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2.
Sci Rep ; 11(1): 14029, 2021 07 07.
Article in English | MEDLINE | ID: mdl-34234237

ABSTRACT

Toxoplasma gondii is an opportunistic protozoan pathogen with a wide geographic distribution. The chronic phase of toxoplasmosis is often asymptomatic in humans and is characterized by tissue cysts throughout the central nervous system and muscle cells. T. gondii and other pathogens with tropism for the central nervous system are considered risk factors in the etiology of several neuropsychiatric disorders, such as schizophrenia and bipolar disorder, besides neurological diseases. Currently, it is known that cerebral toxoplasmosis increases dopamine levels in the brain and it is related to behavioral changes in animals and humans. Here we evaluate whether chronic T. gondii infection, using the cystogenic ME-49 strain, could induce behavioral alterations associated with neuropsychiatric disorders and glutamatergic neurotransmission dysfunction. We observed that the startle amplitude is reduced in the infected animals as well as glutamate and D-serine levels in prefrontal cortical and hippocampal tissue homogenates. Moreover, we did not detect alterations in social preference and spontaneous alternation despite severe motor impairment. Thus, we conclude that behavioral and cognitive aspects are maintained even though severe neural damage is observed by chronic infection of C57Bl/6 mice with the ME-49 strain.


Subject(s)
Glutamic Acid/metabolism , Mental Disorders/etiology , Mental Disorders/metabolism , Reflex, Startle , Serine/metabolism , Toxoplasmosis, Cerebral/complications , Toxoplasmosis, Cerebral/parasitology , Animals , Behavior, Animal , Body Weight , Brain/metabolism , Brain/parasitology , Brain/pathology , Hippocampus/metabolism , Mental Disorders/diagnosis , Mental Disorders/psychology , Mice , Neurotransmitter Agents/metabolism , Prefrontal Cortex/metabolism , Social Behavior , Toxoplasma
3.
Braz. j. biol ; 77(3): 527-534, July-Sept. 2017. tab, graf
Article in English | LILACS | ID: biblio-888778

ABSTRACT

Abstract This study presents a review of scientiometric data about freshwater microcrustaceans (Copepoda, Ostracoda, Branchiopoda: Cladocera, Anostraca, Notostraca and Conchostraca) in Brazil from 1990-2014. This review is based on 179 papers published across four databases, using the following keywords in the search: microcrustaceans, Copepoda, Cyclopoida, Calanoida, Harpacticoida, Ergasilidae, Daphniidae, Moinidae, Cladocera, Ostracoda, Conchostraca, zooplankton, reservoir, river, ponds, reservoirs, wetlands, caves, lakes, limnology, ecology, aquatic, taxonomy, systematics, morphology and biogeography. No studies were identified that addressed freshwater microcrustaceans in four (Amapá, Roraima, Alagoas and Espírito Santo) of the 27 Brazilian Federative States. Forty-five percent of the included studies were concentrated within three of the most populous states (São Paulo, Minas Gerais and Paraná), which also have a long tradition of limnological study. The included studies mostly addressed reservoirs for hydropower generation (22%), multiple environments (22%), rivers (14%) and small artificial reservoirs (11%). Pools, ponds, small lakes, wetlands and phytothelma were not widely studied. Cladocera (48%) and Copepoda (48%) were the most studied groups. No studies were identified that addressed Notostraca, Anostraca or Conchostraca. The sharp increase in the number of published freshwater studies after 2000 is likely a result of increased internet facilities and the implementation of the Scielo platform. Ecology was most frequently the study focus (~50%), followed by taxonomy. Three journals (two Brazilian and one international) accounted for the publication of 44% of the Brazilian studies on microcrustaceans. We expect the frequency of studies employing newer technologies to increase in the coming years. Based on our findings, we propose that future studies should focus on the least well-studied states and should integrate biogeography and systematic approaches. Further data on the fauna within environmental sub-types in Brazil is required.


