To evaluate the role of FOS protein in epileptogenesis, we used an antisense oligonucleotide strategy designed to inhibit its expression in the brain. Experimental and control oligonucleotides were delivered directly into the amygdala just prior to electrical stimulation. Immunocytochemical analysis showed that the administration of c-Fos antisense (but not sense) oligonucleotides inhibited expression of FOS in the amygdala following electrical stimulation. Behaviorally, treatment with c-Fos antisense oligonucleotides significantly accelerated the development of fully kindled (stage V) seizures. These data suggest that the increased FOS expression following electrical stimulation may be part of a protective mechanism which acts to inhibit epileptogenesis in the amygdala.

Amygdala↗
PubMed1996

Effects of chronic morphine pretreatment on amygdaloid kindling development, postictal seizure and suppression and benzodiazepine receptor binding in rats.

Effects of chronic morphine pretreatment on the development of amygdaloid kindling, seizure suppression and benzodiazepine (BDZ) receptor binding in rats were evaluated. The morphine-pretreated animals showed faster acquisition of seizure activity. Further evaluation of the postictal seizure suppression immediately after a fully kindled seizure demonstrated that morphine-pretreated rats had a decreased sensitivity to subsequent kindling stimulations. Twenty-four hours after the last electrical stimulation, saline-pretreated fully kindled rats showed enhanced BDZ receptor binding in dentate gyrus, and decreased binding in cingulate cortex ipsilateral to the stimulation site, compared to saline controls. Morphine-pretreated amygdala-kindled rats had significantly higher BDZ binding in piriform, entorhinal and sensorimotor cortices, basolateral and cortical amygdaloid nuclei, dentate gyrus, CAI-3 areas, substantia nigra pars reticulata and periaqueductal gray. The present study indicates that the previous experience with chronic morphine modifies the kindling process and that the enhanced BDZ receptor binding detected in our experiments may be involved in the enhanced postictal seizure suppression observed in these animals.

Amygdala↗
PubMed1996

Chronic and single administration of pentylenetetrazol modifies benzodiazepine receptor-binding: an autoradiographic study.

Benzodiazepine (BDZ) receptor-binding changes in the rat brain induced by pentylenetetrazol (PTZ) were investigated by in vitro autoradiography. Our experiments revealed that a single PTZ administration produced BDZ-binding decrease in cingulate, frontal, temporal, parietal and piriform cortices; caudate putamen; medial, basolateral and cortical amygdaloid nuclei; medial, ventromedial and ventroposterior thalamic nuclei; substantia nigra pars compacta and periaqueductal gray. Fully kindled rats with chronic PTZ treatment showed reduced BDZ receptor-binding in cingulate, frontal, parietal and piriform cortices; caudate putamen; medial, ventromedial and ventroposterior thalamic nuclei; and periaqueductal gray. These effects resulted from decrease in the binding capacity. Our results support that PTZ-induced chemical kindling may be associated with significant changes of the GABAergic systems and BDZ-binding from the first administration.

Animals↗
PubMed1996

Pentylenetetrazol-induced kindling: early involvement of excitatory and inhibitory systems.

Alterations in the brain of rats receiving a single non-convulsive administration pentylenetetrazol (PTZ), 30 mig/kg, i.p. (single PTZ group) were investigated and compared with those detected in fully PTZ kindled rats (chronic PTZ group). In vitro receptor autoradiography experiments showed that both single and chronic PTZ groups presented mu opioid and benzodiazepine (BDZ) receptor binding in specific brain areas. Using an antibody generated against the delta opioid receptor (DOR-1), it was found that DOR-1 like immunoreactivity was reduced in cortex and amygdala in mice following single and chronic PTZ administration. Microdialysis experiments revealed that the administration of PTZ 30 mg/kg, i.p. in freely moving rats without previous experience with the drug, induces a rise in glutamate release, detected in the first and second 10 min dialysates collected from amygdala (138% and 50%, respectively) and frontal cortex (70% and 45%, respectively) as well as aspartate in frontal cortex in the first and second PTZ-dialysates (143% and 80%, respectively). Subsequently, values returned to basal conditions. It may be speculated that decreased BDZ receptor binding results from enhanced release of GABA. On the other hand, the decrease of mu receptor binding and DOR-1 immunoreactivity observed after PTZ administration may be the result of enhanced levels of opioid peptides probably released over the kindling procedure. In conclusion, the present study indicates that PTZ-kindling is associated with an imbalance between excitatory and inhibitory systems which is apparent early in the epileptogenic process.

Amygdala↗
PubMed1995

Antibacterial phloroglucinols and flavonoids from Hypericum brasiliense.

