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1.
J. bras. psiquiatr ; 71(1): 16-23, jan.-mar. 2022. tab
Article in English | LILACS | ID: biblio-1365058

ABSTRACT

OBJECTIVE: Evaluate the association between levels of mindfulness and sociodemographic characteristics and pattern of drug use of individuals seeking treatment in a University Service Specialized in Substance Use Disorders. METHODS: This is a cross-sectional study with 164 individuals over 18 years of age seeking treatment for the use of psychoactive substances in the June 2018-December 2019 period, using a questionnaire for sociodemographic data, the Mindful Attention Awareness Scale (MAAS) self- -reporting instrument, and the Alcohol, Smoking, and Substance Involvement Screening Test. RESULTS: An association was found between low levels of mindfulness mainly with the individual risk of being a medium/high-risk user of sedative-hypnotic drugs (p = 0.020). A borderline association was also found between MAAS and the risk of the individual being a medium/high risk of alcohol (p = 0.053) and with a more severe pattern of substance use (p = 0.065). CONCLUSION: Individuals seeking treatment for substance use presented impairments in the attentional aspect of mindfulness and levels of mindfulness seem to protect against behaviors related to substance use, especially against the use of high/ moderate risk of sedative-hypnotics.


OBJETIVO: Avaliar a associação entre níveis de mindfulness e características sociodemográficas e padrão do uso de drogas de indivíduos que buscam tratamento em Serviço Universitário Especializado em Transtorno por Uso de Substâncias. MÉTODOS: Estudo de corte transversal de 164 indivíduos acima de 18 anos que buscavam tratamento para uso de substâncias psicoativas no período de junho de 2018 a dezembro de 2019, utilizando questionário para dados sociodemográficos, o instrumento de autorrelato Mindful Attention Awareness Scale (MAAS) e o Alcohol, Smoking and Substance Involvement Screening Test. RESULTADOS: Foi encontrada associação entre baixos níveis de mindfulness principalmente com o risco de o indivíduo ser usuário de médio/alto risco de sedativos-hipnóticos (p = 0,020). Também foi encontrada associação limítrofe entre MAAS com risco de o indivíduo ser usuário de médio/alto risco de álcool (p = 0,053) e com padrão mais grave de uso de substâncias (p = 0,065). CONCLUSÃO: Indivíduos que buscavam tratamento para uso de substâncias apresentaram prejuízos no aspecto atencional de mindfulness, e níveis de mindfulness parecem proteger contra comportamentos relacionados ao uso de substâncias, principalmente contra o uso de alto/moderado risco de sedativos-hipnóticos.


Subject(s)
Humans , Male , Female , Adult , Cognitive Behavioral Therapy/methods , Substance-Related Disorders/psychology , Substance-Related Disorders/therapy , Mindfulness , Benzodiazepinones/pharmacology , Cross-Sectional Studies , Surveys and Questionnaires , Cohort Studies
2.
Journal of Forensic Medicine ; (6): 248-252, 2018.
Article in Chinese | WPRIM | ID: wpr-984931

ABSTRACT

OBJECTIVES@#To identify the new designer drugs which are totally unknown and not in the routine testing list by the technologies such as high-resolution mass spectrometry in drug facilitated sexual assault, in order to solve the problem in actual cases.@*METHODS@#The milky fluid from an actual case was extracted and analyzed using LC-QE, ¹H-NMR and GC-MS, respectively. The accurate masses and cluster ions isotope patterns of unknown compound were obtained by LC-QE. The molecular formula was confirmed as C₁₆H₁₂C₂N₂O based on the protons number of ¹H-NMR. The isomers diclazepam and 4-chlorodiazepam were separated and detected with GC-MS.@*RESULTS@#The new designer benzodiazepine as diclazepam in the milky fluid was identified. The results provided direct evidence for the investigation and qualitative analysis of such cases.@*CONCLUSIONS@#The combined application of various methods, including LC-QE, ¹H-NMR and GC-MS, can be used to detect unknown new psychoactive substances.


Subject(s)
Female , Humans , Male , Benzodiazepines/chemistry , Benzodiazepinones , Chromatography, Liquid/methods , Designer Drugs/chemistry , Gas Chromatography-Mass Spectrometry/methods , Mass Spectrometry/methods , Sex Offenses , Substance Abuse Detection/methods , Toxicology/methods
3.
Rio de Janeiro; s.n; 2017. 261 f p. tab, graf.
Thesis in Portuguese | LILACS | ID: biblio-965959

