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1.
Artigo em Inglês | MEDLINE | ID: mdl-29133563

RESUMO

The search for antiprion compounds has been encouraged by the fact that transmissible spongiform encephalopathies (TSEs) share molecular mechanisms with more prevalent neurodegenerative pathologies, such as Parkinson's and Alzheimer's diseases. Cellular prion protein (PrPC) conversion into protease-resistant forms (protease-resistant PrP [PrPRes] or the scrapie form of PrP [PrPSc]) is a critical step in the development of TSEs and is thus one of the main targets in the screening for antiprion compounds. In this work, three trimethoxychalcones (compounds J1, J8, and J20) and one oxadiazole (compound Y17), previously identified in vitro to be potential antiprion compounds, were evaluated through different approaches in order to gain inferences about their mechanisms of action. None of them changed PrPC mRNA levels in N2a cells, as shown by reverse transcription-quantitative real-time PCR. Among them, J8 and Y17 were effective in real-time quaking-induced conversion reactions using rodent recombinant PrP (rPrP) from residues 23 to 231 (rPrP23-231) as the substrate and PrPSc seeds from hamster and human brain. However, when rPrP from residues 90 to 231 (rPrP90-231), which lacks the N-terminal domain, was used as the substrate, only J8 remained effective, indicating that this region is important for Y17 activity, while J8 seems to interact with the PrPC globular domain. J8 also reduced the fibrillation of mouse rPrP23-231 seeded with in vitro-produced fibrils. Furthermore, most of the compounds decreased the amount of PrPC on the N2a cell surface by trapping this protein in the endoplasmic reticulum. On the basis of these results, we hypothesize that J8, a nontoxic compound previously shown to be a promising antiprion agent, may act by different mechanisms, since its efficacy is attributable not only to PrP conversion inhibition but also to a reduction of the PrPC content on the cell surface.


Assuntos
Chalconas/farmacologia , Drogas em Investigação/farmacologia , Neurônios/efeitos dos fármacos , Oxidiazóis/farmacologia , Proteínas Priônicas/antagonistas & inibidores , Animais , Sítios de Ligação , Linhagem Celular Tumoral , Chalconas/síntese química , Clonagem Molecular , Drogas em Investigação/síntese química , Retículo Endoplasmático/efeitos dos fármacos , Retículo Endoplasmático/metabolismo , Retículo Endoplasmático/ultraestrutura , Escherichia coli/genética , Escherichia coli/metabolismo , Expressão Gênica , Vetores Genéticos/química , Vetores Genéticos/metabolismo , Cinética , Camundongos , Simulação de Acoplamento Molecular , Neurônios/metabolismo , Neurônios/patologia , Oxidiazóis/síntese química , Proteínas Priônicas/química , Proteínas Priônicas/genética , Proteínas Priônicas/metabolismo , Ligação Proteica , Conformação Proteica em alfa-Hélice , Domínios e Motivos de Interação entre Proteínas , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Relação Estrutura-Atividade , Termodinâmica
3.
Int J Sports Med ; 33(10): 773-80, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22499567

RESUMO

This study investigated the influence of chronological (CA) and skeletal ages (SA), anthropometry, aerobic endurance and lower limb explosive strength on developmental changes in repeated-sprint ability (RSA) in soccer players aged 11-17 years. Participants were annually followed over 5 years, resulting in 366 measurements. Multilevel regression modelling analysed longitudinal data aligned by CA and SA (Model 1 and 2, respectively). After diagnosing for multicollinearity, it was possible to predict RSA with 2-level hierarchical models [Model 1 (CA as Level 2 predictor): Log-Likelihood=1,515.29, p<0.01; Model 2 (SA as Level 2 predictor): Log-Likelihood=1,513.89, p<0.01]. Estimating sum of sprints for young soccer players are given by equations: sum of sprints=84.47 - 1.82 × CA + 0.03 × CA2 - 0.05 × aerobic endurance - 0.10 × lower limb explosive strength -0.09 × fat-free mass + 0.13 × fat mass (Model 1); 73.58 - 0.43 × SA - 0.05 × aerobic endurance - 0.10 × lower limb explosive strength - 0.08 × fat-free mass - 0.45 × training experience + 0.13 × fat mass (Model 2). The models produced performance curves that may be used to estimate individual performance across adolescent years. Finally, the validity of each model was confirmed based on corresponding measurements taken on an independent cross-sectional sample.


Assuntos
Determinação da Idade pelo Esqueleto , Extremidade Inferior/fisiologia , Modelos Biológicos , Resistência Física/fisiologia , Corrida/fisiologia , Futebol/fisiologia , Adolescente , Antropometria , Desempenho Atlético/fisiologia , Criança , Estudos Transversais , Feminino , Humanos , Modelos Lineares , Estudos Longitudinais , Extremidade Inferior/crescimento & desenvolvimento , Masculino , Força Muscular/fisiologia , Portugal
4.
Int J Sports Med ; 30(12): 906-12, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19941250

