RESUMEN
Differential diagnoses of subepithelial gastric masses include benign (leiomyoma, lipoma, haemangioma, lymphangioma, neurogenic tumours, glomus tumour) and malignant (leiomyosarcoma, gastric Kaposi's sarcoma, metastases) neoplastic lesions, gastrointestinal stromal tumours (GIST) and lesions of non-neoplastic origin (heterotopic pancreatic tissue, intramural pseudocysts, intramural haematoma). Occasionally, however, suspected gastric wall tumours are caused by extragastral lesions that are not always easily distinguished from genuine gastric wall lesions by endoscopy or radiological imaging. We report the case of a 77-year-old patient undergoing laparoscopy for suspected gastric GIST in our institution in whom splenectomy had been performed 26 years prior to presentation due to traumatic splenic rupture. The tumour revealed to be ectopic splenic tissue located at the parietal peritoneum of the ventral abdominal wall, thereby fulfilling the definition of splenosis. Epidemiology, pathogenesis, diagnostics and therapy of splenosis are discussed in the context of a review of the relevant literature.
Asunto(s)
Enfermedades Peritoneales/diagnóstico , Enfermedades Peritoneales/etiología , Rotura del Bazo/complicaciones , Rotura del Bazo/diagnóstico , Esplenosis/diagnóstico , Esplenosis/etiología , Anciano , Diagnóstico Diferencial , Humanos , Masculino , Enfermedades Raras/diagnósticoRESUMEN
We report a case of tracheal, laryngeal and pulmonary mucormycosis in a patient receiving immunosuppressive medication for an autoinflammatory fever syndrome. Mucormycosis was confirmed by histopathology from tracheal specimens and molecular evidence of Lichtheimia. A surgical approach was not possible because of the multifocal disease pattern and the extent of tracheal involvement. The patient was successfully treated with liposomal amphotericin B followed by posaconazole maintenance therapy. After 9 months, recurrent pulmonary mucormycosis was suspected but emerged as organizing pneumonia without evidence of active fungal infection.
RESUMEN
We investigated the antioxidant and radical scavenging activity of polyphenolic isochromans. To assess the relation between structure and scavenging properties the natural occurring 1-(3'-methoxy-4'-hydroxy)phenyl-6,7-dihydroxy-isochroman (ISO-3, three OH groups) was compared with three newly synthesized derivatives that differ in their degree of hydroxylation by substitution with methoxy-groups (ISO-4: four OH groups; ISO-2: two OH groups and ISO-0: fully methoxylated). We found that ISO-4 is a 2-fold better scavenger for the artificial radical 1,1-diphenyl-2-picrylhydrazyl (DPPH, 100 microM) with an EC50=10.3 microM compared to the natural ISO-3 (EC50=22.4 microM) and to ISO-2 (EC50=25.1 microM), while ISO-0 did not react with DPPH. The scavenging capacity for superoxide enzymatically generated in a hypoxanthin-xanthinoxidase reaction was the highest for ISO-4 (EC50=34.3 microM) compared to those of ISO-3 (EC50=84.0 microM) and ISO-2 (EC50=91.8 microM), while ISO-0 was inactive. In analogy, ISO-4 scavenged peroxynitrite (ONOO-, EC25=23.0 microM) more effective than ISO-3, ISO-2 and ISO-0. When C6 rat glioma cells loaded with the reactive oxygen/nitrogen (ROS/RNS)-sensitive fluorochrome 2,7-dichlorodihydrofluorescein, were exposed to hydrogen peroxide, the lowest stress level as indicated by the fluorescence signal was detected when the cells were pretreated with ISO-4 or ISO-2 but to a much lesser extent with ISO-3, while ISO-0 did not show any effect. All tested hydroxyisochromans superceded the scavenging effect of trolox.The excellent radical and ROS/RNS scavenging features of the hydroxy-1-aryl isochromans and their simple synthesis let these compounds appear to be interesting candidates for pharmaceutical interventions that protect against the deleterious action of ROS/RNS.