ABSTRACT

Esta dissertação objetivou estimar a prevalência, o padrão, e os fatores associados com a incidência de consumo de antidepressivos (AD) e benzodiazepínicos (BDZ) em uma coorte de funcionários de uma universidade. Foi realizado um estudo de coorte concorrente com os dados do Estudo Pró-Saúde, uma investigação longitudinal com funcionários técnico-administrativos do quadro efetivo de uma universidade no Estado do Rio de Janeiro. Os dados foram obtidos utilizando-se questionários autopreenchidos nos anos de 1999 (n=4.030), 2001 (n=3.574), 2006-07 (n=3.058) e 2012 (n=2.933). Foi construído um banco de dados com 5.369 pessoas, abarcando as quatro fases, sendo estimadas prevalências de uso AD e BDZ por fase. Em seguida, foi instituída uma coorte fixa excluindo os indivíduos que entraram no estudo em qualquer fase que não a linha de base (fase 1), e/ou indivíduos que faziam uso de AD e BDZ na fase 1. Modelos de Poisson com estimativa robusta da variância foram utilizados para estimar razões de incidência acumulada (risco relativo) de consumo de AD e BDZ entre 1999 e 2007. Em 1999, as prevalências de uso de AD e de BDZ foram 1,4% (IC 95%: 1,1-1,8) e 4,7% (IC 95%: 4,1-5,4), respectivamente. Em 2012, a prevalência de uso de AD foi de 5,4% (IC 95%: 5,5-6,2) e de BDZ de 6,8% (IC 95%: 6,0-7,8). Os inibidores seletivos da recaptação de serotonina (ISRS) representaram a classe que impulsionou o aumento do consumo dos AD, passando de 17% em 1999 para 67,6% em 2012. As prevalências de consumo de AD e BDZ foram maiores entre as mulheres, assim como entre os entrevistados com pior auto-percepção da saúde geral e mental (mensurada através do GHQ-12). A incidência do consumo de psicofármacos, entre 1999 e 2007, foi de 4,9% (IC 95%: 4,2-5,7) para AD e 8,3% (IC 95%: 7,3-9,3) para BDZ. Quando as fases 2 e 3 foram comparadas, o aumento da incidência de AD foi relativamente maior do que de BDZ. A incidência de uso de AD nas mulheres foi maior do que entre os homens (RR=2,5; IC 95% 1,75-4,04). As mulheres também apresentaram uma incidência de uso de BDZ 58% (IC 95%: 30-110) maior do que a observada para os homens. Aqueles com GHQ-12 positivo mostraram uma incidência 34% maior tanto para o consumo de AD quanto de BDZ. Consistente com a literatura, observou-se um maior risco de iniciar o uso de AD entre os indivíduos consumidores de BDZ na fase 1. Esses resultados sugerem que o aumento na incidência de uso de AD não foi acompanhado de uma queda na incidência do uso de BDZ. É imperativo que as prescrições de AD e BDZ estejam de acordo com as diretrizes atuais de tratamento, principalmente considerando o uso racional dos psicofármacos. Nossos achados apontam para a necessidade de identificar padrões semelhantes aos observados no presente estudo em outras populações, e visam contribuir para as políticas de educação permanente dos profissionais que prestam cuidados em saúde mental


This dissertation aimed to estimate the prevalence, pattern and factors associated with the incidence of antidepressant (AD) and benzodiazepine (BDZ) use in a cohort of university employees. A concurrent cohort study was carried out with data from the Pró-Saúde Study, a longitudinal investigation including all the technical-administrative employees of the actual staff of a university in the State of Rio de Janeiro. Self-administered questionnaires were applied in 1999 (n = 4,030), 2001 (n = 3,574), 2006-07 (n = 3,058) and 2012 (n = 2,933). A database was constructed with 5,369 people covering the four phases, and the prevalence use of AD and BDZ was estimated for each phase. A fixed cohort was defined excluding individuals who entered the study at any phase other than the baseline (phase 1) and/or individuals using AD and BDZ at phase 1. Poisson regression models with robust variance were fitted to estimate the cumulative incidence ratios for the use of AD and BDZ in the period of 1999-2007. The prevalence of use of AD and BDZ in 1999 was 1.4% and 4.7%, respectively. In 2012, the prevalence of use of AD was 5.4% and BDZ was 6.8%. Selective Serotonin Reuptake Inhibitors (SSRI) represented the class responsible for the increase in AD consumption, from 17% in 1999 to 67.6% in 2012. The prevalence use of AD and BDZ were higher among women and those with worse self-perception of general and mental health (measured through GHQ-12). The incidence of psychotropic consumption from 1999 to 2007 was 4.9% (95% CI: 4.2-5.7) for AD and 8.3% (95% CI: 7.3-9.3) for BDZ. When phases 2 and 3 were compared, the increase in the incidence of AD consumption was relatively greater for AD compared to BDZ. The incidence for AD was larger among women compared to men (RR=2.5; 95% CI: 1.75-4.04). Women also had an incidence 58% (95% CI: 30-110) higher for BDZ of use than men. Those with positive GHQ-12 had an incidence 34% greater for both AD and BDZ use. Consistent with the literature, a greater risk of initiating the use of AD was observed among individuals consuming BDZ in phase 1. These results suggest that the increase in the incidence of AD consumption was not followed by a decrease in the incidence of BDZ use. It is imperative that the prescription of AD and BDZ complies with current treatment guidelines, especially considering the rational use of psychotropic drugs. Our findings point to the need to identify patterns similar to those observed in other populations, and aim to contribute to the policies of permanent education of professionals who provide mental health care


Subject(s)
Humans , Psychotropic Drugs/therapeutic use , Benzodiazepinones/therapeutic use , Mental Health , Epidemiology , Incidence , Prevalence , Antidepressive Agents/therapeutic use
4.
Cad. saúde pública ; 31(4): 722-732, 04/2015.
Article in English | LILACS | ID: lil-744848

