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1.
Rev Gastroenterol Mex (Engl Ed) ; 85(3): 257-263, 2020.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-32019715

RESUMO

INTRODUCTION AND AIM: Normally, the bile ducts are sterile, but up to 4.2% of healthy persons can present with positive cultures. Certain circumstances favor that situation, such as gallstones or biliary tree manipulation. The aim of the present study was to determine the factors that influence the presence of bacteriobilia, as well as its implications for clinical practice. MATERIALS AND METHODS: A prospective study was conducted on bile cultures from patients that underwent cholecystectomy at our hospital center within the time frame of 2013 to 2015. RESULTS: The study included 196 patients (42.3% women and 57.7% men) that underwent either open or laparoscopic cholecystectomy and in whom bile fluid samples were taken. The clinical, epidemiologic, and laboratory test characteristics of the patients were analyzed, as well as the surgical indication (urgent surgery or programmed surgery). With respect to microbiology, 47% of the bile cultures were positive: 56.5% presented with one microorganism, 25% with two, and 18.5% with three or more. CONCLUSION: Microbiologic bile analysis should not be systematically performed, given that its result is relevant only in cases that present with demonstrated risk factors. However, in those cases, said analysis is essential to establish adequate antibiotic treatment, in relation to activity spectrum and duration, to prevent complications and an increase in microbial resistance.


Assuntos
Bile/microbiologia , Colecistectomia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
2.
SAR QSAR Environ Res ; 31(3): 209-226, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31916862

RESUMO

The aryl hydrocarbon receptor (AhR) plays an important role in several biological processes such as reproduction, immunity and homoeostasis. However, little is known on the chemical-structural and physicochemical features that influence the activity of AhR antagonistic modulators. In the present report, in vitro AhR antagonistic activity evaluations, based on a chemical-activated luciferase gene expression (AhR-CALUX) bioassay, and an extensive literature review were performed with the aim of constructing a structurally diverse database of contaminants and potentially toxic chemicals. Subsequently, QSAR models based on Linear Discriminant Analysis and Logistic Regression, as well as two toxicophoric hypotheses were proposed to model the AhR antagonistic activity of the built dataset. The QSAR models were rigorously validated yielding satisfactory performance for all classification parameters. Likewise, the toxicophoric hypotheses were validated using a diverse set of 350 decoys, demonstrating adequate robustness and predictive power. Chemical interpretations of both the QSAR and toxicophoric models suggested that hydrophobic constraints, the presence of aromatic rings and electron-acceptor moieties are critical for the AhR antagonism. Therefore, it is hoped that the deductions obtained in the present study will contribute to elucidate further on the structural and physicochemical factors influencing the AhR antagonistic activity of chemical compounds.


Assuntos
Receptores de Hidrocarboneto Arílico/antagonistas & inibidores , Receptores de Hidrocarboneto Arílico/química , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Poluentes Ambientais/química , Poluentes Ambientais/toxicidade , Luciferases/genética , Luciferases/metabolismo , Modelos Moleculares , Relação Quantitativa Estrutura-Atividade , Receptores de Hidrocarboneto Arílico/genética , Receptores de Hidrocarboneto Arílico/metabolismo , Proteínas Recombinantes de Fusão/química , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Reprodutibilidade dos Testes , Bibliotecas de Moléculas Pequenas/química , Bibliotecas de Moléculas Pequenas/toxicidade
3.
Eur J Pharm Sci ; 49(4): 637-41, 2013 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-23727294

RESUMO

The intestinal barrier is a complex system with a dynamic structure that is designed for the maintenance of homeostasis in healthy individuals. Ulcerative colitis, one of the main manifestations of inflammatory bowel disease, is characterized by an inadequate and delayed wound healing. Shikonin, the active principle in the root of Lithospermum erythrorhizon, has demonstrated its ability to attenuate dextran sulfate sodium-induced ulcerative colitis in mice. Moreover, the root of L. erythrorhizon has been used in traditional Chinese medicine for treatment of burns, anal ulcers, hemorrhoids and skin wounds. However, the effect of shikonin on intestinal wound healing is unknown. Using an in vitro model for wound healing, we observed that shikonin enhances cell migration of intestinal epithelial cells through a mechanism that involves TGF-ß1 induction. The combination of shikonin's anti-inflammatory activity together with its wound-healing properties makes it a great potential therapeutic agent for the treatment of injury associated with intestinal inflammation.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Intestinos/lesões , Naftoquinonas/farmacologia , Fator de Crescimento Transformador beta/metabolismo , Cicatrização/efeitos dos fármacos , Animais , Linhagem Celular , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ratos , Fator de Transcrição STAT3/metabolismo , Fator de Transcrição RelA/metabolismo
4.
Curr Med Chem ; 20(23): 2892-8, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23651309

