RESUMEN
Proteases play a pivotal role in many signaling pathways; inhibitors of well-established proteases have shown a substantial therapeutic success. This study aimed to examine the in vivo effects of 3 protease inhibitors isolated from Bauhinia species: i) Bauhinia mollis elastase inhibitor, which blocks human neutrophil elastase (Kiapp 2.8 nM) and cathepsin G (Kiapp 1.0 nM) activities; ii) Bauhinia mollis trypsin inhibitor, a trypsin inhibitor (Kiapp 5.0 nM); and iii) Bauhinia bauhinioides cruzipain inhibitor, which inhibits elastase (Kiapp 2.6 nM), cathepsin G (Kiapp 160.0 nM), and the cysteine proteases cathepsin L (Kiapp 0.2 nM). Bauhinia bauhinioides cruzipain inhibitor, Bauhinia mollis elastase inhibitor, and Bauhinia mollis trypsin inhibitor were isolated using acetone and ammonium sulfate fractionations, DEAE-Sephadex, trypsin-Sepharose, and Resource-Q chromatographies. Mice and rats were treated intraperitoneally with 1 dose of inhibitor; gastric mucosal lesions were induced by cold-restraint stress. Oral pretreatment of mice with Bauhinia mollis elastase inhibitor or Bauhinia mollis trypsin inhibitor (1â-â10 mg/kg) did not show anti-ulcer effect, while Bauhinia bauhinioides cruzipain inhibitor (0.1â-â1.0 mg/kg) produced a similar reduction of the index of mucosal damage at all effective doses (30 to 33% < control). In rats at doses lower than those used in mice, Bauhinia mollis elastase inhibitor and Bauhinia bauhinioides cruzipain inhibitor reduced the index of mucosal damage by 66% and 54% of controls, respectively. The results indicate a protective effect against gastric mucosal lesions associated with elastase inhibition but not inhibition of trypsin activities. Moreover, the lack of Bauhinia mollis elastase inhibitor efficacy observed in mice may possibly be related to the reported structural differences of elastase in mice and rats.
Asunto(s)
Bauhinia , Úlcera Gástrica , Animales , Elastasa de Leucocito , Ratones , Neutrófilos , Proteínas de Plantas , Inhibidores de Proteasas , Ratas , Inhibidores de Serina Proteinasa , Úlcera Gástrica/inducido químicamente , Úlcera Gástrica/tratamiento farmacológicoRESUMEN
OBJECTIVE: One of the limiting factors of employing laser radiation on dental therapies is the potential of causing thermal injuries to pulp tissues. The purpose of this study was to evaluate intra-chamber temperature increase on extracted human teeth exposed to 670 nm wavelength InGaAlP laser diode radiation. MATERIALS AND METHODS: In vitro intra-chamber temperature measurements of 12 standardized human teeth (incisors, canines, premolars, and molars; n = 3) were taken both before and after laser radiation. A type-K thermocouple fast-response thermocouple wire with a 0.5 mm diameter probe was inserted into the tooth pulp chamber (ICEL-Manaus-brand). The laser device Lasotronic-brand InGaAlP laser diode was used to irradiate tooth enamel, perpendicularly to the external surface for 30 sec, with power of levels of 340, 272, 204, 136, and 68 mW. The measurements were taken at three time points: 0, 30 sec, and 3 min after the laser irradiation. Measurements were repeated 24 h after removal and reinsertion of the probe in the pulp chamber. The temperature gradient (ΔT in °C) was calculated (ΔT = final temperature-initial temperature) for each group. Data of ΔT were statistically analyzed by two-way analysis of variance (ANOVA) at the 95% confidence level and compared by Tukey post hoc test (α = 0.05). RESULTS: ANOVA showed statistically significant differences to the interaction of factors (p < 0.05). The highest ΔT values obtained were observed to incisors with 340 mW, 272 mW; 204 mW of power (respectively 4.7°C, 4.2°C, and 3.1°C); and canines presented the lowest ΔT (0.8°C-0.3°C) with no influence of power output. CONCLUSIONS: Since the thermal increase was observed in this study, especially in incisors, attention should be paid to avoid pulpal damage.
