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1.
Sci Rep ; 10(1): 11680, 2020 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-32669617

RESUMO

Bioactive plant peptides have received considerable interest as potential antihypertensive agents with potentially fewer side effects than antihypertensive drugs. Here, the blood pressure-lowering effects of the Bowman-Birk protease inhibitor, BTCI, and its derived peptides, PepChy and PepTry, were investigated using normotensive (Wistar-WR) and spontaneously hypertensive rats (SHR). BTCI inhibited the proteases trypsin and chymotrypsin, respectively, at 6 µM and 40 µM, a 10-fold greater inhibition than observed with PepTry (60 µM) and PepChy (400 µM). These molecules also inhibited angiotensin converting enzyme (ACE) with IC50 values of 54.6 ± 2.9; 24.7 ± 1.1; and 24.4 ± 1.1 µM, respectively, occluding its catalytic site, as indicated by molecular docking simulation, mainly for PepChy and PepTry. Gavage administration of BTCI and the peptides promoted a decrease of systolic and diastolic blood pressure and an increase of renal and aortic vascular conductance. These effects were more expressive in SHR than in WR. Additionally, BTCI, PepChy and PepTry promoted coronary vasodilation and negative inotropic effects in isolated perfused hearts. The nitric oxide synthase inhibitor blunted the BTCI and PepChy, with no cardiac effects on PepTry. The findings of this study indicate a therapeutic potential of BTCI and its related peptides in the treatment of hypertension.


Assuntos
Anti-Hipertensivos/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Contração Miocárdica/efeitos dos fármacos , Peptídeos/farmacologia , Inibidor da Tripsina de Soja de Bowman-Birk/farmacologia , Animais , Anti-Hipertensivos/química , Sítios de Ligação , Quimotripsina/química , Quimotripsina/metabolismo , Vasos Coronários/efeitos dos fármacos , Vasos Coronários/fisiopatologia , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Hipertensão/enzimologia , Hipertensão/fisiopatologia , Masculino , Simulação de Acoplamento Molecular , NG-Nitroarginina Metil Éster/química , NG-Nitroarginina Metil Éster/farmacologia , Óxido Nítrico Sintase Tipo III/antagonistas & inibidores , Óxido Nítrico Sintase Tipo III/química , Óxido Nítrico Sintase Tipo III/metabolismo , Peptídeos/síntese química , Peptidil Dipeptidase A/química , Peptidil Dipeptidase A/metabolismo , Ligação Proteica , Domínios e Motivos de Interação entre Proteínas , Estrutura Secundária de Proteína , Ratos , Ratos Endogâmicos SHR , Ratos Wistar , Tripsina/química , Tripsina/metabolismo , Inibidor da Tripsina de Soja de Bowman-Birk/química , Vasodilatação/efeitos dos fármacos
2.
J Dev Orig Health Dis ; 11(5): 492-498, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32524941

RESUMO

Nutritional disorders during the perinatal period cause cardiometabolic dysfunction, which is observable in the early overfeeding (EO) experimental model. Therefore, severe caloric restriction has the potential of affecting homeostasis through the same epigenetic mechanisms, and its effects need elucidation. This work aims to determine the impact of food restriction (FR) during puberty in early overfed obese and non-obese animals in adult life. Three days after delivery (PN3), Wistar rats were separated into two groups: normal litter (NL; 9 pups) and small litter (SL; 3 pups). At PN30, some offspring were subjected to FR (50%) until PN60, or maintained with free access to standard chow. NL and SL animals submitted to food restriction (NLFR and SLFR groups) were kept in recovery with free access to standard chow from PN60 until PN120. Body weight and food intake were monitored throughout the experimental period. At PN120 cardiovascular parameters were analyzed and the animals were euthanized for sample collection. SLNF and SLFR offspring were overweight and had increased adiposity. Differences in blood pressure were observed only between obese and non-obese animals. Obese and FR animals have cardiac remodeling showing cardiomyocyte hypertrophy and the presence of interstitial and perivascular fibrosis. FR animals also show increased expression of AT1 and AT2 receptors and of total ERK and p-ERK. The present study showed that EO leads to the obese phenotype and cardiovascular disruptions. Interestingly, we demonstrated that severe FR during puberty leads to cardiac remodeling.


