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Biomedical subjects

R M Costa

Publications and source records attributed to R M Costa.

18 recordsLinked to original sources
PubMed2006

Dopamine levels modulate the updating of tastant values.

To survive, animals must constantly update the internal value of stimuli they encounter; a process referred to as incentive learning. Although there have been many studies investigating whether dopamine is necessary for reward, or for the association between stimuli and actions with rewards, less is known about the role of dopamine in the updating of the internal value of stimuli per se. We used a single-bottle forced-choice task to investigate the role of dopamine in learning the value of tastants. We show that dopamine transporter knock-out mice (DAT-KO), which have constitutively elevated dopamine levels, develop a more positive bias towards a hedonically positive tastant (sucrose 400 mM) than their wild-type littermates. Furthermore, when compared to wild-type littermates, DAT-KO mice develop a less negative bias towards a hedonically negative tastant (quinine HCl 10 mM). Importantly, these effects develop with training, because at the onset of training DAT-KO and wild-type mice display similar biases towards sucrose and quinine. These data suggest that dopamine levels can modulate the updating of tastant values, a finding with implications for understanding sensory-specific motivation and reward seeking.

Animals↗
PubMed2006

Spatial and temporal distribution in density and biomass of two Pseudodiaptomus species (Copepoda: Calanoida) in the Caeté river estuary (Amazon region--North of Brazil).

Spatial and temporal density and biomass distribution of the planktonic copepods Pseudodiaptomus richardi and P. acutus along a salinity gradient were investigated in the Caeté River Estuary (North-Brazil) in June and December, 1998 (dry season) and in February and May, 1999 (rainy season). Copepod biomass was estimated using regression parameters based on the relation of dry weight and body length (prosome) of adult organisms. The Caeté River Estuary was characterized by high spatial and temporal variations in salinity (0.8-37.2). Exponential length-weight relationships were observed for both Pseudodiaptomus species. Density and biomass values oscillated between 0.28-46.18 ind. m-3 and 0.0022-0.3507 mg DW. m-3 for P. richardi; and between 0.01-17.02 ind. m-3 and 0.0005-0.7181 mg DW. m-3 for P. acutus. The results showed that the contribution of P. richardi for the secondary production in the Caeté River Estuary is more important in the limnetic zone than in other zones where euhaline-polyhaline regimes were predominant. However, it was not possible to observe a clear pattern of spatial and temporal distribution for P. acutus.

Animals↗
PubMed2001

Learning deficits, but normal development and tumor predisposition, in mice lacking exon 23a of Nf1.

Neurofibromatosis type 1 (NF1) is a commonly inherited autosomal dominant disorder. Previous studies indicated that mice homozygous for a null mutation in Nf1 exhibit mid-gestation lethality, whereas heterozygous mice have an increased predisposition to tumors and learning impairments. Here we show that mice lacking the alternatively spliced exon 23a, which modifies the GTPase-activating protein (GAP) domain of Nf1, are viable and physically normal, and do not have an increased tumor predisposition, but show specific learning impairments. Our findings have implications for the development of a treatment for the learning disabilities associated with NF1 and indicate that the GAP domain of NF1 modulates learning and memory.

Animals↗
PubMed2001

Inducible, pharmacogenetic approaches to the study of learning and memory.

Here we introduce a strategy in which pharmacology is used to induce the effects of recessive mutations. For example, mice heterozygous for a null mutation of the K-ras gene (K-ras+/-) show normal hippocampal mitogen-activated protein kinase (MAPK) activation, long-term potentiation (LTP) and contextual conditioning. However, a dose of a mitogen-activated/extracellular-signal-regulated kinase (MEK) inhibitor, ineffective in wild-type controls, blocks MAPK activation, LTP and contextual learning in K-ras+/- mutants. These indicate that K-Ras/MEK/MAPK signaling is critical in synaptic and behavioral plasticity. A subthreshold dose of NMDA receptor antagonists triggered a contextual learning deficit in mice heterozygous for a point mutation (T286A) in the alphaCaMKII gene, but not in K-ras+/- mutants, demonstrating the specificity of the synergistic interaction between the MEK inhibitor and the K-ras+/- mutation. This pharmacogenetic approach combines the high temporal specificity that pharmacological manipulations offer, with the molecular specificity of genetic disruptions.

Animals↗
PubMed2001

The participation of AtXPB1, the XPB/RAD25 homologue gene from Arabidopsis thaliana, in DNA repair and plant development.