RESUMO

Shikonin is the major constituent of the root of Lithospermum erythrorhizon, which has been used in traditional Chinese medicine to treat external wounds, burns, or dermatitis for centuries. Nowadays, this root is commonly used as an herbal medicine against cancer. Studies carried out over the past 30 years have demonstrated that many of the effects historically associated with the use of this root have a scientific basis, with shikonin and its derivatives being responsible for its pharmacological properties. These include both anti-inflammatory and anticancer effects. While previous summaries have focused on the pharmacokinetics and toxicity of shikonin, the aim of this review is to report on the most current findings with regard to shikonin's antitumor activity by summarizing and comparing the various studies published in the last ten years and discussing the pharmacological aspects that make shikonin a promising anticancer agent.


Assuntos
Antineoplásicos/farmacologia , Medicina Tradicional Chinesa , Naftoquinonas/farmacologia , Naftoquinonas/uso terapêutico , Neoplasias/tratamento farmacológico , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Antineoplásicos/química , Antineoplásicos/uso terapêutico , Humanos , Raízes de Plantas/química
5.
Actas dermo-sifiliogr. (Ed. impr.) ; 104(3): 239-241, abr. 2013. ilus
Artigo em Espanhol | IBECS | ID: ibc-111594

RESUMO

El uso de agentes bloqueadores del factor de necrosis tumoral alfa (anti-TNFα) en pacientes con hepatitis C crónica ha sido descrito en la literatura en su conjunto como seguro y eficaz. Sin embargo, no se han descrito hasta la fecha casos de primoinfección por el virus de la hepatitis C ocurridos durante el tratamiento con un biológico. Presentamos un paciente con psoriasis moderada-severa de larga evolución que, estando en tratamiento con etanercept, sufrió una hepatitis C aguda. Sin suspender el fármaco anti-TNFα recibió tratamiento con interferón pegilado, con respuesta virológica sostenida. Etanercept no interfirió de forma negativa en la evolución de la enfermedad ni en la respuesta al tratamiento antiviral (AU)


According to the literature, the use of tumor necrosis factor (TNF) inhibitors in patients with chronic hepatitis C infection is safe and effective. There have been no reports, however, of primary infection with the hepatitis C virus during treatment with a biologic agent. We report the case of a patient with long-standing moderate to severe psoriasis who developed acute hepatitis C while being treated with etanercept. Biologic therapy was continued and the infection was successfully treated with pegylated interferon, which achieved a sustained virologic response. Etanercept did not have a negative impact on disease outcome or on response to antiviral treatment (AU)


Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Hepatite C/induzido quimicamente , Hepatite C/complicações , Hepatite C/diagnóstico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Psoríase/complicações , Psoríase/diagnóstico , Tratamento Biológico/métodos , Corticosteroides/uso terapêutico , Metotrexato/uso terapêutico , Hepatite C/tratamento farmacológico , Hepatite C/fisiopatologia , Psoríase/tratamento farmacológico , Psoríase/fisiopatologia , Interferons/uso terapêutico
6.
Actas Dermosifiliogr ; 104(3): 239-41, 2013 Apr.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-22579035

RESUMO

According to the literature, the use of tumor necrosis factor (TNF) inhibitors in patients with chronic hepatitis C infection is safe and effective. There have been no reports, however, of primary infection with the hepatitis C virus during treatment with a biologic agent. We report the case of a patient with long-standing moderate to severe psoriasis who developed acute hepatitis C while being treated with etanercept. Biologic therapy was continued and the infection was successfully treated with pegylated interferon, which achieved a sustained virologic response. Etanercept did not have a negative impact on disease outcome or on response to antiviral treatment.


Assuntos
Hepatite C/induzido quimicamente , Imunoglobulina G/efeitos adversos , Receptores do Fator de Necrose Tumoral/antagonistas & inibidores , Doença Aguda , Etanercepte , Humanos , Masculino , Pessoa de Meia-Idade
7.
Rev. esp. anestesiol. reanim ; 59(10): 573-576, dic. 2012.
Artigo em Espanhol | IBECS | ID: ibc-107412

RESUMO

Se describe el procedimiento anestésico en dos pacientes obesos con broncopatía crónica obstructiva que se llevó a cabo mediante la combinación de anestesia epidural y ventilación no invasiva. Esta técnica permitió evitar la intubación, la anestesia general y complicaciones pulmonares perioperatorias(AU)


