Cancer profiles by affinity propagation

The affinity propagation algorithm is applied to a problem of breast cancer subtyping using traditional biologic markers. The algorithm provides a procedure to determine the number of profiles to be considered. A well know breast cancer case series was used to compare the results of the affinity propagation with the results obtained with standard algorithms and indexes for the optimal choice of the number of clusters. Results from affinity propagation are consistent with the results already obtained having the advantage of providing an indication about the number of clusters

Cancer profiles by Affinity Propagation

The Affinity Propagation algorithm is applied to various problems of breast and cutaneous tumours subtyping using traditional biologic markers. The algorithm provides a procedure to determine the number of profiles to be considered. Well know breast cancer case series and cutaneous melanoma were used to compare the results of the Affinity Propagation with the results obtained with standard algorithms and indexes for the optimal choice of the number of clusters.Results from Affinity Propagation are consistent with the results already obtained having the advantage of providing an indication about the number of clusters

Inmunosupresión en donantes renales

La lesión por isquemia y reperfusión (IRI) es uno de los principales problemas en el trasplante. Nuestro objetivo fue evaluar el efecto del pre - acondicionamiento al donante con rapamicina y tacrolimus para prevenir la lesión por IRI. Las ratas Wistar donantes, 12 horas antes de la nefrectomía, recibieron fármacos inmunosupresores. La muestra se dividió en cuatro grupos experimentales: un grupo con intervención simulada (sham), un grupo control sin tratamiento, otro tratado con rapamicina (2 mg/kg) y el restante tratado con tacrolimus (0.3 mg/kg). Se retiró el riñón izquierdo y después de tres horas de isquemia fría, se lo trasplantó. Veinticuatro horas después, el órgano trasplantado se recuperó para el análisis histológico y la evaluación de la expresión de citoquinas. El tratamiento de pre-acondicionamiento con rapamicina o con tacrolimus redujo significativamente el nitrógeno ureico en sangre y los niveles de creatinina en comparación con el control (BUN: p < 0.001; creatinina: p < 0.001). La necrosis tubular aguda fue significativamente menor en las ratas donantes tratadas con inmunosupresores en comparación con el grupo control (p < 0.001). Finalmente, las citoquinas inflamatorias, como TNF-α, IL-6 y rIL-21, mostraron niveles más bajos en el injerto de los animales que recibieron tratamiento. Este estudio experimental exploratorio muestra que el pre-acondicionamiento en donantes con rapamicina y tacrolimus en dos grupos distintos mejora los resultados clínicos y anatomopatológicos en receptores, con una reducción in situ de citoquinas pro-inflamatorias relacionadas con la diferenciación Th17, y de este modo crea un ambiente favorable para la diferenciación de células T regulatorias (Tregs).The ischemia-reperfusion injury (IRI) remains a major problem in transplantation. The objective of this study was to evaluate the effects of preconditioning a donor group with rapamycin and another donor group with tacrolimus to prevent IRI. Twelve hours before nephrectomy, donor Wistar rats received immunosuppressive drugs. The sample was divided into four experimental groups: a sham group, an untreated control group, a group treated with rapamycin (2 mg/kg) and a group treated with tacrolimus (0.3 mg/kg). Left kidneys were removed and, after three hours of cold ischemia, grafts were transplanted. Twenty-four hours later, the transplanted organs were recovered for histological analysis and evaluation of cytokine expression. The pre-conditioning treatment with rapamycin or tacrolimus significantly reduced donor blood urea nitrogen and creatinine levels compared with control group (BUN: p < 0.001 vs. control and creatinine: p < 0.001 vs. control). Acute tubular necrosis was significantly lower in donors treated with immunosuppressant drugs compared with the control group (p < 0.001). Finally, inflammatory cytokines such as TNF-α, IL-6 and rIL-21 showed lower levels in the graft of pre-treated animals. This exploratory experimental study shows that preconditioning donors with rapamycin and tacrolimus in different groups improves clinical outcome and pathology in recipients and reduces in situ pro-inflammatory cytokines associated with Th17 differentiation, creating a favorable environment for the differentiation of regulatory T cells (Tregs)