ABSTRACT

We aimed to verify doctor's perception of the qualitative research method, via a qualitative study of interviews with questions on the academic profile of doctors and on the methodology. We interviewed 42 professionals, of which 18 had experience with the qualitative method and 24 with the quantitative method. The results showed that knowledge on the qualitative method was virtually nil among "quantitative researchers", who did not value qualitative research, although some of those realized that it would be important to be more accepting in clinical practice. Others only considered the method as subsidiary to quantitative. The majority considered qualitative methods as lacking academic structure, taking too long to conduct empirical studies, and being difficult to publish. All of them criticized the misuse of the method, and the "quantitatives" pointed out the problem of being unable to reproduce. We concluded that widening the use of the qualitative method by doctors requires investment from the beginning of the academic career and participation in qualitative research projects.


El objetivo es verificar la percepción de médicos sobre el método de investigación cualitativa. Se trata de un estudio cualitativo por medio de entrevistas con preguntas sobre el perfil de los médicos y sobre el método. Entrevistamos a 42 profesionales, 18 con experiencia en el método cualitativo y 24 con el cuantitativo. Los resultados mostraron que el conocimiento sobre lo cualitativo es casi nulo entre los "cuantitativistas", que no valoran la investigación cualitativa, aunque algunos se dan cuenta de que sería importante tener un enfoque más amplio en la práctica clínica. Otros la ven como subsidiaria a lo cuantitativo. Sus dificultades para utilizar ese abordaje son: falta de formación, cantidad de tiempo que exigen y problemas de publicación. Todos han criticado el mal uso del método. Los "cuantitativistas" han destacado como fragilidad, la no reproductibilidad. Llegamos a la conclusión de que para ampliar el uso de los abordajes cualitativos entre los médicos es importante invertir en su formación desde el inicio del curso y la participación en proyectos de investigación cualitativa.


Objetivamos verificar a percepção de médicos sobre o método qualitativo de pesquisa. Estudo qualitativo por meio de entrevistas com questões sobre o perfil acadêmico do médico e perguntas abertas a respeito do método. Entrevistamos 42 profissionais, sendo 18 com experiência no método qualitativo e 24 com o quantitativo. Os resultados evidenciaram que o conhecimento sobre o qualitativo é quase nulo entre os pesquisadores "quantitativistas", os quais não valorizam a pesquisa qualitativa, embora alguns percebam que seria importante ter uma postura mais compreensiva na prática clínica. Outros só a veem como subsidiária ao quantitativo. As principais dificuldades da maioria são: falta de formação, tempo longo despendido nos estudos empíricos e dificuldade de publicação. Todos os entrevistados criticaram o mau uso do método, e os "quantitativistas" ressaltaram, como problema, sua não reprodutibilidade. Concluímos que ampliar o uso do método qualitativo por médicos exige investimento na formação desde o início da graduação e participação em projetos de pesquisa qualitativa.


Subject(s)
Animals , Humans , Mice , Anilides/pharmacology , Benzodiazepinones/pharmacology , /pharmacology , Protein Kinase Inhibitors/pharmacology , Protein Serine-Threonine Kinases/antagonists & inhibitors , Pyrimidines/pharmacology , Repressor Proteins/antagonists & inhibitors , Cells, Cultured , Cell Movement/drug effects , Cell Proliferation/drug effects , Drug Evaluation, Preclinical , Enzyme Activation/drug effects , Neoplasms/pathology , Protein Kinases/genetics , Protein Serine-Threonine Kinases/genetics , Protein Serine-Threonine Kinases/metabolism , Protein Serine-Threonine Kinases/physiology , Repressor Proteins/agonists , Repressor Proteins/genetics , Substrate Specificity , Tumor Suppressor Proteins/physiology
5.
Acta Pharmaceutica Sinica ; (12): 230-236, 2014.
Article in Chinese | WPRIM | ID: wpr-297988

ABSTRACT

The crude extracts of the fermentation broth from a marine sediment-derived actinomycete strain, Saccharothrix sp. 10-10, showed significant antibacterial activities against drug-resistant pathogens. A genome-mining PCR-based experiment targeting the genes encoding key enzymes involved in the biosynthesis of secondary metabolites indicated that the strain 10-10 showed the potential to produce tetracenomycin-like compounds. Further chemical investigation of the cultures of this strain led to the identification of two antibiotics, including a tetracenomycin (Tcm) analogs, Tcm X (1), and a tomaymycin derivative, oxotomaymycin (2). Their structures were identified by spectroscopic data analysis, including UV, 1D-NMR, 2D-NMR and MS spectra. Tcm X (1) showed moderate antibacterial activities against a number of drug-resistant pathogens, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococci (VRE) pathogens, with the MIC values in the range of 32-64 microg x mL(-1). In addition, 1 also displayed significant cytotoxic activities against human cancer cell lines, including HL60 (leukemia), HepG2 (liver), and MCF-7 (breast) with the IC 50 values of 5.1, 9.7 and 18.0 micromol x L(-1), respectively. Guided by the PCR-based gene sequence analysis, Tcm X (1) and oxotomaymycin (2) were identified from the genus of Saccharothrix and their 13C NMR data were correctly assigned on the basis of 2D NMR spectroscopic data analysis for the first time.


