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1.
Eur J Radiol ; 136: 109525, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33454458

RESUMEN

OBJECTIVES: To assess CT signs to discriminate an appendiceal tumor versus a non-tumoral appendix in an acute appendicitis context. METHODS: A 10-year bicentric retrospective case-control study was performed in adults. Patients with a histopathological appendiceal tumor and appendicitis were paired for age and sex with patients with non-tumorous appendicitis (1/3 ratio, respectively). Two senior radiologists blindly analyzed numerous CT findings with final consensus to perform univariate and multivariate statistical analyses. A diagnostic CT scan score was calculated with a bootstrap internal validation. Reproducibility was assessed based on the kappa statistic. RESULTS: A total of 208 patients (51 +/- 21 years; 114 males) were included (52 patients in the tumor group and 156 in the non-tumor group). In the multivariate analysis, an appendicolith and fat stranding were protective factors with OR = 0.2 (p = 0.01) and OR = 0.3 (p = 0.02), respectively, while mural calcifications (OR = 47, p = 0.0001), an appendix mass (OR = 7.1, p = 0.008), a focal asymmetric wall abnormality (OR = 4.9, p = 0, 001), or a ≥ 15 mm diameter (OR = 3.5, p = 0.009) were positive predictive factors of an underlying tumor. Using a ≥1 cut-off, our diagnostic score had an AUC = 0.87 (95 % CI, 0.82-0.93) and a positive likelihood ratio = 13.5 (95 % CI, 6.7-27.1). CONCLUSION: We developed a reliable scoring system based on CT findings, which is highly predictive of an underlying appendiceal neoplasm in an appendicitis context using a ≥1 cut-off.


Asunto(s)
Neoplasias del Apéndice , Apendicitis , Enfermedad Aguda , Adulto , Neoplasias del Apéndice/diagnóstico por imagen , Apendicitis/diagnóstico por imagen , Apendicitis/cirugía , Estudios de Casos y Controles , Humanos , Masculino , Reproducibilidad de los Resultados , Estudios Retrospectivos , Tomografía Computarizada por Rayos X
2.
Mol Inform ; 35(8-9): 358-68, 2016 09.
Artículo en Inglés | MEDLINE | ID: mdl-27546040

RESUMEN

We present here the development of a novel virtual screening protocol combining Structure-based and Ligand-based drug design approaches for the identification of mouse mPGES-1 inhibitors. We used the existing 3D structural data of the murine enzyme to hypothesize the inhibitors binding mode, which was the starting point for docking simulations, shape screening, and pharmacophore hypothesis screening. The protocol allowed the identification of 16 mouse mPGES-1 inhibitors with low micromolar activity, which, notably, also inhibit the human enzyme in the same concentration range. The inhibitors predicted binding mode is expected to be the base for the rational drug design of new potent dual species inhibitors of human and murine mPGES-1.


Asunto(s)
Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/metabolismo , Prostaglandina-E Sintasas/antagonistas & inhibidores , Animales , Humanos , Ligandos , Ratones , Modelos Moleculares , Simulación del Acoplamiento Molecular/métodos , Unión Proteica/fisiología , Relación Estructura-Actividad
3.
Diagn Interv Imaging ; 97(1): 29-36, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26297508

RESUMEN

A wide range of gastrointestinal diseases may spread to and involve genital organs by different pathways. These pathways result in extension of the pathological process into the extraperitoneal spaces and between the extra- and intraperitoneal spaces. These communications occur either via mesenteries and ligaments or via the posterior parietal peritoneum. Thus, infectious, inflammatory or tumoral digestive diseases can extend into the pelvic organs and present with a misleading clinical picture and/or radiological features, showing the complexity of pelvic diseases in women. This article reviews, illustrates and discusses these different presentations and provides certain clues to help reach a definite diagnosis.


