Heart and systemic effects of statin pretreatment in a rat model of abdominal sepsis. Assessment by Tc99m-sestamibi biodistribition

PURPOSE: To evaluate the heart and the Tc-99m-sestamibi biodistribution after statin pretreatment in a rat model of abdominal sepsis. METHODS: Twenty-four Wistar rats were randomly distributed into four groups (n=6 per group): 1) sepsis with simvastatin treatment, 2) sepsis with vehicle, 3) sham control with simvastatin and 4) sham control with vehicle. 24 hours after cecal ligation and puncture rats received 1.0MBq of Tc-99m-sestamibi i.v. 30min after, animals were euthanized for ex-vivo tissue counting and myocardium histological analysis. RESULTS: Myocardial histologic alterations were not detected 24 hours post-sepsis. There was significantly increased cardiac Tc-99m-sestamibi activity in the sepsis group with simvastatin treatment (1.9$\pm$0.3%ID/g, p<0.001) in comparison to the sepsis group+vehicle (1.0$\pm$0.2% ID/g), control sham group+ simvastatin (1.2$\pm$0.3% ID/g) and control sham group (1.3$\pm$0.2% ID/g). Significant Tc-99m-sestamibi activity in liver, kidney and lungs was also detected in the sepsis group treated with simvastatinin comparison to the other groups. CONCLUSIONS: Statin treatment altered the biodistribution of Tc-99m-sestamibi with increased cardiac and solid organ activity in rats with abdominal sepsis, while no impact on controls. Increased myocardial tracer activity may be a result of a possible protection effect due to increased tissue perfusion mediated by statins

Primary bone lymphomas : comparison of the immunoexpression of apoptosis related proteins and adhesion molecules with nodal lymphomas and lymphomas metastatic to bone

Orientadores: Eliane Maria Ingrid Amstalden, Jose VasalloTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias MedicasResumo: Cerca de 20% a 40% dos linfomas não-Hodgkin (LNH) B são extranodais e caracterizam-se por comportamento biológico distinto, de acordo com o seu sítio de origem e variante histológica. Linfoma ósseo primário (LOP), uma forma extranodal rara, apresenta-se na maior parte dos casos como LNH B de alto grau e evolui com bom prognóstico. Os estudos sobre o LOP são escassos e suas características imunofenotípicas e citogenéticas ainda não estão bem definidas. Neste trabalho, foram analisados três grupos de linfomas difusos de grandes células B (LDGCB): a) ósseos primários, B) nodais e c) metastáticos (com envolvimento ósseo secundário). Foram investigados, nesses grupos, dados clínicos e de sobrevida, aspectos morfológicos, imunofenotípicos e citogenéticos. Na análise imunoistoquímica, foi verificado o estudo das moléculas envolvidas na apoptose e regulação do ciclo celular (Bcl-2, Bax, p53, Bcl-6, p21, pRB) moléculas envolvidas na adesão celular (CD29, CD62L, CD44, CD51) índice de proliferação celular (Ki-67) e expressão das subpopulações de células infiltrantes do sistema imune (CD3, CD4, CD5, CD8, CD57, CD68, Foxp3) com objetivo de melhor caracterizar o LOP. Foram selecionados no total 138 casos de LDGCB, provenientes dos departamentos de Anatomia Patológica FCM-UNICAMP, Hospital AC.-Camargo - Fundação Antônio Prudente, Instituto de Traumatologia e Ortopedia da USP e Centre Hospitalier Universitarie (CHU Purpan). Do total de 138, 76 casos eram linfomas ósseos primários, 46 casos linfomas nodais e 16 casos linfomas com envolvimento ósseo secundário. Nossos resultados demonstraram que o LOP possui características evolutivas que diferem dos demais LDGCB extranodais. Observamos que a maioria dos LDGCB ósseos primários (66%) pertenceram ao imunofenótipo centro germinativo (CG) e não exibiram diferenciação plasmacítica. Os três grupos de LDGCB analisados exibiram forte imunoexpressão das proteínas relacionadas à apoptose e ao ciclo celular enquanto que a imunoexpressão de moléculas de adesão foi fraca ou ausente, na maioria dos casos. O estudo da sobrevida, envolvendo a ausência da imunoexpressão das moléculas de adesão CD29, CD62L e CD51, nos três grupos, revelou-se significativamente associada com melhor sobrevida. O significado biológico deste achado ainda está para ser esclarecido. O CD44 foi o mais fortemente expresso nas células tumorais. As moléculas envolvidas na apoptose Bax e p53 foram relacionadas à pior evolução e o pRB à evolução favorável nos LOP. As proteínas Bcl-2 e Bcl-6 foram expressas nos três grupos de linfomas. Com a análise em 32 casos de LOP das principais translocações em LNH (MYC, BCL2/IGH, BCL6, ALK, IGH/CCND1 e PAX5), conseguimos caracterizar melhor esta entidade. Rearranjos, envolvendo o BCL2 e MYC foram encontrados, entretanto não ocorreram rearranjos do BCL6. Os demais genes não demonstraram translocações. Estes achados indicam que o LOP deve ser considerado uma categoria distinta de LDGCB extranodal, com aspectos genéticos e moleculares mais próximos dos nodaisAbstract: The incidence of extranodal lymphomas is increasing in the last decades. Around 20 to 40% of B-cell non-Hodgkin lymphomas (NHL) arise outside the lymph nodes and may present distinct biological behavior, as compared to the corresponding nodal counterpart of similar histological grade. The heterogeneity of large B-cell lymphomas (LBCL) has been matter of various studies, although morphology alone may be insufficient to separate groups of clinical relevance, immunophenotyping and molecular techniques have demonstrated that different variants of LBCL may present diverse clinical and prognostic features. Primary bone lymphoma (PBL) is rare form of extra nodal NHL, which generally presents a more favorable prognosis than the nodal counterpart. The reason for this is unclear. We selected a large series (n=138) of nodal NHL (N=46), primary (n=76) and metastatic (n=16) bone diffuse large cell lymphomas collected in tissue micro-arrays from several centers in France and Brazil. We investigated to be comparing clinical, morphological and immunophenotypic features. Immunohistochemical detection of proliferation markers, apoptosis related proteins and adhesion molecules was be marked. Our results demonstrated that primary bone LDGCB possesses peculiar clinical characteristics that you differ of the other extranodal LDGCB as the longest evolution and smaller recurrence tax. The three groups of LDGCB exhibited strong immunoexpression of the related proteins the apoptosis and cellular cycle while the immunoexpression of adhesion molecules was weak or absentee in most of the cases. These cases were classified according to the expression of antigens with germinal center (GC) (n=37/62) or non germinal center (non-GC) (n=26/62) stages of B-cell differentiation. The study of the survival involving the absence of the imunoexpressão of the adhesion molecules CD29, CD62L and CD51 in the three groups was revealed significantly associated with better outcome. The biological meaning of this discovery is still to be explained. CD44 was it more strongly expressed in the tumor cells and it demonstrated relationship away with inferior survival without statistical significance. The molecules involved in the apoptosis Bax and p53 were related the worst evolution and the pRB the favorable evolution in PBL. The proteins Bcl-2 and Bcl-6 were expressed in the three lymphomas groups and associated the worst evolution, however without significance. By fluorescence in situ hybridization, we found a substantial number of cases with a rearrangement of BCL2 (n=9/32) and MYC (n= 3/32) whereas PAX5, BCL6, BCL-1/Cyclin D1 and ALK genes were in germ line configuration. Interestingly, one case, with GC phenotype, showed a dual BCL2 and MYC rearrangement. We observed that the majority of the cases with rearrangements were of GC phenotype. These results, associated with the lack of BCL6 rearrangement, suggest that bone DLBCL represents a specific group within extranodal B-cell lymphomas. Keywords: diffuse large cell lymphoma, adhesion molecules, apoptosis, fluorescent in situ hybridizationDoutoradoAnatomia PatologicaDoutor em Ciências Médica

