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Splenic injury is an uncommon complication following a colonoscopy procedure. Splenic laceration typically presents with post-procedural abdominal pain. We present a case of non-specific shoulder pain, following an uneventful routine colonoscopy and highlight the importance of maintaining a high degree of clinical suspicion for the general gastroenterologist.

In an effort to elucidate the mechanism by which indomethacin (IN) lessens the stimulatory effect of estradiol (E2) on rabbit splenic red pulp macrophages (RPMs), 39 female New Zealand White rabbits were divided into 10 groups: ovariectomized (OVX) and OVX/ IN at 0.1 and 5.0 mg/kg body weight (bw)/day; sham OVX (SOVX) and SOVX/IN at 0.1 and 5.0 mg/kg bw/day; OVX/25 mg E2 and OVX/25 mg E2/IN at 0.1 and 5.0 mg/kg bw/day; and intact control. Changes in RPM population in response to treatment were measured using a 0-4 histologic grade. Estradiol treatment resulted in increased RPM grade when compared to the OVX groups. Indomethacin addition lowered mean RPM grade in the SOVX/IN 5.0 group when compared to its E2 control group. Indomethacin administration had no significant effect on levels of prostaglandin E 2 in spleen, urine, or blood. Hematocrits were reduced in both OVX and OVX/E2 groups; this decrease was exacerbated by the high IN dose. In summary, the results from this study suggest that the effect of IN on E2-induced RPM activation may be mediated through a nonprostaglandin pathway. The observed hematocrit changes are possibly the result of direct action of IN and E2 on erythrocytes, resulting in their accelerated clearance from the circulation by splenic RPM.