Asunto(s)
Enfermedades del Sistema Digestivo/diagnóstico por imagen , Enfermedades de los Genitales Femeninos/diagnóstico por imagen , Diagnóstico Diferencial , Enfermedades del Sistema Digestivo/complicaciones , Femenino , Enfermedades de los Genitales Femeninos/etiología , Humanos
4.
Eur Radiol ; 26(3): 631-8, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-26115654

RESUMEN

OBJECTIVES: To describe the imaging findings in a series of patients with mesothelioma of the tunica vaginalis testis. METHODS: We reviewed clinical data, imaging findings and follow-up information in a series of 10 pathology-proven cases of mesothelioma (all had US; 2 had MR) of the tunica vaginalis. RESULTS: A variety of patterns could be observed, the most common (5/10) being a hydrocele with parietal, solid and hypervascular vegetations; one patient had a septated hydrocele with hypervascular walls; one had multiple, solid nodules surrounded by a small, physiological quantity of fluid; one a cystic lesion with thick walls and vegetations compressing the testis; two had a solid paratesticular mass. MR showed multiple small nodules on the surface of the tunica vaginalis in one case and diffuse thickening and vegetations in the other one; lesions had low signal intensity on T2-w images and were hypervascular after contrast injection. CONCLUSIONS: A preoperative diagnosis of mesotheliomas presenting as solid paratesticular masses seems very difficult with imaging. On the contrary, the diagnosis must be considered in patients in whom a hydrocele with parietal vegetations is detected, especially if these show high vascularity. KEY POINTS: Mesotheliomas of the tunica vaginalis are rare, often challenging to diagnose preoperatively. Most common finding is a complex hydrocele with hypervascular parietal vegetations. Septated hydrocele, nodules without hydrocele, a thick-walled paratesticular cyst are less common. Preoperative diagnosis may allow aggressive surgical approach and, possibly, a better prognosis.


Asunto(s)
Imagen por Resonancia Magnética/métodos , Mesotelioma/diagnóstico por imagen , Neoplasias Testiculares/diagnóstico por imagen , Adulto , Anciano , Anciano de 80 o más Años , Medios de Contraste , Diagnóstico Diferencial , Estudios de Seguimiento , Humanos , Masculino , Mesotelioma/irrigación sanguínea , Mesotelioma/diagnóstico , Persona de Mediana Edad , Estudios Retrospectivos , Tasa de Supervivencia , Hidrocele Testicular/diagnóstico , Hidrocele Testicular/diagnóstico por imagen , Neoplasias Testiculares/irrigación sanguínea , Neoplasias Testiculares/diagnóstico , Resultado del Tratamiento , Ultrasonografía Doppler en Color/métodos
5.
Diagn Interv Imaging ; 96(2): 171-86, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25547251

RESUMEN

The retroperitoneum is a space situated behind the parietal peritoneum and in front of the transversalis fascia. It contains further spaces that are separated by the fasciae, between which communication is possible with both the peritoneal cavity and the pelvis, according to the theory of interfascial spread. The perirenal space has the shape of an inverted cone and contains the kidneys, adrenal glands, and related vasculature. It is delineated by the anterior and posterior renal fasciae, which surround the ureter and allow communication towards the pelvis. At the upper right pole, the perirenal space connects to the retrohepatic space at the bare area of the liver. There is communication between these two spaces through the Kneeland channel. The anterior pararenal space contains the duodenum, pancreas, and the ascending and descending colon. There is free communication within this space, and towards the mesenteries along the vessels. The posterior pararenal space, which contains fat, communicates with the preperitoneal space at the anterior surface of the abdomen between the peritoneum and the transversalis fascia, and allows communication with the contralateral posterior pararenal space. This space follows the length of the ureter to the pelvis, which explains the communication between these areas and the length of the pelvic fasciae.