Assuntos
Fenômenos Fisiológicos da Nutrição do Lactente/fisiologia , Desnutrição/complicações , Obesidade/fisiopatologia , Hipernutrição/complicações , Remodelação Ventricular/fisiologia , Animais , Animais Recém-Nascidos , Peso Corporal , Restrição Calórica/efeitos adversos , Modelos Animais de Doenças , Feminino , Ventrículos do Coração/crescimento & desenvolvimento , Humanos , Lactente , Recém-Nascido , Masculino , Desnutrição/diagnóstico , Desnutrição/fisiopatologia , Obesidade/etiologia , Hipernutrição/fisiopatologia , Ratos , Ratos Wistar , Índice de Gravidade de Doença
3.
Int J Med Mushrooms ; 22(10): 931-942, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33426823

RESUMO

Wild edible mushrooms are found around the world, and widely appreciated in gastronomy, medicine, and pharmacology. This study investigated the chemical characterization of Boletus edulis and Lactarius deliciosus wild edible mushrooms, naturally grown in the mountain range of Santa Catarina, Brazil. Mushrooms were separated in stem and cap, and the nutritional composition was conducted in fresh matter. Antioxidant compounds were extracted in three solvents, and total phenolic compounds, flavonoids, antioxidant capacity, and antimicrobial activity were evaluated. The results demonstrate that moisture, ashes, lipids, crude protein, carbohydrates, and calories presented a significant difference according to the species evaluated. Mushrooms presented more than 85% of moisture, high content of crude protein, and carbohydrates. B. edulis had the highest content of antioxidant compounds compared with L. deliciosus, tested by DPPH, ABTS, and FRAP assay. High free radical inhibition and low IC50 values were obtained, demonstrating that B. edulis presents a strong antioxidant capacity. Regarding the antimicrobial activity, B. edulis extracts were effective in controlling Staphylococcus aureus, Escherichia coli, and Klebsiella pneumoniae, demonstrating biological application. Based on the aforementioned, future studies can be addressed in the development of innovative food products, medicines, and pharmaceuticals, using B. edulis and L. deliciosus wild edible mushroom. Therefore, wild edible mushrooms evaluated in this study had the potential to be used in human consumption, providing essential nutrients, phenolic compounds, and flavonoids, with high antioxidant and antimicrobial activity.


Assuntos
Antibacterianos/química , Antioxidantes/química , Basidiomycota/química , Extratos Vegetais/química , Antibacterianos/farmacologia , Antioxidantes/farmacologia , Brasil , Escherichia coli/efeitos dos fármacos , Escherichia coli/crescimento & desenvolvimento , Flavonoides/química , Flavonoides/farmacologia , Radicais Livres , Valor Nutritivo , Fenóis/química , Fenóis/farmacologia , Extratos Vegetais/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/crescimento & desenvolvimento
4.
Neurol Sci ; 40(6): 1199-1207, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30852696

RESUMO

OBJECTIVE: Repetitive Transcranial Magnetic Stimulation (rTMS) has been used to treat post-stroke upper limb spasticity (ULS) in addition to physiotherapy (PT). To determine whether rTMS associated with PT modulates cortical and spinal cord excitability as well as decreases ULS of post-stroke patients. METHODS: Twenty chronic patients were randomly assigned to either the intervention group-1 Hz rTMS on the unaffected hemisphere and PT, or control group-sham stimulation and PT, for ten sessions. Before and after sessions, ULS was measured using the modified Ashworth scale and cortical excitability using the output intensity of the magnetic stimulator (MSO). The spinal excitability was measured by the Hmax/Mmax ratio of the median nerve at baseline, at the end of treatment, and at the 4-week follow-up. RESULTS: The experimental group showed at the end of treatment an enhancement of cortical excitability, i.e., lower values of MSO, compared to control group (p = 0.044) and to baseline (p = 0.028). The experimental group showed a decreased spinal cord excitability at the 4-week follow-up compared to control group (p = 0.021). ULS decreased by the sixth session in the experimental group (p < 0.05). CONCLUSION: One-hertz rTMS associated with PT increased the unaffected hemisphere excitability, decreased spinal excitability, and reduced post-stroke ULS.


Assuntos
Excitabilidade Cortical , Espasticidade Muscular/fisiopatologia , Espasticidade Muscular/reabilitação , Modalidades de Fisioterapia , Medula Espinal/fisiopatologia , Reabilitação do Acidente Vascular Cerebral/métodos , Acidente Vascular Cerebral/complicações , Estimulação Magnética Transcraniana , Idoso , Terapia Combinada , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Espasticidade Muscular/etiologia , Resultado do Tratamento , Extremidade Superior/fisiopatologia
5.
Water Res ; 144: 572-580, 2018 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-30086530

