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1.
J Air Waste Manag Assoc ; 73(12): 902-913, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37843284

RESUMO

The concentration of surface air methane (CH4) measured in parts per million by volume (ppmv) near the soil/atmosphere interface should, in theory, have a positive correlation with surface methane emissions fluxes, measured in grams per square meter per day (gm-2d-1). Some researchers suggest that CH4 flux can be reasonably inferred from simple measurements of CH4 concentrations near the landfill surface. Ground-based and drone-based surface emissions monitoring (SEMs) were performed at several municipal solid waste landfills as tracer correlation method (TCM) testing was being used to measure total methane emissions from the same landfills. The TCM data and SEM data were used to establish a new simple correlation to convert surface methane concentrations in ppmv to localized surface methane emission flux in gm-2d-1.The SEM data obtained from ten ground and drone monitoring campaigns were log-transformed and geospatially treated using inverse distance weighting to the power of 2 to predict methane surface concentrations in the entire footprint of the SEM measurements area. The developed new correlation equation was then used to convert every predicted surface methane concentration to an emissions flux. The total estimate of surface emissions from the entire landfill was obtained by integrating the predicted fluxes over the area of the footprint of the SEM measurement area. The use of the new developed correlation resulted in higher total emissions estimates than other correlations reported in the literature and should be considered more conservative. Not including other factors, the proposed approach provides estimate of total methane emissions with a coefficient of variation of 20%. This study introduces a novel approach that utilizes a developed correlation between surface methane concentrations and surface emissions fluxes to estimate total methane emissions from municipal solid waste landfills or from a specified area. This study provides an additional use of the quarterly SEM data.Implications: The proposed approach provides an occasion for additional use of the easily obtainable quarterly SEMs data that can be performed by most landfills. The SEMs data are the most abundant landfill methane concentrations data. This approach gives them more benefit for the user. It is intended to convert ambient air concentrations to some estimates of surface emissions that can help landfill owners with decision making such as remediation activities or adjustments of their gas collection a systems.


Assuntos
Poluentes Atmosféricos , Eliminação de Resíduos , Resíduos Sólidos , Eliminação de Resíduos/métodos , Metano/análise , Poluentes Atmosféricos/análise , Monitoramento Ambiental/métodos , Instalações de Eliminação de Resíduos
2.
Invest. clín ; 64(1): 15-27, mar. 2023. graf
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1534680

RESUMO

Resumen La dopamina 1, está implicada en trastornos neurodegenerativos que afectan al sistema nervioso central (SNC) tales como la enfermedad de Parkinson, entre otros. Aunque no se dispone aún de ningún fármaco capaz de prevenir, detener o curar la progresión de estas enfermedades, son numerosos los compuestos que han sido diseñados, sintetizados y evaluados farmacológicamente, que han aportado las generalizaciones farmacofóricas del receptor dopaminérgico, necesarias para la búsqueda de un fármaco capaz de mejorar o curar estas patologías. Los derivados 2-aminoindano-N-aralquílicos han mostrado tener actividad selectiva en el sistema dopaminérgico central, de modo tal que los compuestos clorhidratos de N-[(2,4-diclorofenil)-1-metil- etil]-2-aminoindano 2 y N-[(3,4-diclorofenil)-1-metil-etil]-2-aminoindano 3 demostraron tener actividad agonística mediada por mecanismos dopaminérgicos centrales. Con el propósito de contribuir en la búsqueda de nuevos fármacos que permitan restablecer la homeostasis de la transmisión dopaminérgica en la enfermedad de Parkinson, el compuesto N-2,6-dicloro-aralquil-2-aminoindano 4 fue diseñado a través de estrategias de la química medicinal, que contienen las aproximaciones farmacofóricas de los profármacos. La evaluación farmacológica del compuesto 4, en la conducta estereotipada en ratas macho de la cepa Sprague Dawley, demostró tener actividad agonística a través de la activación de los mecanismos dopaminérgicos centrales y mostró mayor selectividad en las respuestas de conductas estereotipadas propias de los ganglios basales sobre las respuestas conductuales propias de las estructuras límbicas.


Abstract Dopamine 1 is involved in neurodegenerative disorders affecting the central nervous system (CNS), such as Parkinson's disease. Despite the absence of some available drugs capable of preventing, stopping or curing the progression of such diseases, there are numerous compounds designed, synthesized, and pharmacologically tested which give rise to pharmacophoric generalizations about the dopaminergic receptor required for the search of a drug able to improve or cure those pathologies. N-aralkyl-2-aminoindane derivatives have shown selective activity in the central dopaminergic system. Both the N-[(2,4-dichlorophenyl)-1-methyl-ethyl]-2-aminoindane hydrochloride 2 and N-[(3,4-dichlorophenyl)-1-methyl-ethyl]-2-aminoindane hydrochloride 3 showed an agonistic activity mediated by central dopaminergic mechanisms. To contribute to the search of new drugs able to re-establish homeostasis in the dopaminergic transmission in Parkinson's disease, the compound N-2,6- dichloro-aralkyl-2-aminoindane 4 was designed through medicinal chemistry strategies that contain pharmacophoric approximations of prodrugs. The pharmacological evaluation of compound 4 in the stereotyped behavior of male Sprague Dawley rats showed agonistic activity through the activation of central dopaminergic mechanisms and a higher selectivity in the responses of stereo- typed behavior characteristic of the basal ganglia over the typical responses from limbic structures.