Asunto(s)
Imagen por Resonancia Magnética , Espacio Retroperitoneal/anatomía & histología , Espacio Retroperitoneal/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Humanos
6.
Abdom Imaging ; 40(6): 1904-25, 2015 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-25532744

RESUMEN

A central element was first described in focal nodular hyperplasia (FNH) as a so-called "central scar," and is normally associated with this entity. However, many other liver masses may present with a central element. Depending on its appearance, and the lesion itself, central elements can be essential, helpful, or confusing for diagnosis. Indeed, nodules that develop on liver vascular disorders, fibrolamellar hepatocellular carcinoma, large hemangioma, peripheral cholangiocarcinoma, or epithelioid hemangioenthelioma often present with a central element, thus increasing the level of diagnostic confidence when present. On the other hand, central elements are rare or atypical in liver metastases, hepatocellular adenoma, or hepatocellular carcinoma. In this setting, the presence of a central element can lead to a misdiagnosis. The description and details of the imaging features of these different central elements, especially on MRI, as well as a thorough evaluation of the entire lesion, can improve the diagnostic performance in these cases.


Asunto(s)
Hiperplasia Nodular Focal/diagnóstico , Neoplasias Hepáticas/diagnóstico , Humanos , Hepatopatías/diagnóstico
7.
Diagn Interv Imaging ; 94(7-8): 771-92, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23759294

RESUMEN

Appendicitis and diverticulitis of the colon are the two main causes of febrile acute abdomen in adults. Diagnosis from imaging (ultrasound and CT) is usually easy. However, an imaging procedure which is not suitable for the clinical situation and an examination performed with the wrong protocol are sources of error and must be avoided. Anatomical variants, inflammatory cancers, complicated forms (perforation, secondary occlusion of the small intestine, peripheral abscesses, fistulae, pylephlebitis, liver abscesses) and associated signs related to a peritoneal inflammatory reaction (reflex ileus, reactive ileitis or salpingitis) can also lead to a wrong diagnosis.


Asunto(s)
Apendicitis/diagnóstico por imagen , Enfermedades del Colon/diagnóstico por imagen , Diverticulitis/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Diagnóstico Diferencial , Errores Diagnósticos , Humanos , Ultrasonografía
8.
Clin Ter ; 163(6): e401-4, 2012 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-23306753

RESUMEN

AIM: Several studies have been undertaken to investigate a possible link between breast cancer and thyroid diseases, notably thyroid carcinoma and autoimmune thyroid diseases, but the issue remains unresolved. The aim of this study is to evaluate, in thyropathic women with and without breast cancer, the following effects: the distribution of different thyroid diseases, the breast-cancer-related prevalence of anti-thyroperoxidase and anti-thyroglobulin antibodies and the role in thyroid pathology of breast-cancer post-surgery therapy with tamoxifene. MATERIALS AND METHODS: One-hundred-ninety thyropathic women with breast cancer (BC group) were recruited, and compared with a control group (C group) of one-hundred-ninety thyropathic women without breast cancer. RESULTS: Nodular disease is the most frequent pathology in both groups. The difference in the incidence of thyroid carcinoma is also not statistically significant. The biochemical increase in the positivity of autoantibodies in BC-group patients is confirmed, but there is no statistically significant difference in the rate of clinical autoimmune diseases between the two groups. No difference in the frequency of any particular thyroid disease is found between those patients who underwent post-operative tamoxifene therapy and those who did not. CONCLUSION: It can be concluded, on the basis of these results, that it is advisable to reduce the clinical weight of the issue. A routine thyroid screening is recommended in women with BC for the management of chronic comorbidities, as would be for women in the general population having the same age and coming from the same iodine-intake area.


Asunto(s)
Neoplasias de la Mama/complicaciones , Enfermedades de la Tiroides/complicaciones , Adulto , Anciano , Anciano de 80 o más Años , Autoanticuerpos/sangre , Neoplasias de la Mama/sangre , Femenino , Humanos , Persona de Mediana Edad , Enfermedades de la Tiroides/sangre
10.
Br J Radiol ; 83(995): 983-90, 2010 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-20965909

RESUMEN

Large bowel volvulus is a rare condition that can occur in patients who present with acute abdominal pain. Radiologists should be able to recognise its appearance on multidetector CT (MDCT) images so that the correct diagnosis can be made and catastrophic consequences can be avoided. In this article, we discuss and illustrate the MDCT and three-dimensional appearance of the various forms of large bowel volvulus. As MDCT allows the precise diagnosis of topography, mechanism and severity, this technique can provide an accurate assessment of large bowel volvulus.