Resumo Esse estudo apresenta uma revisão cienciométrica para trabalhos com microcrustáceos de água doce (Copepoda, Ostracoda, Branchiopoda: Cladocera, Anostraca Notostraca e Conchostraca) no Brasil entre 1990-2014. Essa revisão foi baseada em 179 artigos científicos encontrados em quatro bases de dados, usando as seguintes palavras-chave: Microcrustáceos, Copepoda, Cyclopoida, Calanoida, Harpacticoida, Ergasilidae, Chydoridae, Daphniidae, Moinidae, Cladocera, Ostracoda, Conchostraca, Zooplankton, reservatório, rio, lagoas, áreas inundáveis, cavernas, lagos, limnologia, ecologia, aquático, taxonomia, sistemática, morfologia e biogeografia. Não foram encontrados estudos para microcrustáceos de água doce em quatro (Amapá, Roraima, Alagoas e Espírito Santo) dos 27 Estados da Federação Brasileira. Quarenta e cinco por cento dos estudos foram concentrados em três dos estados mais populosos (São Paulo, Minas Gerais e Paraná), os quais têm longa tradição em estudos limnológicos. A maioria dos estudos analisou reservatórios de hidrelétricas (22%), ambientes múltiplos (22%), rios (14%) e pequenos reservatórios artificiais (11%). Ambientes tais como, pequenos lagos, poças, lagoas, brejos e fitotelmatas não foram muito estudados. Cladocera (48%) e Copepoda (48%) foram os grupos mais estudados. Não foram encontrados trabalhos que analisaram Notostraca, Anostraca ou Conchostraca. O salto no número de estudos publicados depois do ano 2000 parece ser resultado do aumento das facilidades da internet e criação da plataforma Scielo. Ecologia foi a área mais focada nos estudos (~50%), seguida pela taxonomia. Três revistas (duas brasileiras e uma internacional) contêm 44% dos artigos publicados sobre microcrustáceos no Brasil. Espera-se que a frequência de estudos utilizando novas tecnologias aumente nos próximos anos. Baseado nos nossos resultados, propõe-se que trabalhos futuros devam focar os estados menos estudados e integrem abordagens biogeográficas e sistemáticas. Mais dados sobre a fauna de microcrustáceos dentro dos tipos de ambiente menos estudados no Brasil também são necessários.


Subject(s)
Animals , Zooplankton/classification , Zooplankton/physiology , Bibliometrics , Crustacea/anatomy & histology , Crustacea/classification , Crustacea/physiology , Brazil , Lakes , Rivers , Wetlands
4.
Genet Mol Res ; 16(1)2017 Mar 16.
Article in English | MEDLINE | ID: mdl-28362984

ABSTRACT

The availability of common bean cultivars tolerant to Meloidogyne javanica is limited in Brazil. Thus, the present study aimed to evaluate the reactions of 33 common bean genotypes (23 landrace, 8 commercial, 1 susceptible standard and 1 resistant standard) to M. javanica, employing multivariate statistics to discriminate the reaction of the genotypes. The experiment was conducted in a greenhouse using a completely randomized design with seven replicates. The seeds were sown in 1-L pots containing autoclaved soil and sand in a 1:1 ratio (v:v). On day 19, after emergence of the seedlings, the plants were treated with inoculum containing 4000 eggs + second-stage juveniles (J2). At 60 days after inoculation, the seedlings were evaluated based on biometric and parasitism-related traits, such as number of galls, final nematode population per root system, reproduction factor, and percent reduction in the reproduction factor of the nematode (%RRF). The data were subjected to analysis of variance using the F-test. The Mahalanobis generalized distance was used to obtain the dissimilarity matrix, and the average linkage between groups was used for clustering. The use of multivariate statistics allowed groups to be separated according to the resistance levels of genotypes, as observed in the %RRF. The landrace genotypes FORT-09, FORT-17, FORT-31, FORT-32, FORT-34 and FORT-36 presented resistance to M. javanica; thus, these genotypes can be considered potential sources of resistance.


Subject(s)
Disease Resistance , Phaseolus/genetics , Plant Diseases/parasitology , Tylenchoidea/pathogenicity , Animals , Genotype , Host-Parasite Interactions , Multivariate Analysis , Phaseolus/growth & development , Phaseolus/parasitology , Plant Roots/growth & development , Plant Roots/parasitology , Random Allocation , Seeds/growth & development , Seeds/parasitology
5.
Braz J Biol ; 77(3): 527-534, 2017.
Article in English | MEDLINE | ID: mdl-27925015