3.
Birth Defects Res ; 114(20): 1364-1375, 2022 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-36177489

RESUMO

BACKGROUND: We aimed to analyze recent infant and neonatal mortality from congenital heart defects (CHD) in Costa Rica, a middle-income country where CHD mortality was above expectations. METHODS: A descriptive analysis of infant and neonatal mortality rates from CHD (IMR-CHD and NMR-CHD) during 2000-2019 was performed, according to province, sex, specific CHD, and sub-period, using data from the National Institute of Statistics and Censuses. We used joinpoint regression to identify any calendar-year where a significant change in trend occurred; the average annual percent change (AAPC) was determined. Using Poisson regression, marginal means and mortality ratios (MR) for IMR-CHD and NMR-CHD by sub-period (2000-2006-referent-, 2007-2013, 2014-2019) were estimated and compared using Wald's chi-square tests (α ≤ .05). RESULTS: During 2000-2019, CHD accounted for 12% of overall infant mortality. IMR-CHD and NMR-CHD decreased linearly over the study period (AAPC = -3.4; p < .01). IMR-CHD decreased by 41%, from 13.6 per 10,000 in 2000-2006 (13.4% of infant mortality) to 8.1 per 10,000 in 2014-2019 (10% of infant mortality) (MR = 0.59; 95% confidence intervals [CI] = 0.52-0.68). NMR-CHD decreased by 38%, from 7.9 per 10,000 in 2000-2006 (11.1% of neonatal mortality) to 4.9 per 10,000 in 2014-2019 (7.9% of infant mortality) (MR = 0.59; 95% CI = 0.52-0.68). Male presented significantly higher NMR-CHD. The main causes of mortality (2014-2019) were total anomalous pulmonary venous connections, hypoplastic left heart syndrome, and double inlet ventricle. CONCLUSIONS: IMR-CHD, NMR-CHD, and their proportional contribution to mortality by all causes and by birth defects decreased significantly, demonstrating that all improvements implemented in the last decades have yielded favorable results.


Assuntos
Cardiopatias Congênitas , Mortalidade Infantil , Lactente , Recém-Nascido , Humanos , Masculino , Costa Rica/epidemiologia , Renda
4.
Molecules ; 27(17)2022 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-36080388

RESUMO

The coexistence of leishmaniasis, Chagas disease, and neoplasia in endemic areas has been extensively documented. The use of common drugs in the treatment of these pathologies invites us to search for new molecules with these characteristics. In this research, we report 16 synthetic chalcone derivatives that were investigated for leishmanicidal and trypanocidal activities as well as for antiproliferative potential on eight human cancers and two nontumor cell lines. The final compounds 8−23 were obtained using the classical base-catalyzed Claisen−Schmidt condensation. The most potent compounds as parasiticidal were found to be 22 and 23, while compounds 18 and 22 showed the best antiproliferative activity and therapeutic index against CCRF-CEM, K562, A549, and U2OS cancer cell lines and non-toxic VERO, BMDM, MRC-5, and BJ cells. In the case of K562 and the corresponding drug-resistant K562-TAX cell lines, the antiproliferative activity has shown a more significant difference for compound 19 having 10.3 times higher activity against the K562-TAX than K562 cell line. Flow cytometry analysis using K562 and A549 cell lines cultured with compounds 18 and 22 confirmed the induction of apoptosis in treated cells after 24 h. Based on the structural analysis, these chalcones represent new compounds potentially useful for Leishmania, Trypanosoma cruzi, and some cancer treatments.


Assuntos
Doença de Chagas , Chalcona , Leishmania , Leishmaniose , Tripanossomicidas , Trypanosoma cruzi , Doença de Chagas/tratamento farmacológico , Chalcona/farmacologia , Humanos , Leishmaniose/tratamento farmacológico , Naftalenos/uso terapêutico , Relação Estrutura-Atividade , Tripanossomicidas/química
5.
Parasitol Res ; 121(1): 441-451, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34778907

RESUMO

A series of heterocyclic chloroquine hybrids containing either a ß-phenethylamine fragment or a 2-aminoindane moiety were synthesized and screened in vitro as inhibitors of ß-hematin formation and in vivo for their antimalarial activity against chloroquine-sensitive strains of Plasmodium berghei ANKA. Although these new compounds were not found to be more active than chloroquine in vivo, all new compounds significantly reduced heme crystallization with IC50 values < 1 µM. Compounds 12 and 13 were able to inhibit heme crystallization with IC50 values of 0.39 ± 0.09 and 0.48 ± 0.02 µM, respectively, and these values were comparable to that of chloroquine with an IC50 value of 0.18 ± 0.03. It was also determined that the physicochemical and pharmacokinetic properties were moderately favorable after in silico evaluation, derivatives 8 and 10 did not present hepatotoxicity, and the in vitro hemolytic activity against red blood cells was found to be low. Spectral (infrared, nuclear magnetic resonance, and elemental analysis) data for all final compounds were consistent with the proposed structures.


