RESUMEN
BACKGROUND: Pancreatic neuritis is a histopathological hallmark of pancreatic neuropathy and correlates to abdominal neuropathic pain sensation in pancreatic adenocarcinoma (PCa) and chronic pancreatitis (CP). However, inflammatory cell subtypes that compose pancreatic neuritis and their correlation to the neuropathic pain syndrome in PCa and CP are yet unknown. METHODS: Inflammatory cells within pancreatic neuritis lesions of patients with PCa (n = 20) and CP (n = 20) were immunolabeled and colorimetrically quantified with the pan-leukocyte marker CD45, with CD68 (macrophages), CD8 (cytotoxic T-lymphocytes), CD4 (T-helper cells), CD20 (B-lymphocytes), NCL-PC (plasma cells), neutrophil elastase, PRG2 (eosinophils), anti-mast cell (MC) tryptase and correlated to pain sensation. Perineural mast cell subtypes were analyzed by double immunolabeling with MC chymase. Expression and neural immunoreactivity of protease-activated receptor type 1 (PAR-1) and type 2 (PAR-2) were analyzed in PCa and CP and correlated to pain status of the patients. RESULTS: In PCa and CP, nerves were predominantly infiltrated by cytotoxic T-lymphocytes (PCa: 35% of all perineural inflammatory cells, CP: 33%), macrophages (PCa: 39%, CP: 33%) and MC (PCa: 21%, CP: 27%). In both entities, neuropathic pain sensation was associated with a specific increase of perineural MC (PCa without pain: 14% vs. PCa with pain: 31%; CP without pain: 19% vs. CP with pain: 34%), not affecting the frequency of other inflammatory cell subtypes. The vast majority of these MC contained MC chymase. PAR-1 and PAR-2 expression did not correlate to the pain sensation of PCa and CP patients. CONCLUSION: Pancreatic neuritis in PC and CP is composed of cytotoxic T-lymphocytes, macrophages and MC. The specific enrichment of MC around intrapancreatic nerves in neuropathic pain due to PCa and CP suggests the presence of MC-induced visceral hypersensitivity in the pancreas. Therefore, pancreatic and enteric neuropathies seem to share a similar type of neuro-immune interaction in the generation of visceral pain.
Asunto(s)
Adenocarcinoma/patología , Mastocitos/patología , Neuralgia/patología , Neuritis/patología , Páncreas/patología , Neoplasias Pancreáticas/patología , Pancreatitis Crónica/patología , Adenocarcinoma/complicaciones , Adenocarcinoma/inmunología , Anciano , Femenino , Humanos , Macrófagos/inmunología , Macrófagos/patología , Masculino , Mastocitos/inmunología , Persona de Mediana Edad , Neuralgia/complicaciones , Neuralgia/inmunología , Neuritis/complicaciones , Neuritis/inmunología , Páncreas/inmunología , Páncreas/inervación , Neoplasias Pancreáticas/complicaciones , Neoplasias Pancreáticas/inmunología , Pancreatitis Crónica/complicaciones , Pancreatitis Crónica/inmunología , Receptor PAR-1/análisis , Receptor PAR-2/análisis , Linfocitos T Citotóxicos/inmunología , Linfocitos T Citotóxicos/patologíaRESUMEN
OBJECTIVE: Many patients experience problems with sexual functioning after renal transplantation (RTx). Research on the sexual functioning of the partners of those patients and the consequences for relationship satisfaction and quality of life is lacking. This study sought to explore changes in sexual and relationship functioning from before to after RTx in patients and their partners. MATERIAL AND METHODS: Twenty-nine patients (mean ± SD age 53.4 ± 14.2 years) and 13 partners (age 57.1 ± 11.6 years) provided data 12-15 months after RTx. They retrospectively evaluated sexual and relationship functioning as well as general life satisfaction before RTx and, in comparison, in the most recent months. RESULTS: Among the patients, most items on sexual experience indicated deterioration in sexual functioning. Among their partners, the wish for sexual activity with the patient and the actual frequency of sexual activity decreased from before to after RTx. The rate of partners indicating high personal importance for intercourse decreased from 83.3% to 69.2%, as did the rate of partners stating high sexual satisfaction (from 63.6% to 41.7%). Despite these trends, most patients and partners reported high relationship and life satisfaction after RTx. CONCLUSIONS: Partners of patients who had received a kidney transplant seem to be affected by negative changes in the patients' sexual functioning. Nonetheless, many couples maintain high relationship and life satisfaction.