We report two cases of anesthesia for radical retropubic prostatectomy (RRP) in obese-chronic obstructive pulmonary disease (COPD) patients using the combination of epidural anesthesia and non-invasive ventilation (NIV). This technique avoided intubation, general anesthesia and perioperative pulmonary complications(AU)


Assuntos
Humanos , Masculino , Anestesia Epidural/instrumentação , Anestesia Epidural/métodos , Anestesia Epidural , Prostatectomia/métodos , Respiração Artificial/instrumentação , Respiração Artificial/métodos , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Anestesia Epidural/tendências , Obesidade/complicações , Obesidade/diagnóstico , Respiração Artificial/tendências , Respiração Artificial , Doença Pulmonar Obstrutiva Crônica/terapia , Doença Pulmonar Obstrutiva Crônica
8.
Oxid Med Cell Longev ; 2012: 906252, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23150750

RESUMO

This paper compiles the beneficial effects of cocoa polyphenols on human health, especially with regard to cardiovascular and inflammatory diseases, metabolic disorders, and cancer prevention. Their antioxidant properties may be responsible for many of their pharmacological effects, including the inhibition of lipid peroxidation and the protection of LDL-cholesterol against oxidation, and increase resistance to oxidative stress. The phenolics from cocoa also modify the glycemic response and the lipid profile, decreasing platelet function and inflammation along with diastolic and systolic arterial pressures, which, taken together, may reduce the risk of cardiovascular mortality. Cocoa polyphenols can also modulate intestinal inflammation through the reduction of neutrophil infiltration and expression of different transcription factors, which leads to decreases in the production of proinflammatory enzymes and cytokines. The phenolics from cocoa may thus protect against diseases in which oxidative stress is implicated as a causal or contributing factor, such as cancer. They also have antiproliferative, antimutagenic, and chemoprotective effects, in addition to their anticariogenic effects.


Assuntos
Cacau/química , Saúde , Polifenóis/farmacologia , Animais , Antioxidantes/farmacologia , Disponibilidade Biológica , Doença , Humanos , Polifenóis/química
9.
Rev Esp Anestesiol Reanim ; 59(10): 573-6, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22749299

RESUMO

We report two cases of anesthesia for radical retropubic prostatectomy (RRP) in obese-chronic obstructive pulmonary disease (COPD) patients using the combination of epidural anesthesia and non-invasive ventilation (NIV). This technique avoided intubation, general anesthesia and perioperative pulmonary complications.


Assuntos
Anestesia Epidural , Ventilação não Invasiva , Obesidade/complicações , Prostatectomia , Doença Pulmonar Obstrutiva Crônica/complicações , Idoso , Humanos , Masculino , Pessoa de Meia-Idade
10.
Curr Pharm Des ; 18(12): 1663-76, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22443631

RESUMO

Triterpenes have been reported to induce cell death. One relevant group of this family of compounds is cucurbitacins, which have been studied as inducers of apoptosis in various cancer cell lines. The most significant mechanisms with regard to the apoptotic effects of cucurbitacins are their ability to modify transcriptional activities via nuclear factors or genes and their capability to activate or inhibit pro- or anti-apoptotic proteins. Still, while the majority of studies on these compounds have dealt with their apoptotic effects on cancer cell lines, several research groups have also explored their anti-inflammatory activities. In general, cucurbitacins are considered to be selective inhibitors of the JAK/STAT pathways; however, other mechanisms may be implicated in their apoptotic effects, including the MAPK pathway (known to be important for cancer cell proliferation and survival), PARP cleavage, expression of active caspase-3, decreased pSTAT3 and JAK3 levels, as well as decreases in various downstream STAT3 targets such as Mcl-1, Bcl-2, Bcl-xL, and cyclin D3, all of which are implicated in apoptosis and the cell cycle. Taking all these effects into account, cucurbitacins may prove useful in the treatment of different kinds of cancers, especially when used with other cytostatic agents.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Cucurbitacinas/farmacologia , Animais , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacocinética , Antineoplásicos Fitogênicos/uso terapêutico , Ciclo Celular/efeitos dos fármacos , Cucurbitacinas/química , Cucurbitacinas/farmacocinética , Cucurbitacinas/uso terapêutico , Humanos , Transdução de Sinais/efeitos dos fármacos
11.
Br J Pharmacol ; 160(7): 1844-56, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20649584