RESUMO

The Photo-Fenton-like (PF-like) process with minute Fe(III) concentrations and the Hydrogen Peroxide Photolysis (HPP), using Xe-lamp or solar light as sources of irradiation, were efficiently applied to eliminate the herbicide 2,4-D from water. PF-like experiments concerning ferric and H2O2 concentrations of 0.6 mg L-1 and 20 mg L-1 respectively, using Xenon lamps (Xe-lamps) as a source of irradiation and 2,4-D concentrations of 10 mg L-1 at pH 3.6, exhibited complete 2,4-D degradation and 77% dissolved organic carbon (DOC) removal after 30 min and 6 h of irradiation respectively whereas HPP (in absence of ferric ions) experiments showed a 2,4-D reduction and DOC removal of 90% and 7% respectively after 6 h of irradiation. At pH 7.0, HPP process achieved a 2,4-D abatement of approximately 75% and a DOC removal of 4% after 6 h. PF-like exhibited slightly improved 2,4-D and DOC removals (80% and 12% respectively) after the same irradiation time probably due to the low pH reduction (from 7.0 to 5.6). Several chlorinated-aromatic intermediates were identified by HPLC-MS. These by-products were efficiently removed by PF at pH 3.6, whereas at neutral PF-like and acid or neutral HPP, they were not efficiently degraded. With natural solar light irradiation, 10 and 1 mg L-1 of 2,4-D were abated using minor H2O2 concentrations (3, 6, 10 and 20 mg L-1) and iron at 0.6 mg L-1 in Milli-Q water. Similar results to Xe-lamp experiments were obtained, where solar UV-B + A light H2O2 photolysis (HPSP) and solar photo-Fenton-like (SPF-like) played an important role and even at low H2O2 and ferric concentrations of 3 and 0.6 mg L-1 respectively, 2,4-D was efficiently removed at pH 3.6. Simulated surface water at pH 3.6 containing 1 mg L-1 2,4-D, 20 mg L-1 H2O2 and 0.6 mg L-1 Fe(III) under natural sunlight irradiation efficiently removed the herbicide and its main metabolite 2,4-DCP after 30 min of treatment while at neutral pH, 40% of herbicide degradation was achieved. In the case of very low iron concentrations (0.05 mg L-1) at acid pH, 150 min of solar treatment was required to remove 2,4-D.


Assuntos
Ácido 2,4-Diclorofenoxiacético/química , Poluentes Químicos da Água/química , Purificação da Água/métodos , Peróxido de Hidrogênio/química , Concentração de Íons de Hidrogênio , Ferro/química , Fotólise , Raios Ultravioleta , Purificação da Água/instrumentação
6.
Front Physiol ; 9: 1073, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30131720

RESUMO

The search for new antihypertensive drugs has grown in recent years because of high rate of morbidity among hypertensive patients and several side effects that are associated with the first-line medications. The current study sought to investigate the antihypertensive effect of a newly synthesized pyrazole derivative known as 5-(1-(3 fluorophenyl)-1H-pyrazol-4-yl)-2H-tetrazole (LQFM-21). Spontaneously hypertensive rats (SHR) were used to evaluate the effect of LQFM-21 on mean arterial pressure (MAP), heart rate (HR), renal vascular conductance (RVC), arterial vascular conductance (AVC), baroreflex sensitivity (BRS) index, and vascular reactivity. Acute intravenous (iv) administration of LQFM-21 (0.05, 0.1, 0.2, and 0.4 mg kg-1) reduced MAP and HR, and increased RVC and AVC. Chronic oral administration of LQFM-21 (15 mg kg-1) for 15 days reduced MAP without altering BRS. The blockade of muscarinic receptors and nitric oxide synthase by intravenous infusion of atropine and L-NAME, respectively, attenuated cardiovascular effects of LQFM-21. In addition, ex vivo experiments showed that LQFM-21 induced an endothelium-dependent relaxation in isolated aortic rings from SHR. This effect was blocked by guanylyl cyclase inhibitor (ODQ) and L-NAME. These findings suggest the involvement of muscarinic receptor and NO/cGMP pathway in the antihypertensive and vasodilator effects of LQFM-21.

7.
Epidemiol. serv. saúde ; 26(2): 369-378, abr.-jun. 2017. tab, graf
Artigo em Português | LILACS | ID: biblio-953313

RESUMO

OBJETIVO: descrever as proporções de abandono do tratamento segundo características sociodemográficas e clínico-epidemiológicas dos casos novos de tuberculose no estado de Pernambuco, Brasil. MÉTODOS: estudo ecológico descritivo, com dados do Sistema de Informação de Agravos de Notificação (Sinan) referentes ao período 2001-2014; a Gerência Regional de Saúde (GERES) calculou a proporção de abandono. RESULTADOS: dos 57.015 novos casos, 6.474 (11,3%) abandonaram o tratamento, representando decréscimo de 16,4% (2001) para 9,3% (2014); as GERES I Recife, III Palmares, IV Caruaru, VIII Petrolina e IX Ouricuri ainda apresentavam proporção de abandono >5% em 2014; essa proporção foi maior para homens (11,9%), de 20-39 anos (12,7%), com Ensino Fundamental incompleto (12,1%), negros (13,7%), institucionalizados (12,5%) e da forma clínica pulmonar + extrapulmonar (14,1%). CONCLUSÃO: apesar do decréscimo, a proporção de abandono continuava elevada; homens, adultos, com baixa escolaridade, negros, institucionalizados e portadores de tuberculose pulmonar mais extrapulmonar demonstram maior predisposição ao abandono.


