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1.
Anasthesiol Intensivmed Notfallmed Schmerzther ; 49(9): 544-53; quiz 554, 2014 Sep.
Artículo en Alemán | MEDLINE | ID: mdl-25238014

RESUMEN

Trauma resuscitation in children, pregnant women, Jehovah's witnesses or in patients with infectious diseases like HIV is obviously beyond routine. This may result in uncertainty how to manage these patients appropriately. Preparation for such situations is essential. Therefore this article focuses on the specific problems associated with these kinds of patients.


Asunto(s)
Cuidados Críticos/organización & administración , Hospitalización , Traumatismo Múltiple/diagnóstico , Traumatismo Múltiple/terapia , Manejo de Atención al Paciente/organización & administración , Resucitación/métodos , Traumatología/normas , Alemania , Humanos
2.
Cancer Immunol Immunother ; 60(10): 1405-18, 2011 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-21638125

RESUMEN

The ectonucleotidases CD39 and CD73 degrade immune stimulatory ATP to adenosine that inhibits T and NK cell responses via the A(2A) adenosine receptor (ADORA2A). This mechanism is used by regulatory T cells (T(reg)) that are associated with increased mortality in OvCA. Immunohistochemical staining of human OvCA tissue specimens revealed further aberrant expression of CD39 in 29/36 OvCA samples, whereas only 1/9 benign ovaries showed weak stromal CD39 expression. CD73 could be detected on 31/34 OvCA samples. While 8/9 benign ovaries also showed CD73 immunoreactivity, expression levels were lower than in tumour specimens. Infiltration by CD4(+) and CD8(+) T cells was enhanced in tumour specimens and significantly correlated with CD39 and CD73 levels on stromal, but not on tumour cells. In vitro, human OvCA cell lines SK-OV-3 and OaW42 as well as 11/15 ascites-derived primary OvCA cell cultures expressed both functional CD39 and CD73 leading to more efficient depletion of extracellular ATP and enhanced generation of adenosine as compared to activated T(reg). Functional assays using siRNAs against CD39 and CD73 or pharmacological inhibitors of CD39, CD73 and ADORA2A revealed that tumour-derived adenosine inhibits the proliferation of allogeneic human CD4(+) T cells in co-culture with OvCA cells as well as cytotoxic T cell priming and NK cell cytotoxicity against SK-OV3 or OAW42 cells. Thus, both the ectonucleotidases CD39 and CD73 and ADORA2A appear as possible targets for novel treatments in OvCA, which may not only affect the function of T(reg) but also relieve intrinsic immunosuppressive properties of tumour and stromal cells.


Asunto(s)
5'-Nucleotidasa/metabolismo , Antígenos CD/metabolismo , Apirasa/metabolismo , Citotoxicidad Inmunológica , Células Asesinas Naturales/inmunología , Neoplasias Ováricas/enzimología , Receptor de Adenosina A2A/metabolismo , Linfocitos T/inmunología , 5'-Nucleotidasa/inmunología , Adenosina/metabolismo , Antígenos CD/inmunología , Apirasa/inmunología , Línea Celular Tumoral , Separación Celular , Femenino , Citometría de Flujo , Proteínas Ligadas a GPI/inmunología , Proteínas Ligadas a GPI/metabolismo , Humanos , Inmunohistoquímica , Neoplasias Ováricas/inmunología , Neoplasias Ováricas/patología , Interferencia de ARN , Receptor de Adenosina A2A/inmunología
3.
Fertil Steril ; 95(5): 1787.e5-7, 2011 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-21183177

RESUMEN

OBJECTIVE: To illustrate pitfalls in the diagnosis of endometriosis and cervical cancer. DESIGN: Case report. SETTING: University hospital, department of obstetrics and gynecology. PATIENT(S): A 45-year-old woman with menorrhagia, pelvic mass, right-sided hydronephrosis, and unexplained weight loss. INTERVENTION(S): Cervical biopsies were suggestive of cervical endometriosis. Laparoscopy confirmed endometriosis. Associated pleural effusion, without cytologic signs of malignancy, was interpreted as caused by thoracic endometriosis. The patient had a transabdominal hysterectomy and unilateral salpingo-oophorectomy. Histopathologic examination confirmed endometriosis and revealed a residual tubo-ovarian abscess. After surgery, the patient developed spontaneous seropneumothorax. Pleural biopsies revealed a well-differentiated epithelial malignant pleural mesothelioma. The patient underwent hypofractionated radiation of drain sites. She is now observed in our outpatient clinic. MAIN OUTCOME MEASURE(S): Steps to the correct diagnosis. RESULT(S): The patient had an association of cervical and pelvic endometriosis, residual tubo-ovarian abscess, and malignant pleural mesothelioma. CONCLUSION(S): Usually, the simplest diagnosis explaining a complex of symptoms and clinical and diagnostic findings is the one most likely to be correct. This is an application of Occam's razor to medicine. Our case illustrates that occasionally the simplest and therefore most probable diagnosis can be wrong, and on these occasions one should consider a "third man."