Asunto(s)
Antioxidantes/química , Antioxidantes/síntesis química , Cromanos/química , Cromanos/síntesis química , Depuradores de Radicales Libres/química , Depuradores de Radicales Libres/síntesis química , Animales , Antioxidantes/metabolismo , Línea Celular Tumoral , Cromanos/metabolismo , Cromatografía Líquida de Alta Presión , Depuradores de Radicales Libres/metabolismo , Radicales Libres/química , Radicales Libres/metabolismo , Espectrometría de Masas , Microscopía Confocal , Estrés Oxidativo/efectos de los fármacos , RatasRESUMEN
Helicobacter pylori are responsible for the induction of chronic gastric inflammation progressing to atrophy, metaplasia, and gastric cancer. The overexpression of Cathepsin X/Z (Ctsz) in H. pylori-infected mucosa and gastric cancer is mediated predominantly by an augmented migration of ctsz(-/-)positive macrophages and the up-regulation of Ctsz in tumor epithelium. To explore the Ctsz-function in the context of chronic inflammation and the development of preneoplastic lesions, we used Ctsz-deficient mice in a H. pylori gastritis model. Ctsz (-/-) and wild-type (wt) mice were infected with H. pylori strain SS1. The mice were sacrificed at 24, 36, and 50 weeks post infection (wpi). The stomach was removed, and gastric strips were snap-frozen or embedded and stained with H&E. Tissue sections were scored for epithelial lesions and inflammation. Ki-67 and F4/80 immunostaining were used to measure epithelial cell proliferation and macrophage infiltration, respectively. The upregulation of compensating cathepsins and cytokines were confirmed by Western blotting and quantitative RT-PCR. SS1-infected wt and ctsz (-/-) mice showed strong inflammation, foveolar hyperplasia, atrophy, and cystically-dilated glands. However, at 50 wpi, ctsz (-/-) mice developed significantly more severe spasmolytic polypeptide-expressing metaplasia (SPEM), showed enhanced epithelial proliferation, and higher levels of infiltrating macrophages. Induction of cytokines was higher and significantly prolonged in ctsz (-/-) mice compared to wt. Ctsz deficiency supports H. pylori-dependent development of chronic gastritis up to metaplasia, indicating a protective, but not proteolytic, function of Ctsz in inflammatory gastric disease.
Asunto(s)
Catepsina Z/deficiencia , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patología , Infecciones por Helicobacter/genética , Helicobacter pylori , Lesiones Precancerosas/genética , Animales , Catepsina B/genética , Catepsina B/metabolismo , Catepsina Z/genética , Catepsina Z/metabolismo , Citocinas/metabolismo , Dilatación Patológica , Modelos Animales de Enfermedad , Expresión Génica , Hiperplasia , Mediadores de Inflamación/metabolismo , Ratones , Ratones Noqueados , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologíaRESUMEN
Hydroxy-1-aryl-isochromans are a novel class of polyphenolic heterocyclic compounds with potent antioxidative potential. Here we investigated the protective effects of hydroxy-1-aryl-isochroman derivatives against lipid peroxidation and nitrosative stress as a function of their degree of hydroxylation. Measurements of thiobarbituric acid reactive substances (TBARS) in rat brain mitochondria, nitric oxide analysis in microglia cultures, and cell viability analysis were performed. We found that hydroxyl-1-aryl-isochroman derivatives with two, three, and four hydroxyl groups (ISO-2, ISO-3, and ISO-4, respectively) display a higher activity against mitochondrial lipid peroxidation than the corresponding derivative without hydroxyl groups (ISO-0) as well as the reference antioxidant Trolox. However, ISO-0 strongly reduced microglial nitric oxide production, whereas ISO-2 and ISO-4 had a less pronounced effect and ISO-3 was even ineffective. ISO-0 and ISO-3 increased the cell viability of activated microglia, whereas a minor effect of ISO-2 and no significant increase after treatment with ISO-4 could be observed. In conclusion, hydroxy-1-aryl-isochromans exhibit cytoprotective properties, besides their action against reactive oxygen/nitrogen species.