Assuntos
Antimaláricos , Malária , Antimaláricos/uso terapêutico , Cloroquina/uso terapêutico , Humanos , Malária/tratamento farmacológico , Plasmodium berghei , Plasmodium falciparum
6.
Molecules ; 26(22)2021 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-34834070

RESUMO

Several methoxybenzo[h]quinoline-3-carbonitrile analogs were designed and synthesized in a repositioning approach to developing compounds with anti-prostate cancer and anti-Chagas disease properties. The compounds were synthesized through a sequential multicomponent reaction of aromatic aldehydes, malononitrile, and 1-tetralone in the presence of ammonium acetate and acetic acid (catalytic). The effect of the one-pot method on the generation of the target product has been studied. The compounds were in vitro screened against bloodstream trypomastigotes of T. cruzi (NINOA and INC-5 strains) and were most effective at showing a better activity profile than nifurtimox and benznidazole (reference drugs). A study in silico on absorption, distribution, metabolism, excretion, and toxicity (ADME/Tox) profiling to help describe the molecular properties related to the pharmacokinetic aspects in the human body of these compounds was reported. In addition, X-ray data for the compound 2-Amino-5,6-dihydro-4-(3-hydroxy-4-methoxy-phenyl)-8-methoxybenzo[h]quinoline-3-carbonitrile 6 was being reported. Spectral (IR, NMR, and elemental analyses) data on all final compounds were consistent with the proposed structures.


Assuntos
Doença de Chagas , Simulação por Computador , Quinolinas , Tripanossomicidas , Trypanosoma cruzi/crescimento & desenvolvimento , Desenho de Fármacos , Humanos , Quinolinas/síntese química , Quinolinas/química , Quinolinas/farmacologia , Relação Estrutura-Atividade , Tripanossomicidas/síntese química , Tripanossomicidas/química , Tripanossomicidas/farmacologia
7.
Arch Pharm (Weinheim) ; 354(8): e2100092, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33928662

RESUMO

This study describes the direct synthesis of 2-amino-4-(phenylsubstituted)-5H-indeno[1,2-b]pyridine-3-carbonitrile derivatives 5-21, through sequential multicomponent reaction of aromatic aldehydes, malononitrile, and 1-indanone in the presence of ammonium acetate and acetic acid (catalytic). The biological study showed that compound 10 significantly impeded proliferation of the cell lines PC-3, LNCaP, and MatLyLu. The antimetastatic effects of compound 10 could be related with inhibition of MMP9 in the PC-3 and LNCaP human cell lines. On the basis of a study of the structure-activity relationship of these compounds, we propose that the presence of two methoxy groups at positions 6 and 7 of the indeno nucleus and a 4-hydroxy-3-methoxy phenyl substitution pattern at position 4 of the pyridine ring is decisive for these types of molecules to exert very good antiproliferative and antimetastatic activities.


Assuntos
Antineoplásicos/farmacologia , Indenos/farmacologia , Neoplasias da Próstata/tratamento farmacológico , Piridinas/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Humanos , Indenos/síntese química , Indenos/química , Masculino , Metástase Neoplásica/prevenção & controle , Células PC-3 , Neoplasias da Próstata/patologia , Piridinas/síntese química , Piridinas/química , Relação Estrutura-Atividade
8.
J Vector Ecol ; 46(1): 82-95, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-35229585

RESUMO

American trypanosomiasis is a zoonosis caused by the parasite Trypanosoma cruzi and is transmitted mainly by blood-sucking insects belonging to the subfamily Triatominae. The importance of this parasite lies in its wide geographical distribution, high morbidity, and the fact that there has not yet been an effective treatment or vaccine. Previous studies have detailed the interactions between different triatomine species and T. cruzi strains. However, the factors necessary to establish infection in triatomines have not yet been fully elucidated. Furthermore, it is postulated that the coexistence between the parasite and triatomines could modulate the susceptibility to infection in these insects. Accordingly, in this study, we evaluated the susceptibility to T. cruzi infection in the species Triatoma (Meccus) pallidipennis, Triatoma barberi, and Triatoma lecticularia, which were infected with Ninoa, H8, INC-5, Sontecomapan, and Hueypoxtla strains. The criteria used to establish susceptibility were the amount of blood ingested by the insects, percentage of infected triatomines, concentration of parasites in feces, and percentage of metacyclic trypomastigotes in feces. These parameters were analyzed by fresh examination and differential count with Giemsa-stained smears. Our main findings suggest the following order of susceptibility concerning infection with T. cruzi: T. lecticularia > T. barberi > T. (Meccus) pallidipennis. Furthermore, the study concludes that an increased susceptibility to infection of triatomines that share the same geographic region with different strains of T. cruzi is not always a fact.