RESUMO

BACKGROUND AND PURPOSE: Cucurbitacin R, a natural anti-inflammatory product, has been shown to exhibit activity against both adjuvant-induced arthritis and delayed-type hypersensitivity reactions induced by various agents. Previous studies have demonstrated that the effects of cucurbitacin R stem from its inhibition of both cytokine production and lymphocyte proliferation. EXPERIMENTAL APPROACHES: Effects of cucurbitacin R were investigated on lipopolysaccharide-stimulated RAW 264.7 cells. Cell cycle evolution was analysed by flow cytometry, detection of apoptosis by DNA ladder, Bcl-2, p21, p53, Bax, cleaved caspase-1 (p10), caspase-9, and caspase-3, cleaved caspase (p17) and interleukin-1beta detection was followed by Western blot analysis and mRNA expression with quantitative real time reverse transcription-polymerase chain reaction (qRT-PCR). KEY RESULTS: Cucurbitacin R was found to induce apoptosis in lipopolysaccharide-stimulated RAW 264.7 macrophages through the inhibition of Bcl-2 expression, which regulates pro-inflammatory caspase-1 activation and interleukin-1beta release. Also, cucurbitacin R arrested the cell cycle in the G(2)/M phase and increased the subG(0) population in lipopolysaccharide-stimulated RAW 264.7 macrophages. Moreover, it increased the expression of proteins p53 and p21, down-regulated the expression of Bcl-2, activated the activity of caspase-1 and augmented the production of interleukin-1beta. Finally, the transfection of RAW 264.7 macrophages with a Bcl-2 expression plasmid produced the inhibition of apoptosis and caspase-1 activation/interleukin-1beta release induced by cucurbitacin R in RAW 264.7 cells. CONCLUSIONS AND IMPLICATIONS: Taken together, these results point to a new apoptotic process in which interleukin-1beta release is directly regulated by Bcl-2 status; this contributes to the evidence that apoptotic processes do not induce inflammation.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Apoptose/efeitos dos fármacos , Interleucina-1beta/metabolismo , Macrófagos/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-bcl-2/biossíntese , Triterpenos/farmacocinética , Animais , Apoptose/imunologia , Western Blotting , Caspase 1/genética , Caspase 1/metabolismo , Caspase 3/metabolismo , Ciclo Celular/efeitos dos fármacos , Linhagem Celular , Citometria de Fluxo , Lipopolissacarídeos/farmacologia , Macrófagos/imunologia , Macrófagos/metabolismo , Macrófagos/patologia , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos , Proteínas Proto-Oncogênicas c-bcl-2/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-bcl-2/genética , RNA Interferente Pequeno/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transfecção
12.
Br J Pharmacol ; 160(2): 376-88, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-20423347

RESUMO

BACKGROUND AND PURPOSE: In the present paper we studied the effect of shikonin on ear oedema induced by 12-O-tetradecanoylphorbol-13-acetate (TPA), and determined the mechanisms through which shikonin might exert its topical anti-inflammatory action. EXPERIMENTAL APPROACH: Acute ear oedema was induced in mice by topical application of TPA. The in vitro assays used macrophages RAW 264.7 cells stimulated with lipopolysaccharide. Cyclooxygenase-2, inducible nitric oxide synthase, protein kinase Calpha, extracellular signal-regulated protein kinase (ERK), phosphorylated ERK (pERK), c-Jun N-terminal kinase (JNK), pJNK, p38, p-p38, p65, p-p65, inhibitor protein of nuclear factor-kappaB (NF-kappaB) (IkappaBalpha) and pIkappaBalpha were measured by Western blotting, activation and binding of NF-kappaB to DNA was detected by reporter gene and electrophoretic mobility shift assay, respectively, and NF-kappaB p65 localization was detected by immunocytochemistry. KEY RESULTS: Shikonin reduced the oedema (inhibitory dose 50 = 1.0 mg per ear), the expression of cyclooxygenase-2 (70%) and of inducible nitric oxide synthase (100%) in vivo. It significantly decreased TPA-induced translocation of protein kinase Calpha, the phosphorylation and activation of ERK, the nuclear translocation of NF-kappaB and the TPA-induced NF-kappaB-DNA-binding activity in mouse skin. Moreover, in RAW 264.7 cells, shikonin significantly inhibited the binding of NF-kappaB to DNA in a dose-dependent manner and the nuclear translocation of p65. CONCLUSIONS AND IMPLICATIONS: Shikonin exerted its topical anti-inflammatory action by interfering with the degradation of IkappaBalpha, thus inhibiting the activation of NF-kappaB.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Edema/tratamento farmacológico , Inflamação/tratamento farmacológico , Naftoquinonas/farmacologia , Administração Tópica , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Linhagem Celular , Núcleo Celular/metabolismo , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Edema/fisiopatologia , Feminino , Proteínas I-kappa B/efeitos dos fármacos , Proteínas I-kappa B/metabolismo , Inflamação/fisiopatologia , Concentração Inibidora 50 , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Inibidor de NF-kappaB alfa , NF-kappa B/efeitos dos fármacos , NF-kappa B/metabolismo , Naftoquinonas/administração & dosagem , Fosforilação , Transporte Proteico/efeitos dos fármacos , Acetato de Tetradecanoilforbol
13.
Acta Gastroenterol Belg ; 72(4): 402-6, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-20163033