OBJETIVO: describir las proporciones de abandono según características sociodemográficas y clínico-epidemiológicas de los nuevos casos en tratamiento para tuberculosis, en Pernambuco, Brasil. MÉTODOS: estudio ecológico descriptivo con datos del Sistema de Información sobre enfermedades de notificación obligatoria, en el período 2001-2014; la Gerencia Regional de Salud (GERES) calculó la proporción de abandono. RESULTADOS: de los 57.015 nuevos casos, 6.474 (11,3%) abandonaron el tratamiento, disminución del 16,4% (2001) al 9,3% (2014); las GERES I Recife, III Palmares, IV Caruaru, VIII Petrolina y IX Ouricuri tenían una proporción de abandono >5% en 2014; la proporción fue mayor en hombres (11,9%), entre 20-39 años (12,7%), con educación primaria incompleta (12,1%), negros (13,7%), institucionalizados (12,5%) y con presentación clínica pulmonar + extra pulmonar (14,1%). CONCLUSIÓN: a pesar de la disminución, la proporción de abandono se mantuvo alta; hombres, adultos con bajo nivel de educación, negros, institucionalizados y con tuberculosis pulmonar + extra pulmonar demuestran mayor predisposición al abandono.


OBJECTIVE: to describe abandonment rates according to sociodemographic, clinical and epidemiological characteristics of new tuberculosis cases being treated in Pernambuco State, Brazil. METHODS: this is a descriptive ecological study using data from the Information System for Notifiable Diseases from 2001 to 2014; the abandonment rate was calculated by the Regional Administration on Health (GERES). RESULTS: of the 57,015 new cases, 6,474 (11.3%) abandoned treatment, although abandonment decreased from 16.4% (2001) to 9.3% (2014); the abandonment rate in GERES I Recife, III Palmares, IV Caruaru, VIII Petrolina and IX Ouricuri was still >5% in 2014; the rate was higher in males (11.9%), people aged 20-39 (12.7%), people with incomplete elementary school (12.1%), black-skinned people (13.7%), institutionalized people (12.5%) and those with pulmonary + extrapulmonary tuberculosis (14.1%). CONCLUSION: despite the decrease, the abandonment rate remained high; males, adults with low education level, black-skinned people, institutionalized patients and patients with pulmonary + extrapulmonary tuberculosis seemed more prone to abandoning treatment.


Assuntos
Humanos , Masculino , Feminino , Recém-Nascido , Lactente , Pré-Escolar , Criança , Adolescente , Adulto , Pessoa de Meia-Idade , Idoso , Tuberculose , Recusa do Paciente ao Tratamento , Adesão à Medicação , Epidemiologia Descritiva
8.
Epidemiol Serv Saude ; 26(2): 369-378, 2017.
Artigo em Inglês, Português | MEDLINE | ID: mdl-28492778

RESUMO

OBJECTIVE: to describe abandonment rates according to sociodemographic, clinical and epidemiological characteristics of new tuberculosis cases being treated in Pernambuco State, Brazil. METHODS: this is a descriptive ecological study using data from the Information System for Notifiable Diseases from 2001 to 2014; the abandonment rate was calculated by the Regional Administration on Health (GERES). RESULTS: of the 57,015 new cases, 6,474 (11.3%) abandoned treatment, although abandonment decreased from 16.4% (2001) to 9.3% (2014); the abandonment rate in GERES I Recife, III Palmares, IV Caruaru, VIII Petrolina and IX Ouricuri was still >5% in 2014; the rate was higher in males (11.9%), people aged 20-39 (12.7%), people with incomplete elementary school (12.1%), black-skinned people (13.7%), institutionalized people (12.5%) and those with pulmonary + extrapulmonary tuberculosis (14.1%). CONCLUSION: despite the decrease, the abandonment rate remained high; males, adults with low education level, black-skinned people, institutionalized patients and patients with pulmonary + extrapulmonary tuberculosis seemed more prone to abandoning treatment.