“Avverare la realtà”. Letteratura e orizzonte politico

The present issue of Between contains the proceedings of the 2014 Compalit annual conference, The Political Imaginary: Commitment, Resistance, Ideology (Bologna, 17-19 December 2014). It was a brimming, vibrant conference with eleven plenary speeches, over a hundred papers delivered in parallel sessions, the presentation of the previous issue of Between, the launch of the textbook on Comparative Literature edited by Francesco de Cristofaro, and a passionate and crowded evening round table with two members from the Wu Ming collective. Most of the papers presented in Bologna appear in this very rich issue. Clearly, much has changed since the original conception and elaboration of the conference programme: during the presentations and in the ensuing discussions, novel perspectives, reflections and questions have been raised, and many of them have been taken up in the essays collected here. The broad scope of the present issue and the multiplicity of points of view, competences and critical approaches epitomize the dissonance and complexity of the topic under discussion.Questo numero di Between raccoglie gli atti del convegno annuale di Compalit, L’immaginario politico. Impegno, resistenza, ideologia, che si è svolto a Bologna nel dicembre del 2014. È stato un convegno molto ricco e partecipato, che ha visto succedersi undici relazioni plenarie, più di cento comunicazioni organizzate in sessioni parallele, la presentazione di Between e del manuale di Letterature comparate curato da Francesco de Cristofaro, e un’intensa e affollata conversazione serale con due membri del collettivo Wu Ming. E ora questo ricchissimo numero della rivista in cui è confluita gran parte delle relazioni tenute a Bologna. Ovviamente molte cose sono cambiate rispetto al progetto originario e all’elaborazione progressiva del convegno: prospettive inedite, nuovi spunti di riflessione, nodi problematici emersi nel vivo delle sessioni e delle discussioni che ne sono seguite e che hanno trovato espressione nei saggi raccolti qui, ognuno dei quali ha rilanciato a sua volta nuove domande e interrogativi specifici. L’articolazione così ampia del numero, la pluralità di sguardi, competenze e approcci critici rappresentano dunque plasticamente l’orizzonte contraddittorio e problematico in cui ci muoviamo

Amelioration of renal damage by administration of anti-thymocyte globulin to potential donors in a brain death rat model

Brain death (BD), a non-immunological factor of renal injury, triggers an inflammatory process causing pathological signs of cell death in the kidney, such as necrosis and apoptosis. Kidneys from brain dead donors show lower success rates than kidneys from living donors and one strategy to improve transplantation outcome is to precondition the donors. For the first time, anti-rat thymoglobulin (rATG) was administered in an experimental brain death animal model to evaluate if it could ameliorate histopathological damage and improve organ function. Animals were divided into three groups: V (n = 5) ventilated for 2 h; BD (n = 5) brain death and ventilated for 2 h; and BD+rATG (n = 5) brain death, ventilated for 2 h, rATG was administered during brain death (10 mg/kg). We observed lower creatinine levels in treatment groups (means): V, 0·88 ± 0·22 mg/dl; BD, 1·37 ± 0·07 mg/dl; and BD+rATG, 0·64 ± 0·02 mg/dl (BD versus BD+rATG, P < 0·001). In the BD group there appeared to be a marked increase of ATN, whereas ATN was decreased significantly in the rATG group (V, 2·25 ± 0·5 versus BD, 4·75 ± 0·5, P < 0·01; BD+rATG, 2·75 ± 0·5 versus BD 4·75 ± 0·5 P < 0·01). Gene expression was evaluated with reverse transcription–polymerase chain reaction; tumour necrosis factor (TNF)-α, interleukin (IL)-6, C3, CD86 showed no significant difference between groups. Increased IL-10 and decreased CCL2 in BD+rATG compared to BD (both cases P < 0·01). Myeloperoxidase was increased significantly after the brain death setting (V: 32 ± 7·5 versus BD: 129 ± 18). Findings suggest that rATG administered to potential donors may ameliorate renal damage caused by BD. These findings could contribute in the search for specific cytoprotective interventions to improve the quality and viability of transplanted organs.Facultad de Ciencias Médica

Protective effect of immunosuppressive treatment before orthotopic kidney autotransplantation