Asunto(s)
Cavidad Pulpar/efectos de la radiación , Láseres de Semiconductores , Terapia por Luz de Baja Intensidad/métodos , Temperatura , Análisis de Varianza , Diente Premolar/efectos de la radiación , Humanos , Técnicas In Vitro , Incisivo/efectos de la radiaciónRESUMEN
Human plasma kallikrein (huPK) potentiates platelet responses to subthreshold doses of ADP, although huPK itself, does not induce platelet aggregation. In the present investigation, we observe that huPK pretreatment of platelets potentiates ADP-induced platelet activation by prior proteolysis of the G-protein-coupled receptor PAR-1. The potentiation of ADP-induced platelet activation by huPK is mediated by the integrin αIIbß3 through interactions with the KGD/KGE sequence motif in huPK. Integrin αIIbß3 is a cofactor for huPK binding to platelets to support PAR-1 hydrolysis that contributes to activation of the ADP signaling pathway. This activation pathway leads to phosphorylation of Src, AktS473, ERK1/2, and p38 MAPK, and to Ca2+ release. The effect of huPK is blocked by specific antagonists of PAR-1 (SCH 19197) and αIIbß3 (abciximab) and by synthetic peptides comprising the KGD and KGE sequence motifs of huPK. Further, recombinant plasma kallikrein inhibitor, rBbKI, also blocks this entire mechanism. These results suggest a new function for huPK. Formation of plasma kallikrein lowers the threshold for ADP-induced platelet activation. The present observations are consistent with the notion that plasma kallikrein promotes vascular disease and thrombosis in the intravascular compartment and its inhibition may ameliorate cardiovascular disease and thrombosis.
Asunto(s)
Adenosina Difosfato/farmacología , Calicreína Plasmática/farmacología , Agregación Plaquetaria/efectos de los fármacos , Humanos , Fosforilación/efectos de los fármacos , Complejo GPIIb-IIIa de Glicoproteína Plaquetaria/metabolismo , Receptor PAR-1/metabolismo , Transducción de Señal/efectos de los fármacosRESUMEN
Este trabalho tem como objetivo a análise dos discursos materializados nas práticas discursivas de líderes políticos pertencentes à bancada evangélica e/ou ultraconservadores frente às políticas educacionais de combate à homofobia. Procurou-se compreender os vários discursos produzidos por esses líderes em função de iniciativas de reconhecimento da diversidade sexual e de políticas públicas de combate à homofobia no contexto da escola. Para analisar tais objetivos, ancoramo-nos na análise do discurso apresentada por Michel Foucault (1969/2008). Utilizamos como corpus os vídeos localizados no site youTube contendo o pronunciamento, a pregação, o debate ou a preleção de três líderes políticos e religiosos contrários às políticas públicas educacionais de combate à homofobia. Os resultados indicam que os sujeitos são atravessados por discursos de cunho moral, pseudocientífico, cultural e religioso que sustentam a heteronormatividade.
This study aims to analyze the discourses produced in the discursive practices of the religious and political leaders belonging to the evangelical churches and /or ultra-conservative political parties regarding educational policies to combat homophobia. The authors engage in the task of analyzing the various speeches made by these leaders in relation to initiatives that promote sexual diversity and public policies that combat homophobia in schools. To achievethese goals, the study uses the discourse analysis developed by Michel Foucault (1969/2008).The corpus consists of videos located on YouTube that contain statements, preaching, debates or conferences involving three political and religious leaders opposed to educational policies thatcombat homophobia. The results indicate that the subjects produce discourses that are based on moral, pseudo-scientific, cultural and religious positions to argue for heteronormativity.