Assuntos
Antituberculosos/administração & dosagem , Adesão à Medicação/estatística & dados numéricos , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Brasil , Criança , Pré-Escolar , Escolaridade , Feminino , Humanos , Lactente , Recém-Nascido , Sistemas de Informação , Masculino , Pessoa de Meia-Idade , Adulto Jovem
9.
Blood Cells Mol Dis ; 55(4): 347-50, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26460258

RESUMO

We report an extremely rare case of a female child who presented the onset of primary myelofibrosis (PMF) harboring JAK2 (Janus Kinase 2 gene) mutation (JAK2V617F) when she was 15 months old. She was monitored over 25 years, a period in which she was treated with spleen radiotherapy and recombinant interferon α. She also underwent splenectomy when she was 13 years old, due to massive splenomegaly, anemia and various infection disease episodes. The longstanding evolution of the patient enabled us to verify that there were no complications related to post-splenectomy events and/or blast transformation. To the best of our knowledge, this is the first reported case of severe PMF with JAK2 mutation in a child. We provide evidence that a better quality of life and long survival in pediatric PMF may be provided by splenectomy.


Assuntos
Janus Quinase 2/genética , Mutação , Mielofibrose Primária/diagnóstico , Mielofibrose Primária/genética , Feminino , Seguimentos , Humanos , Lactente , Fenótipo
10.
Artigo em Inglês | MEDLINE | ID: mdl-25960756

RESUMO

This study's aim was to determine the effect of hydroalcoholic extract of M. cauliflora (HEMC) on vascular tension and blood pressure in rats. In our in vitro studies using precontracted isolated aortas from rats, HEMC and acetylcholine (positive control) induced relaxation only in vessels with endothelium. Pretreatment with L-NAME (NO synthase inhibitor) or ODQ (soluble guanylyl cyclase (sGC) inhibitor) abolished the HEMC-induced relaxation. The treatment with MDL-12,330A (adenylyl cyclase (AC) inhibitor) or diclofenac (COX inhibitor) reduced HEMC-induced vasorelaxation. The blockade of muscarinic and ß-adrenergic receptors (by atropine and propranolol, resp.) did not promote changes in HEMC-induced vasorelaxation. In our in vivo studies, catheters were inserted into the right femoral vein and artery of anesthetized rats for HEMC infusion and the measurement of blood pressure, heart rate, and aortic blood flow. The intravenous infusion of HEMC produced hypotension and increased aortic blood flow with no changes in heart rate. These findings showed that HEMC induces endothelium-dependent vascular relaxation and hypotension with no alteration in heart rate. The NO/sGC/cGMP pathway seems to be the main cellular route involved in the vascular responsiveness.

11.
ScientificWorldJournal ; 2014: 496121, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25485300

RESUMO

Changes in plasma osmolarity, through central and peripheral osmoreceptors, activate the median preoptic nucleus (MnPO) that modulates autonomic and neuroendocrine adjustments. The present study sought to determine the participation of MnPO in the cardiovascular recovery induced by hypertonic saline infusion (HSI) in rats submitted to hemorrhagic shock. The recordings of mean arterial pressure (MAP) and renal vascular conductance (RVC) were carried out on male Wistar rats (250-300 g). Hemorrhagic shock was induced by blood withdrawal over 20 min until the MAP values of approximately 60 mmHg were attained. The nanoinjection (100 nL) of GABAA agonist (Muscimol 4 mM; experimental group (EXP)) or isotonic saline (NaCl 150 mM; control (CONT)) into MnPO was performed 2 min prior to intravenous overload of sodium through HSI (3 M NaCl, 1.8 mL/kg, b.wt.). Hemorrhagic shock reduced the MAP in control (62 ± 1.1 mmHg) and EXP (61 ± 0.4 mmHg) equipotently. The inhibition of MnPO impaired MAP (CONT: 104 ± 4.2 versus EXP: 60 ± 6.2 mmHg) and RVC (CONT: 6.4 ± 11.4 versus EXP: -53.5 ± 10.0) recovery 10 min after HSI. The overall results in this study demonstrated, for the first time, that the MnPO plays an essential role in the HSI induced resuscitation during hypovolemic hemorrhagic shock.


Assuntos
Sistema Cardiovascular/fisiopatologia , Área Pré-Óptica/fisiopatologia , Recuperação de Função Fisiológica/efeitos dos fármacos , Solução Salina Hipertônica/farmacologia , Solução Salina Hipertônica/uso terapêutico , Choque Hemorrágico/tratamento farmacológico , Choque Hemorrágico/fisiopatologia , Animais , Pressão Sanguínea/efeitos dos fármacos , Sistema Cardiovascular/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Hematócrito , Hipovolemia/fisiopatologia , Masculino , Concentração Osmolar , Área Pré-Óptica/efeitos dos fármacos , Ratos Wistar , Sódio/sangue
12.
Molecules ; 19(11): 17536-58, 2014 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-25361421