Background: Ischemia reperfusion injury (IRI) is one of the risk factors for delayed graft function, acute rejection and long term allograft survival after kidney transplantation. IRI is an independent antigen inflammatory process that produces tissue damage. Our objective was to study the impact of immunosuppressive treatment (IS) on IRI applying only one dose of IS before orthotopic kidney autotransplantation. Methods: Twenty-four rats allocated in four groups were studied. One group served as control (G1: autotransplanted rats without IS) and the rest received IS 12. h before kidney autotransplantation (G2: Rapamycin, G3: Mycophenolate mofetil and G4: Tacrolimus). Results: Improved renal function and systemic inflammatory response were found among IS groups compared to the control group (Delta Urea p < 0.0001; Delta Creatinine p < 0.0001; Delta C3 p < 0.001). The number of apoptotic nuclei in renal medulla in G1 was higher than in IS groups (p < 0.0001). Tubular damage was less severe in IS groups respecting G1 (p < 0.001). C3, TNF-γ and IL-6 expression in kidney samples was reduced when IS was used compared to the control group. No differences were observed among the different immunosuppressive drugs tested. However, Heme oxygenase-1(HO-1) was increased only in Rapamycin treatment. Conclusions: These data suggest that the use of IS administered before transplant attenuates the IRI process after kidney transplantation in an animal model.Fil: Cicora, Federico. Universidad Nacional de La Plata. Facultad de Ciencias Médicas; Argentina. Hospital Alemán; Argentina. Fundación Para la Investigación y Asistencia de la Enfermedad Renal; ArgentinaFil: Lausada, Natalia Raquel. Universidad Nacional de La Plata. Facultad de Ciencias Médicas; ArgentinaFil: Vasquez, Daniela Noris. Fundación Para la Investigación y Asistencia de la Enfermedad Renal; ArgentinaFil: Cicora, Paola. Fundación Para la Investigación y Asistencia de la Enfermedad Renal; ArgentinaFil: Guerrieri, Diego. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Farmacología; ArgentinaFil: Gonzalez, Pedro. Universidad Nacional de La Plata. Facultad de Ciencias Médicas; ArgentinaFil: Zalazar, Gustavo. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas; ArgentinaFil: Stringa, Pablo Luis. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Médicas; ArgentinaFil: Raimondi, Jorge Clemente. Universidad Nacional de La Plata. Facultad de Ciencias Médicas; Argentin

Preconditioning donor with a combination of tacrolimus and rapamacyn to decrease ischaemia-reperfusion injury in a rat syngenic kidney transplantation model

Reperfusion injury remains one of the major problems in transplantation. Repair from ischaemic acute renal failure (ARF) involves stimulation of tubular epithelial cell proliferation. The aim of this exploratory study was to evaluate the effects of preconditioning donor animals with rapamycin and tacrolimus to prevent ischaemia–reperfusion (I/R) injury. Twelve hours before nephrectomy, the donor animals received immunosuppressive drugs. The animals were divided into four groups, as follows: group 1 control: no treatment; group 2: rapamycin (2 mg/kg); group 3 FK506 (0, 3 mg/kg); and group 4: FK506 (0, 3 mg/kg) plus rapamycin (2 mg/kg). The left kidney was removed and after 3 h of cold ischaemia, the graft was transplanted. Twenty-four hours after transplant, the kidney was recovered for histological analysis and cytokine expression. Preconditioning treatment with rapamycin or tacrolimus significantly reduced blood urea nitrogen and creatinine compared with control [blood urea nitrogen (BUN): P < 0·001 versus control and creatinine: P < 0·001 versus control]. A further decrease was observed when rapamycin was combined with tacrolimus. Acute tubular necrosis was decreased significantly in donors treated with immunosuppressants compared with the control group (P < 0·001 versus control). Moreover, the number of apoptotic nuclei in the control group was higher compared with the treated groups (P < 0·001 versus control). Surprisingly, only rapamycin preconditioning treatment increased anti-apoptotic Bcl2 levels (P < 0·001). Finally, inflammatory cytokines, such as tumour necrosis factor (TNF)-α and interleukin (IL)-6, showed lower levels in the graft of those animals that had been pretreated with rapamycin or tacrolimus. This exploratory study demonstrates that preconditioning donor animals with rapamycin or tacrolimus improves clinical outcomes and reduce necrosis and apoptosis in kidney I/R injury.Facultad de Ciencias MédicasComisión de Investigaciones Científicas de la provincia de Buenos Aire

