ABSTRACT
Cancer pain may be the consequence of physical nerve compression by a growing tumor. We employed a murine model to study whether gabapentin was able to regulate tumor growth, in addition to controlling hyperalgesic symptoms. A fluorescent melanoma cell line (B16-BL6/Zs green) was inoculated into the proximity of the sciatic nerve in male C57BL/6 mice. The tumor gradually compressed the nerve, causing hypersensitivity. Tumor growth was characterized via in vivo imaging techniques. Every other day, gabapentin (100 mg/Kg) or saline was IP administered to each animal. In the therapeutic protocol, gabapentin was administered once the tumor had induced increased nociception. In the preventive protocol, gabapentin was administered before the appearance of the positive signs. Additionally, in vitro experiments were performed to determine gabapentin's effects on cell-line proliferation, the secretion of the chemokine CCL2, and calcium influx. In the therapeutically treated animals, baseline responses to noxious stimuli were recovered, and tumors were significantly reduced. Similarly, gabapentin reduced tumor growth during the preventive treatment, but a relapse was noticed when the administration stopped. Gabapentin also inhibited cell proliferation, the secretion of CCL2, and calcium influx. These results suggest that gabapentin might represent a multivalent strategy to control cancer-associated events in painful tumors.
Subject(s)
Analgesics/pharmacology , Antineoplastic Agents/pharmacology , Cancer Pain/drug therapy , Gabapentin/pharmacology , Animals , Cancer Pain/diagnosis , Cell Line, Tumor , Disease Models, Animal , Disease Progression , Hyperalgesia/drug therapy , Melanoma, Experimental , Mice , Pain Management , Pain Measurement , Xenograft Model Antitumor AssaysABSTRACT
PURPOSE: To determine if susceptibility to systemic endotoxin-induced uveitis is an age-related phenomenon in the rabbit. METHODS: Young and adult rabbits were injected intravenously with 2.5 microg/kg of E. coli endotoxin or saline. Thereafter, the number of exudating cells at 2, 6, 12, 24 and 48 hours were determined. The levels of lipopolysaccharide-binding protein, total protein, prostaglandin-E2, nitric oxide and interleukin-6 in aqueous humor were also determined 24 hours after the injections. RESULTS: A significant increase in the number of exudating cells and the levels of lipopolysaccharide-binding protein, total protein, prostaglandin-E2 and nitric oxide in aqueous humor was observed only in adult rabbits 24 hours after endotoxin injection. No differences were observed in the increased IL-6 levels. CONCLUSIONS: Life stage seems to be a critical factor in developing an eye-inflammatory response induced by systemic endotoxin. This could be a consequence of a differential specific activation of the ocular immune response.
Subject(s)
Aging/pathology , Neutrophils/pathology , Uveitis/pathology , Age Factors , Aging/metabolism , Animals , Aqueous Humor/cytology , Aqueous Humor/metabolism , Biomarkers/metabolism , Dinoprostone/metabolism , Disease Models, Animal , Eye Proteins/metabolism , Interleukin-6/metabolism , Lipopolysaccharides/toxicity , Nitric Oxide/metabolism , Rabbits , Uveitis/chemically induced , Uveitis/metabolismABSTRACT
Debido a su vida media corta, su elevado contenido en triptófano y su pequeño "pool" corporal, los niveles séricos de prealbúmina han sido considerados como un indicador sensible de la deficiencia proteica y/o calórica. Además, la prealbúmina disminuye durante la respuesta de fase aguda desencadenada por infección o injuria tisular. Se determinaron los niveles séricos de prealbúmina en niños desnutridos con o sin infección clínica asociada y en sus controles infectados o no infectados comparables por edad, sexo, raza y condición socieconómica. En los grupos sin infección clínica asociada, los niveles séricos de prealbúmina eran significativamente menores en los niños desnutridos, que en los controles. Los niveles de prealbúmina también se encontraron significativamente desprimidos en presencia de infección asociada, disminuyendo a niveles casi similares en los niños desnutridos y controles con infección clínica, al compararlos con los observados en niños pertenecientes al mismo estadío nutricional, pero sin infección manifiesta. Se encontró correlación positiva significativa entre la prealbúmiba sérica y tanto el score-Z de peso-edad como de talla-edad y peso-talla en el grupo sin infección manifiesta, las cuales desaparecían en presencia de infección. Portanto, la prealbúmina es un marcador adecuado de desnutrición en ausencia de infección y podría ser un indicador más precoz y sensible de desnutrición actual, causada por los efectos metabólicos de citoquinas inflamatorias producidas durante la infección, que las medidas antropométricas aquí utilizadas