RESUMO

As people age, they experience a decline in immune responses. Unusually heavy acute or chronic exercise could increase the risk of upper respiratory tract infection (URTI) whereas regular moderate physical activity may reduce URTI symptomatology. The purpose of the present study was to determine whether an aerobic exercise program would promote chronic adaptations in plasma IgA, IgG and IgM, and salivary IgA (Sal-IgA) in both elderly women and men. Forty-three independently living men and women, aged between 65 and 96 years, were randomly assigned to an aerobic exercising or a control group. Each participant underwent three evaluations (pre, post at 16 weeks and follow-up at 32 weeks). The aerobic exercise group increased resting plasma IgA concentration from 1.08 g. L (-1)+/-0.50 g. L (-1) to 2.29 g. L (-1)+/-0.93 g. L (-1), whereas salivary IgA concentration was unchanged. The control group maintained the plasma IgA values but experienced a decrease in Sal-IgA. The IgG and IgM plasma concentrations increased in both groups, however, only the exercise group maintained higher values in the final follow-up evaluation. Regular aerobic exercise may be effective in promoting IgA immunity and protecting against the deterioration in Sal-IgA values observed in the control group. No gender differences in the immunoglobulin responses to aerobic training were observed.


Assuntos
Exercício Físico , Imunoglobulina A/metabolismo , Imunoglobulina G/metabolismo , Imunoglobulina M/metabolismo , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Imunoglobulina A/sangue , Imunoglobulina A Secretora/metabolismo , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Masculino , Saliva/imunologia
5.
Exp Oncol ; 41(2): 112-122, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31262159

RESUMO

BACKGROUND: Photodynamic therapy (PDT) is an anticancer therapy that associates the photosensitizer (PS), oxygen and light to destroy cancer cells. Methylene blue (MB) is considered a second generation phenothiazine dye with excellent photochemical properties. AIM: To evaluate whether MB-mediated PDT can induce oxidative stress and inflammation, therefore, interfering tumor growth. MATERIALS AND METHODS: The study was conducted on Wistar rats transplanted with Walker 256 carcinosarcoma (W256). The proinflammatory interleukins levels (IL-1ß, IL-6, IL-10, TNF-α) were determined by ELISA, mRNA expression of COX-1, COX-2, iNOS and eNOS by RT-PCR, lipid peroxidation was measured by the TBARS method. Moreover, myeloperoxidase (MPO) activity in neutrophils was determined by MPO activity assay. All indices mentioned above were determined in tumor tissue. Kaplan - Meier and Gehan - Breslow - Wilcoxon tests were used for survival analysis. RESULTS: We found that the treatment of W256 with 0.1% MB + 1 J/cm2 provoked a significant increase in the interleukins levels (IL-1ß, IL-6, IL-10, TNF-α), prostaglandin E2, the mRNA expression of COX-2, iNOS, lipid peroxidation and MPO activity in tumor tissue, which were statistically different (p < 0.05) compared to other experimental and control groups. The results of the estimation of survival curves show a greater probability of survival in 0.1% MB + 1 J/cm2 (total energy dose =142.8 J/cm2) treated group. CONCLUSION: Our results suggest that treatment of W256 with 0.1% MB + 1 J/cm2 was able to promote cytotoxic effects in tumor tissue by the generation of reactive oxygen species causing inflammation and thus interfering in the tumor growth.


Assuntos
Carcinoma 256 de Walker/tratamento farmacológico , Azul de Metileno/farmacologia , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Animais , Proteínas de Transporte/sangue , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Ciclo-Oxigenase 1/metabolismo , Feminino , Inflamação/induzido quimicamente , Interleucina-10/sangue , Interleucina-1beta/sangue , Interleucina-6/sangue , Peroxidação de Lipídeos , Proteínas de Membrana/metabolismo , Neutrófilos/imunologia , Óxido Nítrico Sintase Tipo II/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar
6.
Artigo em Inglês | MEDLINE | ID: mdl-17923400

RESUMO

Ginger, the rhizome of Zingiber officinalis Roscoe (Zingiberaceae), is a common constituent of diets around the world and its extracts have been reported to exhibit several pharmacological activities. We investigated the effect of crude hydroalcoholic extract of ginger on the rat trachea hyperreactivity (RTHR) and lung inflammation induced by lipopolysaccharide (LPS). Our results demonstrate that ginger extract and celecoxib attenuated RTHR 90 min and 48 h after LPS. Ginger and celecoxib reduced the serum level of prostaglandin (PGE2) and thromboxane (TXA2) 90 min after LPS. Celecoxib and ginger also reduced myeloperoxidase activity and the number of cells in rat bronchoalveolar lavage 48 h post-LPS. On lung parenchyma, ginger and celecoxib reduced the release of PGE2 and TXA2 48 h post-LPS. These results suggest that ginger exerts an anti-inflammatory effect on lung attenuating RTHR and COX metabolites seem to be involved in these processes.


