Biomedical subjects

Mariluz Hernández

Publications and source records attributed to Mariluz Hernández.

4 recordsLinked to original sources

PubMed2004

Behavioral and molecular changes elicited by acute administration of SR141716 to Delta9-tetrahydrocannabinol-tolerant rats: an experimental model of cannabinoid abstinence.

Whether chronic cannabinoid consumption produces a dependent state comparable to that occurring with other drugs (e.g. the appearance of withdrawal signs when consumption is interrupted), and whether chronic cannabinoid consumption increases the risk of consuming other drugs of greater addictive power, are probably the two questions relating to cannabinoid addiction that provoke the most controversy. The present study was designed to further explore these two questions in laboratory animals. Firstly, we examined the effects of an acute challenge with SR141716 (an antagonist for the cannabinoid CB(1) receptor) in Delta(9)-tetrahydrocannabinol (Delta(9)-THC)-tolerant rats. This antagonist has been reported to precipitate a cannabinoid withdrawal syndrome. Thus, the administration of SR141716 to Delta(9)-THC-tolerant rats reduced inactivity in the open-field test and enhanced responses as tremor, turning and retropulsion-these responses that were only slightly enhanced in control rats. The administration of SR141716 increased the plasma prolactin and the corticosterone concentration in controls, but these increases were much lesser in Delta(9)-THC-tolerant rats. In addition, CRF-mRNA levels in the paraventricular hypothalamic nucleus, while reduced in SR141716-treated controls, were significantly increased in Delta(9)-THC-tolerant rats. The analysis of endocannabinoids also revealed that the administration of SR141716, which was mostly inactive in control rats, was able to reverse the changes in anandamide or 2-arachidonoylglycerol concentrations found in Delta(9)-THC-tolerant rats, in the striatum, limbic forebrain, diencephalon, cerebellum and brainstem, but not in the midbrain and hippocampus. As a second objective, we evaluated whether Delta(9)-THC-tolerant rats were more vulnerable to morphine in a self-administration paradigm. The Delta(9)-THC-tolerant and control rats self-administered morphine to a similar extent, in concordance with the similar values of dopaminergic activity in limbic and motor regions. In summary, our data indicate that Delta(9)-THC-tolerant rats were not more vulnerable to the reinforcing properties of morphine. However, they responded to the blockade of CB(1) receptors by exhibiting slightly but possibly relevant differences in behavioral, endocrine and molecular parameters compared to the response in non-tolerant rats. This is indicative of the existence of a withdrawal syndrome in cannabinoid-tolerant rats that is mild compared with abstinence in opioid-dependent rats.

Animals↗

PubMed2004

Cannabinoids and gene expression during brain development.

Cannabis is the most commonly used illicit drug in western societies, in particular among young people. It is consumed even by women during pregnancy and lactation, which result in a variety of disturbances in the development of their offspring, because, like other habit-forming drugs, cannabinoids, the psychoactive ingredients of marijuana, can cross the placental barrier and be secreted in the maternal milk. Through this way, cannabinoids affect the ontogeny of various neurotransmitter systems leading to changes in different behavioral patterns. Dopamine and endogenous opioids are among the neurotransmitters that result more affected by perinatal cannabinoid exposure, which, when animals mature, produce changes in motor activity, drug-seeking behavior, nociception and other processes. These disturbances are likely originated by the capability of cannabinoids to influence the expression of key genes for both neurotransmitters, in particular, the enzyme tyrosine hydroxylase and the opioid precursor proenkephalin. In addition, cannabinoids seem to be also able to influence the expression of genes encoding for neuron-glia cell adhesion molecules, which supports a potential influence of cannabinoids on the processes of cell proliferation, neuronal migration or axonal elongation in which these proteins are involved. In support of this possibility, CB1 receptors, which represent the major targets for the action of cannabinoids, are abundantly expressed in certain brain regions, such as the subventricular areas, which have been involved in these processes during brain development. Finally, cannabinoids might also be involved in the apoptotic death that occurs during brain development, possibly by influencing the expression of Bcl-2/Bax system. Also in support of this option, CB1 receptors are transiently expressed during brain development in different group of neurons which do not contain these receptors in the adult brain. This paper will review all evidence relating cannabinoids to the expression of key genes for neural development, trying to establish the future research addressed to elucidate the mechanisms involved in the epigenetic action of cannabinoids during brain development.

Brain↗

PubMed2003

Prenatal cannabinoid and gene expression for neural adhesion molecule L1 in the fetal rat brain.

