Role of TRPV4 Channel in Human White Adipocytes Metabolic Activity

Background@#Intracellular calcium (Ca2+) homeostasis plays an essential role in adipocyte metabolism and its alteration is associated with obesity and related disorders. Transient receptor potential vanilloid 4 (TRPV4) channels are an important Ca2+ pathway in adipocytes and their activity is regulated by metabolic mediators such as insulin. In this study, we evaluated the role of TRPV4 channels in metabolic activity and adipokine secretion in human white adipocytes. @*Methods@#Human white adipocytes were freshly cultured and the effects of the activation and inhibition of TRPV4 channels on lipolysis, glucose uptake, lactate production, and leptin and adiponectin secretion were evaluated. @*Results@#Under basal and isoproterenol-stimulated conditions, TRPV4 activation by GSK1016709A decreased lipolysis whereas HC067047, an antagonist, increased lipolysis. The activation of TRPV4 resulted in increased glucose uptake and lactate production under both basal conditions and insulin-stimulated conditions; in contrast HC067047 decreased both parameters. Leptin production was increased, and adiponectin production was diminished by TRPV4 activation and its inhibition had the opposite effect. @*Conclusion@#Our results suggested that TRPV4 channels are metabolic mediators involved in proadipogenic processes and glucose metabolism in adipocyte biology. TRPV4 channels could be a potential pharmacological target to treat metabolic disorders.

Decellularization and In Vivo Recellularization of Abdominal Porcine Fascial Tissue

BACKGROUND@#Tissue decellularization has evolved as a promising approach for tissue engineering applications. @*METHODS@#In this study, we harvested fascial tissue from porcine anterior abdominal wall and the samples were decellularized with a combination of agents such as Triton X-100, trypsin and DNAase. Afterwards, we evaluated cell removal by histological analysis and DNA quantification. Mechanical functionality was evaluated by applying a range of hydrostatic pressures. A sample of decellularized fascia was transplanted into a rabbit and after 15 days a biopsy of this tissue was examined; the animal was observed during 6 months after surgery. @*RESULTS@#The extracellular matrix was retained with a complete decellularization as evidenced by histologic examination. The DNA content was significantly reduced. The scaffold preserved its tensile mechanical properties. The graft was incorporated into a full thickness defect made in the rabbit abdominal wall. This tissue was infiltrated by granulation and inflammatory cells and the histologic structure was preserved 15 days after surgery. The animal did not develop hernias, infections or other complications, after a 6-months of follow up. @*CONCLUSIONS@#The protocol of decellularization of fascial tissue employed in this study proved to be efficient. The mechanical test demonstrated that the samples were not damaged and maintained its physical characteristics; clinical evolution of the rabbit, recipient of the decellularized fascia, demonstrated that the graft was effective as a replacement of native tissue.In conclusion, a biological scaffold derived from porcine fascial tissue may be a suitable candidate for tissue engineering applications.

Decellularization and In Vivo Recellularization of Abdominal Porcine Fascial Tissue

BACKGROUND@#Tissue decellularization has evolved as a promising approach for tissue engineering applications. @*METHODS@#In this study, we harvested fascial tissue from porcine anterior abdominal wall and the samples were decellularized with a combination of agents such as Triton X-100, trypsin and DNAase. Afterwards, we evaluated cell removal by histological analysis and DNA quantification. Mechanical functionality was evaluated by applying a range of hydrostatic pressures. A sample of decellularized fascia was transplanted into a rabbit and after 15 days a biopsy of this tissue was examined; the animal was observed during 6 months after surgery. @*RESULTS@#The extracellular matrix was retained with a complete decellularization as evidenced by histologic examination. The DNA content was significantly reduced. The scaffold preserved its tensile mechanical properties. The graft was incorporated into a full thickness defect made in the rabbit abdominal wall. This tissue was infiltrated by granulation and inflammatory cells and the histologic structure was preserved 15 days after surgery. The animal did not develop hernias, infections or other complications, after a 6-months of follow up. @*CONCLUSIONS@#The protocol of decellularization of fascial tissue employed in this study proved to be efficient. The mechanical test demonstrated that the samples were not damaged and maintained its physical characteristics; clinical evolution of the rabbit, recipient of the decellularized fascia, demonstrated that the graft was effective as a replacement of native tissue.In conclusion, a biological scaffold derived from porcine fascial tissue may be a suitable candidate for tissue engineering applications.

Transplante hematopoyetico alogenico con celulas progenitoras extraidas de la sangre periferica / Allogenic hematopoietic transplantation with peripheral blood progenitor cells

Cinquenta y tres pacientes (ptes) recibieron transplante alogénico con células progenitoras extraídas de la sangre periférica (PSP); 25 ptes eran mujeres y 28 varones. La edad media del grupo fue de 20 años, (rango 2-550. Los diagnósticos fueron leucemia mieloide aguda (LMA) en 16 ptes, leucemia linfoblástica aguda (LLA) en 15, leucemia mieloide crónica (LMC) en primera fase crónica en 12, aplasia medular en 4, síndrome mielodisplásico en 3 y Enfermedad de Hodgkin en recaída luego de trasplante autólogo, talasemia mayor y síndrome de Hunter en 1 caso, respectivamente. Los acondicionamientos fueron en 38 ptes radioterapia corporal total 1200 cGy y ciclofosfamida 120 mg/kg EV; en 10 ptes busulfán 16 mg/kg y ciclosfosfamida 120 mg/kg EV, 3 ptes radioterapia linfoide total (RLT) y ciclosfosfamida, 2 ptes con otros agentes quimioterápicos. Los PSP se infundieron a través de un catéter sin ningún tipo de manipulación. La profilaxis de injerto vs huésped (EICH) se realizó con ciclosporina y metotrexato. Los donantes fueron familiares con HLA compatibles 6/6 y un caso 5/6 de los antígenos. Previo a la extración de PSP, recibieron G-DSF (filgrastim) 10 mug/kg/día sc. Cuatro días. El quinto día se realizó la féresis, en los primeros treinta casos se hizo la extracción adicional de médula ósea. Las medias de CD34, CD3, CD4, CD8, CD56, CD19 (cel x 10(6)/kg de peso) 4.12; 4.59; 2.57; 1.9; 0.55 y 0.68 respectivamente. La mediana de recuperación de nuetrófilos > 500 se obtuvo el día = 11 y de plaquetas > 20000, + 13. El tiempo de internación fue de 26 días (18-39) y la media de días con antibióticos parenterales fue de 12.2 días (5-45). La mortalidad relacionada al trasplante fue del 15 por ciento. EICH aguda se observó en el 43.4 por ciento de los ptes, con sólo 5 ptes con EICH aguda grado III o IV. En 43 ptes se pudo evaluar la aparición de EICH crónica con un tiempo medio de seguimiento de 18 meses (4-39). En la presente experiencia el trasplante de PSP alogénicos mantuvo una aceptable incidencia de EICH crónica; dados los recientes informes de aumento de esta complicación, parece lógico desaconsejar el uso de PSP en patología no maligna en la que no importaría la potencia del efecto injerto versus leucemia.