Subject(s)
Humans , Actinomycetales , Chemistry , Genetics , Anti-Bacterial Agents , Chemistry , Pharmacology , Antineoplastic Agents , Chemistry , Pharmacology , Benzodiazepinones , Chemistry , Pharmacology , Cell Line, Tumor , Data Mining , Methods , Drug Resistance, Bacterial , Enterococcus faecalis , Fermentation , Genomics , Inhibitory Concentration 50 , Marine Biology , Methicillin-Resistant Staphylococcus aureus , Microbial Sensitivity Tests , Molecular Structure , Naphthacenes , Chemistry , Pharmacology , Phylogeny , Staphylococcus epidermidis
6.
Acta Pharmaceutica Sinica ; (12): 688-694, 2011.
Article in Chinese | WPRIM | ID: wpr-348899

ABSTRACT

HIV-1 trans-activator of transcription (Tat) plays a critical role in HIV-1 transcription. Based on the beta-turn motif present in HIV-1 Tat, a series of novel benzodiazepine analogs were designed as beta-turn mimetics and prepared from p-chloro-nitrobenzene/2-phenylacetonitrile, p-toluidine/benzoyl chloride, or (Z)-7-nitro-5-phenyl-1H-benzo[e][1, 4]diazepin-2(3H)-one (nitrazepam) through different synthetic routes. Preliminary biological evaluation indicated that compound 30 exhibited inhibitory activity on HIV-1 tat-mediated LTR transcription with EC50 of 25.0 micromol x L(-1) and showed no obvious cytotoxic effects on TZM-BI cells under the concentration of 100 micromol x L(-1).


Subject(s)
Humans , Benzodiazepinones , Chemistry , Pharmacology , Cell Line, Tumor , HIV Long Terminal Repeat , Genetics , HIV-1 , Genetics , Transcription, Genetic , tat Gene Products, Human Immunodeficiency Virus
7.
Braz. j. pharm. sci ; 46(2): 297-303, Apr.-June 2010. tab
Article in English | LILACS | ID: lil-564897

ABSTRACT

A study was conducted on 22,158 special B prescriptions (notificações B) containing amphetamine-type anorectic drugs or benzodiazepines, obtained from compounding pharmacies or drugstores located in the city of Natal, RN, Brazil. The data obtained were compared with those from other Brazilian cities. Results showed that compounding pharmacies dispensed 85.4 percent of the prescriptions, indicating that these pharmacies filled out nearly 10 times more of these prescriptions than did the drugstores. The majority (83.5 percent) of B prescriptions issued for the compounding pharmacies were for women, where the female/male patient ratio ranged from 7.1/1.0 for mazindol to 10.3/1.0 for amfepramone. Similar results were obtained for the benzodiazepines with ratios of 1.9/1.0 for clonazepam to 15.6/1.0 for oxazepam. Omissions and mistakes were present in the B prescriptions, including missing information about the patient (in 49.6 percent of the documents) or about the pharmacies or drugstores (50.4 percent). There were cases where the name and/or CRM of the physician was lacking. It was noted that one medical doctor made out 1855 B prescriptions within one year. The same patient's name appeared on 138 prescriptions, and the same RG (identification card number) was present in 125 others. Comparison of Natal's data with those of several other Brazilian cities disclosed a striking similarity throughout Brazil, from Pelotas - Rio Grande do Sul State to Belem-Para State, revealing a practically identical medical/pharmaceutical behavior. This pattern of prescription/dispensation of amphetamine-type substances mostly to women for weight loss is therefore for cosmetic reasons. Consequently, there is an urgent need for an ethical review of this behavior.


Foram examinadas 22.158 notificações B contendo substâncias anoréticas tipo-anfetamina ou de benzodiazepínicos, obtidas de drogarias e de farmácias de manipulação. Os dados foram comparados com os de outras cidades do Brasil, obtendo-se uma visão nacional sobre o assunto. Os achados mostraram que as farmácias de manipulação, dispensaram 85,4 por cento das notificações, ou seja, as farmácias de manipulação atenderam cerca de 10 vezes mais do que as drogarias. A maioria (83,5 por cento) das notificações B nas farmácias de manipulação eram destinadas às mulheres sendo a relação entre pacientes femininos/masculinos de 7,1/1,0 no caso do mazindol e de 10,3/1,0 para a anfepramona. Dados semelhantes foram obtidos para os benzodiazepínicos: relação de 1,9/1,0 para o clonazepam até 15,6/1,0 para o oxazepam. Falhas e erros gritantes foram também observados no preenchimento das notificações B: ausência de dados de pacientes (em 49,6 por cento dos documentos), do fornecedor (50,4 por cento) etc. Houve casos de notificações sem o nome ou CRM do médico e um único médico prescreveu 1.855 notificações B; o nome de uma mesma compradora apareceu em 138 notificações e um mesmo RG em 125 outras. A comparação destes achados com os de outras cidades mostrou uma surpreendente semelhança, ao longo do país, desde Pelotas-RS até Belém-PA; evidenciando um padrão de comportamento médico/farmacêutico praticamente idêntico. Este padrão de prescrição para mulheres destina-se mais para uma finalidade cosmética (perda de peso) do que para uma real necessidade terapêutica. É necessária uma revisão ética sobre este problema, que também tem sido observado e igualmente criticado em vários países.