RESUMO

BACKGROUND AND STUDY AIMS: There is little information on the incidence of autoimmune hepatitis (AIH) because on many occasions the disease can progress asymptomatically, different diagnostic criteria have been proposed during the last 20 years, and many epidemiological studies are based on retrospective clinical series. The aim of this study was to determine the incidence of AIH in the province of Valencia, Spain, during the year 2003. PATIENTS AND METHODS: The Services of Gastroenterology of eight acute-care reference hospitals in the province of Valencia, Spain, covering 1,774,736 inhabitants over 14 years of age, participated in a prospective study. All newly diagnosed patients with AIH between January 1, 2003 and December 31, 2003 were eligible. The diagnosis was based on criteria of the International Autoimmune Hepatitis Group revised in 1999. RESULTS: There were 19 new cases of AIH, 18 females and 1 male [mean (SD) age of 54.3 (11.2) years, range 23-73]. Incidence peaked in the 45-54 year age group. Eighteen cases were classified as AIH type 1 and one case as AIH type 2. The incidence rate of AIH for the year 2003 in people older than 14 years of age was 1.07 new cases per 100,000 inhabitants, with 1.96 cases per 100,000 inhabitants in females and 0.12 cases per 100,000 inhabitants in males. CONCLUSIONS: The 2003 annual incidence of AIH in Valencia, Spain, was similar to that reported in other European countries. AIH occurred more frequently in women and in the 45-54 year age group, type 1 being the most common.


Assuntos
Hepatite Autoimune/epidemiologia , Adolescente , Adulto , Distribuição por Idade , Idoso , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Espanha/epidemiologia , Adulto Jovem
14.
Phytother Res ; 22(3): 297-302, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18058987

RESUMO

Ranunculus (Crowfoot) species are numerous and they are all reputed to be counter-irritants and are used in several topical conditions. In order to study the pharmacological mechanisms of action underlying this popular use, a methanol extract of Ranunculus peltatus was tested in vitro in various assays involving eicosanoid and human elastase release by intact cells as well as in vivo, with models of delayed-type hypersensitivity (DTH) contact dermatitis. The extract proved to be a selective inhibitor of the cyclooxygenase-1 pathway, producing the total inhibition of 12-(S)-HHTrE release at 200 microg/mL, while leaving both 5-lipoxygenase and 12-lipoxygenase activities unaffected at the same dose. The n-hexane, chloroform and ethyl acetate fractions of the crude methanol extract inhibited LTB(4) release by intact rat peritoneal neutrophils, but more polar fractions were inactive and did not increase the 5-LOX activity as seen previously for extracts of other Ranunculus species. In the in vivo models, the methanol extract reduced the dinitrofluorobenzene (DNFB)-induced oedema by 40%, but failed to inhibit the oedema brought on by oxazolone. The results agree with the age-old assertion that Water Crowfoot species can be used as a topical antiinflammatory remedy without the prominent irritant action that accompanies the application of non-aquatic Ranunculus species.


Assuntos
Dermatite Alérgica de Contato/tratamento farmacológico , Eicosanoides/biossíntese , Neutrófilos/efeitos dos fármacos , Fitoterapia , Ranunculus/química , Animais , Sobrevivência Celular/efeitos dos fármacos , Ciclo-Oxigenase 1/efeitos dos fármacos , Ciclo-Oxigenase 1/metabolismo , Inibidores Enzimáticos/farmacologia , Enzimas/análise , Enzimas/efeitos dos fármacos , Feminino , Humanos , Metanol/química , Camundongos , Modelos Animais , Extratos Vegetais/farmacologia , Ratos , Ratos Wistar , Fatores de Tempo
15.
Br J Pharmacol ; 152(8): 1272-82, 2007 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17934513