Asunto(s)
Enfermedades Funcionales del Colon/diagnóstico por imagen , Procesamiento de Imagen Asistido por Computador , Vólvulo Intestinal/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Medios de Contraste , Humanos , Imagenología Tridimensional , Ilustración Médica
11.
J Radiol ; 90(7-8 Pt 2): 918-36, 2009.
Artículo en Francés | MEDLINE | ID: mdl-19752831

RESUMEN

Pancreatic surgery is a frequent therapeutic approach for benign and malignant conditions. CT has become the imaging method of reference to detect early postoperative complications and to detect recurrent disease during long-term follow-up. Knowledge of the normal postoperative anatomy is essential for accurate interpretation of CT scans. The purpose of this paper is to illustrate the normal and abnormal CT appearances of common surgical procedures involving the pancreas.


Asunto(s)
Adenocarcinoma/cirugía , Duodeno/cirugía , Páncreas/cirugía , Pancreatectomía/métodos , Neoplasias Pancreáticas/cirugía , Pancreaticoduodenectomía/métodos , Complicaciones Posoperatorias/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Medios de Contraste , Duodeno/diagnóstico por imagen , Estudios de Seguimiento , Derivación Gástrica , Humanos , Masculino , Persona de Mediana Edad , Páncreas/diagnóstico por imagen , Fístula Pancreática/etiología , Pancreatoyeyunostomía , Pancreatitis Aguda Necrotizante/etiología , Radiología Intervencionista , Recurrencia , Factores de Tiempo
12.
Langenbecks Arch Surg ; 393(5): 721-4, 2008 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-18690473

RESUMEN

INTRODUCTION: Actually, thyroid volume >25 ml, obtained by preoperative ultrasound evaluation, is a very important exclusion criteria for minimally invasive thyroidectomy. So far, among different imaging techniques, two-dimensional ultrasonography has become the more accepted method for the assessment of thyroid volume (US-TV). The aims of this study were: (1) to estimate the preoperative thyroid volume in patients undergoing minimally invasive total thyroidectomy using a mathematical formula and (2) to verify its validity by comparing it with the postsurgical TV (PS-TV). MATERIALS AND METHOD: In 53 patients who underwent minimally invasive total thyroidectomy (from January 2003 to December 2007), US-TV, obtained by ellipsoid volume formula, was compared to PS-TV determined by the Archimedes' principle. A mathematical formula able to predict the TV from the US-TV was applied in 34 cases in the last 2 years. RESULTS: Mean US-TV (14.4 +/- 5.9 ml) was significantly lower than mean PS-TV (21.7 +/- 10.3 ml). This underestimation was related to gland multinodularity and/or nodular involvement of the isthmus. A mathematical formula to reduce US-TV underestimation and predict the real TV was developed using a linear model. Mean predicted TV (16.8 +/- 3.7 ml) perfectly matched mean PS-TV, underestimating PS-TV in 19% of cases. We verified the accuracy of this mathematical model in patients' eligibility for minimally invasive total thyroidectomy, and we demonstrated that a predicted TV <25 ml was confirmed post-surgery in 94% of cases. CONCLUSIONS: We demonstrated that using a linear model, it is possible to predict from US the PS-TV with high accuracy. In fact, the mean predicted TV perfectly matched the mean PS-TV in all cases. In particular, the percentage of cases in which the predicted TV perfectly matched the PS-TV increases from 23%, estimated by US, to 43%. Moreover, the percentage of TV underestimation was reduced from 77% to 19%, as well as the range of the disagreement from up to 200% to 80%. This study shows that two-dimensional US can provide the accurate estimation of thyroid volume but that it can be improved by a mathematical model. This may contribute to a more appropriate surgical management of thyroid diseases.