RESUMO

The hydrolysis of bradykinin (Bk) by different classes of proteases in plasma and tissues leads to a decrease in its half-life. Here, Bk actions on smooth muscle and in vivo cardiovascular assays in association with a protease inhibitor, Black eyed-pea trypsin and chymotrypsin inhibitor (BTCI) and also under the effect of trypsin and chymotrypsin were evaluated. Two synthetic Bk-related peptides, Bk1 and Bk2, were used to investigate the importance of additional C-terminal amino acid residues on serine protease activity. BTCI forms complexes with Bk and analogues at pH 5.0, 7.4 and 9.0, presenting binding constants ranging from 103 to 104 M-1. Formation of BTCI-Bk complexes is probably driven by hydrophobic forces, coupled with slight conformational changes in BTCI. In vitro assays using guinea pig (Cavia porcellus) ileum showed that Bk retains the ability to induce smooth muscle contraction in the presence of BTCI. Moreover, no alteration in the inhibitory activity of BTCI in complex with Bk and analogous was observed. When the BTCI and BTCI-Bk complexes were tested in vivo, a decrease of vascular resistance and consequent hypotension and potentiating renal and aortic vasodilatation induced by Bk and Bk2 infusions was observed. These results indicate that BTCI-Bk complexes may be a reliable strategy to act as a carrier and protective approach for Bk-related peptides against plasma serine proteases cleavage, leading to an increase in their half-life. These findings also indicate that BTCI could remain stable in some tissues to inhibit chymotrypsin or trypsin-like enzymes that cleave and inactivate bradykinin in situ.


Assuntos
Bradicinina/metabolismo , Fabaceae/química , Peptídeos/metabolismo , Inibidores de Proteases/farmacologia , Sementes/química , Animais , Sistema Cardiovascular/efeitos dos fármacos , Sistema Cardiovascular/metabolismo , Quimotripsina/metabolismo , Cobaias , Meia-Vida , Interações Hidrofóbicas e Hidrofílicas , Íleo/efeitos dos fármacos , Íleo/metabolismo , Contração Muscular/efeitos dos fármacos , Músculo Liso/efeitos dos fármacos , Músculo Liso/metabolismo , Proteínas de Plantas/antagonistas & inibidores , Proteínas de Plantas/metabolismo , Serina Proteases/metabolismo , Vasodilatação/efeitos dos fármacos
13.
PLoS One ; 9(10): e109620, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25279805

RESUMO

Hypernatremia stimulates the secretion of oxytocin (OT), but the physiological role of OT remains unclear. The present study sought to determine the involvement of OT and renal nerves in the renal responses to an intravenous infusion of hypertonic saline. Male Wistar rats (280-350 g) were anesthetized with sodium thiopental (40 mg. kg(-1), i.v.). A bladder cannula was implanted for collection of urine. Animals were also instrumented for measurement of mean arterial pressure (MAP) and renal blood flow (RBF). Renal vascular conductance (RVC) was calculated as the ratio of RBF by MAP. In anesthetized rats (n = 6), OT infusion (0.03 µg • kg(-1), i.v.) induced renal vasodilation. Consistent with this result, ex vivo experiments demonstrated that OT caused renal artery relaxation. Blockade of OT receptors (OXTR) reduced these responses to OT, indicating a direct effect of this peptide on OXTR on this artery. Hypertonic saline (3 M NaCl, 1.8 ml • kg(-1) b.wt., i.v.) was infused over 60 s. In sham rats (n = 6), hypertonic saline induced renal vasodilation. The OXTR antagonist (AT; atosiban, 40 µg • kg(-1) • h(-1), i.v.; n = 7) and renal denervation (RX) reduced the renal vasodilation induced by hypernatremia. The combination of atosiban and renal denervation (RX+AT; n = 7) completely abolished the renal vasodilation induced by sodium overload. Intact rats excreted 51% of the injected sodium within 90 min. Natriuresis was slightly blunted by atosiban and renal denervation (42% and 39% of load, respectively), whereas atosiban with renal denervation reduced sodium excretion to 16% of the load. These results suggest that OT and renal nerves are involved in renal vasodilation and natriuresis induced by acute plasma hypernatremia.


Assuntos
Vias Eferentes , Hipernatremia/fisiopatologia , Ocitocina/farmacologia , Artéria Renal/patologia , Solução Salina Hipertônica/farmacologia , Vasodilatação/efeitos dos fármacos , Animais , Frequência Cardíaca , Masculino , Ocitócicos/farmacologia , RNA Mensageiro/genética , Ratos , Ratos Wistar , Reação em Cadeia da Polimerase em Tempo Real , Receptores de Ocitocina/genética , Receptores de Ocitocina/metabolismo , Artéria Renal/efeitos dos fármacos , Reação em Cadeia da Polimerase Via Transcriptase Reversa
14.
Life Sci ; 112(1-2): 90-6, 2014 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-25072354