Assuntos
Hiper-Reatividade Brônquica/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Pneumonia/tratamento farmacológico , Traqueia/fisiopatologia , Zingiber officinale/química , Animais , Hiper-Reatividade Brônquica/induzido quimicamente , Líquido da Lavagem Broncoalveolar/citologia , Celecoxib , Dinoprostona/sangue , Lipopolissacarídeos , Masculino , Masoprocol/farmacologia , Fitoterapia , Pneumonia/induzido quimicamente , Pirazóis/farmacologia , Ratos , Ratos Wistar , Rizoma/química , Sulfonamidas/farmacologia , Tromboxano A2/sangue , Traqueia/efeitos dos fármacos
7.
Photomed Laser Surg ; 25(2): 112-7, 2007 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17508847

RESUMO

OBJECTIVE: The aim of this study was to investigate if low-level laser therapy (LLLT) can modulate formation of hemorrhagic lesions induced by immune complex. BACKGROUND DATA: There is a lack of information on LLLT effects in hemorrhagic injuries of high perfusion organs, and the relative efficacy of LLLT compared to anti-inflammatory drugs. METHODS: A controlled animal study was undertaken with 49 male Wistar rats randomly divided into seven groups. Bovine serum albumin (BSA) i.v. was injected through the trachea to induce an immune complex lung injury. The study compared the effect of irradiation by a 650-nm Ga-Al-As laser with LLLT doses of 2.6 Joules/cm(2) to celecoxib, dexamethasone, and control groups for hemorrhagic index (HI) and myeloperoxide activity (MPO) at 24 h after injury. RESULTS: The HI for the control group was 4.0 (95% CI, 3.7-4.3). Celecoxib, LLLT, and dexamethasone all induced significantly (p < 0.01) lower HI than control animals at 2.5 (95% CI, 1.9-3.1), 1.8 (95% CI, 1.2-2.4), and 1.5 (95% CI, 0.9-2.1), respectively, for all comparisons to control. Dexamethasone, but not celecoxib, induced a slightly, but significantly lower HI than LLLT (p = 0.04). MPO activity was significantly decreased in groups receiving celecoxib at 0.87 (95% CI, 0.63-1.11), dexamethasone at 0.50 (95% CI, 0.24-0.76), and LLLT at 0.7 (95% CI, 0.44-0.96) when compared to the control group, at 1.6 (95% CI, 1.34-1.96; p < 0.01), but there were no significant differences between any of the active treatments. CONCLUSION: LLLT at a dose of 2.6 Joules/cm(2) induces a reduction of HI levels and MPO activity in hemorrhagic injury that is not significantly different from celecoxib. Dexamethasone is slightly more effective than LLLT in reducing HI, but not MPO activity.


Assuntos
Hemorragia/radioterapia , Doenças do Complexo Imune/complicações , Terapia com Luz de Baixa Intensidade , Pneumopatias/radioterapia , Animais , Anti-Inflamatórios/farmacologia , Celecoxib , Dexametasona/farmacologia , Hemorragia/tratamento farmacológico , Hemorragia/etiologia , Pneumopatias/tratamento farmacológico , Pneumopatias/etiologia , Masculino , Pirazóis/farmacologia , Ratos , Ratos Wistar , Sulfonamidas/farmacologia
8.
Br J Sports Med ; 40(1): 76-80; discussion 76-80, 2006 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-16371497

RESUMO

BACKGROUND: Low level laser therapy (LLLT) has gained increasing popularity in the management of tendinopathy and arthritis. Results from in vitro and in vivo studies have suggested that inflammatory modulation is one of several possible biological mechanisms of LLLT action. OBJECTIVE: To investigate in situ if LLLT has an anti-inflammatory effect on activated tendinitis of the human Achilles tendon. SUBJECTS: Seven patients with bilateral Achilles tendinitis (14 tendons) who had aggravated symptoms produced by pain inducing activity immediately before the study. METHOD: Infrared (904 nm wavelength) LLLT (5.4 J per point, power density 20 mW/cm2) and placebo LLLT (0 J) were administered to both Achilles tendons in random blinded order. RESULTS: Ultrasonography Doppler measurements at baseline showed minor inflammation through increased intratendinous blood flow in all 14 tendons and measurable resistive index in eight tendons of 0.91 (95% confidence interval 0.87 to 0.95). Prostaglandin E2 concentrations were significantly reduced 75, 90, and 105 minutes after active LLLT compared with concentrations before treatment (p = 0.026) and after placebo LLLT (p = 0.009). Pressure pain threshold had increased significantly (p = 0.012) after active LLLT compared with placebo LLLT: the mean difference in the change between the groups was 0.40 kg/cm2 (95% confidence interval 0.10 to 0.70). CONCLUSION: LLLT at a dose of 5.4 J per point can reduce inflammation and pain in activated Achilles tendinitis. LLLT may therefore have potential in the management of diseases with an inflammatory component.


Assuntos
Tendão do Calcâneo , Dinoprostona/metabolismo , Terapia com Luz de Baixa Intensidade/métodos , Tendinopatia/radioterapia , Tendão do Calcâneo/diagnóstico por imagem , Tendão do Calcâneo/metabolismo , Adulto , Método Duplo-Cego , Humanos , Microdiálise/métodos , Pessoa de Meia-Idade , Medição da Dor , Tendinopatia/diagnóstico por imagem , Resultado do Tratamento , Ultrassonografia
9.
Photomed Laser Surg ; 24(1): 33-7, 2006 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-16503786

