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1.
Rev Gastroenterol Mex (Engl Ed) ; 85(3): 257-263, 2020.
Artículo en Inglés, Español | MEDLINE | ID: mdl-32019715

RESUMEN

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.


Asunto(s)
Bilis/microbiología , Colecistectomía , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos
2.
SAR QSAR Environ Res ; 31(3): 209-226, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-31916862

RESUMEN

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.


Asunto(s)
Receptores de Hidrocarburo de Aril/antagonistas & inhibidores , Receptores de Hidrocarburo de Aril/química , Animales , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Contaminantes Ambientales/química , Contaminantes Ambientales/toxicidad , Luciferasas/genética , Luciferasas/metabolismo , Modelos Moleculares , Relación Estructura-Actividad Cuantitativa , Receptores de Hidrocarburo de Aril/genética , Receptores de Hidrocarburo de Aril/metabolismo , Proteínas Recombinantes de Fusión/química , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/metabolismo , Reproducibilidad de los Resultados , Bibliotecas de Moléculas Pequeñas/química , Bibliotecas de Moléculas Pequeñas/toxicidad
3.
Eur J Pharm Sci ; 49(4): 637-41, 2013 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-23727294

RESUMEN

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.


Asunto(s)
Antiinflamatorios no Esteroideos/farmacología , Intestinos/lesiones , Naftoquinonas/farmacología , Factor de Crecimiento Transformador beta/metabolismo , Cicatrización de Heridas/efectos de los fármacos , Animales , Línea Celular , Movimiento Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Ratas , Factor de Transcripción STAT3/metabolismo , Factor de Transcripción ReIA/metabolismo
4.
Curr Med Chem ; 20(23): 2892-8, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23651309

RESUMEN

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.


Asunto(s)
Antineoplásicos/farmacología , Medicina Tradicional China , Naftoquinonas/farmacología , Naftoquinonas/uso terapéutico , Neoplasias/tratamiento farmacológico , Antiinflamatorios/química , Antiinflamatorios/farmacología , Antineoplásicos/química , Antineoplásicos/uso terapéutico , Humanos , Raíces de Plantas/química
5.
Actas dermo-sifiliogr. (Ed. impr.) ; 104(3): 239-241, abr. 2013. ilus
Artículo en Español | IBECS | ID: ibc-111594

RESUMEN

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)


Asunto(s)
Humanos , Masculino , Persona de Mediana Edad , Hepatitis C/inducido químicamente , Hepatitis C/complicaciones , Hepatitis C/diagnóstico , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Psoriasis/complicaciones , Psoriasis/diagnóstico , Tratamiento Biológico/métodos , Corticoesteroides/uso terapéutico , Metotrexato/uso terapéutico , Hepatitis C/tratamiento farmacológico , Hepatitis C/fisiopatología , Psoriasis/tratamiento farmacológico , Psoriasis/fisiopatología , Interferones/uso terapéutico
6.
Actas Dermosifiliogr ; 104(3): 239-41, 2013 Apr.
Artículo en Inglés, Español | MEDLINE | ID: mdl-22579035

RESUMEN

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.


Asunto(s)
Hepatitis C/inducido químicamente , Inmunoglobulina G/efectos adversos , Receptores del Factor de Necrosis Tumoral/antagonistas & inhibidores , Enfermedad Aguda , Etanercept , Humanos , Masculino , Persona de Mediana Edad
7.
Rev. esp. anestesiol. reanim ; 59(10): 573-576, dic. 2012.
Artículo en Español | IBECS | ID: ibc-107412

RESUMEN

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)


Asunto(s)
Humanos , Masculino , Anestesia Epidural/instrumentación , Anestesia Epidural/métodos , Anestesia Epidural , Prostatectomía/métodos , Respiración Artificial/instrumentación , Respiración Artificial/métodos , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Anestesia Epidural/tendencias , Obesidad/complicaciones , Obesidad/diagnóstico , Respiración Artificial/tendencias , Respiración Artificial , Enfermedad Pulmonar Obstructiva Crónica/terapia , Enfermedad Pulmonar Obstructiva Crónica
8.
Oxid Med Cell Longev ; 2012: 906252, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-23150750

RESUMEN

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.


Asunto(s)
Cacao/química , Salud , Polifenoles/farmacología , Animales , Antioxidantes/farmacología , Disponibilidad Biológica , Enfermedad , Humanos , Polifenoles/química
9.
Rev Esp Anestesiol Reanim ; 59(10): 573-6, 2012 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-22749299

RESUMEN

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.