RESUMO

AIMS: Clinical complaints on the first-line of cardiovascular medications make continuous search for new drugs a necessity. This study evaluated the cardiovascular effects and mechanism of 4-[(1-phenyl-1H-pyrazol-4-yl)methyl]1-piperazine carboxylic acid ethyl ester (LQFM008). MAIN METHODS: Normotensive male Wistar or spontaneously hypertensive rats (anesthetized or conscious) were used to evaluate the effect of LQFM008 on the mean arterial pressure (MAP), heart rate (HR), arterial blood flow (ABF), arterial vascular conductance (AVC), baroreflex effectiveness index (BI), systolic blood pressure (SBP), diastolic blood pressure (DBP) and vascular function. KEY FINDINGS: In anesthetized normotensive rats, LQFM008 (7.3, 14.3 or 28.6 µmol/kg, i.v.) reduced MAP (-21.1±2.7; -23.9±4.7 or -32.4±8.3 mmHg, respectively) and AVC (22%, 32% or 38%) in a dose-dependent manner. LQFM008 elicited a temporal reduction in the SBP and DBP without changes to the BI of conscious normotensive rats. In hypertensive rats, LQFM008 (7.3, 14.3 or 28.6 µmol/kg, i.v.) reduced MAP (-2.3±2.6; -29.3±2.7 or -38.4±2.8 mmHg, respectively) and increased HR (1.6±3.7; 15.4±4.9 or 25.5±6.2 bmp, respectively) in a dose-dependent manner. A week of oral administration of LQFM008 47.7 µmol/kg elicited a temporal reduction in SBP of hypertensive rats. Pretreatments with atropine, WAY-100635 or L-NAME blocked the effect of LQFM008. In addition, LQFM008-induced endothelium-dependent vascular relaxation was inhibited by L-NAME. SIGNIFICANCE: Our findings showed hypotensive, antihypertensive and vasorelaxant effects of LQFM008 and suggest the participation of nitric oxide, 5-HT1A and muscarinic receptors.


Assuntos
Anti-Hipertensivos/farmacologia , Aorta/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Piperazinas/farmacologia , Pirazóis/farmacologia , Administração Oral , Animais , Aorta/fisiopatologia , Atropina/farmacologia , Barorreflexo/efeitos dos fármacos , Velocidade do Fluxo Sanguíneo/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Hipertensão/fisiopatologia , Masculino , NG-Nitroarginina Metil Éster/farmacologia , Piridinas/farmacologia , Ratos , Ratos Endogâmicos SHR , Ratos Wistar , Técnicas de Cultura de Tecidos , Vasodilatação/efeitos dos fármacos
15.
Anal Bioanal Chem ; 406(4): 1173-9, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23877180

RESUMO

This paper reports a novel fluorescence polarization (FP) chiral sensor approach based on a catalytic DNA. This platform involves an enzyme module (E), which was able to trigger the L-histidine-dependent cleavage of an RNA phosphoester bond of a substrate domain (S), whereas it did not accept the D-enantiomer as cofactor. Two assay formats were proposed, based on bi- and unimolecular strategies. The bimolecular design was related to the use of separate E and fluorescently labelled S* sequences. The two oligonucleotide strands were pre-assembled via complementary regions at their extremities. As the result of the large molecular volume of the formed assembly, the S* probe displayed a high fluorescence anisotropy signal. Upon addition of the L-histidine, the DNAzyme cleaved the phosphoester bond of the S* component, leading to the loss of stem stability and the release of single-stranded products of lower size. This was accompanied by a significant decrease in the fluorescence anisotropy response. As a simpler alternative, the unimolecular design, where E and S sequences are linked together through a loop to form a single fluorescent probe E-S*, was also investigated. It was found that the unimolecular approach provided an improved FP response relative to the bimolecular one. Under optimized operating conditions, such a chiral sensing platform allowed the detection of as low as 0.05% of the L-histidine enantiomer in a non-racemic mixture.


Assuntos
Técnicas Biossensoriais/métodos , DNA Catalítico/química , Histidina/química , Aptâmeros de Nucleotídeos/química , Polarização de Fluorescência , Isomerismo , Oligonucleotídeos/química
16.
J Appl Oral Sci ; 19(5): 469-75, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21986651