Three known phloroglucinols (japonicine A, uliginosin A and isouliginosin B) and a new phloroglucinol (hyperbrasiol A) have been isolated from a petrol extract of the leaves and flowers of Hypericum brasiliense. Their structures were established by spectroscopic methods (UV, DCI-MS, 1H and 13CNMR, including SINEPT, HMBC, HSQC, DQFCOSY experiments). The substitution pattern of hyperbrasilol A was confirmed by X-ray crystallography. All four phloroglucinols were antibacterial against Bacillus subtilis in a TLC bioautographic assay. The flavonoids, kaempferol, luteolin, quercetin, quercitrin, isoquercitrin, hyperoside and guaijaverin, were isolated from a methanol extract of the same organs.

Anti-Bacterial Agents↗
PubMed1994

Microdialysis reveals changes in extracellular opioid peptide levels in the amygdala induced by amygdaloid kindling stimulation.

Enkephalins released in basolateral nucleus of the amygdala in response to electrical stimulation were determined in amygdala kindled and nonkindled freely moving rats using microdialysis. Enkephalin release was enhanced after a single and repetitive electrical stimulation (233 and 130% above control levels, respectively) in nonkindled rats. In fully kindled rats, the extracellular enkephalin levels decreased (35% below the control levels) within the first 20 min after onset of stage V kindled seizures, reaching baseline level 40 to 60 min following the generalized seizure activity. HPLC analysis identified the majority of recovered immunoreactive material from the amygdala as Met-enkephalin. On the basis of our results it is suggested that the enhanced enkephalin release in the amygdala during the early kindling stages might have a suppressive effect which may represent a homeostatic mechanism to avoid the spread of the afterdischarge to other structures. The decreased extracellular level of enkephalin in the amygdala after stage V kindled seizures could reflect a general impairment of inhibitory mechanisms in this structure with subsequent production of seizure activity.

Amygdala↗
PubMed1994

Chronic pretreatment with naloxone modifies benzodiazepine receptor binding in amygdaloid kindled rats.

Male Sprague-Dawley rats received either naloxone (75 micrograms/h) or saline (0.5 microliter/h) s.c. for 14 days delivered with osmotic minipumps. Two days after termination of either treatment, daily amygdala kindling stimulation was applied until the animals experienced stage V kindled seizures. Benzodiazepine (BDZ) binding sites were labeled with [3H]flunitrazepam (2 nM), and changes in specific brain areas were determined by in vitro quantitative autoradiography. Twenty-four hours after the last electrical stimulation, the saline pretreated fully kindled rats showed enhanced BDZ receptor binding in dentate gyrus, and decreased binding in cingulate cortex ipsilateral to the stimulation compared to saline controls. Twenty-eight days after the last stage V kindled seizure, the significant alterations were no longer evident. In agreement with a previous study, we found that naloxone pretreated amygdala kindled rats showed stage V kindled seizures followed by intervals of 3-5 days in which the same electrical stimulation failed to induce any behavioral and EEG alterations. In comparison with the saline pretreated kindled and saline control groups, the naloxone pretreated kindled rats had significantly higher BDZ binding in different cortical areas, amygdala complex, hippocampus, substantia nigra and periaqueductal gray, 24 h after the last electrical stimulation. The present study indicates that previous chronic exposure to naloxone increases BDZ receptor binding in kindled rats, and suggests that this effect may be associated with the enhanced seizure suppression observed in these animals.

Amygdala↗
PubMed1994

An antifungal gamma-pyrone and xanthones with monoamine oxidase inhibitory activity from Hypericum brasiliense.

A new gamma-pyrone (hyperbrasilone), three known xanthones (1,5-dihydroxyxanthone, 5-hydroxy-1-methoxyxanthone and 6-deoxyjacareubin) and betulinic acid have been isolated from a dichloromethane extract of stems and roots of Hypericum brasiliense. Their structures were established by spectroscopic methods (UV, EI-MS, 1H and 13C NMR) and that of the gamma-pyrone was confirmed by X-ray crystallography. Hyperbrasilone and the xanthones were all antifungal against Cladosporium cucumerinum, while the three xanthones showed differing degrees of inhibition of monoamine oxidase A and B.

Animals↗
PubMed1993

Benzodiazepine receptor binding following chronic treatment with naloxone, morphine and met-enkephalin in normal rats.

The effects of chronic administration of naloxone, morphine and met-enkephalin on benzodiazepine (BDZ) receptor binding in rat brain were determined 2 and 50 days after treatments were accomplished. Two days after naloxone treatment (75 micrograms/h s.c. for 14 days), enhanced BDZ receptor binding was observed in cingulate, frontal, piriform, entorhinal and sensorimotor cortices; amygdala complex, hippocampus, substantia nigra and central gray. Two days after morphine treatment (20 mg/kg i.p. daily for 6 days), increased BDZ receptor binding was detected in cingulate, frontal, piriform, entorhinal and sensorimotor cortices; amygdala complex, hippocampus and substantia nigra. Two days after met-enkephalin treatment (10 micrograms/h i.c.v. for 6 days) enhanced BDZ receptor binding was shown only in sensorimotor cortex. No significant changes were observed 50 days after the treatments were completed. These data indicate an important interaction between GABAergic and opioid peptide systems.

