RESUMEN
REG3γ is considered to have a protective role against infection with Gram-positive bacteria due to its bactericidal activity, but evidence from in vivo studies is lacking. We generated a REG3γ(-/-) mouse, and investigated the effect of lack of REG3γ on intestinal mucus distribution, spatial compartmentalization of bacteria, and expression of innate immunity genes. Infection studies were also performed with Gram-positive and Gram-negative pathogens to investigate the antimicrobial role of REG3γ. REG3γ(-/-) mice display altered mucus distribution, increased bacterial contact with the epithelium, and elevated inflammatory markers in the ileum without histological evidence of pathology. Infection response pathway genes were differentially expressed in both Listeria monocytogenes and Salmonella enteritidis infected REG3γ(-/-) and wild-type (wt) mice. Higher amounts of myeloperoxidase and interleukin-22 transcripts were present in the ileal mucosa of REG3γ(-/-) than wt mice, but translocation to the organs was unaffected. We concluded that REG3γ has a protective role against mucosal infection with pathogenic Listeria and Salmonella in vivo. REG3γ is equally distributed throughout the mucus and its absence results in increased epithelial contact with the microbiota resulting in low-grade inflammation. REG3γ can bind to Gram-negative and Gram-positive bacteria and influence mucus distribution in the ileum, properties which may contribute to mucosal protection.
Asunto(s)
Íleon/inmunología , Íleon/metabolismo , Inflamación/genética , Inflamación/inmunología , Mucosa Intestinal/inmunología , Mucosa Intestinal/metabolismo , Moco/metabolismo , Proteínas/genética , Animales , Modelos Animales de Enfermedad , Perfilación de la Expresión Génica , Íleon/microbiología , Inmunidad Innata , Inflamación/microbiología , Factores Reguladores del Interferón/metabolismo , Interferones/metabolismo , Interleucina-1beta/metabolismo , Mucosa Intestinal/microbiología , Listeria monocytogenes/fisiología , Ratones , Ratones Noqueados , Microbiota , Factor 88 de Diferenciación Mieloide/metabolismo , Proteínas Asociadas a Pancreatitis , Factor de Transcripción STAT1/metabolismo , Factor de Transcripción STAT3/metabolismo , Salmonella enteritidis/fisiología , Transducción de Señal , Receptor Toll-Like 3/metabolismoRESUMEN
PURPOSE: To evaluate the accuracy of computed tomography (CT) and magnetic resonance imaging (MRI) in staging renal carcinoma. MATERIAL AND METHODS: 33 renal carcinomas were preoperatively examined for tumour staging by CT and MR imaging and correlated with histopathological staging. CT imaging was performed at first as a non-contrast scan. Finally incremental images (10 mm) after intravenous contrast injection were obtained. In MR imaging we performed a transversal T1-weighted GE sequence (112/5) with and without GDTPA, a transversal fat-suppressed double-echo sequence (3900/22/90), a coronal T1-weighted GE sequence with and without GDTPA and a coronal T2-weighted TSE sequence (2800/128). In addition, dynamic T1-weighted GE imaging after GDTPA injection as well as TOF angiography in coronal direction were performed. Finally CT and MRI findings were correlated with surgical and histopathological staging results. RESULTS: CT and MRI staging was correct in 27 and 28 of 33 tumours. Sensitivity and specificity for tumour stage T3b to T4 was for MRI and CT 88.9% and 95.8%. With MRI 4 out of 7 thrombi were correctly diagnosed with high accuracy, but via CT none. CONCLUSION: In early stage renal carcinoma CT and MR imaging yielded similar staging accuracies. In advanced renal carcinoma MRI was superior to CT imaging, especially in diagnosing tumour thrombus. Consequently the extent of tumour thrombus may be assessed by MRI which may therefore replace conventional cavography.
Asunto(s)
Carcinoma de Células Renales/patología , Neoplasias Renales/patología , Imagen por Resonancia Magnética , Tomografía Computarizada por Rayos X , Adulto , Anciano , Carcinoma de Células Renales/diagnóstico , Medios de Contraste , Femenino , Gadolinio DTPA , Humanos , Yohexol/análogos & derivados , Neoplasias Renales/diagnóstico , Metástasis Linfática , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Estudios Prospectivos , Sensibilidad y Especificidad , Tomografía Computarizada por Rayos X/métodosRESUMEN
Based on in vitro results it was found that the pharmacokinetic parameters of the hydrophilic drug bretylium (2) can be influenced by an ion-pair-formation with the lipophilic hexylsalicyclic acid (1). After simultaneous i.v. application of 1 and 2 on rabbits a significant increase of the AUC of 2 was observed. Under these conditions a marked increase of the AUC and the MRT of 1 was also obtained, since the blood levels of 2 are high enough for such an influence. A combined rectal application of 1 and 2 causes an increase of the AUC of 2.
Asunto(s)
Compuestos de Bretilio/farmacocinética , Salicilatos/farmacología , Administración Oral , Animales , Compuestos de Bretilio/administración & dosificación , Interacciones Farmacológicas , Inyecciones Intravenosas , Conejos , Salicilatos/administración & dosificaciónRESUMEN
Using hexylsalicylic acid it was demonstrated that alkylated derivatives of salicylic acid are able to increase partition and transport of ionized basic drugs across lipophilic membranes. The influence of different donor concentrations on the relation of transport was studied by means of pholedrine in combination with hexylsalicylic acid. In order to explain the mechanism of the ion-pair-transport experiments were carried out which show beside the mentioned increase of transport the occurrence of a countertransport of protons and lithium-ions, respectively. The lipophilic counterion hexylsalicylate acts inside of this mechanism as a carrier for the ionized drugs.
Asunto(s)
Membrana Dobles de Lípidos , Salicilatos/análisis , Fenómenos Químicos , Química , Química Física , Concentración de Iones de Hidrógeno , Metanfetamina/análogos & derivados , Metanfetamina/análisisRESUMEN
The medical and social care of the aged is a substantial task of General Practitioners in the GDR Public Health. Increasing consideration must be given to the individual social situation. According to Public Health directives covering all sectors of geriatric care we built a "geriatric care Commitee" whose members are a G.P., a geriatric welfare worker, the district nurses, a representative of the local plant health organisation and one of the elected munifipal council members. Tasks are described and achieved results are related. Significance of purposely coordination of all sectors participating in care for the aged is stressed.