Este trabajo tiene como objetivo analizar los discursos materializados en las prácticas discursivas de los líderes religiosos y políticos que pertenecen a la bancada evangélicay/o ultraconservadores en función de las políticas educativas para combatir la homofobia. Se buscó comprender los diversos discursos de estos líderes debido a las iniciativas de reconocimiento de la diversidad sexual y las políticas públicas para combatir la homofobia en el contexto escolar. Para analizar estos objetivos, nos apoyamos en el análisis del discurso presentada por Michel Foucault(1969/2008). Usamos como corpus los videos localizados en el sitio de YouTube que contienen la declaración, la predicación, el debate o una conferencia de tres políticos y líderes religiosos que se oponen a la política pública educativa para combatir la homofobia. Los resultados indican que los sujetos están atravesados por discursos de naturaleza moral, pseudo-científica, cultural y religiosa que sostienen heteronormatividad.
Asunto(s)
Humanos , Masculino , Identidad de Género , Homofobia , Religión y Psicología , Instituciones Académicas , BrasilRESUMEN
Increasing evidence suggests that plant-derived extracts and their isolated components are useful for treatment of seizures and, hence, constitute a valuable source of new antiepileptic drugs with improved efficacy and better adverse effect profile. ß-Caryophyllene is a natural bicyclic sesquiterpene that occurs in a wide range of plant species and displays a number of biological actions, including neuroprotective activity. In the present study, we tested the hypothesis that ß-caryophyllene displays anticonvulsant effects. In addition, we investigated the effect of ß-caryophyllene on behavioral parameters and on seizure-induced oxidative stress. Adult C57BL/6 mice received increasing doses of ß-caryophyllene (0, 10, 30, or 100mg/kg). After 60 min, we measured the latencies to myoclonic and generalized seizures induced by pentylenetetrazole (PTZ, 60 mg/kg). We found that ß-caryophyllene increased the latency to myoclonic jerks induced by PTZ. This result was confirmed by electroencephalographic analysis. In a separate set of experiments, we found that mice treated with an anticonvulsant dose of ß-caryophyllene (100mg/kg) displayed an improved recognition index in the object recognition test. This effect was not accompanied by behavioral changes in the open-field, rotarod, or forced swim tests. Administration of an anticonvulsant dose of ß-caryophyllene (100mg/kg) did not prevent PTZ-induced oxidative stress (i.e., increase in the levels of thiobarbituric acid-reactive substances or the decrease in nonprotein thiols content). Altogether, the present data suggest that ß-caryophyllene displays anticonvulsant activity against seizures induced by PTZ in mice. Since no adverse effects were observed in the same dose range of the anticonvulsant effect, ß-caryophyllene should be further evaluated in future development of new anticonvulsant drugs.
Asunto(s)
Anticonvulsivantes/uso terapéutico , Convulsivantes , Pentilenotetrazol , Convulsiones/inducido químicamente , Convulsiones/tratamiento farmacológico , Sesquiterpenos/uso terapéutico , Animales , Relación Dosis-Respuesta a Droga , Electroencefalografía/efectos de los fármacos , Epilepsias Mioclónicas/inducido químicamente , Epilepsias Mioclónicas/tratamiento farmacológico , Epilepsias Mioclónicas/psicología , Ratones , Ratones Endogámicos C57BL , Actividad Motora/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Sesquiterpenos Policíclicos , Equilibrio Postural/efectos de los fármacos , Reconocimiento en Psicología , Convulsiones/psicología , Natación/psicologíaRESUMEN
The Bauhinia bauhinioides Kallikrein Inhibitor (BbKI) is a Kunitz-type serine peptidase inhibitor of plant origin that has been shown to impair the viability of some tumor cells and to feature a potent inhibitory activity against human and rat plasma kallikrein (Kiapp 2.4 nmol/L and 5.2 nmol/L, respectively). This inhibitory activity is possibly responsible for an effect on hemostasis by prolonging activated partial thromboplastin time (aPTT). Because the association between cancer and thrombosis is well established, we evaluated the possible antithrombotic activity of this protein in venous and arterial thrombosis models. Vein thrombosis was studied in the vena cava ligature model in Wistar rats, and arterial thrombosis in the photochemical induced endothelium lesion model in the carotid artery of C57 black 6 mice. BbKI at a concentration of 2.0 mg/kg reduced the venous thrombus weight by 65% in treated rats in comparison to rats in the control group. The inhibitor prolonged the time for total artery occlusion in the carotid artery model mice indicating that this potent plasma kallikrein inhibitor prevented thrombosis.