Asunto(s)
Relaciones Interpersonales , Trasplante de Riñón/efectos adversos , Calidad de Vida , Disfunciones Sexuales Fisiológicas/psicología , Disfunciones Sexuales Psicológicas/psicología , Parejas Sexuales/psicología , Adulto , Anciano , Femenino , Humanos , Fallo Renal Crónico/fisiopatología , Fallo Renal Crónico/psicología , Fallo Renal Crónico/cirugía , Masculino , Persona de Mediana Edad , Conducta Sexual/psicología , Disfunciones Sexuales Fisiológicas/etiología , Disfunciones Sexuales Psicológicas/etiología , Encuestas y CuestionariosRESUMEN
Transplantation of pancreatic islets is a promising strategy for restoring insulin secretion in diabetes mellitus. To monitor transplanted islets, a method to evaluate the distribution in a non-invasive manner in vivo is needed. INS-1E, a stable differentiated insulin secreting cell line, and rodent islets were used to monitor cell transplantation by MRI. For labeling INS-1E cells in vitro, increasing concentrations of Resovist in culture medium were tested. For MR imaging in a clinical 3T scanner, we placed a layer of labeled INS-1E cells between two layers of 4% gelatin. Viability assay was performed. Cell function was evaluated by static incubation assay to assess insulin secretion. For in vivo imaging, iron labeled rodent islets were transplanted into the liver of streptozotocin induced diabetic rats and visualized by MRI. Blood sugar values were controlled and liver tissue was removed for histological analysis. SPIO labeled INS-1E cells did not show altered viability or reduced glucose stimulated insulin secretion in vitro. Double staining of labeled and unlabeled INS-1E cells showed no difference in the staining pattern. Labeling of rodent islets with SPIOs does not reduce their secretory activity or alter their viability. We visualized SPIO-labeled INS-1E cells and rat islets in vitro using a clinical 3T scanner. Diabetic rats transplanted with SPIO-labeled islets became normoglycemic. MR imaging successfully verified the distribution of labeled transplanted cells in vivo. Labeling INS-1E cells and rat islets with SPIOs does not alter their viability, while enabling MR imaging of labeled cells in vitro and within the living organism.
Asunto(s)
Medios de Contraste/química , Dextranos/química , Diabetes Mellitus Experimental/cirugía , Trasplante de Islotes Pancreáticos , Islotes Pancreáticos/citología , Imagen por Resonancia Magnética/métodos , Nanopartículas de Magnetita/química , Imagen Molecular/métodos , Animales , Técnicas de Cultivo de Célula , Línea Celular Tumoral , Movimiento Celular , Supervivencia Celular , Diabetes Mellitus Experimental/metabolismo , Insulina/metabolismo , Secreción de Insulina , Islotes Pancreáticos/metabolismo , Islotes Pancreáticos/fisiología , Ratas , Coloración y EtiquetadoRESUMEN
OBJECTIVE: Abrogation of the function of TP53 gene is supposed to lead to a more aggressive breast cancer phenotype that produces a less favorable clinical outcome. The p21 gene on chromosome 6p21.2 can be stimulated by an activated TP53 gene. A product of transcription, the p21 protein, an inhibitor of cyclin-dependent kinases, has its function in gene repair and angiogenesis during cell division, and can regulate apoptosis. The purpose of this analysis was to examine for an association between the genotypes measured on two single nucleotide polymorphisms (SNPs) located within the TP53 and p21 genes. METHODS: In a clinical epidemiological case-control study, 814 individuals were recruited. 550 samples (275 cases/275 control) of peripheral blood obtained from women (aged 22-87 years) with breast cancer and from healthy women (aged 23-87 years) were genotyped for frequencies of the following gene variances: R72P/rs1042522 (gene TP53) and S31R/ss4388499 (gene p21). RESULTS: For the variance in gene TP53 no significant differences between the control group and women with breast cancer could be estimated. For the variance in gene p21 a statistically significant association between the SNP measured within p21 and breast cancer status was observed. The odds ratio for the increased risk for those carrying the CA genotype as opposed to the CC genotype is 1.74 (95% confidence ratio = 1.00-3.05). CONCLUSION: Despite this finding p21 does not appear to act as an exclusive prognostic marker for breast cancer disease.