ABSTRACT

This study presents a review of scientiometric data about freshwater microcrustaceans (Copepoda, Ostracoda, Branchiopoda: Cladocera, Anostraca, Notostraca and Conchostraca) in Brazil from 1990-2014. This review is based on 179 papers published across four databases, using the following keywords in the search: microcrustaceans, Copepoda, Cyclopoida, Calanoida, Harpacticoida, Ergasilidae, Daphniidae, Moinidae, Cladocera, Ostracoda, Conchostraca, zooplankton, reservoir, river, ponds, reservoirs, wetlands, caves, lakes, limnology, ecology, aquatic, taxonomy, systematics, morphology and biogeography. No studies were identified that addressed freshwater microcrustaceans in four (Amapá, Roraima, Alagoas and Espírito Santo) of the 27 Brazilian Federative States. Forty-five percent of the included studies were concentrated within three of the most populous states (São Paulo, Minas Gerais and Paraná), which also have a long tradition of limnological study. The included studies mostly addressed reservoirs for hydropower generation (22%), multiple environments (22%), rivers (14%) and small artificial reservoirs (11%). Pools, ponds, small lakes, wetlands and phytothelma were not widely studied. Cladocera (48%) and Copepoda (48%) were the most studied groups. No studies were identified that addressed Notostraca, Anostraca or Conchostraca. The sharp increase in the number of published freshwater studies after 2000 is likely a result of increased internet facilities and the implementation of the Scielo platform. Ecology was most frequently the study focus (~50%), followed by taxonomy. Three journals (two Brazilian and one international) accounted for the publication of 44% of the Brazilian studies on microcrustaceans. We expect the frequency of studies employing newer technologies to increase in the coming years. Based on our findings, we propose that future studies should focus on the least well-studied states and should integrate biogeography and systematic approaches. Further data on the fauna within environmental sub-types in Brazil is required.


Subject(s)
Bibliometrics , Crustacea , Zooplankton , Animals , Brazil , Crustacea/anatomy & histology , Crustacea/classification , Crustacea/physiology , Lakes , Rivers , Wetlands , Zooplankton/classification , Zooplankton/physiology
6.
Braz. j. biol ; 76(2): 279-291, Apr.-June 2016. tab, graf
Article in English | LILACS | ID: lil-781407

ABSTRACT

Abstract This study evaluated changes in the community of rotifers and microcrustaceans associated with the construction of a large and dendritic reservoir in Iguaçu River (Brazil), as the last reservoir of a sequence of five cascading systems. Differences were clear between pre-filling and post-filling phases for organisms and some of environmental variables. In the pre-filling phase, the community was more homogeneous along the downstream river gradient, and spatial compartmentalization in the new reservoir was common during the post-filling phase. From 140 identified taxa, 10 species occurred exclusively in the pre-filling phase and 32 in the post-filling phase. After completion of the fifth reservoir filling-up, opportunistic, pioneer and fast-developing species quickly dominated, and downstream of the fourth reservoir the pre-filling decreasing gradient of richness, diversity and evenness disappeared. Richness of rotifers and cladocerans, cladocerans diversity, and evenness of rotifers, cladocerans and copepods were generally higher in the post-filling phase. A non-metric multidimensional analysis based on a presence/absence matrix depicted a homogeneous and dense group of species associated to the pre-filling phase and a second, dispersed group related to the post-filling phase. Spearman correlations pointed out significant positive effects of transparency on rotifer species richness in the post-filling phase, and negative effects on the microcrustacean richness in the pre-filling phase. Dam construction caused disruption of the downstream lotic gradient along the series of dams, leading to the development of distinct species in lentic spatial compartments.


Resumo Esse estudo analisou os efeitos da construção de um reservatório largo e dendrítico no Brasil sobre a comunidade de rotíferos e microcrustáceos, sendo o último reservatório de uma cascata de cinco. Houve claras diferenças entre as fases pré e pós-enchimento para os organismos e para algumas variáveis ambientais. Na fase pré-enchimento, a comunidade foi mais homogênea no gradiente longitudinal no rio a jusante, e na fase pós-enchimento houve compartimentalização espacial no novo reservatório. Dos 140 táxons identificados, dez espécies ocorreram exclusivamente na fase pré-enchimento e 32 na fase pós-enchimento. Após o enchimento, espécies oportunistas, pioneiras e de rápido desenvolvimento foram dominantes, e desapareceu o gradiente de decréscimo a jusante do quarto reservatório para a riqueza, diversidade e equitabilidade durante a fase pré-enchimento. A riqueza de rotíferos e cladóceros, a diversidade de cladóceros, e a equitabilidade de rotíferos, cladóceros e copépodes foram elevadas na fase pós-enchimento. A análise de escalonamento multidimensional não-métrico sobre a matriz de presença e ausência mostrou um grupo homogêneo e denso de espécies e meses de amostragem na fase pré-enchimento, e outro grupo disperso na fase pós-enchimento. Correlações de Spearman apontaram efeitos significativos da transparência sobre a riqueza de rotíferos na fase pós-enchimento, e efeitos negativos sobre a riqueza de microcrustáceos na outra fase. Os efeitos da construção do reservatório causaram rompimento no gradiente lótico contínuo a jusante do quarto reservatório observado na fase pré-enchimento, permitindo o desenvolvimento de espécies em compartimentos espaciais lênticos.