Asunto(s)
Fibrinolíticos/farmacología , Proteínas de Plantas/farmacología , Trombosis/tratamiento farmacológico , Animales , Bauhinia , Coagulación Sanguínea/efectos de los fármacos , Modelos Animales de Enfermedad , Humanos , Masculino , Ratones , Distribución Aleatoria , Ratas , Ratas Wistar , Trombina/antagonistas & inhibidores , Trombina/farmacología , Trombosis/sangreRESUMEN
This study aims at identifying the most meaningful characters in the social imaginary and narrating its experience. This is a social-historical study in which oral (semi-structured interviews) and written documental sources were used. The interpretation of data was based on the archeological studies by Foucault on the history of madness and on other authors who worked with the themes: psychiatric madness and psychiatric reform. The narration of madness in the scenery of Crato indicates the existence of a multiplicity that reveals diversity, transcending the traditional psychiatric paradigm, which has as its principle the idea that the "mad person" should be isolated from society. We expect that this study contribute to the debate of nursing professional in the field of psychiatric and mental health.
Asunto(s)
Trastornos Mentales , Brasil , Libertad , Humanos , Trastornos Mentales/psicologíaRESUMEN
Mediators released from polymorphonuclear neutrophils, in particular elastase, are known to induce acute edematous lung injury. In this study we show that the pulmonary edema in isolated perfused rabbit lungs caused by activated neutrophils via release of elastase is significantly decreased by the Kunitz-type Inhibitor BbCI (10(-5) M) from Bauhinia bauhinoides to the same degree as by eglin C (10(-5) M) from Hirudo medicinalis, which was used as a reference. The highly homologous proteinase inhibitor BrPI (10(-5) M) from Bauhinia rufa, however, did not reduce edema formation. The major difference between these inhibitors is the much higher Ki value of BrPI (Ki = 38 nM) for elastase compared to BbCI (Ki = 5.3 nM) and eglin C (Ki = 0.2 nM), respectively. Elastase liberation from activated PMNs was not influenced by the inhibitors. Our results indicate that BbCI can be a useful tool to study the role of neutrophil elastase in pathophysiological processes.
Asunto(s)
Neutrófilos/inmunología , Péptidos/farmacología , Proteínas de Plantas/farmacología , Edema Pulmonar/inmunología , Edema Pulmonar/patología , Animales , Bauhinia , Presión Sanguínea/efectos de los fármacos , Humanos , Elastasa de Leucocito/metabolismo , Pulmón/efectos de los fármacos , Pulmón/patología , Neutrófilos/enzimología , Tamaño de los Órganos/efectos de los fármacos , Edema Pulmonar/tratamiento farmacológico , ConejosRESUMEN
The Chagas Disease Control Program in São Paulo State, Brazil, now in the entomological surveillance phase, includes a serological examination of individuals residing in domiciliary units infested with vector triatomines infected with Trypanosoma cruzi. From 1990 to 1999, this action included area in which triatomine searches were conducted either as a routine procedure, according to their levels of intra- or peridomiciliary infestation, or at the request of local residents. Among residents of the 1,415 UDs inspected, we collected 5,587 blood samples for serological examination, 87 of which (1.56%) tested positive, seven of which from individuals under 29 years of age. The species most frequently captured were Panstrongylus megistus, Triatoma sordida, and Triatoma tibiamaculata in the adult stage. No association was found between presence of seropositive residents and triatomines infected with Tr. cruzi (OR = 1.498; 0.875 < OR < 2.564, 95% C.I.). Our purpose was to use serological testing to investigate the situation of areas identifiable as being at risk of Chagas disease transmission and to compare the results with extant data about Tr. cruzi infection both in humans and vector triatomines.