Asunto(s)
Anestesia Epidural , Ventilación no Invasiva , Obesidad/complicaciones , Prostatectomía , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Anciano , Humanos , Masculino , Persona de Mediana Edad
10.
Curr Pharm Des ; 18(12): 1663-76, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22443631

RESUMEN

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.


Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Apoptosis/efectos de los fármacos , Cucurbitacinas/farmacología , Animales , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/farmacocinética , Antineoplásicos Fitogénicos/uso terapéutico , Ciclo Celular/efectos de los fármacos , Cucurbitacinas/química , Cucurbitacinas/farmacocinética , Cucurbitacinas/uso terapéutico , Humanos , Transducción de Señal/efectos de los fármacos
11.
Br J Pharmacol ; 160(7): 1844-56, 2010 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-20649584

RESUMEN

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.


Asunto(s)
Antiinflamatorios no Esteroideos/farmacología , Apoptosis/efectos de los fármacos , Interleucina-1beta/metabolismo , Macrófagos/efectos de los fármacos , Proteínas Proto-Oncogénicas c-bcl-2/biosíntesis , Triterpenos/farmacocinética , Animales , Apoptosis/inmunología , Western Blotting , Caspasa 1/genética , Caspasa 1/metabolismo , Caspasa 3/metabolismo , Ciclo Celular/efectos de los fármacos , Línea Celular , Citometría de Flujo , Lipopolisacáridos/farmacología , Macrófagos/inmunología , Macrófagos/metabolismo , Macrófagos/patología , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Ratones , Proteínas Proto-Oncogénicas c-bcl-2/antagonistas & inhibidores , Proteínas Proto-Oncogénicas c-bcl-2/genética , ARN Interferente Pequeño/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Transfección
12.
Br J Pharmacol ; 160(2): 376-88, 2010 May.
Artículo en Inglés | MEDLINE | ID: mdl-20423347

RESUMEN

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.


Asunto(s)
Antiinflamatorios no Esteroideos/farmacología , Edema/tratamiento farmacológico , Inflamación/tratamiento farmacológico , Naftoquinonas/farmacología , Administración Tópica , Animales , Antiinflamatorios no Esteroideos/administración & dosificación , Línea Celular , Núcleo Celular/metabolismo , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Edema/fisiopatología , Femenino , Proteínas I-kappa B/efectos de los fármacos , Proteínas I-kappa B/metabolismo , Inflamación/fisiopatología , Concentración 50 Inhibidora , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Ratones , Inhibidor NF-kappaB alfa , FN-kappa B/efectos de los fármacos , FN-kappa B/metabolismo , Naftoquinonas/administración & dosificación , Fosforilación , Transporte de Proteínas/efectos de los fármacos , Acetato de Tetradecanoilforbol
13.
Acta Gastroenterol Belg ; 72(4): 402-6, 2009.
Artículo en Inglés | MEDLINE | ID: mdl-20163033

RESUMEN

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.


Asunto(s)
Hepatitis Autoinmune/epidemiología , Adolescente , Adulto , Distribución por Edad , Anciano , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , España/epidemiología , Adulto Joven
14.
Phytother Res ; 22(3): 297-302, 2008 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-18058987

RESUMEN

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.


Asunto(s)
Dermatitis Alérgica por Contacto/tratamiento farmacológico , Eicosanoides/biosíntesis , Neutrófilos/efectos de los fármacos , Fitoterapia , Ranunculus/química , Animales , Supervivencia Celular/efectos de los fármacos , Ciclooxigenasa 1/efectos de los fármacos , Ciclooxigenasa 1/metabolismo , Inhibidores Enzimáticos/farmacología , Enzimas/análisis , Enzimas/efectos de los fármacos , Femenino , Humanos , Metanol/química , Ratones , Modelos Animales , Extractos Vegetales/farmacología , Ratas , Ratas Wistar , Factores de Tiempo
15.
Br J Pharmacol ; 152(8): 1272-82, 2007 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-17934513

RESUMEN

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.


Asunto(s)
Citocinas/efectos de los fármacos , Flavonas/farmacología , Hipersensibilidad Tardía/tratamiento farmacológico , Mediadores de Inflamación/metabolismo , Linfocitos T/efectos de los fármacos , Animales , Apoptosis/efectos de los fármacos , Caspasa 3/efectos de los fármacos , Caspasa 3/metabolismo , Proliferación Celular/efectos de los fármacos , Citocinas/biosíntesis , Dinitrofluorobenceno , Modelos Animales de Enfermedad , Eritrocitos/efectos de los fármacos , Eritrocitos/metabolismo , Femenino , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Humanos , Hipersensibilidad Tardía/fisiopatología , Ratones , Óxido Nítrico/biosíntesis , Óxido Nítrico Sintasa de Tipo II/efectos de los fármacos , Óxido Nítrico Sintasa de Tipo II/metabolismo , Oxazolona , Ovinos , Linfocitos T/metabolismo
16.
Br J Pharmacol ; 152(3): 366-73, 2007 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-17660848

RESUMEN

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.