Assuntos
Doença de Chagas , Triatoma , Triatominae , Trypanosoma cruzi , Animais , Doença de Chagas/parasitologia , Insetos Vetores/parasitologia , Triatoma/parasitologia , Triatominae/parasitologia
9.
Front Microbiol ; 11: 559660, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33133034

RESUMO

In a recent work we demonstrated that Trypanosoma cruzi trypomastigotes change their motility patterns in the presence of mammalian cells, that the extent of the changes depends on the cell line, and that this extent is positively correlated with the efficiency with which parasites invade the different cell lines. These results open the question of what cellular characteristics are relevant for parasite identification and invasion. In the present work, we tackled such question. We performed infection-kinetics experiments on various cell lines, and developed a mathematical model to simulate the experimental outcomes. An analysis of the cell-parasite mechanisms included in the model, together with the parameter values that allowed it to replicate the experimental results, suggests that a process related to the cell replication rate may strongly influence the parasite invasion efficiency, and the infection dynamics in general.

10.
Sci Rep ; 10(1): 15894, 2020 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-32985548

RESUMO

Numerous works have demonstrated that trypanosomatid motility is relevant for parasite replication and sensitivity. Nonetheless, although some findings indirectly suggest that motility also plays an important role during infection, this has not been extensively investigated. This work is aimed at partially filling this void for the case of Trypanosoma cruzi. After recording swimming T. cruzi trypomastigotes (CL Brener strain) and recovering their individual trajectories, we statistically analyzed parasite motility patterns. We did this with parasites that swim alone or above monolayer cultures of different cell lines. Our results indicate that T. cruzi trypomastigotes change their motility patterns when they are in the presence of mammalian cells, in a cell-line dependent manner. We further performed infection experiments in which each of the mammalian cell cultures were incubated for 2 h together with trypomastigotes, and measured the corresponding invasion efficiency. Not only this parameter varied from cell line to cell line, but it resulted to be positively correlated with the corresponding intensity of the motility pattern changes. Together, these results suggest that T. cruzi trypomastigotes are capable of sensing the presence of mammalian cells and of changing their motility patterns accordingly, and that this might increase their invasion efficiency.


Assuntos
Movimento Celular/fisiologia , Doença de Chagas/parasitologia , Trypanosoma cruzi/fisiologia , Animais , Linhagem Celular , Humanos , Camundongos
11.
Acta méd. costarric ; 60(4): 172-181, oct.-dic. 2018. tab, graf
Artigo em Espanhol | LILACS | ID: biblio-973525

RESUMO

Resumen Justificación: alrededor del mundo las cardiopatías congénitas ocupan las primeras causas de mortalidad infantil. En Costa Rica son el grupo de defectos congénitos más frecuentes, con una prevalencia de 6 x 1000 nacimientos (IC95 % 5 -7 x 1000 nacimientos), que representan cerca del 13 % de la mortalidad infantil. El objetivo del estudio fue analizar la supervivencia a cinco años de edad de los niños nacidos con defectos cardiacos en Costa Rica. Métodos: se analizó una cohorte retrospectiva de 543 niños nacidos con cardiopatías congénitas entre enero de 2006 y junio de 2007 en Costa Rica; utilizando los registros médicos y la base nacional de defunciones se brindó un seguimiento mínimo de 5 años en todos los casos. Se obtuvo estimados de supervivencia de Kaplan-Meier al mes, año y cinco años de vida, y se evaluaron factores pronóstico empleando el modelo de riesgos proporcionales de Cox. Se estimaron riesgos relativos crudos y ajustados con su respectivo intervalo de confianza del 95 %. Resultados: la prevalencia de cardiopatías congénitas fue de 5,14 por 1000 nacimientos (IC95 % 4,73-5,60; n: 543) para el período de estudio. La mortalidad fue del 27,9 % (IC 95 % = 24,21- 31,73; n: 152). La supervivencia acumulada al año y cinco años fue del 76,1 % y el 72,4 %, respectivamente, frente al 99,1 % y 98,8 % sobrevivencia de la cohorte de nacimientos nacional (con y sin cardiopatía) de la misma edad. La edad temprana al diagnóstico, severidad, cardiopatías congénitas múltiples y la asociación de defectos congénitos mayores se asociaron significativamente (p≤0,05) a una menor probabilidad de supervivencia. Conclusiones: la cohorte de niños con cardiopatías congénitas estudiada presentó una alta mortalidad al año y cinco años. El peor pronóstico de supervivencia fue para aquellos que necesitaban una cirugía cardíaca a temprana edad.