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No. of bitstreams: 1 maronezi_mc_me_jabo.pdf: 1008361 bytes, checksum: 61c06a0623c77a91cd63571d5a013b0d (MD5) Previous issue date: 2016-02-12 / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / O baço é um órgão que desenvolve inúmeras funções importantes no organismo e é um dos principais locais para o desenvolvimento de tumores primários, metastáticos e afecções do sistema hematopoiético, por isso realizar uma avaliação apurada neste órgão é de suma importância, em Medicina veterinária, particularmente em cães devido à importância econômica, afetiva e de similaridade cientifica para o homem. Todavia, a maioria dos métodos utilizados para o diagnóstico conclusivo de enfermidades esplênicas são métodos invasivos, sendo que os nãos invasivos perdem em sensibilidade e especificidade, dificultando que se proceda a um correto diagnóstico. Sendo assim, este estudo prospectivo visou avaliar a aplicabilidade das novas técnicas ultrassonográficas para avaliação esplênica de caninos, utilizando a elastografia ARFI (qualitativa e quantitativa), Doppler e ultrassonografia por contraste com microbolhas, com o intuito de determinar valores ainda não descritos na veterinária, as quais forneçam subsídios suficientes para se obter um diagnóstico conclusivo sobre a condição esplênica, nesta espécie. Os resultados obtidos nos cães saudáveis, por meio da ultrassonografia modo B apresentaram-se normais, sendo que na elastografia qualitativa, as porções esplênicas avaliadas apresentaram-se não deformáveis, com parênquima homogêneo de cor cinza escuro (hard). Na elastografia quantitativa os valores médios da velocidade de cisalhamento foram de 2,32 m/s para a cabeça, 2,16 m/s para o corpo e 2,25 m/s para a cauda do baço, não apresentando diferença estatística (P > 0,05). Ao exame contrastado, foram avaliados animais com erliquiose na fase subclínica, e estes apresentaram ao exame modo-B, esplenomegalia com presença de bordas arredondadas, ecotextura heterogênea e ecogenicidade mista do baço. Ao Doppler, verificou-se valores para os índices vasculares da artéria esplênica: velocidade sistólica: 22,59 ± 8,07 cm/s; velocidade diastólica: 5,25 ± 4,66 cm/s; e índice de resistência: 0,71 ± 0,14. Pela ultrassonografia com contraste observaram-se valores para wash-in de 5,31 ± 0,7s, pico de realce de 18,56 ± 2,90s e wash-out: 94,56 ± 35,21s. A elastografia ARFI é um método recente que pode fornecer dados de base para o baço e permitir a utilização futura desta técnica, na avaliação de cães com doença esplênica. A ultrassonografia convencional do baço de cães com erliquiose associado com a utilização do método Doppler e ultrassonografia contrastada são importantes ferramentas na triagem diagnóstica e podem auxiliar a monitoração e evolução de animais na fase subclínica. / The spleen is an organ develops much important functions in the body and the spleen is one of the main organs prone to the development of primary tumors, metastasis and a broad range of diseases of the hematopoietic system perform assessment of spleen is important. In veterinary medicine, principally in dogs because of economic importance, affective and scientific similarity to humans. However, the most of the methods used for conclusive diagnosis of splenic diseases are invasive methods, noninvasive lose in sensitivity and specificity difficulting proceed to a correct diagnosis. Thus, this study aimed to perform the ultrasound scan of dogs spleen using the elastographic (qualitative and quantitative) Doppler and contrast enhanced ultrasonography. Determining values not described in veterinary, which provide sufficient subsidies to get a conclusive diagnosis of the splenic condition in this species. The results in healthy dogs showed, all splenic segments visualized with the B-mode ultrasonography appeared normal. Different splenic segments examined with qualitative elastography were free of any detectable malformations and the images appeared as homogeneous dark areas. The mean shear velocity values were 2.32 m/s for head, 2.16 m/s for body and 2.25 m/s for tail of the spleen, and they did not vary between the different age groups (P>0.05). In dogs with ehrlichiosis in subclinical phase showed, by B-mode examination, observed splenomegaly with presence of rounded borders and heterogeneous echotexture and mixed echogenicity in spleen. For Doppler found values for vascular indices of the splenic artery: systolic velocity: 22.59 ± 8.07 cm/s; diastolic velocity: 5.25 ± 4.66 cm/s; and resistance index: 0.71 ± 0.14. For contrast enhanced ultrasonography observed values for wash-in: 5.31 ± 0.7s, peak enhancement: 18.56 ± 2.90s and wash-out: 94.56 ± 35.21s. The ARFI elastography is a new method and it may aid in the diagnosis and evaluation of splenic abnormalities routinely assessed in veterinary practice. The conventional ultrasonography of the spleen in dogs with ehrlichiosis associated with hemodynamic evaluation by Doppler and contrast enhanced ultrasonography are important tools for diagnosis trial and could help the monitoring clinical evolution in subclinical phase. / FAPESP: 2013/26197-5

The progressive growth of tumors in human cancer patients and experimental animals has frequently been associated with a generalized depression of immunological responsiveness. Suppressor cells have been implicated as mediators of tumor-associated immunosuppression, but the identities of the cells causing suppression and the mechanisms by which they act have been unclear. The object of this thesis was thus to determine: if suppressor cells capable of non specifically suppressing immune responses were present in anergic mice bearing methylcholanthrene-induced sarcomas; the cell types responsible for suppression; and the mechanisms by which suppression occurs. The spleens of mice with large tumors were found to contain two distinct populations of non specific suppressor cells. One population inhibited the proliferative responses of normal lymphocytes to the T cell mitogen, Concanavalin A (Con A) and the B cell mitogen, lipopolysaccharide (LPS). These cells also inhibited the generation of antibody forming cells by normal lymphoid cells stimulated in vitro with the T cell dependent antigen, sheep red blood cells (SRBC) and the T cell independent antigen, dinitrophenylated-lipopolysaccharide (DNP-LPS). These suppressor cells appeared to be from the macrophage/monocyte line since they adhered to plastic and nylon wool, were removed by carbonyl iron and magnet, and were inactivated by carragheenan treatment, but were not removed by anti-Thy-1 or anti-mouse immunoglobulin sera plus complement. They were among the less dense spleen cells since they were retained in the light fraction after centrifugation on hypaque-ficoll of specific gravity 1.08 and did not appear to require cell division in order to suppress- since mitomycin C treatment did not inactivate them. Cell-cell contact appeared to be essential for suppression. The second population of suppressor cells, which pelleted to the bottom of a hypaque-ficoll gradient, inhibited only the generation of plaque forming cells to the T cell dependent antigen, SRBC. These cells appeared to be T cells since they were non adherent to plastic or nylon wool, were not removed by carbonyl iron and magnet, but were removed by anti-Thy-1 serum plus complement. Cell division was necessary since suppressive activity was totally removed by mitomycin C treatment. Suppression by this cell type appeared to be mediated by a soluble factor with a molecular weight of about 3,500 to 12,000. / Science, Faculty of / Microbiology and Immunology, Department of / Graduate