RESUMO

OBJECTIVE: The aim of this study was to investigate if low-level laser therapy (LLLT) can modulate acute inflammation and tumor necrosis factor (TNFalpha) levels. BACKGROUND DATA: Drug therapy with TNFalpha-inhibitors has become standard treatment for rheumatoid arthritis, but it is unknown if LLLT can reduce or modulate TNFalpha levels in inflammatory disorders. METHODS: Two controlled animal studies were undertaken, with 35 male Wistar rats randomly divided into five groups each. Rabbit antiserum to ovalbumin was instilled intrabronchially in one of the lobes, followed by the intravenous injection of 10 mg of ovalbumin in 0.5 mL to induce acute lung injury. The first study served to define the time profile of TNFalpha activity for the first 4 h, while the second study compared three different LLLT doses to a control group and a chlorpromazine group at a timepoint where TNFalpha activity was increased. The rats in LLLT groups were irradiated within 5 min at the site of injury by a 650-nm Ga-Al-As laser. RESULTS: There was a time-lag before TNFalpha activity increased after BSA injection. TNFalpha levels increased from < or =6.9 (95% confidence interval [CI], 5.6-8.2) units/mL in the first 3 h to 62.1 (95% CI, 60.8-63.4) units/mL (p < 0.001) at 4 h. An LLLT dose of 0.11 Joules administered with a power density of 31.3 mW/cm(2) in 42 sec significantly reduced TNFalpha level to 50.2 (95% CI, 49.4-51.0), p < 0.01 units/mL versus control. Chlorpromazine reduced TNFalpha level to 45.3 (95% CI, 44.0-46.6) units/mL, p < 0.001 versus control. CONCLUSION: LLLT can reduce TNFalpha expression after acute immunocomplex lung injury in rats, but LLLT dose appears to be critical for reducing TNFalpha release.


Assuntos
Líquido da Lavagem Broncoalveolar/química , Inflamação/metabolismo , Terapia com Luz de Baixa Intensidade , Fator de Necrose Tumoral alfa/análise , Animais , Pulmão/metabolismo , Masculino , Modelos Animais , Dosagem Radioterapêutica , Ratos , Ratos Wistar , Traumatismo por Reperfusão/metabolismo
10.
Plant Physiol ; 114(2): 475-481, 1997 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-12223721

RESUMO

The influence of various environmental factors on biomass partitioning between shoots and roots in transgenic tobacco (Nicotiana tabacum) plants expressing the movement protein (MP) of tobacco mosaic virus (TMV) was investigated. TMV-MP-expressing transgenic plants exhibited a root-to-shoot ratio that was approximately 40% below that of transgenic vector control plants. When transgenic plants expressing the TMV-MP were subjected to water-stress conditions, the root-to-shoot ratio was increased to a value comparable to that of control plants subjected to the same water-stress treatment. Although the root-to-shoot ratio was increased by N or P deficiencies, the TMV-MP-induced alteration in biomass partitioning was not overcome. Surprisingly, under K+-deficient growth conditions, both TMV-MP-expressing and control plants exhibited reduced root-to-shoot ratios when compared with plants grown in the presence of sufficient K+. Furthermore, plant growth under K+-deficient conditions did not alleviate the influence of the TMV-MP over resource allocation to the roots. These results are discussed in terms of possible mechanisms by which stress signals could cause an alteration in biomass partitioning between shoots and roots in control and transgenic tobacco plants expressing the TMV-MP.

11.
Br J Pharmacol ; 113(1): 81-6, 1994 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-7529116

RESUMO

1. The roles of the tissue kallikrein-kinin system and nitric oxide (NO) release in Phoneutria nigriventer venom-induced relaxations of rabbit corpus cavernosum (RbCC) smooth muscle have been investigated by use of a bioassay cascade. 2. Phoneutria nigriventer venom (10-30 micrograms), porcine pancreatic kallikrein (100 mu), rabbit urinary kallikrein (10 mu), bradykinin (BK, 0.3-3 nmol), acetylcholine (ACh, 0.3-30 nmol) and glyceryl trinitrate (GTN, 0.5-10 nmol) caused relaxations of the RbCC strips. Captopril (1 microM) substantially potentiated Phoneutria nigriventer venom- and BK-induced RbCC relaxations without affecting those elicited by GTN. 3. The bradykinin B2 receptor antagonist, Hoe 140 (D-Arg-[Hyp3,Thi5,D- Tic7,Oic8]-BK, 50 nM), aprotinin (10 micrograms ml-1) and the tissue kallikrein inhibitor, Pro-Phe-Aph-Ser-Val- Gln-NH2 (KIZD-06, 1.3 microM) significantly inhibited Phoneutria nigriventer venom-induced RbCC relaxations, without affecting those provoked by GTN and ACh. The B1 receptor antagonist, [Leu9]des Arg10BK (0.5 microM) and soybean trypsin inhibitor (SBTI, 10 micrograms ml-1) had no effect on Phoneutria nigriventer venom-induced RbCC relaxations. 4. The relaxations induced by Phoneutria nigriventer venom, porcine pancreas kallikrein, BK and ACh were significantly inhibited by N omega-nitro-L-arginine methyl ester (L-NAME, 10 microM) but not by D-NAME (10 microM). L-NAME did not affect GTN-induced relaxations. L-Arginine (300 microM), but not D-arginine (300 microM), significantly reversed the inhibitory effect of L-NAME. 5. Our results indicate that Phoneutria nigriventer venom activates the tissue kallikrein-kininogen-kinin system in RbCC strips leading to NO release and suggest a functional role for this system in penile erection.