Asunto(s)
Endometriosis/diagnóstico , Mesotelioma/diagnóstico , Neoplasias Pleurales/diagnóstico , Enfermedades del Cuello del Útero/diagnóstico , Neoplasias del Cuello Uterino/diagnóstico , Diagnóstico Diferencial , Endometriosis/complicaciones , Endometriosis/cirugía , Femenino , Humanos , Masculino , Mesotelioma/complicaciones , Persona de Mediana Edad , Rol del Médico , Neoplasias Pleurales/complicaciones , Derivación y Consulta/estadística & datos numéricos , Enfermedades del Cuello del Útero/complicaciones , Enfermedades del Cuello del Útero/cirugía
4.
J Immunol Methods ; 361(1-2): 51-6, 2010 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-20692262

RESUMEN

Extracellular adenosine exerts powerful paracrine effects on immune cells. Thus, adenosine signaling has to be strictly regulated. This is achieved by its rapid internalization or enzymatic degradation. Consequently, free adenosine is extremely difficult to measure in cell culture systems and may escape from detection by time-consuming endpoint measurements like high-performance liquid chromatography (HPLC). Therefore, we have now developed a highly sensitive assay which enables the quantification of biologically relevant extracellular adenosine via the activation of an ectopically expressed Adenosine 2a-receptor (ADORA2A) in HEK-293 reporter cells. Binding of the short-lived nucleoside to this receptor induces a cAMP-dependent signal which can be detected via a cAMP-responsive luciferase construct. Tests with exogenously added adenosine confirmed that the resulting luminescence signals correlate with the respective adenosine levels and thus allow quantitative measurements in a range from 20 nM to 80 µM free extracellular adenosine. Inhibition of adenosine uptake by dipyridamole further increased the sensitivity of the assay. We further validated our approach by quantifying the adenosine levels that are generated by regulatory T cells via ectonucleotidase-mediated cleavage of ATP. As expected, values returned to baseline when ADORA2A was inhibited. This confirmed that this new cell-based reporter assay constitutes a biologically relevant, technically easy, versatile, scalable and cost-effective approach that allows the non-radioactive quantification of adenosine as a signaling intermediate.


Asunto(s)
Adenosina/metabolismo , Espacio Extracelular/metabolismo , Luciferasas/metabolismo , Mediciones Luminiscentes/métodos , Receptores Purinérgicos P1/metabolismo , Transducción de Señal/fisiología , Adenosina/análisis , Línea Celular , Dipiridamol/farmacología , Humanos
5.
Am J Physiol Heart Circ Physiol ; 284(6): H2100-5, 2003 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-12560208

RESUMEN

The present study investigated the effect of tumor necrosis factor (TNF)-alpha on myocardial energy metabolism as estimated by myocardial oxygen consumption (MVo(2)). MVo(2) of electrically stimulated isolated trabeculae of right ventricular Wistar rat myocardium was analyzed using a Clark-type oxygen probe. After the initial data collection in the absence of TNF-alpha, measurements were repeated after TNF-alpha stimulation. In separate experiments, pretreatment with the nitric oxide (NO) synthase inhibitor N(G)-nitro-l-arginine methyl ester (l-NAME) or the ceramidase inhibitor n-oleoylethanolamine (NOE) was done to investigate NO/sphingosine-related effects. TNF-alpha impaired myocardial economy at increasing stimulation frequencies without altering baseline MVo(2). Incubation with TNF-alpha in the presence of l-NAME further impaired myocardial economy. NOE preincubation abrogated the TNF-alpha effect on myocardial economy. Moreover, the negative inotropic effect of TNF-alpha was observed in NOE-pretreated but not l-NAME-pretreated muscle fibers. Exogenous sphingosine mimicked the TNF-alpha effect on mechanics and energetics. We conclude that TNF-alpha impairs the economy of chemomechanical energy transduction primarily through a sphingosine-mediated pathway.


Asunto(s)
Miocardio/metabolismo , Consumo de Oxígeno/fisiología , Transducción de Señal/efectos de los fármacos , Esfingosina/fisiología , Factor de Necrosis Tumoral alfa/farmacología , Amidohidrolasas/antagonistas & inhibidores , Animales , Calcio/metabolismo , Ceramidasas , Endocannabinoides , Metabolismo Energético/efectos de los fármacos , Inhibidores Enzimáticos/farmacología , Etanolaminas/farmacología , Técnicas In Vitro , Fibras Musculares Esqueléticas/efectos de los fármacos , Fibras Musculares Esqueléticas/enzimología , Contracción Miocárdica/efectos de los fármacos , NG-Nitroarginina Metil Éster/farmacología , Óxido Nítrico Sintasa/antagonistas & inhibidores , Óxido Nítrico Sintasa/biosíntesis , Óxido Nítrico Sintasa de Tipo III , Ácidos Oléicos , Ratas
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