Subject(s)
Appetite Depressants , Benzodiazepinones , Drug Prescription of Special Control , Drug Prescriptions/statistics & numerical data , Brazil , Obesity/rehabilitation , Technology, Pharmaceutical
8.
RBCF, Rev. bras. ciênc. farm. (Impr.) ; 44(4): 613-620, out.-dez. 2008. graf, tab
Article in Portuguese | LILACS | ID: lil-507911

ABSTRACT

Os benzodiazepínicos estão entre as drogas mais freqüentemente prescritas em razão de suas propriedades ansiolíticas. O objetivo deste trabalho foi avaliar a influência do diazepam sobre a resposta inflamatória peritoneal aguda induzida por lipopolissacarídeo. Para tanto, camundongos Swiss foram tratados com diazepam (1 ou 10 mg/kg de peso), em dose única, por via subcutânea, uma hora antes do desafio intraperitoneal com lipopolissacarídeo bacteriano. Após 16 horas do desafio, os animais foram sacrificados, coletando-se os lavados peritoneais para determinação do número total de células e das subpopulações de mononucleares e polimorfonucleares, além da atividade de TNF-α e da porcentagem de macrófagos espraiados. Observou-se que o tratamento com diazepam, nas doses de 1 ou 10 mg/kg, reduziu significativamente a porcentagem de macrófagos estimulados por LPS e a liberação de TNF-α independente de estímulo. Houve também significativa redução da migração de leucócitos nos animais estimulados com LPS e tratados com 10 mg/kg de diazepam em relação aqueles não tratados. Concluímos que a administração do diazepam, em dose única, pode influenciar significativamente o influxo celular, a estimulação de macrófagos e a atividade de TNF-α na resposta inflamatória aguda induzida por LPS em camundongos, com possíveis implicações na eficiência da resposta anti-infecciosa.


Benzodiazepines are one of the most frequently prescribed drugs due to their anxiolytic properties. The aim of this study was to evaluate the effects of diazepam on lipopolysaccharide-induced peritoneal acute inflammatory responses. Swiss mice were treated with diazepam in a single dose of 1 or 10 mg/kg- subcutaneously 1 h before an intraperitoneal injection of lipopolysaccharide or sterile saline solution. The mice were killed 16 h after and the cells were washed from the peritoneal cavity to determine the total number of cells and the mononuclear and polimorfonuclear subpopulations, as well as the TNF-alpha activity and percentage of spread macrophages. Our results showed that the diazepam treatment (1 and 10 mg/kg) induced a significant reduction in the LPS-induced macrophage stimulation and TNF-α activity. Diazepam (10 mg/kg) also reduced the inflammatory cellular migration when compared to the control. It can be concluded that the diazepam treatment in a single dose is able to influence the inflammatory cellular influx, macrophage stimulation and TNF-α activity in the acute inflammatory response in mice, having possible implications on the anti-infectious response efficiency.


Subject(s)
Animals , Female , Mice , Benzodiazepinones/metabolism , Biological Assay/methods , Tumor Necrosis Factor-alpha/analysis , Lipopolysaccharides/pharmacology
9.
Chinese Journal of Oncology ; (12): 4-8, 2007.
Article in Chinese | WPRIM | ID: wpr-316257

ABSTRACT

<p><b>OBJECTIVE</b>To study the effect of gastrin on the mRNA and protein expression of urokinase-type plasminogen activator (u-PA) in human colon cancer cells and detect the role of p38 MAPK in this process.</p><p><b>METHODS</b>Lipofectin method was used to transfect pCR3. 1/CCK2R vector expressing gastrin receptor into a colon cancer cell line colo320. Gastrin and gastrin antagonist were used to up-regulate and down-regulate the signaling pathway, respectively. Human colon cancer colo320 cells and colo320/ CCK2,R cells were cultured and then stimulated with gastrin for different time; SB203580 was added into culture medium to prevent p38 kinase pathway before incubating with gastrin; Western blot and RT-PCR were used to examine the u-PA expression. Western blot was employed to detect p38 kinase phosphorylation.</p><p><b>RESULTS</b>Gastrin increased evidently the mRNA and protein expressions of u-PA and induced p38 kinase phosphorylation in colo320/CCK,R cells time-dependently. However, the extent of enhancement of u-PA and p38 MAPK expression in colo320 cells was much less than that in colo320/CCK2R cells. The gastrin antagonist L-365, 260 showed an effect of competitive inhibition on gastrin-induced u-PA expression and p38 kinase phosphorylation. The inhibitor SB203580 could sufficiently suppress gastrin-induced p38 kinase phosphorylation and significantly attenuate gastrin-induced u-PA mRNA and protein expressions in colo320/ CCK2 R cells in a dose-dependent manner.</p><p><b>CONCLUSION</b>Gastrin-gastrin receptor signal transduction pathway can obviously induce u-PA expression in human colon cancer cells via activating the phosphorylation of p38 kinase.</p>