Immunosuppression in kidney donors with rapamycin and tacrolimus: Proinflammatory cytokine expression

La lesión por isquemia y reperfusión (IRI) es uno de los principales problemas en el trasplante. Nuestro objetivo fue evaluar el efecto del pre - acondicionamiento al donante con rapamicina y tacrolimus para prevenir la lesión por IRI. Las ratas Wistar donantes, 12 horas antes de la nefrectomía, recibieron fármacos inmunosupresores. La muestra se dividió en cuatro grupos experimentales: un grupo con intervención simulada (sham), un grupo control sin tratamiento, otro tratado con rapamicina (2 mg/kg) y el restante tratado con tacrolimus (0.3 mg/kg). Se retiró el riñón izquierdo y después de tres horas de isquemia fría, se lo trasplantó. Veinticuatro horas después, el órgano trasplantado se recuperó para el análisis histológico y la evaluación de la expresión de citoquinas. El tratamiento de pre-acondicionamiento con rapamicina o con tacrolimus redujo significativamente el nitrógeno ureico en sangre y los niveles de creatinina en comparación con el control (BUN: p < 0.001; creatinina: p < 0.001). La necrosis tubular aguda fue significativamente menor en las ratas donantes tratadas con inmunosupresores en comparación con el grupo control (p < 0.001). Finalmente, las citoquinas inflamatorias, como TNF-α, IL-6 y rIL-21, mostraron niveles más bajos en el injerto de los animales que recibieron tratamiento. Este estudio experimental exploratorio muestra que el pre-acondicionamiento en donantes con rapamicina y tacrolimus en dos grupos distintos mejora los resultados clínicos y anatomopatológicos en receptores, con una reducción in situ de citoquinas pro-inflamatorias relacionadas con la diferenciación Th17, y de este modo crea un ambiente favorable para la diferenciación de células T regulatorias (Tregs).The ischemia-reperfusion injury (IRI) remains a major problem in transplantation. The objective of this study was to evaluate the effects of preconditioning a donor group with rapamycin and another donor group with tacrolimus to prevent IRI. Twelve hours before nephrectomy, donor Wistar rats received immunosuppressive drugs. The sample was divided into four experimental groups: a sham group, an untreated control group, a group treated with rapamycin (2 mg/kg) and a group treated with tacrolimus (0.3 mg/kg). Left kidneys were removed and, after three hours of cold ischemia, grafts were transplanted. Twenty-four hours later, the transplanted organs were recovered for histological analysis and evaluation of cytokine expression. The pre-conditioning treatment with rapamycin or tacrolimus significantly reduced donor blood urea nitrogen and creatinine levels compared with control group (BUN: p < 0.001 vs. control and creatinine: p < 0.001 vs. control). Acute tubular necrosis was significantly lower in donors treated with immunosuppressant drugs compared with the control group (p < 0.001). Finally, inflammatory cytokines such as TNF-α, IL-6 and rIL-21 showed lower levels in the graft of pre-treated animals. This exploratory experimental study shows that preconditioning donors with rapamycin and tacrolimus in different groups improves clinical outcome and pathology in recipients and reduces in situ pro-inflammatory cytokines associated with Th17 differentiation, creating a favorable environment for the differentiation of regulatory T cells (Tregs).Fil: Cicora, Federico. Universidad Nacional de La Plata. Facultad de Ciencias Médicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Roberti, Javier. Universidad de Belgrano; ArgentinaFil: Lausada, Natalia Raquel. Universidad Nacional de La Plata. Facultad de Ciencias Médicas; ArgentinaFil: Gonzalez, Pedro. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas; ArgentinaFil: Guerrieri, Diego. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Stringa, Pablo Luis. Universidad Nacional de La Plata. Facultad de Ciencias Médicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Raimondi, Clemente. Universidad Nacional de La Plata. Facultad de Ciencias Médicas; Argentin