RESUMO

BACKGROUND AND PURPOSE: Our aim was to examine the effect of demethylnobiletin on various experimental models of delayed-type hypersensitivity (DTH) reactions and to determine its influence on the mediators and enzymes involved in these reactions. EXPERIMENTAL APPROACH: DTH was induced in mice by oxazolone, dinitrofluorobenzene (DNFB) and sheep red blood cells (SRBC). The effect of demethylnobiletin on the ensuing DTH was studied, especially in relation to oedema formation, cell infiltration and tissue damage. Its activity on different mediators implicated in DTH reactions was also determined and its effect on nitric oxide synthase (NOS)-2 analysed. Finally, its influence on T lymphocyte proliferation, apoptosis and caspase 3 activity was tested. KEY RESULTS: DTH reactions were all reduced by demethylnobiletin. The experimental results suggest that the compound may act by reducing cell infiltration and by suppressing mediators such as interleukin-2 (IC50=1.63 microM), interleukin-4 (IC50=2.76 microM), tumour necrosis factor-alpha (IC50=0.66 microM), interferon-gamma (IC50=1.35 microM), and interleukin-1 beta (46% at 2.5 microM) and by concomitantly increasing the production of the anti-inflammatory cytokine, interleukin-10. In addition, while demethylnobiletin affected nitric oxide production, it did not modify NOS-2 expression. Finally, demethylnobiletin inhibited proliferation of T cells and induced their apoptosis. CONCLUSIONS AND IMPLICATIONS: Demethylnobiletin decreased DTH reactions induced by various agents. This finding, along with the fact that the compound has a low toxicity and exhibits several other interesting properties, could pave the way for other structurally related citroflavonoids to be used as pharmacological agents in complementary therapies.


Assuntos
Citocinas/efeitos dos fármacos , Flavonas/farmacologia , Hipersensibilidade Tardia/tratamento farmacológico , Mediadores da Inflamação/metabolismo , Linfócitos T/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Caspase 3/efeitos dos fármacos , Caspase 3/metabolismo , Proliferação de Células/efeitos dos fármacos , Citocinas/biossíntese , Dinitrofluorbenzeno , Modelos Animais de Doenças , Eritrócitos/efeitos dos fármacos , Eritrócitos/metabolismo , Feminino , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Humanos , Hipersensibilidade Tardia/fisiopatologia , Camundongos , Óxido Nítrico/biossíntese , Óxido Nítrico Sintase Tipo II/efeitos dos fármacos , Óxido Nítrico Sintase Tipo II/metabolismo , Oxazolona , Ovinos , Linfócitos T/metabolismo
16.
Br J Pharmacol ; 152(3): 366-73, 2007 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17660848

RESUMO

BACKGROUND AND PURPOSE: The phenolic compounds isoprenylhydroquinone glucoside (IHG), 3,5-dicaffeoylquinic acid (DCA), and its methyl ester (DCE) have previously been shown to inhibit both contact hypersensitivity (CHS) and peroxynitrite reactivity. The present work seeks to establish a relationship between the anti-inflammatory effect and the release of cytokines and tyrosine nitration in skin. EXPERIMENTAL APPROACH: Murine CHS was developed by means of sensitization and challenge with dinitrofluorobenzene (DNFB) or oxazolone. Ear swelling was measured 24 and 96 h after challenge. Interleukin (IL)-1beta, IL-4, and tumour necrosis factor (TNF)-alpha were measured by ELISA; and the expression of inducible nitric oxide synthase (iNOS) was detected by Western blotting. Histological samples were analysed for 3-nitrotyrosine. KEY RESULTS: In the oxazolone model, DCE reduced the 24 h swelling by 54% whereas the effect of DCA was lower (40% inhibition). All the test compounds reduced IL-1beta values 24 h after challenge with DNFB or oxazolone, DCE particularly inhibited IL-4 production (74% and 78%, respectively; P<0.01). Tyrosine nitration was also markedly reduced by DCE. In general, the test compounds limited the presence of polymorphonuclear (PMN) leukocytes in the skin. CONCLUSIONS AND IMPLICATIONS: These results suggest that the effect of 3,5-dicaffeoylquinic esters on CHS is associated with a decrease in the production of interleukins, but not with the inhibition of iNOS expression. Moreover, esterification of the carboxyl group at C-1 enhanced protection against tyrosine nitration in the skin.