Asunto(s)
Bocio Nodular/diagnóstico por imagen , Bocio Nodular/cirugía , Hipertiroidismo/diagnóstico por imagen , Hipertiroidismo/cirugía , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Glándula Tiroides/diagnóstico por imagen , Glándula Tiroides/patología , Neoplasias de la Tiroides/diagnóstico por imagen , Neoplasias de la Tiroides/cirugía , Nódulo Tiroideo/diagnóstico por imagen , Nódulo Tiroideo/cirugía , Tiroidectomía/métodos , Adulto , Cicatriz/etiología , Estética , Femenino , Estudios de Seguimiento , Humanos , Modelos Lineales , Masculino , Persona de Mediana Edad , Tamaño de los Órganos/fisiología , Dimensión del Dolor , Dolor Postoperatorio/etiología , Complicaciones Posoperatorias/etiología , Ultrasonografía
13.
J Radiol ; 87(4 Pt 2): 479-93, 2006 Apr.
Artículo en Francés | MEDLINE | ID: mdl-16691177

RESUMEN

Thickening of the gallbladder wall may result from a large spectrum of pathological conditions, intrinsic as well as extrinsic to the biliary tract, and may have different appearances. Accurate diagnosis is usually established after a correlation of imaging findings, laboratory data and clinical history. US remains the initial imaging modality for the evaluation of acute right upper quadrant pain. CT and MRI are complementary to US and have an increasing role in assessing a thickened-wall gallbladder.


Asunto(s)
Enfermedades de la Vesícula Biliar/diagnóstico , Colecistitis Alitiásica/diagnóstico , Colecistitis Alitiásica/diagnóstico por imagen , Adenocarcinoma/diagnóstico , Adenocarcinoma/diagnóstico por imagen , Adenoma/diagnóstico , Adenoma/diagnóstico por imagen , Adenomioma/diagnóstico , Adenomioma/diagnóstico por imagen , Colecistitis Aguda/diagnóstico , Colecistitis Aguda/diagnóstico por imagen , Colecistolitiasis/diagnóstico por imagen , Diagnóstico Diferencial , Femenino , Vesícula Biliar/diagnóstico por imagen , Vesícula Biliar/patología , Enfermedades de la Vesícula Biliar/diagnóstico por imagen , Neoplasias de la Vesícula Biliar/diagnóstico , Neoplasias de la Vesícula Biliar/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Tomografía Computarizada por Rayos X , Ultrasonografía
15.
J Radiol ; 86(6 Pt 2): 759-79; quiz 779-80, 2005 Jun.
Artículo en Francés | MEDLINE | ID: mdl-16142070

RESUMEN

Pancreatic cancer remains the fourth most common cause of cancer death. Surgery remains the only option for cure. Accurate diagnosis and staging are essential for appropriate management of patients with pancreatic cancer. This paper reviews the state of the art for imaging modalities in the diagnosis and staging of pancreatic adenocarcinoma. The crucial role of CT has increased with the new generation of multidetector CT.


Asunto(s)
Adenocarcinoma/diagnóstico , Diagnóstico por Imagen , Neoplasias Pancreáticas/diagnóstico , Endosonografía , Humanos , Imagen por Resonancia Magnética , Estadificación de Neoplasias , Planificación de Atención al Paciente , Tomografía Computarizada Espiral/métodos
16.
Inflamm Res ; 51(5): 252-8, 2002 May.
Artículo en Inglés | MEDLINE | ID: mdl-12056513