Abstract Background: Around the world, congenital heart defects occupy the first causes of infant mortality. In Costa Rica heart malformations are the most frequent group of birth defects, with a prevalence of 6 x 1000 births (95% CI 5-7 x 1000 births). They represent about 13% of infant mortality and are. the leading cause of death due to birth defects. The objective of this study is to analyze the survival of children with CC in Costa Rica. Methods: A retrospective cohort of 543 children born with CC between January 2006 and June 2007 in Costa Rica was analyzed. Using medical records and the national database of deaths, a minimum follow-up of 5 years was given in all cases. Kaplan-Meier survival estimates were obtained at month, year and five years of life. Prognostic factors were assessed using the Cox proportional hazards model. Raw and adjusted relative risks were estimated with their respective 95% confidence interval. Results: The prevalence of CC was 5.14 per 1000 births (95% CI: 4.73-5.60; n: 543) for the study period. Mortality was 27.9% (95% CI: 24.21-31.73; n: 152). Cumulative survival at one year and five years was 76.1% and 72.4%, respectively, compared to 99.1% and 98.8% of survival in the same national birth cohort (with and without CC), at the same age. Early age at diagnosis, severity, multiple CC and the association of major BD were significantly associated (p≤0.05) with a lower probability of survival. Conclusions: The cohort of children with congenital heart disease studied had a high mortality rate at one year and five years. The worst prognosis of survival was for those who needed cardiac surgery at an early age.


Assuntos
Recém-Nascido , Lactente , Pré-Escolar , Criança , Costa Rica , Cardiopatias Congênitas/mortalidade
12.
PLoS One ; 10(11): e0142478, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26544863

RESUMO

The present work is aimed at characterizing the motility of parasite T. cruzi in its epimastigote form. To that end, we recorded the trajectories of two strains of this parasite (a wild-type strain and a stable transfected strain, which contains an ectopic copy of LYT1 gene and whose motility is known to be affected). We further extracted parasite trajectories from the recorded videos, and statistically analysed the following trajectory-step features: step length, angular change of direction, longitudinal and transverse displacements with respect to the previous step, and mean square displacement. Based on the resulting observations, we developed a mathematical model to simulate parasite trajectories. The fact that the model predictions closely match most of the experimentally observed parasite-trajectory characteristics, allows us to conclude that the model is an accurate description of T. cruzi motility.


Assuntos
Trypanosoma cruzi/fisiologia , Animais , Doença de Chagas/parasitologia , Flagelos/fisiologia , Interações Hospedeiro-Parasita , Humanos , Processamento de Imagem Assistida por Computador , Modelos Biológicos , Movimento , Organismos Geneticamente Modificados , Trypanosoma cruzi/genética , Trypanosoma cruzi/crescimento & desenvolvimento
13.
Invest. clín ; 56(2): 137-154, jun. 2015. ilus, graf
Artigo em Espanhol | LILACS | ID: biblio-841074

RESUMO

En las últimas décadas son muchos los compuestos con actividad dopaminérgica central que se han diseñado, sintetizado y evaluado farmacológicamente. A pesar de ello, no se ha logrado obtener un fármaco capaz de mejorar o curar las patologías que involucran la regulación dopaminérgica en el sistema nervioso central tales como la Enfermedad de Parkinson y la esquizofrenia, entre otras. Tomando en consideración el término de “farmacóforo atípico” y a partir del compuesto 5, se incorporó el fragmento aralquil y se sintetizaron los compuestos 10, 11, 13a-h y 14a-h. Tanto los compuestos 10 y 13a-h bajo su forma metoxilada como los compuestos 11 y 14a-h bajo su forma fenólica, fueron evaluados farmacológicamente para determinar su actividad agonística y antagonística sobre el sistema dopaminérgico central. Para ello se determinó el efecto de la inyección intracerebroventricular de dichos compuestos sobre el balance hidromineral y la conducta estereotipada en ratas. Los resultados de la evaluación farmacológica preliminar muestran una acción central a través de mecanismos dopaminérgicos, siendo que los compuestos 10, 11, 13d-h y 14a mostraron respuestas como agonistas, mientras que los compuestos 14b-h, tuvieron respuestas como antagonistas.


In recent decades, many compounds with central dopaminergic activity have been designed, synthesized and evaluated pharmacologically. However, it has not been possible to obtain a drug able to improve or cure diseases involving dopaminergic regulation in the central nervous system, such as Parkinson’s disease and schizophrenia, among others. Taking into consideration the term “atypical pharmacophore” and from the compound 5, the aralkyl fragment was incorporated, and the compounds 10, 11, 13a-h and 14a-h were synthesized. Both the compounds 10 and 13a-h under its methoxylated form and the compounds 11 and 14a-h under the phenolic form, were evaluated to determine their pharmacologically agonistic and antagonistic effects on central dopaminergic activity. For this, the effect of intracerebroventricular injection of said compounds on the hydromineral balance and stereotyped behavior in rats, was determined. The results of the preliminary pharmacological evaluation show a centrally acting action through dopamine mechanisms, in which the compounds 10, 11, 13d-h and 14a showed responses as agonists, whereas compounds 14b-h, had responses as antagonists.