Assuntos
Anti-Inflamatórios/farmacologia , Ácido Clorogênico/análogos & derivados , Dermatite de Contato/tratamento farmacológico , Glucosídeos/farmacologia , Hidroquinonas/farmacologia , Animais , Asteraceae/química , Western Blotting , Ácido Clorogênico/farmacologia , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Interleucina-1beta/efeitos dos fármacos , Interleucina-1beta/metabolismo , Interleucina-4/metabolismo , Camundongos , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Distribuição Aleatória , Pele/efeitos dos fármacos , Pele/patologia , Fator de Necrose Tumoral alfa/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismo , Tirosina/análogos & derivados , Tirosina/efeitos dos fármacos , Tirosina/metabolismo
17.
Eur J Pharm Sci ; 26(2): 162-9, 2005 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-15982859

RESUMO

Sesquiterpene acids are natural products that, in contrast with the thoroughly studied sesquiterpene lactones, have received little pharmacological attention. A good source of this class of compounds is Inula viscosa (Asteraceae), a plant with documented anti-inflammatory effects. The present paper gives the results of our investigations on the biochemical mechanisms involved in the anti-inflammatory activity of one such compound, dehydrocostic acid. The most salient findings were that in vitro dehydrocostic acid inhibits leukotriene B(4) production (IC(50)=22 microM), elastase activity (IC(50)=43 microM) and bee venom phospholipase A(2) activity (IC(50)=17 microM). Furthermore, this sesquiterpenoid was effective on some models of acute edema induced by PLA(2) and 12-O-tetradecanoylphorbol 13-acetate (TPA) Comparison of these data with that known for ilicic acid firmly suggests that the presence of a semiplanar ring A is essential for an improved inhibitory activity on inflammatory mediators.


Assuntos
Anti-Inflamatórios/farmacologia , Inibidores de Ciclo-Oxigenase/farmacologia , Inula/química , Neutrófilos/efeitos dos fármacos , Sesquiterpenos/farmacologia , Animais , Anti-Inflamatórios/isolamento & purificação , Células Cultivadas , Inibidores de Ciclo-Oxigenase/isolamento & purificação , Dermatite/prevenção & controle , Relação Dose-Resposta a Droga , Edema/induzido quimicamente , Edema/prevenção & controle , Feminino , Concentração Inibidora 50 , Leucotrieno B4/antagonistas & inibidores , Leucotrieno B4/metabolismo , Camundongos , Neutrófilos/metabolismo , Elastase Pancreática/antagonistas & inibidores , Fosfolipases A/administração & dosagem , Fosfolipases A/antagonistas & inibidores , Componentes Aéreos da Planta/química , Ratos , Ratos Wistar , Sesquiterpenos/isolamento & purificação , Acetato de Tetradecanoilforbol , Fatores de Tempo
18.
Rev Neurol ; 40(1): 34-7, 2005.
Artigo em Espanhol | MEDLINE | ID: mdl-15696424

RESUMO

INTRODUCTION: It is very rare for cerebral infarction to be the first symptom of an intracranial tumour. Only three cases have been reported in which cerebral infarction is thought to have been caused by the arterial compromise triggered by incipient high grade gliomas that are not yet visible in radiological tests. CASE REPORT: A 46-year-old male with no relevant medical history or cardiovascular risk factors who presented with acute hemiplegia on the right-hand side of the body and a significantly impaired level of consciousness. Computerised axial tomography of the brain showed a left frontal malignant ischemic infarct that exerted an important mass effect. The patient was submitted to a left-side frontoparietal decompressive craniectomy. Post-operative progress was good and the patient even recovered his normal level of consciousness, although he was left with right hemiparesis and conduction dysphasia. Seven months after the craniectomy the patient experienced a progressive deterioration with symptoms of endocranial hypertension. Magnetic resonance imaging of the brain revealed the presence of a highly malignant tumour in the previously infarcted territory. A histological study of the excised lesion showed it to be a glioblastoma multiforme. CONCLUSIONS: The proximity in time, as well as the identical location of the two lesions, led us to think that the glioblastoma, although not yet visible in radiological explorations, affected a branch of the middle cerebral artery and gave rise to the infarct. Therefore, in the presence of a cerebral infarct in patients with no risk factors for suffering a brain vascular pathology, it is advisable to carry out a radiological follow-up so as to be able to diagnose a possible lesion due to a tumour.


Assuntos
Infarto Cerebral , Glioblastoma , Infarto Cerebral/diagnóstico , Infarto Cerebral/etiologia , Infarto Cerebral/patologia , Glioblastoma/complicações , Glioblastoma/diagnóstico , Glioblastoma/patologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X
19.
Rev. neurol. (Ed. impr.) ; 40(1): 34-37, 1 ene., 2005. ilus
Artigo em Es | IBECS | ID: ibc-037101