Asunto(s)
Antiinflamatorios/farmacología , Ácido Clorogénico/análogos & derivados , Dermatitis por Contacto/tratamiento farmacológico , Glucósidos/farmacología , Hidroquinonas/farmacología , Animales , Asteraceae/química , Western Blotting , Ácido Clorogénico/farmacología , Modelos Animales de Enfermedad , Ensayo de Inmunoadsorción Enzimática , Femenino , Regulación de la Expresión Génica/efectos de los fármacos , Interleucina-1beta/efectos de los fármacos , Interleucina-1beta/metabolismo , Interleucina-4/metabolismo , Ratones , Neutrófilos/efectos de los fármacos , Neutrófilos/metabolismo , Óxido Nítrico Sintasa de Tipo II/metabolismo , Distribución Aleatoria , Piel/efectos de los fármacos , Piel/patología , Factor de Necrosis Tumoral alfa/efectos de los fármacos , Factor de Necrosis Tumoral alfa/metabolismo , Tirosina/análogos & derivados , Tirosina/efectos de los fármacos , Tirosina/metabolismo
17.
Eur J Pharm Sci ; 26(2): 162-9, 2005 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-15982859

RESUMEN

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.


Asunto(s)
Antiinflamatorios/farmacología , Inhibidores de la Ciclooxigenasa/farmacología , Inula/química , Neutrófilos/efectos de los fármacos , Sesquiterpenos/farmacología , Animales , Antiinflamatorios/aislamiento & purificación , Células Cultivadas , Inhibidores de la Ciclooxigenasa/aislamiento & purificación , Dermatitis/prevención & control , Relación Dosis-Respuesta a Droga , Edema/inducido químicamente , Edema/prevención & control , Femenino , Concentración 50 Inhibidora , Leucotrieno B4/antagonistas & inhibidores , Leucotrieno B4/metabolismo , Ratones , Neutrófilos/metabolismo , Elastasa Pancreática/antagonistas & inhibidores , Fosfolipasas A/administración & dosificación , Fosfolipasas A/antagonistas & inhibidores , Componentes Aéreos de las Plantas/química , Ratas , Ratas Wistar , Sesquiterpenos/aislamiento & purificación , Acetato de Tetradecanoilforbol , Factores de Tiempo
18.
Rev Neurol ; 40(1): 34-7, 2005.
Artículo en Español | MEDLINE | ID: mdl-15696424

RESUMEN

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.


Asunto(s)
Infarto Cerebral , Glioblastoma , Infarto Cerebral/diagnóstico , Infarto Cerebral/etiología , Infarto Cerebral/patología , Glioblastoma/complicaciones , Glioblastoma/diagnóstico , Glioblastoma/patología , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Tomografía Computarizada por Rayos X
19.
Rev. neurol. (Ed. impr.) ; 40(1): 34-37, 1 ene., 2005. ilus
Artículo en Es | IBECS | ID: ibc-037101

RESUMEN

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


Asunto(s)
Masculino , Persona de Mediana Edad , Humanos , Glioma/complicaciones , Infarto Cerebral/etiología , Neoplasias Encefálicas/patología , Tomografía Computarizada por Rayos X/métodos , Manitol/administración & dosificación , Midazolam/administración & dosificación , Dopamina/administración & dosificación , Norepinefrina/administración & dosificación , Craneotomía , Glioblastoma/patología
20.
Fitoterapia ; 75(2): 179-86, 2004 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-15030922

RESUMEN

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.


Asunto(s)
Bupleurum , Inhibidores de la Ciclooxigenasa/farmacología , Isoenzimas/antagonistas & inhibidores , Elastasa de Leucocito/antagonistas & inhibidores , Lipooxigenasa/efectos de los fármacos , Fitoterapia , Extractos Vegetales/farmacología , Animales , Ciclooxigenasa 1 , Inhibidores de la Ciclooxigenasa/administración & dosificación , Inhibidores de la Ciclooxigenasa/uso terapéutico , Flores , Humanos , Concentración 50 Inhibidora , Proteínas de la Membrana , Componentes Aéreos de las Plantas , Extractos Vegetales/administración & dosificación , Extractos Vegetales/uso terapéutico , Raíces de Plantas , Prostaglandina-Endoperóxido Sintasas , Ratas , Ratas Wistar
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