Assuntos
Animais , Masculino , Ratos , Comportamento Estereotipado/efeitos dos fármacos , Antagonistas de Dopamina/farmacologia , Agonistas de Dopamina/farmacologia , Indanos/farmacologia , Relação Estrutura-Atividade , Comportamento Animal/efeitos dos fármacos , Ratos Sprague-Dawley , Antagonistas de Dopamina/síntese química , Antagonistas de Dopamina/química , Agonistas de Dopamina/síntese química , Agonistas de Dopamina/química , Indanos/síntese química , Indanos/química , Injeções Intraventriculares
14.
Invest New Drugs ; 30(4): 1426-33, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21748298

RESUMO

Quinolines and acrylates are chemical compounds which were previously described as potential antitumor agents. In this study, a series of seven new quinolinyl acrylate derivatives were synthesized and evaluated against human prostate cancer cells PC-3 and LNCaP in vitro and in vivo. The most effective compound (E)-methyl 2-(7-chloroquinolin-4-ylthio)-3-(4 hydroxyphenyl) acrylate reduced the viability in both cell lines in a time- and dose-dependent manner. Inhibitory effects were also observed on the adhesion, migration, and invasion of the prostate cancer cells as well as on the neoangiogenesis, clonogenic and MMP-9 activity. The effect in vivo was studied in PC-3 xenografts in nude mice. The results were concordant with the in vitro effects and showed decreased tumor growth in treated animals compared to controls. The study suggests the multi-target efficacy of the quinolinyl derivate against human prostate cancer cells and supports its potential therapeutic usefulness.


Assuntos
Acrilatos/uso terapêutico , Neoplasias da Próstata/tratamento farmacológico , Quinolinas/uso terapêutico , Acrilatos/síntese química , Acrilatos/química , Acrilatos/farmacologia , Inibidores da Angiogênese/farmacologia , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Adesão Celular/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Galinhas , Células Clonais , Relação Dose-Resposta a Droga , Humanos , Concentração Inibidora 50 , Masculino , Metaloproteinase 9 da Matriz/metabolismo , Camundongos , Camundongos Nus , Invasividade Neoplásica , Neovascularização Fisiológica/efeitos dos fármacos , Neoplasias da Próstata/enzimologia , Neoplasias da Próstata/patologia , Quinolinas/síntese química , Quinolinas/química , Quinolinas/farmacologia , Fatores de Tempo , Ensaios Antitumorais Modelo de Xenoenxerto
15.
Rev Panam Salud Publica ; 30(1): 31-8, 2011 Jul.
Artigo em Espanhol | MEDLINE | ID: mdl-22159648

RESUMO

OBJECTIVE: Characterize the population of children born with congenital heart disease (CHD) in Costa Rica and evaluate the country's registry processes. METHODS: Exploratory observational study that included all children with CHD diagnosed at the National Children's Hospital between 1 May 2006 and 1 May 2007. Considering children under 1 year of age and their respective birth cohort, prevalence was estimated by sex, type of heart disease, age at diagnosis, maternal age, habitual residence, and associated extracardiac malformations, with 95% confidence intervals (95% CI). The data was compared with those of the Congenital Disease Registry Center (CREC). RESULTS: During the period studied, 534 cases with CHD were diagnosed. There were 473 cases in children under 1 year of age in a birth cohort of 77 140 children. Prevalence was 0.6% (95% CI: 0.5-0.7). Based on CREC data, it was demonstrated that 71% of the cases were not detected at birth. The average age of diagnosis in infants under 1 year of age was 46.6 days. There were no differences by sex. Prevalence of CHD in children of mothers aged 35 years or over was significantly higher. However, when chromosomal abnormalities were excluded, the risk was no longer statistically significant. The provinces in the country with maritime ports were the areas with the highest risk in children of adolescent mothers. The most common CHDs were ventricular and atrial septal defects, patent ductus arteriosus, pulmonary valve stenosis, atrioventricular septal defects, coarctation of the aorta, and tetralogy of Fallot. Thirty-four percent of the cases of CHD were multiple, 11.2% were associated with chromosomal abnormalities, and 19% had associated congenital malformations. CONCLUSIONS: CHD prevalence in Costa Rica is within the range reported globally. Significant underreporting of CHD was found in the CREC, primarily due to the age criteria applied. The results suggest that maternal age (under 20 and over 34) is a factor associated with CHD.


Assuntos
Cardiopatias Congênitas/epidemiologia , Sistema de Registros , Anormalidades Múltiplas/epidemiologia , Adulto , Costa Rica/epidemiologia , Estudos Transversais , Diagnóstico Tardio , Feminino , Cardiopatias Congênitas/classificação , Cardiopatias Congênitas/diagnóstico , Hospitais Pediátricos/estatística & dados numéricos , Hospitais Estaduais/estatística & dados numéricos , Humanos , Lactente , Recém-Nascido , Masculino , Idade Materna , Pessoa de Meia-Idade , Gravidez , Prevalência , Estudos Retrospectivos , Fatores Socioeconômicos , Adulto Jovem
16.
Recurso educacional aberto em Espanhol | CVSP - Costa Rica | ID: oer-1986