Assuntos
Sistema Calicreína-Cinina/fisiologia , Músculo Liso Vascular/fisiologia , Pênis/fisiologia , Antagonistas Adrenérgicos beta/farmacologia , Sequência de Aminoácidos , Animais , Aprotinina/farmacologia , Arginina/análogos & derivados , Arginina/farmacologia , Bradicinina/análogos & derivados , Bradicinina/farmacologia , Captopril/farmacologia , Técnicas In Vitro , Sistema Calicreína-Cinina/efeitos dos fármacos , Calicreínas/antagonistas & inibidores , Calicreínas/urina , Masculino , Dados de Sequência Molecular , Relaxamento Muscular/efeitos dos fármacos , Músculo Liso Vascular/efeitos dos fármacos , NG-Nitroarginina Metil Éster , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico/fisiologia , Oligopeptídeos/farmacologia , Pênis/efeitos dos fármacos , Coelhos , Venenos de Aranha/farmacologia
12.
Br J Pharmacol ; 123(3): 435-42, 1998 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-9504384

RESUMO

1. The effect of Tityus serrulatus scorpion venom and its toxin components on the rabbit isolated corpus cavernosum was investigated by use of a bioassay cascade. 2. Tityus serrulatus venom (3-100 microg), acetylcholine (ACh; 0.3-30 nmol) and glyceryl trinitrate (GTN; 0.5-10 nmol) dose-dependently relaxed rabbit isolated corpus cavernosum preparations precontracted with noradrenaline (3 microM). The selective soluble guanylate cyclase inhibitor 1H-[1,2,4] oxadiazolo [4,3,-alquinoxalin-1-one] (ODQ; 30 microM) increased the basal tone of the rabbit isolated corpus cavernosum and abolished the relaxations induced by the agents mentioned above. Methylene blue (30 microM) also inhibited the relaxations induced by Tityus serrulatus venom but, in contrast to ODQ, the inhibition was irreversible. 3. The non-selective NO synthase (NOS) inhibitors Nomega-nitro-L-arginine methyl ester (L-NAME; 10 microM) and NG-iminoethyl-L-ornithine (L-NIO; 30 microM) also increased the tone of the rabbit isolated corpus cavernosum and markedly reduced both ACh- and Tityus serrulatus venom-induced relaxations without affecting those evoked by GTN. The inhibitory effect was reversed by infusion of L-arginine (300 microM), but not D-arginine (300 microM). The neuronal NOS inhibitor 1-(2-trifluoromethylphenyl) imidazole (TRIM, 100 microM) did not affect either the tone of the rabbit isolated corpus cavernosum or the relaxations induced by ACh, bradykinin (Bk), Tityus serrulatus venom and GTN. TRIM was approximately 1,000 times less potent than L-NAME in inhibiting rabbit cerebellar NOS in vitro, as measured by the conversion of [3H]-L-arginine to [3H]-L-citrulline. 4. The protease inhibitor aprotinin (Trasylol; 10 microg ml[-1]) and the bradykinin B2 receptor antagonist Hoe 140 (D-Arg-[Hyp3,Thi5,D-Tic7, Oic8]-BK; 50 nM) did not affect the rabbit isolated corpus cavernosum relaxations induced by Tityus serrulatus venom. The ATP-dependent K+ channel antagonist glibenclamide (10 microm) and the Ca2+-activated K+ channel antagonists apamin (0.1 microM) and charybdotoxin (0.1 microM) also failed to affect the venom-induced relaxations. Similarly, the K+ channel blocker tetraethylammonium (TEA; 10 microM) had no effect on the venom-induced relaxations. 5. Capsaicin (3 and 10 nmol) relaxed the rabbit isolated corpus cavernosum in a dose-dependent and non-tachyphylactic manner. Ruthenium red (30 microM), an inhibitor of capsaicin-induced responses, markedly reduced the relaxations caused by capsaicin, but failed to affect those induced by Tityus serrulatus venom. L-NAME (10 microM) had no effect on the capsaicin-induced relaxations of the rabbit isolated corpus cavernosum. 6. The sodium channel blocker tetrodotoxin (TTX; 1 microM) abolished the relaxations of the rabbit isolated corpus cavernosum induced by Tityus serrulatus venom without affecting those evoked by capsaicin, ACh and GTN. Tetrodotoxin (1 microM) also promptly reversed the response to the venom when infused during the relaxation phase. 7. The bioassay cascade of the toxin components purified from Tityus serrulatus venom revealed that only fractions X, XI and XII caused dose-dependent relaxations of the rabbit isolated corpus cavernosum and these were markedly reduced by either TTX (1 microM) or L-NAME (10 microM). 8. Our results indicate that Tityus serrulatus scorpion venom (and the active fractions X, XI and XII) relaxes rabbit corpus cavernosum via the release of NO. This release is specifically triggered by the activation of capsaicin-insensitive cavernosal non-adrenergic non-cholinergic (NANC) fibres, that may possibly be nitrergic neurones. Tityus serrulatus venom may therefore provide an important tool for understanding further the mechanism of NANC nitrergic nerve activation.