Subject(s)
Animals , Rotifera/physiology , Zooplankton/physiology , Rivers , Seasons , Brazil , Population Dynamics , Population Density , Aquaculture/methods , Copepoda/physiology , Ecological and Environmental Phenomena , Hydrobiology
7.
Braz J Biol ; 76(2): 279-91, 2016 Jun.
Article in English | MEDLINE | ID: mdl-26983084

ABSTRACT

This study evaluated changes in the community of rotifers and microcrustaceans associated with the construction of a large and dendritic reservoir in Iguaçu River (Brazil), as the last reservoir of a sequence of five cascading systems. Differences were clear between pre-filling and post-filling phases for organisms and some of environmental variables. In the pre-filling phase, the community was more homogeneous along the downstream river gradient, and spatial compartmentalization in the new reservoir was common during the post-filling phase. From 140 identified taxa, 10 species occurred exclusively in the pre-filling phase and 32 in the post-filling phase. After completion of the fifth reservoir filling-up, opportunistic, pioneer and fast-developing species quickly dominated, and downstream of the fourth reservoir the pre-filling decreasing gradient of richness, diversity and evenness disappeared. Richness of rotifers and cladocerans, cladocerans diversity, and evenness of rotifers, cladocerans and copepods were generally higher in the post-filling phase. A non-metric multidimensional analysis based on a presence/absence matrix depicted a homogeneous and dense group of species associated to the pre-filling phase and a second, dispersed group related to the post-filling phase. Spearman correlations pointed out significant positive effects of transparency on rotifer species richness in the post-filling phase, and negative effects on the microcrustacean richness in the pre-filling phase. Dam construction caused disruption of the downstream lotic gradient along the series of dams, leading to the development of distinct species in lentic spatial compartments.


Subject(s)
Copepoda/physiology , Rivers , Rotifera/physiology , Zooplankton/physiology , Animals , Aquaculture/methods , Brazil , Ecological and Environmental Phenomena , Hydrobiology , Population Density , Population Dynamics , Seasons
8.
J Proteomics ; 97: 126-40, 2014 Jan 31.
Article in English | MEDLINE | ID: mdl-23886778

ABSTRACT

Blood vessel invasion is a key feature of invasive aspergillosis. This angioinvasion process contributes to tissue thrombosis, which can impair the access of leukocytes and antifungal drugs to the site of infection. It has been demonstrated that human umbilical vein endothelial cells (HUVECs) are activated and assume a prothrombotic phenotype following contact with Aspergillus fumigatus hyphae or germlings, a process that is independent of fungus viability. However, the molecular mechanisms by which this pathogen can activate endothelial cells, together with the endothelial pathways that are involved in this process, remain unknown. Using a label-free approach by High Definition Mass Spectrometry (HDMS(E)), differentially expressed proteins were identified during HUVEC-A. fumigatus interaction. Among these, 89 proteins were determined to be up- or down-regulated, and another 409 proteins were exclusive to one experimental condition: the HUVEC control or HUVEC:AF interaction. The in silico predictions provided a general view of which biological processes and/or pathways were regulated during HUVEC:AF interaction, and they mainly included cell signaling, immune response and hemostasis pathways. This work describes the first global proteomic analysis of HUVECs following interaction with A. fumigatus germlings, the fungus morphotype that represents the first step of invasion and dissemination within the host. BIOLOGICAL SIGNIFICANCE: A. fumigatus causes the main opportunistic invasive fungal infection related to neutropenic hematologic patients. One of the key steps during the establishment of invasive aspergillosis is angioinvasion but the mechanism associated with the interaction of A. fumigatus with the vascular endothelium remains unknown. The identification of up- and down-regulated proteins expressed by human endothelial cells in response to the fungus infection can contribute to reveal the mechanism of endothelial response and, to understand the physiopathology of this high mortality disease. This article is part of a Special Issue entitled: Trends in Microbial Proteomics.