Subject(s)
Humans , Benzodiazepinones , Pharmacology , Blotting, Western , Cell Line, Tumor , Colonic Neoplasms , Genetics , Metabolism , Pathology , Gastrins , Pharmacology , Gene Expression Regulation, Neoplastic , Genetic Vectors , Imidazoles , Pharmacology , Phenylurea Compounds , Pharmacology , Phosphorylation , Pyridines , Pharmacology , RNA, Messenger , Genetics , Receptor, Cholecystokinin B , Genetics , Metabolism , Reverse Transcriptase Polymerase Chain Reaction , Signal Transduction , Transfection , Urokinase-Type Plasminogen Activator , Genetics , Metabolism , p38 Mitogen-Activated Protein Kinases , Metabolism
10.
Acta Physiologica Sinica ; (6): 13-18, 2007.
Article in Chinese | WPRIM | ID: wpr-258694

ABSTRACT

Opening of mitochondrial permeability transition (MPT) pores leads to mitochondrial injury during oxidative stress. The peripheral benzodiazepine receptor (PBR) located at mitochondrial outer-membrane has been shown to be involved in several mitochondrial functions. In the present study, we used Ro5-4864, a PBR agonist, to test if activation of PBR could prevent MPT pore opening during Ca(2+) overloading. Cardiac mitochondria isolated from Sprague-Dawley rats were treated by 150 mmol/L Ca(2+) to induce MPT. Ro5-4864 (50, 100 and 200 micromol/L) was added into incubation buffer before adding 150 micromol/L Ca(2+). In additional group, atractyloside (ATR, 20 micromol/L), an opener of MPT pores was added 5 min before the addition of 100 micromol/L Ro5-4864. The change of absorbance at 520 nm was monitored with a spectrophotometer at 30 degrees C for 10 min. Western blot was used to detect cytochrome C loss. The mitochondrial membrane potential was monitored with the fluorescence dye JC-1. Ro5-4864 inhibited the decrease of absorbance at 520 nm compared to that in the untreated Ca(2+) group (P<0.01, P<0.05). In the presence of ATR, Ro5-4864 was not able to prevent MPT anymore. Opening of MPT pores by Ca(2+) decreased the content of cytochrome C in mitochondria, but increased cytochrome C content in cytosol. Ro5-4864 preserved cytochrome C content in mitochondria and led to less cytochrome C release to cytosol. ATR treatment reversed the protective effect of Ro5-4864 on cytochrome C content. Opening of MPT pores led to mitochondrial depolarization, whereas Ro5-4864 treatment maintained mitochondrial membrane potential. Thus, prevention of MPT by activation of PBR during calcium overloading maintains mitochondrial cytochrome C content and membrane potential. Activation of PBR during cardiac ischemia and reperfusion may be an alternative way for cardioprotection.


Subject(s)
Animals , Female , Male , Rats , Atractyloside , Pharmacology , Benzodiazepinones , Pharmacology , Carrier Proteins , Metabolism , Physiology , Membrane Potential, Mitochondrial , Physiology , Radiation Effects , Mitochondria, Heart , Physiology , Mitochondrial Membrane Transport Proteins , Physiology , Rats, Sprague-Dawley , Receptors, GABA-A , Metabolism , Physiology
11.
Cad. saúde pública ; 16(2): 351-62, abr.-jun. 2000. tab
Article in Portuguese | LILACS | ID: lil-265328

ABSTRACT

Apesar das recomendaçöes contra o uso prolongado de benzediazepínicos em idosos, as pesquisas indicam que o uso desses medicamentos aumenta com a idade. O padräo de uso de benzodiazepínicos e os fatores associados ao uso prolongado destes foram examinados com base em um questionário padronizado, aplicado a 634 mulheres com mais de sessenta anos, participantes de um centro de convivência para idosos no Rio de Janeiro, entre maio de 1992 e dezembro de 1995. A prevalência de uso de benzodiazepínicos na última quinzena foi estimada em 21,3 por cento (IC 95 por cento 1,1-24,5), e a prevalência de uso diário por 12 meses ou mais em 7,4 por cento (IC 95 por cento 5,4-9,4). Em uma análise multivariada, o número de medicamentos consumidos mostrou uma associaçäo importante e progressiva com o uso prolongado de benzodiazepínicos, com OR = 2,77 (IC 95 por cento 1,17-6,57) para aquelas que consomem entre quatro a seis medicamentos e OR = 7,62 (IC 95 por cento 3,18-18,26) para aquelas que consomem mais de sete medicamentos. Questöes de insônia (OR = 8,87 IC 95 por cento 2,53-31,06) e cefaléia (OR = 3,53 IC 95 por cento 1,82-6,89) também estiveram fortemente associadas a este padräo de uso.