RESUMO

El principal objetivo fue caracterizar la población de niños que nacen con cardiopatías congénitas (CC) en Costa Rica y evaluar sus procesos de registro. Estudio observacional exploratorio que incluyó a todos los niños con CC diagnosticadas en el Hospital Nacional de Niños Dr. Carlos Sáenz Herrera entre el 1 de mayo de 2006 y el 1 de mayo de 2007. Se tomó en cuenta los niños menores de un año y su respectiva cohorte de nacimientos, se estimaron prevalencias con intervalos de confianza de 95% (IC95%) según sexo, tipo de cardiopatía, edad al diagnóstico, edad materna, residencia habitual y malformaciones extracardiacas asociadas. Se compararon los datos con el Centro de Registro de Enfermedades Congénitas (CREC). Durante el período estudiado se diagnosticaron 534 casos con CC. Los casos en menores de un año fueron 473 dentro de una cohorte de nacimientos de 77 140 prevalencia de 0,6% (IC95%: 0,5–0,7). Con base en datos del CREC, se demostró que al nacimiento no se detectan 71% de los casos. La edad promedio al diagnóstico en niños menores de un año fue de 46,6 días. No hubo diferencias por sexo. La prevalencia de CC en hijos de madres de 35 años o más fue significativamente mayor, aunque al excluir las cromosomopatías este riesgo perdió su significancia estadística. Las provincias del país con puertos marítimos fueron las de mayor riesgo en hijos de madres adolescentes. Las CC más frecuentes fueron los defectos del tabique interventricular e interauricular, persistencia del conducto arterioso, estenosis valvular pulmonar, defectos del tabique aurículo ventricular, coartación de aorta y tetralogía de Fallot. Treinta y cuatro por ciento de las CC fueron múltiples, 11,2% se asociaron a cromosomopatías y 19% tenían malformaciones congénitas asociadas. La prevalencia de CC en Costa Rica está dentro del rango informado en el ámbito mundial. Se encontró que en el CREC había un importante subregistro de CC debido principalmente a los criterios de edad aplicados. Los resultados sugieren que la edad materna (menores de 20 años y mayores de 34 años) es un factor asociado a la ocurrencia de CC.


Assuntos
Anormalidades Congênitas , Anormalidades Congênitas , Anormalidades Congênitas , Cardiopatias Congênitas , /epidemiologia
17.
Rev. bras. farmacogn ; 21(5): 824-828, Sept.-Oct. 2011. ilus, tab
Artigo em Inglês | LILACS | ID: lil-600970

RESUMO

Lupinus aschenbornii S. Schauer, Fabaceae, grows in the Central Highlands of Mexico, at altitudes between 2800 to 4300 m above sea level. The alkaloid patterns in organs of L. aschenbornii were analyzed by Gas-Liquid Chromatography-Mass Spectrometry (GLC-MS). Quinolizidine alkaloids (QA) were identified according to their mass fragmentation patterns, in combination with their Kovats retention indeces. Total QA content in organs differed substantially: seed contained 3.3 mg/g dry weight, flowers 2.8 mg/g DW, leaves 1.9 mg/g DW, stems 1.5 mg/g DW, and pods 1.4 mg/g DW. Roots do not accumulate QA and their profiles differed considerably: while seed stored N-formylangustifoline (17 percent), 17-oxolupanine (16 percent), multiflorine (11 percent) and an unidentified alkaloid (n.i.) 2869 (11 percent) as main QA, sparteine was absent. In flowers, sparteine reached 73 percent, in leaves up to 80 percent, in stems up to 32 percent and in pods up to 96 percent. Other QA present were lupanine (32 percent in stem, 9 percent in flower and 7 percent in seed); N-formylangustifoline (9 percent in stem and 4 percent in flower); multiflorine (6 percent in stem and 3 percent in flower). Differences in QA profile might be a strategy of lupins to avoid adaptation of possible predators because the different QA have different pharmacological properties.

18.
Rev. panam. salud pública ; 30(1): 31-38, jul. 2011. ilus, tab
Artigo em Espanhol | LILACS | ID: lil-608285

RESUMO

OBJETIVO: Caracterizar la población de niños que nacen con cardiopatías congénitas (CC) en Costa Rica y evaluar sus procesos de registro. MÉTODOS: Estudio observacional exploratorio que incluyó a todos los niños con CC diagnosticadas en el Hospital Nacional de Niños entre el 1 de mayo de 2006 y el 1 de mayo de 2007. Tomando en cuenta los niños menores de 1 año y su respectiva cohorte de nacimientos, se estimaron prevalencias con intervalos de confianza de 95 por ciento (IC95 por ciento) según sexo, tipo de cardiopatía, edad al diagnóstico, edad materna, residencia habitual y malformaciones extracardiacas asociadas. Se compararon los datos con el Centro de Registro de Enfermedades Congénitas (CREC). RESULTADOS: Durante el período estudiado se diagnosticaron 534 casos con CC. Los casos en menores de 1 año fueron 473 dentro de una cohorte de nacimientos de 77 140 -prevalencia de 0,6 por ciento (IC95 por ciento: 0,5-0,7). Con base en datos del CREC, se demostró que al nacimiento no se detectan 71 por ciento de los casos. La edad promedio al diagnóstico en niños menores de 1 año fue de 46,6 días. No hubo diferencias por sexo. La prevalencia de CC en hijos de madres de 35 años o más fue significativamente mayor, aunque al excluir las cromosomopatías este riesgo perdió su significancia estadística. Las provincias del país con puertos marítimos fueron las de mayor riesgo en hijos de madres adolescentes. Las CC más frecuentes fueron los defectos del tabique interventricular e interauricular, persistencia del conducto arterioso, estenosis valvular pulmonar, defectos del tabique aurículo ventricular, coartación de aorta y tetralogía de Fallot. El 34 por ciento de las CC fueron múltiples, 11,2 por ciento se asociaron a cromosomopatías y 19 por ciento tenían malformaciones congénitas asociadas. CONCLUSIONES: La prevalencia de CC en Costa Rica está dentro del rango informado a nivel mundial. Se halló que en el CREC había un importante subregistro de CC debido principalmente a los criterios de edad aplicados. Los resultados sugieren que la edad materna (menores de 20 años y mayores de 34 años) es un factor asociado a la ocurrencia de CC.


