RESUMEN
The liver is an immunoregulatory organ in which a tolerogenic microenvironment mitigates the relative "strength" of local immune responses. Paradoxically, necro-inflammatory diseases create the need for most liver transplants. Treatment of hepatitis B virus, hepatitis C virus, and acute T cell-mediated rejection have redirected focus on long-term allograft structural integrity. Understanding of insults should enable decades of morbidity-free survival after liver replacement because of these tolerogenic properties. Studies of long-term survivors show low-grade chronic inflammatory, fibrotic, and microvascular lesions, likely related to some combination of environment insults (i.e. abnormal physiology), donor-specific antibodies, and T cell-mediated immunity. The resultant conundrum is familiar in transplantation: adequate immunosuppression produces chronic toxicities, while lightened immunosuppression leads to sensitization, immunological injury, and structural deterioration. The "balance" is more favorable for liver than other solid organ allografts. This occurs because of unique hepatic immune physiology and provides unintended benefits for allografts by modulating various afferent and efferent limbs of allogenic immune responses. This review is intended to provide a better understanding of liver immune microanatomy and physiology and thereby (a) the potential structural consequences of low-level, including allo-antibody-mediated injury; and (b) how liver allografts modulate immune reactions. Special attention is given to the microvasculature and hepatic mononuclear phagocytic system.
Asunto(s)
Inmunidad Celular/inmunología , Trasplante de Hígado , Aloinjertos , Animales , HumanosRESUMEN
I/R injury is a major deleterious factor of successful kidney transplantation (KTx). Carbon monoxide (CO) is an endogenous gaseous regulatory molecule, and exogenously delivered CO in low concentrations provides potent cytoprotection. This study evaluated efficacies of CO exposure to excised kidney grafts to inhibit I/R injury in the pig KTx model. Porcine kidneys were stored for 48 h in control UW or UW supplemented with CO (CO-UW) and autotransplanted in a 14-day follow-up study. In the control UW group, animal survival was 80% (4/5) with peak serum creatinine levels of 12.0 +/- 5.1 mg/dL. CO-UW showed potent protection, and peak creatinine levels were reduced to 6.9 +/- 1.4 mg/dL with 100% (5/5) survival without any noticeable adverse event or abnormal COHb value. Control grafts at 14 days showed significant tubular damages, focal fibrotic changes and numerous infiltrates. The CO-UW group showed significantly less severe histopathological changes with less TGF-beta and p-Smad3 expression. Grafts in CO-UW also showed significantly lower early mRNA levels for proinflammatory cytokines and less lipid peroxidation. CO in UW provides significant protection against renal I/R injury in the porcine KTx model. Ex vivo exposure of kidney grafts to CO during cold storage may therefore be a safe strategy to reduce I/R injury.
Asunto(s)
Monóxido de Carbono/administración & dosificación , Trasplante de Riñón , Daño por Reperfusión/prevención & control , Animales , Western Blotting , Carboxihemoglobina/metabolismo , Modelos Animales de Enfermedad , Supervivencia de Injerto , Malondialdehído/metabolismo , ARN Mensajero/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Soluciones , PorcinosRESUMEN
BACKGROUND: Coughing may be produced by a number of different disorders in distinct anatomic sites. Chronic cough causes major functional limitation in a considerable patient population and requires careful evaluation. METHODS: Seventy-eight nonsmoking patients of both genders who complained of cough for > or =3 weeks and had normal findings on plain chest radiographs were studied prospectively. Their histories were obtained, and physical examinations were performed. The diagnostic workup included pulmonary function tests, CT of the paranasal sinuses and chest, carbachol provocation test, fiberoptic rhinoscopy, fiberoptic bronchoscopy, and 24-h esophageal pH monitoring. The final diagnosis depended on clinical, radiologic, and laboratory findings; a successful response to therapy was required for confirmation. RESULTS: The causes of chronic cough were determined in all patients. Coughing was due to a single cause in 30 patients (38.5%) and multiple causes in 48 patients (61.5%). The five most important causative factors were asthma (46 patients; 58.9%), postnasal drip syndrome (PNDS; 45 patients; 57.6%), gastroesophageal reflux disease (GERD; 32 patients; 41.1%), bronchiectasis (14 patients; 17.9%), and tracheobronchial collapse (11 patients; 14.1%). INTERPRETATION: Asthma, PNDS, and GERD, alone or in combination, were responsible for 93.6% of the cases of chronic cough. The presence of these three conditions was so frequent that the expression "pathogenic triad of chronic cough" should be acknowledged in specialized literature. It is essential to consider pulmonary and extrapulmonary causes in order to prescribe a successful specific therapy for chronic cough.