Subject(s)
Aspergillosis/metabolism , Aspergillus fumigatus/physiology , Host-Pathogen Interactions , Human Umbilical Vein Endothelial Cells/metabolism , Mass Spectrometry/methods , Proteome/metabolism , Aspergillosis/pathology , Human Umbilical Vein Endothelial Cells/microbiology , Human Umbilical Vein Endothelial Cells/pathology , Humans
9.
Int J Tuberc Lung Dis ; 17(12): 1581-6, 2013 Dec.
Article in English | MEDLINE | ID: mdl-24200272

ABSTRACT

OBJECTIVES: To evaluate the population-based impact of a comprehensive intervention to strengthen tuberculosis (TB) control in Rocinha, the largest urban slum in Rio de Janeiro, Brazil. DESIGN: In July 2003, 40 lay persons were hired and trained as community health workers to supervise treatment, implement educational activities and establish a supportive social network for anti-tuberculosis treatment. Between July 2005 and June 2008, a door-to-door active case finding campaign was conducted. Data were obtained from the Brazilian National Reporting System, which collects information from the TB notification form for every reported case. RESULTS: Between January 2001 and December 2008, 2623 TB cases were reported, 852 before and 1771 after the start of the program. Following the intervention, treatment success rates increased (67.6% vs. 83.2%, P < 0.001) and default rates dropped (17.8% vs. 5.5%, P < 0.001). Compared to the pre-intervention period, the TB case rate declined by an average of 39 cases per 100,000 population per 6 months (P = 0.003) in the post-intervention period, although this may have been due to secular trends already in place at the start of the intervention. Case rates declined from 591/100,000 in 2001 to 496/100,000 in 2008. CONCLUSION: With proper planning and effective community involvement, a successful intervention can lead to high cure rates and may contribute to a decrease in TB notification rates.


Subject(s)
Antitubercular Agents/therapeutic use , Community Health Services , Directly Observed Therapy , Poverty Areas , Tuberculosis/drug therapy , Urban Health Services , Vulnerable Populations , Adolescent , Adult , Brazil/epidemiology , Community Health Services/organization & administration , Community Health Workers , Disease Notification , Female , Health Knowledge, Attitudes, Practice , Humans , Incidence , Male , Organizational Objectives , Patient Education as Topic , Program Evaluation , Social Support , Time Factors , Treatment Outcome , Tuberculosis/diagnosis , Tuberculosis/epidemiology , Tuberculosis/transmission , Urban Health Services/organization & administration , Young Adult
11.
ABCD (São Paulo, Impr.) ; 17(1): 38-41, 2004.
Article in Spanish, Portuguese | LILACS | ID: lil-390558

ABSTRACT

Racional - As lesões da via biliar são complicações graves tanto na era atual da videolaparoscopia como na cirurgia por via aberta ou por laparotomia. Objetivo - Estabelecer a frequência de lesões iatrogênicas da via biliar em um hospital de ensino no Brasil, e analisar os resultados imediatos e tardios do seu tratamento...


Subject(s)
Male , Female , Adult , Middle Aged , Cholecystectomy, Laparoscopic/methods , Postoperative Complications , Laparotomy/methods , Chi-Square Distribution , Bile Duct Diseases/surgery
14.
J Pharm Biomed Anal ; 33(5): 1127-33, 2003 Dec 04.
Article in English | MEDLINE | ID: mdl-14656603

ABSTRACT

A rapid, simple and accurate high performance liquid chromatography (HPLC) method was developed and validated for the determination of LASSBio-581 (1-[1-(4-chloro-phenyl)-1H-[1,2,3]triazol-4-ylmethyl]-4-phenyl-piperazine) in rat plasma using ketoconazole as internal standard. Plasma samples were deproteinized with methanol. A good chromatographic separation was achieved using a reversed phase C18 column. Mobile phase consisting of sodium dihydrogen phosphate monohydrate (pH 4.5, 0.02 M) and methanol mixture (35:65, v/v) was used at a flow rate of 1.0 ml/min. The eluate was monitored using a UV detector at 248 nm. The retention times of LASSBio-581 and the internal standard were approximately 3.8 and 5.6 min, respectively. The calibration curves were linear over the concentration range of 0.25-8.0 microg/ml with correlation coefficients >0.99. The limit of quantitation was 0.25 microg/ml. The accuracy of the method was >90%. The intra-day relative standard deviation (R.S.D.) ranged from 6.15 to 10.52% at 0.4 microg/ml, 7.44 to 13.81% at 1.5 microg/ml and 6.10 to 13.94% at 6.0 microg/ml. The inter-day R.S.D. were 9.54, 8.42 and 8.25% at 0.4, 1.5 and 6.0 microg/ml, respectively. No interference from endogenous substances or metabolites were observed. The method has been used to measure plasma concentrations of LASSBio-581 in pharmacokinetic studies in rats.