Asunto(s)
Neoplasias de la Mama/genética , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/genética , Polimorfismo de Nucleótido Simple/genética , Proteína p53 Supresora de Tumor/genética , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Estudios de Cohortes , Femenino , Genotipo , Alemania , Humanos , Persona de Mediana Edad , Adulto JovenRESUMEN
Bradykinin and its kinin B(2) receptor are autocrine and paracrine mediators in foetal membranes and decidua. As a first step we characterized the intracellular morphology of decidual cells. Cultured decidua tissue-derived cells immunolabel for vimentin fibrils, and are considered to be of mesenchymal origin. They show characteristics of macrophages and can be distinguished from endothelial cells and cells of the trophoblast lineage. These cellular features were determined by means of immunocytochemistry. Furthermore cultured decidua tissue-derived cells express kinin B(2) receptors and in this context we demonstrated its expression at mRNA level by in situ reverse transcriptase polymerase chain reaction. Following stimulation with bacterial lipopolysaccharide, we have observed a marginal upregulation of the expression of kinin B(1) receptors and carboxypeptidase M by quantitative RT-PCR. Equilibrium binding experiments with [(3)H]des-Arg(10)-kallidin, the kinin B(1) receptor agonist, did not result in detectable binding sites.
Asunto(s)
Decidua/citología , Decidua/metabolismo , Receptor de Bradiquinina B2/metabolismo , Anticuerpos Monoclonales/inmunología , Antígenos CD/inmunología , Antígenos de Diferenciación Mielomonocítica/inmunología , Femenino , Proteínas Ligadas a GPI , Humanos , Interleucina-1beta/farmacología , Queratinas/inmunología , Leucosialina/inmunología , Lipopolisacáridos/farmacología , Metaloendopeptidasas/genética , Metaloendopeptidasas/metabolismo , Molécula-1 de Adhesión Celular Endotelial de Plaqueta/inmunología , ARN Mensajero/metabolismo , Receptor de Bradiquinina B1/genética , Receptor de Bradiquinina B1/metabolismo , Receptor de Bradiquinina B2/genética , Vimentina/inmunologíaRESUMEN
During dermal injury and inflammation the serine proteases kallikreins cleave endogenous, multifunctional substrates (kininogens) to form bradykinin and kallidin. The actions of kinins are mediated by preferential binding to constitutively expressed kinin-B2 receptors or inducible kinin-B1 receptors. A feature of the kinin-B1 receptors is that they show low levels of expression, but are distinctly upregulated following tissue injury and inflammation. Because recent evidence suggested that kinin-B1 receptors may perform a protective role during inflammation, we investigated the specific occurrence of the kallikrein-kinin components in skin biopsies obtained from normal skin, patients undergoing surgery, basalioma, lichenificated atopic eczema, and psoriasis. The tissue was immunolabeled in order to determine the localisation of tissue pro-kallikrein, kallikrein, kininogen and kinin receptors. The kinin components were visualised in normal, diseased and traumatised skin, except that no labelling was observed for kininogen in normal skin. Of the five types of tissue examined, upregulation of kinin-B1 receptors was observed only in skin biopsies obtained following surgery. In essence, the expression of kinin-B1 receptors did not appear to be enhanced in the other biopsies. Within the multiple steps of the inflammatory cascade in wound healing, our results suggest an important regulatory role for kinin-B1 receptors during the first phase of inflammation following injury.
Asunto(s)
Quininógenos/metabolismo , Cininas/metabolismo , Receptores de Superficie Celular/metabolismo , Enfermedades de la Piel/metabolismo , Piel/metabolismo , Calicreínas de Tejido/metabolismo , Heridas y Lesiones/metabolismo , Anciano , Preescolar , Humanos , Inmunohistoquímica , Lactante , Persona de Mediana EdadRESUMEN
In this study we compare the role of kinin-B1 and B2 receptors during ischaemia/reperfusion of rat pancreas. Our investigations were prompted by the observation that infusion of a kinin-B2 receptor antagonist produced significant improvement in acute experimental pancreatitis. In an acute model with two hours of ischaemia/two hours of reperfusion, application of the kinin-B1 receptor antagonist (CP-0298) alone, or in combination with kinin-B2 receptor antagonist (CP-0597), significantly reduced the number of adherent leukocytes in post-capillary venules. In a chronic model with five days of reperfusion, the continuous application of kinin-B1 receptor antagonist or a combination of kinin-B1 and B2 receptor antagonists markedly reduced the survival rate. In kinin-receptor binding studies kinin-B1 receptor showed a 22-fold increase in expression during the time of ischaemia/reperfusion. Carboxypeptidase M activity was up-regulated 10-fold following two hours of ischaemia and two hours of reperfusion, provided the appropriate specific ligand, des-Arg10-kallidin and/or des-Arg9-bradykinin, was used. The occurrence of kinin-B1 receptor binding sites on acinar cell membranes was demonstrated by micro-autoradiography. With a specific antibody, the localisation of kinin-B1 receptor protein was confirmed at the same sites. In conclusion, we have demonstrated the up-regulation of the pancreatic acinar cell kinin-B1 receptors during ischaemia/reperfusion. The novel functional finding was that antagonism of the kinin-B1 receptors decreased the survival rate in an experimental model of pancreatitis.