Assuntos
Óxido Nítrico/fisiologia , Pênis/efeitos dos fármacos , Venenos de Escorpião/farmacologia , Animais , Aprotinina/farmacologia , Atropina/farmacologia , Bradicinina/análogos & derivados , Bradicinina/farmacologia , Inibidores Enzimáticos/farmacologia , Técnicas In Vitro , Masculino , Óxido Nítrico Sintase/antagonistas & inibidores , Óxido Nítrico Sintase/metabolismo , Pênis/inervação , Pênis/metabolismo , Bloqueadores dos Canais de Potássio , Coelhos , Receptores Adrenérgicos/metabolismo , Receptores Colinérgicos/metabolismo , Bloqueadores dos Canais de Sódio , Tetrodotoxina/farmacologia
13.
Brain Res ; 827(1-2): 79-92, 1999 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-10320696

RESUMO

Activation of glutamate receptors has been implicated in excitotoxicity. Here, we have investigated whether subtoxic concentrations of glutamate can modulate neuronal death in the developing retina. Explants of rat retinas were pre-incubated with glutamate, N-methyl-d-aspartate (NMDA), kainate, quisqualate or trans-1-amino-1,3-cyclopentanedicarboxylic acid (t-ACPD) for 18 h. Then, glutamate (6 mM) was added to the explants for an additional 6 h. Glutamate-induced degeneration was restricted to the emerging inner nuclear layer. Pre-incubation with glutamate, NMDA, or both, reduced glutamate-induced neuronal death and protected against neuronal death induced by irradiation (2 Gy). The NMDA receptor antagonists, 2-amino-5-phosphonovaleric acid (d-APV; 30 microM) or 5-methyl-10,11-dihydro-5H-dibenzocyclohepten-5,10-imine hydrogen maleate (MK-801; 30 microM), prevented glutamate-induced neuroprotection. To investigate whether this neuroprotection was mediated by neurotrophins, we incubated retinal explants with either brain-derived neurotrophic factor or neurotrophin-4. Both treatments resulted in partial protection against glutamate-induced neurotoxicity. Furthermore, NMDA mediated neuroprotection was totally reversed when a soluble form of the specific tyrosine kinase receptor B was simultaneously added to the explants. Our results suggest that activation of NMDA receptors may control neuronal death in the retina during development. This modulation seems to depend, at least in part, on the release of neurotrophins within the retina.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/farmacologia , Ácido Glutâmico/toxicidade , Fatores de Crescimento Neural/fisiologia , Receptores de N-Metil-D-Aspartato/fisiologia , Retina/citologia , 2-Amino-5-fosfonovalerato/farmacologia , Animais , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Cicloleucina/análogos & derivados , Cicloleucina/farmacologia , Maleato de Dizocilpina/farmacologia , Agonistas de Aminoácidos Excitatórios/farmacologia , Antagonistas de Aminoácidos Excitatórios/farmacologia , Ácido Caínico/farmacologia , N-Metilaspartato/farmacologia , Fármacos Neuroprotetores/farmacologia , Quinoxalinas/farmacologia , Ácido Quisquálico/farmacologia , Ratos , Ratos Endogâmicos , Receptores Proteína Tirosina Quinases/metabolismo , Receptor do Fator Neutrófico Ciliar , Receptores de Fator de Crescimento Neural/metabolismo , Retina/efeitos dos fármacos
14.
Naunyn Schmiedebergs Arch Pharmacol ; 359(6): 505-11, 1999 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-10431763

RESUMO

The hypothesis that platelet-activating factor (PAF) plays a role in the modulation of the vasomotor tone and blood pressure was put forward by our group in previous in vivo studies in anaesthetised rabbits. The present study was undertaken to investigate the putative role of this lipid mediator in the vascular reactivity of the renal circulation, using the experimental model of the isolated perfused rabbit kidney. Dose-response curves to noradrenaline-induced vasoconstriction were performed before and after continuous infusions of two different PAF-receptor antagonists (WEB 2086 and yangambin) and of the phospholipase A2 inhibitor mepacrine. The increases in renal perfusion pressure elicited by noradrenaline were potentiated by all the above-mentioned treatments in a dose-dependent manner. Moreover, prostaglandin F2alpha-induced vasoconstriction was also potentiated by the administration of the PAF receptor antagonists and mepacrine. Furthermore, the administration of PAF into the renal circulation induced dose-related and long-lasting vasodilator responses, which were blocked by the PAF receptor antagonists. Nevertheless, PAF-induced renal vasodilation was also abolished by a pretreatment with mepacrine or with the cyclooxygenase inhibitor indomethacin, suggesting that it enhances the secondary formation of vasodilator arachidonic acid metabolites. The data indicate that PAF is involved in the modulation of the vasomotor tone in the renal circulation, through the release of cyclooxygenase products, constituting an additional mechanism of modulation of smooth muscle cell contractility to the ones exerted by well-known vasoactive substances of endothelial origin such as nitric oxide.


Assuntos
Tono Muscular/fisiologia , Músculo Liso Vascular/fisiologia , Fator de Ativação de Plaquetas/fisiologia , Circulação Renal/fisiologia , Animais , Azepinas/farmacologia , Dinoprosta/farmacologia , Inibidores Enzimáticos/farmacologia , Feminino , Furanos/farmacologia , Técnicas In Vitro , Rim/fisiologia , Lignanas/farmacologia , Masculino , Norepinefrina/farmacologia , Fosfolipases A/antagonistas & inibidores , Fosfolipases A2 , Inibidores da Agregação Plaquetária/farmacologia , Quinacrina/farmacologia , Coelhos , Triazóis/farmacologia , Vasoconstritores/farmacologia
15.
Toxicon ; 34(10): 1141-7, 1996 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-8931254