Subject(s)
Heterocyclic Compounds/blood , Piperazines/blood , Animals , Chromatography, High Pressure Liquid/methods , Heterocyclic Compounds/administration & dosage , Heterocyclic Compounds/pharmacokinetics , Male , Piperazines/administration & dosage , Piperazines/pharmacokinetics , Rats , Rats, Wistar
15.
Braz. j. med. biol. res ; 36(5): 625-629, May 2003. ilus, tab
Article in English | LILACS | ID: lil-331451

ABSTRACT

Dopamine constitutes about 80 percent of the content of central catecholamines and has a crucial role in the etiology of several neuropsychiatric disorders, including Parkinson's disease, depression and schizophrenia. Several dopaminergic drugs are used to treat these pathologies, but many problems are attributed to these therapies. Within this context, the search for new more efficient dopaminergic agents with less adverse effects represents a vast research field. The aim of the present study was to report the structural design of two N-phenylpiperazine derivatives, compound 4: 1-[1-(4-chlorophenyl)-1H-4-pyrazolylmethyl]-4-phenylhexahydropyrazine and compound 5: 1-[1-(4-chlorophenyl)-1H-1,2,3-triazol-4-ylmethyl]-4-phenylhexahydropyrazine, planned to be dopamine ligands, and their dopaminergic action profile. The two compounds were assayed (dose range of 15-40 mg/kg) in three experimental models: 1) blockade of amphetamine (30 mg/kg, ip)-induced stereotypy in rats; 2) the catalepsy test in mice, and 3) apomorphine (1 mg/kg, ip)-induced hypothermia in mice. Both derivatives induced cataleptic behavior (40 mg/kg, ip) and a hypothermic response (30 mg/kg, ip) which was not prevented by haloperidol (0.5 mg/kg, ip). Compound 5 (30 mg/kg, ip) also presented a synergistic hypothermic effect with apomorphine (1 mg/kg, ip). Only compound 4 (30 mg/kg, ip) significantly blocked the amphetamine-induced stereotypy in rats. The N-phenylpiperazine derivatives 4 and 5 seem to have a peculiar profile of action on dopaminergic functions. On the basis of the results of catalepsy and amphetamine-induced stereotypy, the compounds demonstrated an inhibitory effect on dopaminergic behaviors. However, their hypothermic effect is compatible with the stimulation of dopaminergic function which seems not to be mediated by D2/D3 receptors


Subject(s)
Animals , Male , Mice , Rats , Dopamine Antagonists , Psychotropic Drugs , Catalepsy , Dopamine Antagonists , Hypothermia , Psychotropic Drugs , Rats, Wistar , Stereotyped Behavior , Structure-Activity Relationship
16.
Braz J Med Biol Res ; 36(5): 625-9, 2003 May.
Article in English | MEDLINE | ID: mdl-12715082

ABSTRACT

Dopamine constitutes about 80% of the content of central catecholamines and has a crucial role in the etiology of several neuropsychiatric disorders, including Parkinson's disease, depression and schizophrenia. Several dopaminergic drugs are used to treat these pathologies, but many problems are attributed to these therapies. Within this context, the search for new more efficient dopaminergic agents with less adverse effects represents a vast research field. The aim of the present study was to report the structural design of two N-phenylpiperazine derivatives, compound 4: 1-[1-(4-chlorophenyl)-1H-4-pyrazolylmethyl]-4-phenylhexahydropyrazine and compound 5: 1-[1-(4-chlorophenyl)-1H-1,2,3-triazol-4-ylmethyl]-4-phenylhexahydropyrazine, planned to be dopamine ligands, and their dopaminergic action profile. The two compounds were assayed (dose range of 15-40 mg/kg) in three experimental models: 1) blockade of amphetamine (30 mg/kg, ip)-induced stereotypy in rats; 2) the catalepsy test in mice, and 3) apomorphine (1 mg/kg, ip)-induced hypothermia in mice. Both derivatives induced cataleptic behavior (40 mg/kg, ip) and a hypothermic response (30 mg/kg, ip) which was not prevented by haloperidol (0.5 mg/kg, ip). Compound 5 (30 mg/kg, ip) also presented a synergistic hypothermic effect with apomorphine (1 mg/kg, ip). Only compound 4 (30 mg/kg, ip) significantly blocked the amphetamine-induced stereotypy in rats. The N-phenylpiperazine derivatives 4 and 5 seem to have a peculiar profile of action on dopaminergic functions. On the basis of the results of catalepsy and amphetamine-induced stereotypy, the compounds demonstrated an inhibitory effect on dopaminergic behaviors. However, their hypothermic effect is compatible with the stimulation of dopaminergic function which seems not to be mediated by D2/D3 receptors.