OBJECTIVE: Characterize the population of children born with congenital heart disease (CHD) in Costa Rica and evaluate the country's registry processes. METHODS: Exploratory observational study that included all children with CHD diagnosed at the National Children's Hospital between 1 May 2006 and 1 May 2007. Considering children under 1 year of age and their respective birth cohort, prevalence was estimated by sex, type of heart disease, age at diagnosis, maternal age, habitual residence, and associated extracardiac malformations, with 95 percent confidence intervals (95 percent CI). The data was compared with those of the Congenital Disease Registry Center (CREC). RESULTS: During the period studied, 534 cases with CHD were diagnosed. There were 473 cases in children under 1 year of age in a birth cohort of 77 140 children. Prevalence was 0.6 percent (95 percent CI: 0.5-0.7). Based on CREC data, it was demonstrated that 71 percent of the cases were not detected at birth. The average age of diagnosis in infants under 1 year of age was 46.6 days. There were no differences by sex. Prevalence of CHD in children of mothers aged 35 years or over was significantly higher. However, when chromosomal abnormalities were excluded, the risk was no longer statistically significant. The provinces in the country with maritime ports were the areas with the highest risk in children of adolescent mothers. The most common CHDs were ventricular and atrial septal defects, patent ductus arteriosus, pulmonary valve stenosis, atrioventricular septal defects, coarctation of the aorta, and tetralogy of Fallot. Thirtyfour percent of the cases of CHD were multiple, 11.2 percent were associated with chromosomal abnormalities, and 19 percent had associated congenital malformations. CONCLUSIONS: CHD prevalence in Costa Rica is within the range reported globally. Significant underreporting of CHD was found in the CREC, primarily due to the age criteria applied. The results suggest that maternal age (under 20 and over 34) is a factor associated with CHD.


Assuntos
Humanos , Masculino , Feminino , Gravidez , Recém-Nascido , Lactente , Adulto , Pessoa de Meia-Idade , Adulto Jovem , Cardiopatias Congênitas/epidemiologia , Sistema de Registros , Anormalidades Múltiplas/epidemiologia , Costa Rica/epidemiologia , Estudos Transversais , Diagnóstico Tardio , Cardiopatias Congênitas/classificação , Cardiopatias Congênitas/diagnóstico , Hospitais Pediátricos/estatística & dados numéricos , Hospitais Estaduais/estatística & dados numéricos , Idade Materna , Prevalência , Estudos Retrospectivos , Fatores Socioeconômicos
20.
Mem Inst Oswaldo Cruz ; 104(6): 865-70, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19876558

RESUMO

E-2-chloro-8-methyl-3-[(4'-methoxy-1'-indanoyl)-2'-methyliden]-quinoline (IQ) is a new quinoline derivative which has been reported as a haemoglobin degradation and ss-haematin formation inhibitor. The haemoglobin proteolysis induced by Plasmodium parasites represents a source of amino acids and haeme, leading to oxidative stress in infected cells. In this paper, we evaluated oxidative status in Plasmodium berghei-infected erythrocytes in the presence of IQ using chloroquine (CQ) as a control. After haemolysis, superoxide dismutase (SOD), catalase, glutathione cycle and NADPH + H+-dependent dehydrogenase enzyme activities were investigated. Lipid peroxidation was also assayed to evaluate lipid damage. The results showed that the overall activities of glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase were significantly diminished by IQ (by 53.5% and 100%, respectively). Glutathione peroxidase activity was also lowered (31%) in conjunction with a higher GSSG/GSH ratio. As a compensatory response, overall SOD activity increased and lipid peroxidation decreased, protecting the cells from the haemolysis caused by the infection. CQ shared most of the effects showed by IQ; however it was able to inhibit the activity of isocitrate dehydrogenase and glutathione-S-transferase. In conclusion, IQ could be a candidate for further studies in malaria research interfering with the oxidative status in Plasmodium berghei infection.


Assuntos
Cloroquina/farmacologia , Eritrócitos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Plasmodium berghei/efeitos dos fármacos , Quinolinas/farmacologia , Animais , Eritrócitos/parasitologia , Peroxidação de Lipídeos , Camundongos , Camundongos Endogâmicos BALB C , Plasmodium berghei/metabolismo , Superóxido Dismutase/metabolismo
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