RESUMEN

OBJECTIVE: This study was designed to evaluate therapeutic effects of bindarit, an indazolic derivative able to inhibit monocyte chemoattractant protein-1 (MCP-1) production, in adjuvant induced arthritis in rats. MATERIALS AND METHODS: Arthritis was induced by Freund's complete adjuvant injection. Bindarit was given as a 0.5% medicated diet starting on day 11 after adjuvant injection. The course of arthritis was monitored by sequential paw volume measurement and by radiologic and histologic evaluations. Human osteoblast cell line Saos-2 stimulated with Interleukin-1 (IL-1) was used to assess in vitro bindarit effect on MCP-1 release. In addition, in vivo effects of bindarit on cytokine production were studied in mice injected with lipopolysaccharide (LPS). Immune function studies were performed in mice by evaluating ex vivo antibody response to ovalbumin and splenocytes proliferation to Concanavalin A (Con A). RESULTS: In adjuvant-induced arthritis in rats, bindarit possessed therapeutic activity resulting in a significant inhibition of paw inflammation. Evidence for a disease-modifying activity was also indicated by amelioration of radiologic alterations and by histological evaluation of joints. Additional evidence for beneficial effects in osseous inflammation was provided by an in vitro assay in which bindarit inhibited the release of MCP-1 from IL-1 stimulated osteoblast cells. Moreover, in a murine model of LPS-induced cytokine production bindarit reduced MCP-1 and tumor necrosis factor (TNF)-alpha increase without affecting IL-1 and IL-6 levels. Finally, the drug, given as a 0.5% medicated diet for 14 days, did not affect either anti-ovalbumin serum antibody production or splenocytes proliferative response in mice. CONCLUSIONS: Results obtained indicate that bindarit beneficial effects in experimental arthritis are correlated to MCP-1 and TNF-alpha inhibition and suggest that the control of cytokines and chemokines production can have considerable relevance as regards strategies for the treatment of chronic inflammatory diseases.


Asunto(s)
Artritis Experimental/tratamiento farmacológico , Quimiocina CCL2/antagonistas & inhibidores , Indazoles/uso terapéutico , Propionatos/uso terapéutico , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Animales , Artritis Experimental/diagnóstico por imagen , Artritis Experimental/patología , Línea Celular , Quimiocina CCL2/biosíntesis , Citocinas/biosíntesis , Miembro Posterior/patología , Humanos , Inmunidad/efectos de los fármacos , Lipopolisacáridos , Masculino , Ratones , Ratones Endogámicos BALB C , Osteoblastos/efectos de los fármacos , Ovalbúmina/inmunología , Radiografía , Ratas , Factor de Necrosis Tumoral alfa/biosíntesis
18.
Exp Nephrol ; 8(1): 37-43, 2000.
Artículo en Inglés | MEDLINE | ID: mdl-10644881

RESUMEN

Interleukin (IL) 6, an autocrine growth factor for mesangial cells, and chemokines, which are released from activated mesangial cells and induce leukocyte infiltration, play a critical role in the progression of immune system mediated renal diseases. Since the reciprocal relationship between IL-6 and chemokines in renal inflammation has been barely investigated, we have analyzed whether IL-6 (500 ng/ml), alone or in combination with the soluble form of its receptor (sIL-6R, 200 ng/ml), can induce normal human mesangial cells (NHMC) to release alpha and/or beta chemokines: MCP-1 (monocyte chemoattractant protein 1), IL-8, Rantes (regulated on activation, normal T cell expressed and secreted), and MIP-1alpha (macrophage inflammatory protein 1alpha). Whereas IL-6 or sIL-6R alone were ineffective in inducing significant chemokine release from NHMC, the simultaneous treatment with IL-6 and sIL-6R showed a significant interaction, leading to a strong synergic effect on MCP-1 synthesis and release without exerting any relevant activity on IL-8, Rantes, or MIP-1alpha. Consistently with the unresponsiveness to IL-6, mRNA and protein expression analysis of the two subunits which form the functional IL-6 receptor showed that NHMC express only the gp130 signal-transducing chain and not the subunit-specific IL-6R (gp80). These findings support an unexpected role of the IL-6 system in kidney inflammatory reactions through the selective regulation of monocyte recruitment.