Nucleotide excision repair in Arabidopsis thaliana differs from other eukaryotes as it contains two paralogous copies of the corresponding XPB/RAD25 gene. In this work, the functional characterization of one copy, AtXPB1, is presented. The plant gene was able to partially complement the UV sensitivity of a yeast rad25 mutant strain, thus confirming its involvement in nucleotide excision repair. The biological role of AtXPB1 protein in A. thaliana was further ascertained by obtaining a homozygous mutant plant containing the AtXPB1 genomic sequence interrupted by a T-DNA insertion. The 3' end of the mutant gene is disrupted, generating the expression of a truncated mRNA molecule. Despite the normal morphology, the mutant plants presented developmental delay, lower seed viability and a loss of germination synchrony. These plants also manifested increased sensitivity to continuous exposure to the alkylating agent MMS, thus suggesting inefficient DNA damage removal. These results indicate that, although the duplication seems to be recent, the features described for the mutant plant imply some functional or timing expression divergence between the paralogous AtXPB genes. The AtXPB1 protein function in nucleotide excision repair is probably required for the removal of lesions during seed storage, germination and early plant development.

Arabidopsis↗
PubMed2001

Bioequivalence of two lamivudine tablet formulations.

The present study describes the determination of the bioavailability of a new commercial tablet formulation of lamivudine (CAS 134678-17-4) compared with a reference formulation. The comparative bioequivalence of the test and a reference formulation (each 3 x 150 mg) was assessed in 24 healthy volunteers by means of a randomized two-way crossover design. Prior to the study both the test and reference formulations were examined for conformation to chromatographic purity and drug content. Each volunteer received the test (T) and the reference formulation (R) with a one-week drug-free interval between administrations. The plasma concentrations of T were monitored over a period of 12 h after drug administration using a sensitive HPLC method. Pharmacokinetic parameters for T were determined from plasma concentration-time data. Statistical tests were carried out at 90% confidence intervals using a parametric method (three-way ANOVA) for AUC and Cmax, and non-parametric method for Tmax. The present study showed that both formulations were bioequivalent for the geometric mean of AUC(0-12), AUC0-infinity), Cmax, and Tmax at the 90% confidence interval. The bioavailability of the test (%) was 96.7, 93.3, 99.7, 100.3, respectively. The T:R ratio was, in each case, well within the acceptable range of 100 +/- 20%.

Adult↗
PubMed2000

Molecular and cellular mechanisms of cognitive function: implications for psychiatric disorders.

Recent studies on the molecular and cellular basis of learning and memory have brought us closer than ever to understanding the mechanisms of synaptic plasticity and their relevance to memory formation. Genetic approaches have played a central role in these new findings because the same mutant mice can be studied with molecular, cellular, circuit, and behavioral tools. Therefore, the results can be used to construct models that cut across levels of analytical complexity, forging connections from the biochemistry of the modified protein to the behavior of the mutant mice. These findings are not only improving our understanding of learning and memory, they are also enriching our understanding of cognitive disorders, such as neurofibromatosis type I. Mechanisms underlying long-term changes in synaptic function are likely to be at the heart of many cognitive and emotional processes in humans. Therefore, molecular and cellular insights into learning and memory undoubtedly will have a profound impact on the understanding and treatment of psychiatric disorders.

Animals↗
PubMed2000

Atrazine degradation in a containerized rhizosphere system.

The effect of atrazine (2-chloro-4-ethylamino-6-isopropylamino-s-triazine) on rhizosphere microorganisms and its fate in a containerized rhizosphere system was studied. The rhizosphere system consisted of corn grown in pot containing a defined potting mix of sand and bark with atrazine. Sterilized potting mix and a container without plants served as controls. Atrazine was extracted and analyzed via HPLC. Fluorescent pseudomonad populations increased 100-fold in the rhizposphere during a 60-day incubation period as compared to the nonvegetated control. Atrazine degradation was higher in the rhizosphere system (half-life of 7 days) compared to the nonvegetated control (half-life of greater than 45 days). The major degradation product detected in the rhizosphere system was deisopropylatrazine; other products detected included deethylatrazine, deethylhydroxyatrazine, deisopropylatrazine and hydroxyatrazine. Hydroxyatrazine was detected in the nonvegetated and sterile controls. The containerized rhizosphere system provides an experimental system to study the fate of pesticidal chemicals as well as the effects on microbial populations.

Atrazine↗
PubMed1998

Cloning of a cDNA from Arabidopsis thaliana homologous to the human XPB gene.

The human gene XPB, defective in xeroderma pigmentosum patients complementation group B, encodes a DNA helicase involved in several DNA metabolic pathways, including DNA repair and transcription. The high conservation of this gene has allowed the cloning of homologs in various species, such as mouse, yeast and Drosophila. Not much information on the molecular basis of nucleotide excision repair in plants is available, but these organisms may have similar mechanisms to other eukaryotes. A homolog of XPB was isolated in Arabidopsis thaliana by using polymerase chain reaction (PCR) with degenerate oligonucleotides based on protein domains which are conserved among several species. Screening of an Arabidopsis cDNA library led to the identification and isolation of a cDNA clone with 2670 bp encoding a predicted protein of 767 amino acids, denoted araXPB. Genomic analysis indicated that this is a nuclear single copy gene in plant cells. Northern blot with the cDNA probe revealed a major transcript which migrated at approx. 2,800 b, in agreement with the size of the cDNA isolated. The araXPB protein shares approximately 50% identical and 70% conserved amino acids with the yeast and human homologs. The plant protein maintains all the functional domains found in the other proteins, including nuclear localization signal, DNA-binding domain and helicase motifs, suggesting that it might also act as part of the RNA transcription apparatus, as well as nucleotide excision repair in plant cells.