Heart and systemic effects of statin pretreatment in a rat model of abdominal sepsis. Assessment by Tc99m-sestamibi biodistribition

PURPOSE:To evaluate the heart and the Tc-99m-sestamibi biodistribution after statin pretreatment in a rat model of abdominal sepsis.METHODS:Twenty-four Wistar rats were randomly distributed into four groups (n=6 per group): 1) sepsis with simvastatin treatment, 2) sepsis with vehicle, 3) sham control with simvastatin and 4) sham control with vehicle. 24 hours after cecal ligation and puncture rats received 1.0MBq of Tc-99m-sestamibi i.v. 30min after, animals were euthanized for ex-vivo tissue counting and myocardium histological analysis.RESULTS: Myocardial histologic alterations were not detected 24 hours post-sepsis. There was significantly increased cardiac Tc-99m-sestamibi activity in the sepsis group with simvastatin treatment (1.9±0.3%ID/g, p<0.001) in comparison to the sepsis group+vehicle (1.0±0.2%ID/g), control sham group+ simvastatin (1.2±0.3%ID/g) and control sham group (1.3±0.2%ID/g). Significant Tc-99m-sestamibi activity in liver, kidney and lungs was also detected in the sepsis group treated with simvastatinin comparison to the other groups.CONCLUSIONS:Statin treatment altered the biodistribution of Tc-99m-sestamibi with increased cardiac and solid organ activity in rats with abdominal sepsis, while no impact on controls. Increased myocardial tracer activity may be a result of a possible protection effect due to increased tissue perfusion mediated by statins

Heart and systemic effects of statin pretreatment in a rat model of abdominal sepsis. Assessment by Tc99m-sestamibi biodistribition

PURPOSE:To evaluate the heart and the Tc-99m-sestamibi biodistribution after statin pretreatment in a rat model of abdominal sepsis.METHODS:Twenty-four Wistar rats were randomly distributed into four groups (n=6 per group): 1) sepsis with simvastatin treatment, 2) sepsis with vehicle, 3) sham control with simvastatin and 4) sham control with vehicle. 24 hours after cecal ligation and puncture rats received 1.0MBq of Tc-99m-sestamibi i.v. 30min after, animals were euthanized for ex-vivo tissue counting and myocardium histological analysis.RESULTS: Myocardial histologic alterations were not detected 24 hours post-sepsis. There was significantly increased cardiac Tc-99m-sestamibi activity in the sepsis group with simvastatin treatment (1.9±0.3%ID/g, p<0.001) in comparison to the sepsis group+vehicle (1.0±0.2%ID/g), control sham group+ simvastatin (1.2±0.3%ID/g) and control sham group (1.3±0.2%ID/g). Significant Tc-99m-sestamibi activity in liver, kidney and lungs was also detected in the sepsis group treated with simvastatinin comparison to the other groups.CONCLUSIONS:Statin treatment altered the biodistribution of Tc-99m-sestamibi with increased cardiac and solid organ activity in rats with abdominal sepsis, while no impact on controls. Increased myocardial tracer activity may be a result of a possible protection effect due to increased tissue perfusion mediated by statins