RESUMO

Introducción. La primera manifestación de un tumor intracraneal raramente es la aparición de un infarto cerebral. Tan sólo se han documentado tres casos en los que se considera como causa de un infarto cerebral la afectación arterial provocada por gliomas incipientes de alto grado aún no visibles radiológicamente. Caso clínico. Se trata de un varón de 46 años sin antecedentes médicos de interés ni factores de riesgo cardiovasculares que presentó de manera aguda una manifiesta hemiplejía derecha y deterioro importante del nivel de conciencia. En la tomografía axial computarizada craneal se demostró un infarto isquémico maligno frontal izquierdo que ejercía un gran efecto de masa. Se practicó una craniectomía descompresiva frontoparietal izquierda. El posoperatorio fue favorable y el paciente recuperó hasta la normalidad su nivel de conciencia, aunque quedó con una hemiparesia derecha y disfasia de conducción. Siete meses después de la craniectomía, experimentó un deterioro progresivo con clínica de hipertensión endocraneal. La resonancia magnética cerebral demostró la presencia de un tumor de alto grado de malignidad sobre el territorio previamente infartado. El estudio histológico de la lesión resecada determinó que se trataba de un glioblastoma multiforme. Conclusión. La cercanía en el tiempo, así como la idéntica localización de ambas lesiones, hace pensar que el glioblastoma, no siendo aún visible radiológicamente, comprimió o invadió una rama de la arteria cerebral media y originó el infarto. Por tanto, ante la presencia de un infarto cerebral en un paciente sin factores de riesgo para sufrir patología vascular cerebral, sería recomendable realizar un seguimiento radiológico posterior con el fin de diagnosticar una posible lesión tumoral


Introduction. It is very rare for cerebral infarction to be the first symptom of an intracranial tumour. Only three cases have been reported in which cerebral infarction is thought to have been caused by the arterial compromise triggered by incipient high grade gliomas that are not yet visible in radiological tests. Case report. A 46-year-old male with no relevant medical history or cardiovascular risk factors who presented with acute hemiplegia on the right-hand side of the body and a significantly impaired level of consciousness. Computerised axial tomography of the brain showed a left frontal malignant ischemic infarct that exerted an important mass effect. The patient was submitted to a left-side frontoparietal decompressive craniectomy. Post-operative progress was good and the patient even recovered his normal level of consciousness, although he was left with right hemiparesis and conduction dysphasia. Seven months after the craniectomy the patient experienced a progressive deterioration with symptoms of endocranial hypertension. Magnetic resonance imaging of the brain revealed the presence of a highly malignant tumour in the previously infarcted territory. A histological study of the excised lesion showed it to be a glioblastoma multiforme. Conclusions. The proximity in time, as well as the identical location of the two lesions, led us to think that the glioblastoma, although not yet visible in radiological explorations, affected a branch of the middle cerebral artery and gave rise to the infarct. Therefore, in the presence of a cerebral infarct in patients with no risk factors for suffering a brain vascular pathology, it is advisable to carry out a radiological follow-up so as to be able to diagnose a possible lesion due to a tumour


Assuntos
Masculino , Pessoa de Meia-Idade , Humanos , Glioma/complicações , Infarto Cerebral/etiologia , Neoplasias Encefálicas/patologia , Tomografia Computadorizada por Raios X/métodos , Manitol/administração & dosagem , Midazolam/administração & dosagem , Dopamina/administração & dosagem , Norepinefrina/administração & dosagem , Craniotomia , Glioblastoma/patologia
20.
Fitoterapia ; 75(2): 179-86, 2004 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-15030922

RESUMO

The effect of the methanol extract from aerial parts of Bupleurum fruticescens on the release of eicosanoids and hydrolytic enzymes was determined on in vitro cell systems. The extract had a significant effect on 5-lipoxygenase (5-LOX) activity, inhibiting both LTB4 and 5(S)-HETE production with IC50 values of 112 microg/ml and 95 microg/ml, respectively. At concentrations of 200 microg/ml, the extract also inhibited cyclooxygenase-1 (90%) and elastase activities (54%). The 12-LOX activity in intact platelets was not affected; a fact, which suggests that phospholipase A2 (PLA2) activity, is not modified by the extract.


Assuntos
Bupleurum , Inibidores de Ciclo-Oxigenase/farmacologia , Isoenzimas/antagonistas & inibidores , Elastase de Leucócito/antagonistas & inibidores , Lipoxigenase/efeitos dos fármacos , Fitoterapia , Extratos Vegetais/farmacologia , Animais , Ciclo-Oxigenase 1 , Inibidores de Ciclo-Oxigenase/administração & dosagem , Inibidores de Ciclo-Oxigenase/uso terapêutico , Flores , Humanos , Concentração Inibidora 50 , Proteínas de Membrana , Componentes Aéreos da Planta , Extratos Vegetais/administração & dosagem , Extratos Vegetais/uso terapêutico , Raízes de Plantas , Prostaglandina-Endoperóxido Sintases , Ratos , Ratos Wistar
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