RESUMO

UNLABELLED: Dental roots that have been exposed to the oral cavity and periodontal pocket environment present superficial changes, which can prevent connective tissue reattachment. Demineralizing agents have been used as an adjunct to the periodontal treatment aiming at restoring the biocompatibility of roots. OBJECTIVE: This study compared four commonly used demineralizing agents for their capacity of removing smear layer and opening dentin tubules. METHODS: Fifty fragments of human dental roots previously exposed to periodontal disease were scaled and randomly divided into the following groups of treatment: 1) CA: demineralization with citric acid for 3 min; 2) TC-HCl: demineralization with tetracycline-HCl for 3 min; 3) EDTA: demineralization with EDTA for 3 min; 4) PA: demineralization with 37% phosphoric acid for 3 min; 5) CONTROL: rubbing of saline solution for 3 min. Scanning electron microscopy was used to check for the presence of residual smear layer and for measuring the number and area of exposed dentin tubules. RESULTS: Smear layer was present in 100% of the specimens from the groups PA and control; in 80% from EDTA group; in 33.3% from TC-HCl group and 0% from CA group. The mean numbers of exposed dentin tubules in a standardized area were: TC-HCl=43.8±25.2; CA=39.3±37; PA=12.1±16.3; EDTA=4.4±7.5 and CONTROL=2.3±5.7. The comparison showed significant differences between the following pairs of groups: TC-HCl and CONTROL; TC-HCl and EDTA; CA and CONTROL; and CA and EDTA. The mean percentages of area occupied by exposed dentin tubules were: CA=0.12±0.17%; TC-HCl=0.08±0.06%; PA=0.03±0.05%; EDTA=0.01±0.01% and CONTROL=0±0%. The CA group differed significantly from the others except for the TC-HCl group. CONCLUSION: There was a decreasing ability for smear layer removal and dentin tubule widening as follows: AC>TC-HCl>PA>EDTA. This information can be of value as an extra parameter for choosing one of them for root conditioning.


Assuntos
Condicionamento Ácido do Dente/métodos , Preparo da Cavidade Dentária/métodos , Dentina/efeitos dos fármacos , Camada de Esfregaço , Raiz Dentária/efeitos dos fármacos , Análise de Variância , Ácido Cítrico/farmacologia , Dentina/ultraestrutura , Ácido Edético/farmacologia , Humanos , Microscopia Eletrônica de Varredura , Ácidos Fosfóricos/farmacologia , Estatísticas não Paramétricas , Propriedades de Superfície/efeitos dos fármacos , Tetraciclina/farmacologia , Fatores de Tempo , Raiz Dentária/ultraestrutura
17.
J. appl. oral sci ; 19(5): 469-475, Sept.-Oct. 2011. ilus, tab
Artigo em Inglês | LILACS | ID: lil-600847

RESUMO

Dental roots that have been exposed to the oral cavity and periodontal pocket environment present superficial changes, which can prevent connective tissue reattachment. Demineralizing agents have been used as an adjunct to the periodontal treatment aiming at restoring the biocompatibility of roots. OBJECTIVE: This study compared four commonly used demineralizing agents for their capacity of removing smear layer and opening dentin tubules. METHODS: Fifty fragments of human dental roots previously exposed to periodontal disease were scaled and randomly divided into the following groups of treatment: 1) CA: demineralization with citric acid for 3 min; 2) TC-HCl: demineralization with tetracycline-HCl for 3 min; 3) EDTA: demineralization with EDTA for 3 min; 4) PA: demineralization with 37 percent phosphoric acid for 3 min; 5) Control: rubbing of saline solution for 3 min. Scanning electron microscopy was used to check for the presence of residual smear layer and for measuring the number and area of exposed dentin tubules. RESULTS: Smear layer was present in 100 percent of the specimens from the groups PA and control; in 80 percent from EDTA group; in 33.3 percent from TC-HCl group and 0 percent from CA group. The mean numbers of exposed dentin tubules in a standardized area were: TC-HCl=43.8±25.2; CA=39.3±37; PA=12.1±16.3; EDTA=4.4±7.5 and Control=2.3±5.7. The comparison showed significant differences between the following pairs of groups: TC-HCl and Control; TC-HCl and EDTA; CA and Control; and CA and EDTA. The mean percentages of area occupied by exposed dentin tubules were: CA=0.12±0.17 percent; TC-HCl=0.08±0.06 percent; PA=0.03±0.05 percent; EDTA=0.01±0.01 percent and Control=0±0 percent. The CA group differed significantly from the others except for the TC-HCl group. CONCLUSION: There was a decreasing ability for smear layer removal and dentin tubule widening as follows: AC>TC-HCl>PA>EDTA. This information can be of value as an extra parameter for choosing one of them for root conditioning.


Assuntos
Humanos , Condicionamento Ácido do Dente/métodos , Preparo da Cavidade Dentária/métodos , Dentina/efeitos dos fármacos , Camada de Esfregaço , Raiz Dentária/efeitos dos fármacos , Análise de Variância , Ácido Cítrico/farmacologia , Dentina/ultraestrutura , Ácido Edético/farmacologia , Microscopia Eletrônica de Varredura , Ácidos Fosfóricos/farmacologia , Estatísticas não Paramétricas , Propriedades de Superfície/efeitos dos fármacos , Fatores de Tempo , Tetraciclina/farmacologia , Raiz Dentária/ultraestrutura
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