Animals↗
PubMed1993

Characterization of mu opioid receptor binding during amygdala kindling in rats and effects of chronic naloxone pretreatment: an autoradiographic study.

Using in vitro autoradiography, mu receptor binding in rat brain was characterized at different amygdala kindling stages and in amygdaloid kindled animals pretreated chronically with naloxone. Male Sprague-Dawley rats implanted with bipolar electrodes in the right amygdala received one of the following pretreatments s.c. for 14 days via osmotic minipumps: normal saline solution, 0.5 microliters/h, or naloxone HCl, 75 micrograms/h. Two days after treatments were accomplished animals were stimulated daily. Our data showed different patterns of mu receptor binding during the normal kindling process: during stage II-III, pronounced binding increase was detected in cingulate, temporal and entorhinal cortices, anterior amygdala, caudate putamen, thalamic nuclei, ventrolateral and dorsolateral portions of central gray, substantia nigra pars compacta and pars reticulata. Twenty-four hours after the last stage V kindled seizure, enhanced binding was observed in cingulate and frontoparietal cortices, anterior amygdala, caudate putamen and ventromedial thalamic nucleus. Twenty-eight days after the last stage V kindled seizure, binding augmentation was noticed in cingulate and frontoparietal cortices, whereas decreased binding was detected in amygdala complex, substantia nigra pars reticulata, piriform, perirhinal, parietal, temporal and entorhinal cortices. Mu receptor binding in kindled rats chronically pretreated with naloxone was significantly higher in several structures when compared with control and normal kindled groups. Our data indicate different regional selective patterns of mu receptor binding during amygdala kindling which may depend on epileptogenesis and long-term changes induced by this process. In addition, even higher mu receptor binding results from chronic naloxone administration prior to kindling.

Amygdala↗
PubMed1991

Naloxone effects on the visual evoked potentials recorded from the main and accessory visual pathways of the cat.

1. The effects produced by repetitive i.v. administration of naloxone (1, 2 or 4 mg/kg) on the visual evoked potentials (VEPs) recorded along the main and accessory visual pathways were investigated in a modified "encéphale isolé" cat preparation. 2. Naloxone provoked a progressive amplitude enhancement and latency reduction of some components, depending on the structure analyzed, the dose used and the number of administrations applied. Electroretinogram (ERG) and N1-P1 VEP components of optic chiasm (OCh), lateral geniculate body (LGB) and visual cortex (VC) did not present significant changes. 3. Late-latency components (more than 200 msec) appeared in the VEPs of LGB and VC, mainly when 4 mg/kg were used. 4. Our results suggest that endogenous opioids have a modulatory role in the processing of sensory information at different levels of the visual system.

Animals↗
PubMed1990

Group work in a primary care medical setting.

A group work program was developed for low-income, minority patients of a primary care medical setting who were misusing medical resources to work on psychosocial issues. Multiple groups were established using an action-oriented approach to enhance patients' ability to cope with health, mental health, and environmental problems. The program was demonstrated to be beneficial for the participants and the primary care clinic.

Adaptation, Psychological↗
PubMed1988

Naloxone facilitates sensory precipitation of focal and generalized seizures: evoked potentials and power spectral analysis in the cat.

To analyze the role of endogenous opioids on epileptogenesis the effect of repeated doses of naloxone alone (NA) (2, 4, and 8 mg/kg every 15 min) or along with intermittent photic stimulation (NPS) (1, 3, and 10 Hz) was tested on acute "Encephale isolé" cats. The electrical activity recordings of sensorimotor cortex (SMC), visual cortex, and right and left amygdalae revealed progressive changes as naloxone was administered: (A) slow spindle activity (4-6 Hz) in SMC, (B) 12 Hz rhythmic activity in both amygdalae, (C) generalized paroxysms, and (D) spontaneous tonic-clonic electrographic seizures. These changes occurred in both experimental groups (NA, NPS), and their onset was dose-related. Photic stimulation precipitated these phenomena. The amplitude of the visual evoked potential components (N1-P1, P1-N2, N2-P2) and power spectral analysis of spontaneous and evoked activity underwent progressive changes. Our results confirm a facilitatory effect of naloxone on epileptogenesis and suggest a possible role of endogenous opioids in this process and on sensory pathways' excitability.

Amygdala↗