The consumption by women of cannabis derivatives during pregnancy and/or lactation affects the development of their offspring because like other psychoactive drugs, cannabinoids, the psychoactive ingredients of marijuana, can cross the placental barrier and be secreted into the maternal milk. Through this way, cannabinoids are able to affect the expression of key genes for neural developmental leading to neurotransmitter and behavioral disturbances. In this present study, we wanted to explore the influence of prenatal cannabinoid exposure on the gene expression of a key protein for brain development, the neural adhesion molecule L1, which plays an important role in processes of cell proliferation and migration, neuritic elongation and guidance, and synaptogenesis. To this end, pregnant rats were daily treated with delta9-tetrahydrocannabinol (delta9-THC) since the 5th day of gestation up to the day before birth (GD21), day at which rats were killed and their pups removed for analysis of L1-mRNA levels in different brain structures. Our results confirmed that the levels of L1 transcripts were significantly increased after prenatal delta9-THC exposure in several regions such as the fimbria, stria terminalis, stria medullaris and corpus callosum, which share the properties of being white matter regions and containing, exclusively during development, an abundant population of cannabinoid CB1 receptors, the major targets for the action of plant-derived cannabinoids. L1-mRNA levels were also increased in grey matter structures such as the septum nuclei and the habenula, but remained unchanged in most of the grey matter structures analyzed (cerebral cortex, basolateral amygdaloid nucleus, hippocampus, thalamic and hypothalamic nuclei, basal ganglia and subventricular zones) and also in a few white matter structures (fornix and fasciculus retroflexus). An important aspect of these observations is that the increase in L1-mRNA levels reached statistical significance only in the case of delta9-THC-exposed males but not in the case of delta9-THC-exposed females where only trends or no effects were detected, this supporting previous evidence on a sexual dimorphism, with greater effects in male fetuses, for the action of cannabinoids in the developing brain. In summary, cannabinoids seem to influence the expression of L1 in specific brain structures during the prenatal period, which, considering the role played by this protein in different events related to neural development, might explain the neurotransmitter and behavioral disturbances reported after prenatal consumption of marijuana.

Animals↗

PubMed2003

[Effectiveness of the antibiotics chloramphenicol and rifampin in the treatment of Streptococcus pneumoniae-induced meningitis and systemic infections].

Streptococcus pneumoniae, a common pathogen in pediatric infections, has become resistant to penicillin and make these infections difficult to treat. Rifampin and chloramphenicol have been recommended as alternative therapies, since they are less costly and more accessible to communities with limited resources. However, their use may be restricted by the differing levels of resistance found in target populations. The objective was to determine minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) for chloramphenicol and rifampin in strains of S. pneumoniae. These strains were newly isolated from children under age 5 that had demonstrated systemic infections and meningitis. A subgroup of 107 isolates of S. pneumoniae was selected from 324 strains isolated during a period of 2 years (1994-1996). Among these isolates, 60 were penicillin-resistant and 47 were susceptible; 53 isolates were from children with meningitis. MIC and MBC for chloramphenicol and rifampicin were obtained by standard methods recommended by the National Committee for Clinical Laboratory Standards (NCCLS). S. pneumoniae ATCC strain 49619 served as the control. An isolate was considered susceptible to chloramphenicol when MIC = 4 microg/ml and resistant when MIC = 8 microg/ml. A strain was considered susceptible to rifampin when MIC = 1 microg/ml and resistant when MIC = 4 microg/ml. MBC was determined by recording the lower concentration of the antibiotic that inhibited 99.9% of the initial inoculum. Chloramphenicol resistance was found in 21% of the 107 isolates. In the group susceptible to penicillin, 11% were resistant to chloramphenicol and in the group resistant to penicillin 28% was resistant to chloramphenicol as well. MBC was found > 4 microg/ml in 28% of the isolates susceptible to penicillin and in 60% of the resistant isolates. No isolates were found resistant to rifampin. However, 2 penicillin resistant isolates showed CBM > 1 microg/ml to rifampin, and one with CIM = 1 microg/ml had a MBC to rifampicin of 16 microg/ml. Meningitis isolates showed higher CIM and CBM than the group of total isolates. These data suggest that chloramphenicol is not recommended for invasive infections caused by S. pneumoniae in Colombia. Rifampin is a more effective therapy in combination with other antibiotics for treatment of this kind of infections. Further studies are necessary to clarify the significance of low levels of MBC to rifampin found in some strains, since this may affect the efficacy of therapies that include this antibiotic.

Anti-Bacterial Agents↗