Amino Acid Sequence↗
PubMed1994

Plasma membrane phospholipid and cholesterol distribution of skin fibroblasts from drug-naive patients at the onset of psychosis.

Contents of plasma membrane major phospholipids, cholesterol, and cholesteryl esters of fibroblasts from drug-naive psychotic patients were compared with those from normal controls. Total membrane lipids were extracted and individual lipids were separated on high-performance thin-layer chromatography. The contents of lipid bands were quantitated by densitometric scanning and comparing with standards. Contents of total phospholipids as well as phosphatidylserine, phosphatidylinositol and phosphatidylethanolamine were significantly lower in fibroblasts from patients than in those from normal controls (P < 0.001, < 0.005, < 0.05 respectively). Total cholesterol fraction and cholesteryl esters were also significantly lower in fibroblasts from patient (P < 0.005, < 0.001 respectively). These changes were not related to differences in age or sex. These data support the hypothesis that schizophrenia is associated with disordered membrane lipid metabolism, and that this predates the onset of psychosis.

Adolescent↗
PubMed1989

Demonstration of anti-bradykinin compounds in callus cultures of Mandevilla velutina.

Calluses from stems and leaves of Mandevilla velutina were grown in culture for 30, 45 and 60 days. Thin-layer chromatography of ethyl acetate extracts of calluses from stems of M. velutina revealed the presence of 6 compounds. Two of them had RF values identical to those of the anti-bradykinin (BK) compounds MV8609 and MV8610 previously isolated from the natural plant. The ethyl acetate extract (20 to 80 micrograms/ml) from stem callus culture antagonized in a concentration-dependent and reversible manner contractions caused by BK (0.1-1000 nM) in the isolated rat uterus. The extracts obtained from calluses cultured for 30, 45 and 60 days were about 79-, 63- and 31-fold more potent, respectively, in antagonizing BK than the crude extract obtained from the rhizome of the plant.

Animals↗
PubMedDate not supplied

An urban outbreak of visceral leishmaniasis in Natal, Brazil.

The epidemiological pattern of visceral leishmaniasis in north-eastern Brazil is changing. The disease was typically seen in rural, endemic areas, but is now occurring as an epidemic in the city of Natal where 316 cases have been reported since 1989; 49% were in children less than 5 years of age. The principle clinical and laboratory findings were weight loss, fever, hepato-splenomegaly, anaemia, leucopenia and hypergammaglobulinaemia. Elevated transaminases and hyperbilirubinaemia were also observed. The diagnosis was confirmed in 87% of cases by identifying amastigotes in aspirates from bone marrow or spleen. Five isolates were identified as Leishmania (L.) chagasi by isoenzyme analysis. The mortality rate was 9%; all deaths occurred during the first week in hospital. One person had concurrent human immunodeficiency virus infection. Among 210 household contacts and neighbours of patients from the endemic area examined for evidence of L. (L.) chagasi infection, 6 additional cases of visceral leishmaniasis were diagnosed. Thirty-eight percent of house-mates and neighbours gave a positive Montenegro skin test reaction, indicating prior subclinical infection.

Adolescent↗
PubMedDate not supplied

[Information-related changes in attitude to mucocutaneous leishmaniasis of a population from an endemic region of the south of Bahia].

The mutilant nature of the mucosal form of leishmaniasis can cause alterations in personal relations. To identify the level of understanding of leishmaniasis and the psychological reaction to it patients and houseowners in an endemic area of Bahia were interviewed. Several false beliefs were identified and there was a strong tendency to reject mutilated patients among the population for a false fear of contagion. Possibly future clarification of the real nature of leishmaniasis could change such a negative attitude among the resident population.

Brazil↗
PubMedDate not supplied

"Pararamose": an occupational arthritis caused by lepidoptera (Premolis semirufa). An epidemiological study.

The frequency of "pararama" occupational accidents between 1988 and 1990 as well as some associated clinical manifestations are herein reported. Data were collected at an industrial rubber tree plantation, in the northern part of Brazil and compared with data similarly collected from 1971 to 1974 on the same plantation, before starting protective measures. "Pararama" is the popular name of the larval form of a native insect of the Amazonian region, Premolis semirufa. During the study period, the annual average number of latex extractors was 337 and 60 accidents caused by "pararama" were registered. The annual average number of accidents per worker from 1971 to 1974 was 0.117 and in the period of this study, 0.063 (p = 0.061). Nineteen injured subjects were clinically evaluated and 13 of them were symptomatic. There was a statistically significant association between multiple accidents and the presence of symptoms (p = 0.001). "Pararamose", an occupational arthropathy, which may evolve with functional impairment of the affected joint, can be prevented with the latex extractors education and the institution of prophylactic measures, such as the use of gloves, boots and protective glasses.

Animals↗