RESUMO

The venom of the Brazilian spider Phoneutria nigriventer was fractionated using a C18 microBondapack reverse-phase high-performance liquid chromatography column. The resulting fractions were assayed in the rabbit perfused corpus cavernosum tissue to identify those fractions responsible for the corpus cavernosum relaxation. Two fractions (A and B) with retention times of 18.1 and 36.7 min, respectively, induced relaxation of corpus cavernosum strips. Fraction A was selected for further biochemical characterization. Repurification of this fraction revealed the presence of a polypeptide (named PNV4) which migrates in sodium dodecyl sulphate-polyacrylamide gel electrophoresis as a single band consistent with a mol. wt close to 16,600. The amino acid composition of PNV4 showed the presence of 147 residues, a high content of Cys and a calculated mol. wt of 17,213 + Trp. The N-terminal amino acid sequence of PNV4 determined for its first 48 residues was AELTSCFPVGHECDGDASNCNCCGDDVYCGCGWGRWNCKCKVADQSYA.


Assuntos
Pênis/efeitos dos fármacos , Peptídeos/isolamento & purificação , Venenos de Aranha/isolamento & purificação , Sequência de Aminoácidos , Animais , Masculino , Dados de Sequência Molecular , Peptídeos/farmacologia , Coelhos , Venenos de Aranha/química , Venenos de Aranha/farmacologia
16.
J Photochem Photobiol B ; 74(2-3): 101-7, 2004 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-15157905

RESUMO

The purpose of the present study was to investigate the effect of the low power laser therapy on the acute inflammatory process. Male Wistar rats were used. The rat paw oedema was induced by sub-plantar injection of carrageenan, the paw volume was measured before and 1, 2, 3 and 4 h after the injection using a hydroplethysmometer. To investigate the mechanism action of the Ga-Al-As laser on inflammatory oedema, parallel studies were performed using adrenallectomized rats or rats treated with sodium diclofenac. Different laser irradiation protocols were employed for specific energy densities (EDs), exposure times and repetition rates. The rats were irradiated with the Ga-Al-As laser during 80 s each hour. The ED that produced an anti-inflammatory effect were 1 and 2.5 J/cm(2), reducing the oedema by 27% (P<0.05) and 45.4% (P<0.01), respectively. The ED of 2.5 J/cm(2) produced anti-inflammatory effects similar to those produced by the cyclooxigenase inhibitor sodium diclofenac at a dose of 1 mg/kg. In adrenalectomized animals, the laser irradiation failed to inhibit the oedema. Our results suggest that low power laser irradiation possibly exerts its anti-inflammatory effects by stimulating the release of adrenal corticosteroid hormones.


Assuntos
Alumínio , Arseniatos , Carragenina/farmacologia , Edema/induzido quimicamente , Edema/radioterapia , Extremidades/efeitos da radiação , Gálio , Terapia com Luz de Baixa Intensidade , Adrenalectomia , Animais , Diclofenaco/farmacologia , Edema/tratamento farmacológico , Edema/patologia , Extremidades/patologia , Inflamação/induzido quimicamente , Inflamação/patologia , Inflamação/radioterapia , Masculino , Ratos , Ratos Wistar , Fatores de Tempo
18.
Arq. bras. med. vet. zootec ; 66(5): 1442-1448, Sep-Oct/2014. tab
Artigo em Português | LILACS | ID: lil-729744

RESUMO

Estudou-se o efeito da idade sobre a fertilidade de éguas inseminadas com sêmen asinino diluído, resfriado e armazenado. Os ciclos foram acompanhados por palpação transretal e rufiação, sendo as inseminações realizadas às terças, quintas e sábados, a partir da detecção de um folículo de 3,0 a 3,5cm de diâmetro, em um dos ovários, até a ovulação. O sêmen de cinco jumentos da raça Pêga foi diluído nos diluidores de leite em pó desnatado-glicose ou glicina-gema de ovo, resfriado a 5ºC e armazenado por 12 horas, sendo a dose inseminante de 400 x 106 espermatozoides móveis (no momento da diluição final, pré-resfriamento). Os resultados de 195 ciclos estrais, referentes a 141 éguas, foram agrupados em classes, de acordo com a idade das éguas: 2,5 a 6 anos, 6,5 a 10 anos, 10,5 a 14 anos e 14,5 a 19 anos. As taxas de concepção, ao primeiro ciclo, foram de 68,42%, 50,75%, 46,88% e 52,17% e, após quatro ciclos, de 69,57%, 47,92%, 46,34% e 45,71% para as faixas etárias de 2,5 a 6, 6,5 a 10, 10,5 a 14 e 14,5 a 19 anos, respectivamente (P>0,05). A idade não teve efeito sobre a fertilidade das éguas inseminadas com sêmen asinino diluído e resfriado...


The effect of the mare age on fertility of mares inseminated with diluted, cooled and stored jackass semen was studied. The females were controlled by transrectal palpation and teasing, and inseminated every Tuesday, Thursday and Saturday, since the detection of a 3.0 to 3.5cm follicle diameter, in one of the ovaries, until ovulation. The semen of five Pêga jackasses was diluted in skim milk-glucose or in egg yolk-glicine extender and cooled at 5ºC for 12 hours, with the inseminate dose of 400 x 106 motile spermatozoa (at the moment of the final dilution, before cooling). The results of 195 cycles of 141 mares were grouped, in accordance with the age: 2.5 to 6 years, 6.5 to 10 years, 10.5 to 14 years and 14.5 to 19 years. The pregnancy rates for the first cycle were 68.42%, 50.75%, 46.88% and 52.17%, and after four cycles, the pregnancy rates/cycle were 69.57%, 47.92%, 46.34% and 45.71%, respectively for 2.5 to 6, 6.5 to 10, 10.5 to 14 and 14.5 to 19 years (P>0,05). The mare age had no influence on fertility, using diluted and cooled jackass semen...