Subject(s)
Dopamine Antagonists/chemistry , Piperazines/chemistry , Psychotropic Drugs/chemistry , Pyrazoles/chemistry , Triazoles/chemistry , Animals , Catalepsy/chemically induced , Dopamine Antagonists/pharmacology , Hypothermia/chemically induced , Male , Mice , Piperazines/pharmacology , Psychotropic Drugs/pharmacology , Pyrazoles/pharmacology , Rats , Rats, Wistar , Stereotyped Behavior/drug effects , Structure-Activity Relationship , Time Factors , Triazoles/pharmacology
17.
Cerebrovasc Dis ; 15(1-2): 78-83, 2003.
Article in English | MEDLINE | ID: mdl-12499715

ABSTRACT

To describe early symptomatic and late seizures in a cohort of patients with acute cerebral vein and dural sinus thrombosis (CVDST) and to identify their determinants, we performed a prospective registry and follow-up study of CVDST patients admitted to 20 Portuguese hospitals, from June 1995 to June 1998. Of 91 registered patients, 31 (34%) had early symptomatic seizures; 29 (31.9%) as a presenting feature and 2 (2.1%) after admission. Early symptomatic seizures were more frequent in patients with motor and sensory deficits and in those with focal oedema/ischaemic infarcts or haemorrhages on admission CT/MR. On multivariate logistic regression analysis, sensory defects (OR = 7.8; 95% CI = 0.8-74.8) and a parenchymal lesion on admission CT/MR (OR = 3.7, 95% CI = 1.4-9.4) were found to be significant predictors of early symptomatic seizures. Seizures were directly related to acute death in 2 patients. Eight (9.5%) patients had late seizures, which were multiple in 4 (4.8%). Late seizures were more frequent in patients with early symptomatic seizures and with haemorrhage on admission CT/MR. Neither early symptomatic seizures nor late seizures were related to functional prognosis at the last follow-up (median = 1 year). There is a moderate risk of seizure recurrence early in the course and during the first year after CVDST. Seizures can be a cause of acute death, but might not have an independent influence on functional outcome. Pharmacological prevention of seizures after CVDST should probably be limited to patients with early symptomatic seizures and cerebral lesions on admission CT/MR.


Subject(s)
Cerebral Veins/pathology , Dura Mater/blood supply , Dura Mater/pathology , Seizures/diagnosis , Sinus Thrombosis, Intracranial/diagnosis , Adult , Anticonvulsants/therapeutic use , Cerebral Veins/diagnostic imaging , Cohort Studies , Dura Mater/diagnostic imaging , Female , Follow-Up Studies , Humans , Length of Stay , Magnetic Resonance Imaging , Male , Middle Aged , Neurosurgical Procedures , Patient Admission , Portugal , Predictive Value of Tests , Prognosis , Prospective Studies , Recurrence , Seizures/epidemiology , Seizures/therapy , Sensitivity and Specificity , Sinus Thrombosis, Intracranial/epidemiology , Sinus Thrombosis, Intracranial/therapy , Survival Analysis , Time Factors , Tomography, X-Ray Computed , Treatment Outcome
18.
Proc Natl Acad Sci U S A ; 98(26): 15282-7, 2001 Dec 18.
Article in English | MEDLINE | ID: mdl-11734626

ABSTRACT

To investigate the regulation of endocytosis by Ca(2+), we have made capacitance measurements in the synaptic terminal of depolarizing bipolar cells from the retina of goldfish. After a brief depolarization, all of the excess membrane was retrieved rapidly (tau approximately 1 s). But when the rise in free [Ca(2+)] was reduced by the introduction of Ca(2+) buffers [1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetate (BAPTA) or EGTA], a large fraction of the membrane was retrieved by a second, slower mechanism (tau > or = 10 s). The block of fast endocytosis by EGTA could be overcome by increasing the amplitude of the Ca(2+) current, demonstrating that Ca(2+) influx was the trigger for fast endocytosis. These manipulations of the Ca(2+) signal altered the relative proportions of fast and slow endocytosis but did not modulate the rate constants of these processes. A brief stimulus that triggered fast endocytosis did not generate a significant rise in the spatially averaged [Ca(2+)], indicating that Ca(2+) regulated endocytosis through an action close to the active zone. The slow mode of retrieval occurred at the resting [Ca(2+)]. These results demonstrate that Ca(2+) influx couples fast endocytosis and exocytosis at this synapse.