Asunto(s)
Quimiocina CCL2/metabolismo , Mesangio Glomerular/efectos de los fármacos , Interleucina-6/farmacología , Receptores de Interleucina-6/fisiología , Northern Blotting , Línea Celular , Quimiocina CCL2/genética , Quimiocinas/metabolismo , Regulación de la Expresión Génica , Mesangio Glomerular/citología , Mesangio Glomerular/metabolismo , Humanos , Interleucina-1/farmacología , Interleucina-8/metabolismo , Lipopolisacáridos/farmacología , ARN Mensajero/efectos de los fármacos , ARN Mensajero/genética , ARN Mensajero/metabolismo , Receptores de Interleucina-6/genética , Solubilidad
19.
Eur Cytokine Netw ; 10(3): 437-42, 1999 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-10477401

RESUMEN

Blocking chemokine production or action is a major target for pharmacological intervention in different human diseases. Bindarit (2-methyl-2-[[1-(phenylmethyl)-1H-indazol-3yl]methoxy]propan oic acid) dose-dependently inhibited MCP-1 and TNF-alpha production induced in vitro in monocytes by LPS and Candida albicans. It did not affect the production of the cytokines IL-1, IL-6, or the chemokines IL-8, MIP-1alpha and RANTES. In the air pouch model in mice, oral treatment reduced monocyte recruitment and local MCP-1 production, induced by carrageenan or IL-1 injection. In NZB/W mice, a model of lupus nephritis, oral treatment prolonged survival and delayed the onset of proteinuria. The results presented here show that bindarit is a preferential inhibitor of the production of MCP-1 in vitro and in vivo and suggest that its beneficial effects in models of joint and kidney inflammation are related to its anti-MCP-1 action. It is therefore possible to selectively and differentially regulate chemokines by targeting their production with small synthetic molecules.


Asunto(s)
Quimiocina CCL2/antagonistas & inhibidores , Indazoles/farmacología , Propionatos/farmacología , Animales , Línea Celular , Quimiocina CCL2/biosíntesis , Quimiocinas/biosíntesis , Citocinas/biosíntesis , Femenino , Humanos , Ratones , Monocitos/efectos de los fármacos , Monocitos/metabolismo
20.
Eur J Pharmacol ; 360(1): 55-64, 1998 Oct 30.
Artículo en Inglés | MEDLINE | ID: mdl-9845273

RESUMEN

Deposition of beta-amyloid in the brain triggers an inflammatory response which accompanies the neuropathologic events of Alzheimer's disease and contributes to the destruction of brain tissue. The present study shows that beta-amyloid can stimulate human astrocytoma cells (T98G) to secrete the proinflammatory factors interleukin-6 and prostaglandins. Furthermore, prostaglandins can stimulate T98G to secrete interleukin-6, which in turn triggers the formation of additional prostaglandins. Prostaglandins are, therefore, a key element in the induction and maintenance of a state of chronic inflammation in the brain which may exacerbate the fundamental pathology in Alzheimer patients. Paracetamol (0.01-1000 microM), an unusual analgesic/antipyretic drug which acts preferentially by reducing prostaglandin production within the central nervous system, and indomethacin (0.001-10 microM) caused a clear dose-dependent reduction of prostaglandin E2 production by stimulated T98G cells whereas interleukin-6 release was not affected. These data provide further evidence of the involvement of non-steroidal anti-inflammatory drugs in the inflammatory processes that can be generated by glial cells in intact brain.


Asunto(s)
Péptidos beta-Amiloides/farmacología , Mediadores de Inflamación/metabolismo , Acetaminofén/farmacología , Analgésicos no Narcóticos/farmacología , Astrocitoma , Medios de Cultivo Condicionados/análisis , Medios de Cultivo Condicionados/metabolismo , Ciclooxigenasa 1 , Ciclooxigenasa 2 , Dinoprostona/metabolismo , Dinoprostona/farmacología , Humanos , Mediadores de Inflamación/farmacología , Interleucina-1/genética , Interleucina-1/metabolismo , Interleucina-1/farmacología , Interleucina-6/genética , Interleucina-6/metabolismo , Interleucina-6/farmacología , Isoenzimas/genética , Proteínas de la Membrana , Prostaglandina-Endoperóxido Sintasas/genética , Prostaglandinas/farmacología , Prostaglandinas/fisiología , ARN Mensajero/efectos de los fármacos , ARN Mensajero/metabolismo , Células Tumorales Cultivadas/citología , Células Tumorales Cultivadas/efectos de los fármacos , Células Tumorales Cultivadas/metabolismo
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