Assuntos
Animais , Fatores Etários , Equidae/embriologia , Fármacos para a Fertilidade , Perda do Embrião/veterinária , Inseminação Artificial/veterinária , Sêmen
19.
Arq. bras. med. vet. zootec ; 66(6): 1655-1661, 12/2014. tab
Artigo em Português | LILACS | ID: lil-735752

RESUMO

Estudou-se o efeito da categoria reprodutiva sobre a fertilidade de éguas inseminadas com sêmen asinino diluído, resfriado e armazenado. Os ciclos foram acompanhados por palpação retal e rufiação, sendo as inseminações realizadas às terças, quintas e sábados, a partir da detecção de um folículo de 3,0 a 3,5cm de diâmetro, em um dos ovários, até a ovulação. O sêmen de cinco jumentos da raça Pêga foi diluído nos diluidores de leite em pó desnatado-glicose ou glicina-gema de ovo, resfriado a 5ºC e armazenado por 12 horas, sendo a dose inseminante de 400 x 106 espermatozoides móveis (no momento da diluição final, pré-resfriamento) depositada no corpo do útero. O diagnóstico de gestação foi realizado por meio de palpação transretal, rufiação e ultrassonografia, realizada a cada 14 dias. Os resultados de 195 ciclos, referentes a 141 éguas, foram agrupados de acordo com a categoria reprodutiva a que pertenciam: potra, égua solteira, égua parida e no "cio do potro". As taxas de concepção, ao primeiro ciclo, foram de 60,00%, 48,28%, 75,00% e 47,17% e, após quatro ciclos, de 61,54%, 47,13%, 54,76% e 47,17%, na mesma ordem para as categorias descritas anteriormente. A categoria reprodutiva não teve efeito (P>0,05) sobre a fertilidade das éguas inseminadas com sêmen asinino resfriado, sendo as potras, éguas solteiras, éguas paridas e no "cio do potro" igualmente eficientes para o uso na reprodução...


The effect of the mare status on fertility of mares inseminated with diluted, cooled and stored jackass semen, was studied. The cycles were controlled by transrectal palpation and teasing, and mares were inseminated every Tuesday, Thursday and Saturday, from the detection of a follicle with 3.0 to 3.5cm diameter in one of the ovaries until ovulation. The semen of five Pêga jackasses was diluted in skim milk-glucose or in egg yolk-glycine extender and cooled at 5ºC for 12 hours, with the inseminate dose of 400 x 106 motile spermatozoa (at the moment of the final dilution, before cooling). The inseminations were carried out in the uterine body. Pregnancy was detected using transrectal palpation, teasing and ultrasound exams every 14 days. The results of 195 cycles of 141 mares were grouped according to the mare status: maiden, barren, lactation or in foal heat. Pregnancy rates for the first cycle were 60.00%, 48.28%, 75.00% and 47.17%, and after four cycles, the pregnancy rates/cycle were 61.54%, 47.13%, 54.76% and 47.17%, respectively for maiden, barren, lactation and in foal heat mares (P>0,05). The mare status did not affect pregnancy rates of mares inseminated with diluted and cooled jackass semen and were efficient to use on reproduction...


Assuntos
Animais , Equidae , Fármacos para a Fertilidade , Técnicas Reprodutivas , Fertilidade , Análise do Sêmen , Preservação do Sêmen
20.
Rev Neurol ; 46(3): 135-8, 2008.
Artigo em Espanhol | MEDLINE | ID: mdl-18297618

RESUMO

AIM: To verify the muscular force and resistance to the movement of the flexor and extensor muscles of the knee of patients with spasticity after treatment with neuromuscular electrical stimulation (NMES) and isotonic exercises. PATIENTS AND METHODS: The patients this study were divided into group 1 (NMES) and group 2 (isotonic exercises). Their muscular torque and resistance to the movement of the flexor and extensor knee muscles were measured by the isokinetic dynamometer and the degree of spasticity by the modified Ashworth scale before and after ten sessions. RESULTS: Alterations in the scores of the modified Ashworth scale were not observed. An increase in the flexor torque in group 1 (p = 0.041) and in group 2 (p = 0.001) was verified. In the passive mode, group 1 presented a reduction of resistance to the flexion movement (p = 0.026), while in group 2, a reduction of resistance to both the flexion (p = 0,029) and extension movements (p = 0.019) was verified. CONCLUSIONS: The two therapeutical resources had their efficiency proven only for the increase of the force of the flexor muscles. The resistance to movement, the isotonic exercises were more effective because they promoted a reduction in the resistance of the flexor and extensor knee muscles.


Assuntos
Terapia por Estimulação Elétrica , Terapia por Exercício , Hemiplegia/reabilitação , Feminino , Humanos , Joelho , Masculino , Pessoa de Meia-Idade , Músculo Esquelético
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