Subject(s)
Calcium/metabolism , Egtazic Acid/analogs & derivatives , Endocytosis , Presynaptic Terminals/metabolism , Retina/metabolism , Buffers , Chelating Agents , Ion Transport , Membrane Potentials , Presynaptic Terminals/physiology , Retina/cytology , Retina/physiology
19.
J Physiol ; 535(Pt 3): 809-24, 2001 Sep 15.
Article in English | MEDLINE | ID: mdl-11559777

ABSTRACT

1. We investigated the properties of Ca2+-sensitive steps in the cycling of synaptic vesicles by comparing the actions of Ca2+, Ba2+ and Sr2+ in the synaptic terminal of depolarizing bipolar cells isolated from the retina of goldfish. FM1-43 fluorescence and capacitance measurements demonstrated that exocytosis, endocytosis and vesicle mobilization were maintained when external Ca2+ was replaced by either Ba2+ or Sr2+. 2. The rapidly releasable pool of vesicles (RRP) was equivalent to 1.5 % of the membrane surface area when measured in the presence of 2.5 mM Ca2+, but only 0.4 % in 2.5 mM Sr2+. The relative sizes of the RRP in Ca2+, Sr2+ and Ba2+ were 1.0, 0.28 and 0.1, respectively. We conclude that a smaller proportion of docked vesicles are available for fast exocytosis triggered by the influx of Sr2+ or Ba2+ compared to Ca2+. 3. The slow phase of exocytosis was not altered when Ca2+ was replaced by Ba2+, but it was accelerated 1.6-fold in Sr2+. The peak concentrations of Ca2+, Sr2+ and Ba2+ (measured using Mag-fura-5) were approximately 4, approximately 14 and approximately 60 microM, respectively. The order of efficiency for the stimulation of slow exocytosis was Ca2+ approximately Sr2+ > Ba2+. 4. Exocytosis was prolonged after the influx of Sr2+ and Ba2+. Sr2+ was cleared from the synaptic terminal with the same time constant as Ca2+ (1.3 s), but Ba2+ was cleared 10-100 times more slowly. Although Ba(2+) stimulates the slow release of a large number of vesicles, it did so less efficiently than Ca2+ or Sr2+. 5. The recovery of the membrane capacitance was equally rapid in Sr2+ and Ca2+, demonstrating that the fast mode of endocytosis could be triggered by either cation.


Subject(s)
Barium/pharmacology , Endocytosis/drug effects , Exocytosis/drug effects , Neurons/metabolism , Presynaptic Terminals/drug effects , Strontium/pharmacology , Animals , Barium/metabolism , Calcium/metabolism , Electric Capacitance , Fluorescent Dyes , Goldfish , In Vitro Techniques , Ion Channels/drug effects , Neurons/drug effects , Pyridinium Compounds , Quaternary Ammonium Compounds , Strontium/metabolism , Synaptic Vesicles/drug effects , Synaptic Vesicles/metabolism
20.
Phytother Res ; 14(8): 661, 2000 Dec.
Article in English | MEDLINE | ID: mdl-11114012

ABSTRACT

The original article to which this Erratum refers was published in Phytotherapy Research 14(5) 2000, 344-346. Following the publication of this paper in the August 2000 issue of Phytotherapy Research (14(5):344-346), it has come to our attention that there is a misleading statement regarding conclusions cited from the work of Butterweck et al. 1998. The discussion in the recent PTR paper states that those authors are 'in favour of the hypothesis that the antidepressant activity is due to the hypericin only'. We wish to make it clear that this is not the case, and the Butterweck paper actually concludes that 'both naphthodianthrones must be considered as active constituents of the crude extract of H. perforatum. However, previous studies indicate that the other consitutuents of the crude drug also have activity'. The authors apologize for this error and are happy to correct it.

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