Subject(s)
Aged , Benzodiazepinones/therapeutic use , Women , Universities
14.
Arq. neuropsiquiatr ; 55(4): 757-61, dez. 1997. tab
Article in English | LILACS | ID: lil-209374

ABSTRACT

Fifty children, 24 female and 26 male, with ages varying from 6 to 72 months (mean=23.7 m.) that experienced at least one febrile seizure (FS) entered a prospective study of intermittent therapy with clobazam. Cases with severe neurological abnormalities, progressive neurological disease, afebrile seizures, sympromatic seizures of other nature, or seizures during a central nervous system infection were excluded. Seizures were of the simple type in 25 patients, complex in 20 and unclassified in 5. The mean follow-up period was 7.9 months (range=1 to 23 m.), and the age at the first seizure varied from 5 to 42 months (mean=16.8 m.). Clobazam was administered orally during the febrile episode according to the child's weight: up to 5 kg, 5 mg/day; from 5 to 10 kg, 10 mg/day; from 11 to 15 kg, 15 mg/day, and over 15 kg, 20 mg/day. There were 219 febrile episodes, with temperature above 37.8 degrees Celsius, in 40 children during the study period. Twelve children never received clobazam and 28 received the drug at least once. Drug efficacy was measured by comparing FS recurrence in the febrile episodes that were treated with clobazam with those in which only antipyretic measures were taken. Ten children (20 percent) experienced a FS during the study period. Of the 171 febrile episodes treated with clobazam there were only 3 recurrences (1.7 percent), while of the 48 episodes treated only with antipyretic measures there were 11 recurrences (22.9 percent), a difference highly significant (p<0.0001). Adverse effects occurred in 10/28 patients (35.7 percent), consisting maily in vomiting, somnolene and hyperactivity. Only one patient had recurrent vomiting which lead to drug interruption. These effects did not necessarily ocurred in every instance the drug was administered, being present in one febrile episode and not in the others. We conclude that clonazepam is safe and efficacious in preventing FS recurrence. It may be an alternative to deazepam in the intermittent treatment of FS recurrence.


Subject(s)
Child , Child, Preschool , Infant , Female , Humans , Anticonvulsants/therapeutic use , Benzodiazepinones/therapeutic use , Seizures, Febrile , Anticonvulsants , Benzodiazepinones , Prospective Studies , Recurrence
15.
Yonsei Medical Journal ; : 405-411, 1996.
Article in English | WPRIM | ID: wpr-213087

ABSTRACT

To determine the adequate models for studying the functions of pancreatic acinar cells, secretory responses to CCK and to CCK receptor antagonist, L-364, 718 were examined in freshly isolated cells and confluent monolayer cells. The results showed that as CCK concentration increased, releases of amylase and lipase increased dose-dependently reaching a maximum at 10(-9) M in acinar cells cultured in serum-containing media as well as in serum-free media. Acinar response to CCK was partially inhibited by L-364, 718, L-364, 718 itself had no effect on the releases of both amylase and lipase. Confluent monolayer of acinar cells released relatively low levels of enzymes and exhibited less response to CCK. In conclusion, short-term culture of acinar cells would be suitable to study the regulation of pancreatic enzyme secretion, and serum factors do not influence acina response to the secretagogues. However, confluency of the acinar cells resulted in the loss of their secretory potential in the aspect of amylase and lipase release.


Subject(s)
Male , Rats , Amylases/metabolism , Animals , Benzodiazepinones/pharmacology , Cells, Cultured , Cholecystokinin/pharmacology , Devazepide , Dose-Response Relationship, Drug , Hormone Antagonists/pharmacology , Lipase/metabolism , Pancreas/cytology , Rats, Sprague-Dawley , Receptors, Cholecystokinin/antagonists & inhibitors
16.
Acta physiol. pharmacol. ther. latinoam ; 46(4): 247-55, 1996. graf
Article in English | LILACS | ID: lil-187394

ABSTRACT

Diazepam and Ro5-4864 effects on noradrenaline-induced rat vas deferend contractions were studied. We investigated whether central or peripheral type benzodiazepine receptors were involved, by studying the effects of the selective central or peripheral benzodiazepine receptor antagonists, flumazenil (Ro 151788) or PK 11195 respectively. Diazepam interactions with GABA, adenosine, theophylline, and hypercalcic medium (3.5mM) were studied. Also, we investigate diazepam effect on KC1 depolarized vas deferens. Results showed that diazepam (10(-4) to 1.7x10(-4) M)) and Ro 5-4864 (10(-5) to 5.5x10(-5)M) inhibited NA-induced vas deferens contractions and that neither flumazenil nor PK 11195 antagonized diazepam or Ro 5-4864 inhibitory effects respectively. GABA, adenosine and theophylline did not modify neither NA vas deferens response nor diazepam inhibitory action. Diazepam effect was significantly reduced in an 3.5 mM calcium medium and KC1 vas deferense was inhibited by diazepam 1.3x10(-5) and 1.3 x 10(-4) M. It is concluded that in rat vas deferens diazepam effect seems to be related with calcium mobilization.


Subject(s)
Rats , Animals , Male , Adenosine/pharmacology , Adrenergic alpha-Agonists/pharmacology , Benzodiazepinones/pharmacology , Calcium Channels/drug effects , Calcium/physiology , Diazepam/pharmacology , GABA Agents/pharmacology , In Vitro Techniques , Norepinephrine/pharmacology , Potassium Chloride/pharmacology , Vas Deferens/drug effects , Rats, Wistar
17.
Arq. neuropsiquiatr ; 51(1): 66-71, mar.-maio 1993. tab
Article in Spanish | LILACS | ID: lil-126157

ABSTRACT

Se presenta el estudio de 20 pacientes en edad pediátrica con diagnóstico de epilepsia de difícil control, en los cuales fue usado el clobazan como terapia anticonvulsivante coadyuvante, vistos entre Enero-1986 y Julio-1990 en el consultorio externo de Neuropediatría del Hospital General Base Cayetano Heredia y práctica privada, con un seguimiento entre 6 y 5 meses. La edad de inicio para la epilepsia fue en promedio 22 meses y la forma mas frecuente los sindromes de epilepsia generalizada, tanto secundaria como idiopática. Se obtuvo disminución de frecuencia de crisis en rango significativo en 60// de los pacientes con control completo en 35// del total, habiendose encontrado los mejores resultados en epilepsias generalizadas secundarias tipo Lennox-Gastaut y West. Se encontro fenómeno de tolerancia en 25// y efecto psicotrópico en tres pacientes. Sugerimos el uso de esta 1,5 benzodiazepina en epilepsias de dificil control en niños, en nuestro medio


Subject(s)
Humans , Male , Female , Infant , Child, Preschool , Child , Benzodiazepinones/administration & dosage , Epilepsy/drug therapy , Benzodiazepinones/therapeutic use , Drug Combinations , Drug Evaluation , Electroencephalography , Epilepsy/blood , Epilepsy/etiology , Follow-Up Studies
19.
Braz. j. med. biol. res ; 24(9): 865-81, Sept. 1991. tab
Article in English | LILACS | ID: lil-102093

ABSTRACT

1. Recent evidence indicates that post-training memory processes are down-regulated by benzodiazepine/GABA-A systems inthe amygdala, septum and hippocampus. Havituation and avoidance learning are accompanied by a decrease of benzodiazepine-like immunoreactivity in the three structures, explainable by a release of benzodiazepines. Immediate post-training microinjection of the benzodiazepine antagonist flumazenil into the hippocampus enhances retention of habituation. The post-training administration of glumazenil into any of the three structures enhances relation of avoidance learning. 2. The mode of operation of these systems was studied in detail in the amygdala using avoidance paradigms. The release of endogenous benzodiazepines during and particularly after training enhances sensitivity of local GABA-A receptors to muscimol, activation of the GABA-A receptors opens chloride channels that can be selectively blocked by picrotoxin and by Ro-4864. Training enhances, and fluazenil reduces, sensitivity of the amygdala to the amnestic effect of locally injected muscimol by a factor of 100. Post-training intra-amygdala administration of picrotoxin or Ro5-4864 enhances retention. 3. These findings suggest that the endogenous benzoidiazepine/GABA-A mechanisms that down-regulate memory int he amygdala, septum and hippocampus are activated in response to the anxiety and/or stress associated with each task. Memory lability which occurs in the psot-training period and characterizes consolidation would thus be a consequence of the brain's response to anxiety or stress


Subject(s)
Animals , Rats , Benzodiazepines , Cerebrum/physiology , Memory , Avoidance Learning , Benzodiazepines/antagonists & inhibitors , Benzodiazepinones/pharmacology , Convulsants/pharmacology , Down-Regulation , Flumazenil/pharmacology , Habituation, Psychophysiologic , Muscimol/pharmacology , Brain Chemistry
20.
Indian J Exp Biol ; 1990 Dec; 28(12): 1160-5
Article in English | IMSEAR | ID: sea-56887

ABSTRACT

Adenosinergic agents such as adenosine, 2-chloro-adenosine, N6-cyclohexyladenosine produced dose-dependent protective effect against DMCM- and Ro 5-4864-induced convulsions and mortality. N6-cyclohexyladenosine produced most significant protective e ect against Ro 5-4864-induced convulsions whereas 2-chloroadenosine was more effective than N6-cyclohexyladenosine in antagonising DMCM-induced convulsions. Pretreatment of animals with subprotective doses of adenosine and dipyridamole significantly prolonged the latencies for the onset of myoclonic jerks and convulsions due to both DMCM and Ro 5-4864. DMCM and Ro 5-4864-induced mortality rate was also significantly reduced by pretreatment with subprotective doses of adenosine and dipyridamole. Similarly, subprotective doses of adenosine and diazepam further delayed the latencies for myoclonic jerks and convulsions due to DMCM and Ro 5-4864 treatment. The results suggest that adenosine and adenosine receptor agonists, 2-chloroadenosine and N6-cyclohexyladenosine are protective against both DMCM- and Ro 5-4864-induced convulsions. It is suggested that adenosinergic agents via activation of central A1 adenosine receptors may modulate the convulsant effects mediated by DMCM and Ro 5-4864. This study further supports the notion that adenosinergic mechanisms mediate neuroprotective e ects in the central nervous system.


Subject(s)
Adenosine/analogs & derivatives , Animals , Benzodiazepines/pharmacology , Benzodiazepinones/pharmacology , Carbolines/pharmacology , Convulsants , Female , Male , Mice
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