Endoscopic retrograde cholangiopancreatography (ERCP) is an invasive procedure with significant complications. Splenic hematoma is an extremely rare but known complication following ERCP that has been increasingly reported in the past several years. We report the case of a 44-year-old patient with a history of sleeve gastrectomy who underwent an ERCP that was complicated by both acute pancreatitis and splenic hematoma. She was managed conservatively under close monitoring in the intensive care unit. Clinicians should be aware of this potentially life-threatening complication to make a prompt diagnosis and begin early appropriate management.

A vascularização arterial do baço do eqüino foi estudada por meio de radiografias contrastadas, cintilografias, dissecações e moldes. O baço está situado no antímero esquerdo e a sua posição na cavidade abdominal determina uma face parietal lisa e levemente convexa, enquanto que a face intestinal, onde estão localizados os vasos, nervos e ligamentos, é levemente côncava determinando uma área com menor espessura. O estudo da vascularização arterial demonstrou uma área paucivascular que coincide justamente com a área côncava onde a espessura é menor. Este comportamento foi observado tanto nos adultos como nos fetos. Baseado na distribuição dos vasos arteriais a região onde a espessura é menor foi indicada como local de eleição para a incisão no caso de esplenectomias parciais, dividindo o baço do eqüino em dois segmentos anátomo-cirúrgicos. A cirurgia de ressecção parcial do baço não foi descrita, no cavalo, conforme atesta a literatura atual. Duas cirurgias experimentais foram realizadas para comprovar a indicação, demonstrando que a proposta é exeqüível. A análise proporcional da área mostrou que a ressecção parcial na região indicada preserva em média 50% do parênquima. / Observation on the mode of parenchymal distribution of equine splenic artery was studied using arteriography, scintigraphy, dissection and corrosion cast. The spleen is situated in the left region of the abdomen. The parietal surface is convex and the visceral surface, where the blood vessels, nerves and ligaments are situated, is concave. The vascular arrangement may lead to division the organ into two anatomicosurgical segments. No literature is available on partial splenectomy in horses. Two partial resection was performed successfully by the method described, this partial resection preserve 50% of spleen parenchyma.

Chronic Lymphocytic Leukemia (CLL) is defined by the accumulation of clonally expanded CD5+ and CD19+ B lymphocytes in blood and secondary lymphoid organs with impaired apoptotic mechanisms. CLL represents one third of all leukemia cases with an average age of 72 years at diagnosis making it the most common adult leukemia. The Eµ-Tcl1 mouse serves as an excellent model to study the development of CLL as they progress to a CLL like disease by 9-14 months of age, due to overexpression of an oncogene, T cell Leukemia 1(Tcl1), specifically in B cells through the Ig VH promoter and Eµ enhancer (Bichi et al. PNAS. 2002). In an adoptive transfer model, intravenous or intraperitoneal injection of primary CD5+CD19+ CLL cells from the Eµ-Tcl1 CLL mouse into recipient syngeneic mice leads to the development of a CLL like disease within 3-8 weeks of transfer. We have characterized the growth of CLL cells in these mice by periodic submandibular bleeding, spleen ultrasonography and flow cytometry. We find that Eµ-Tcl1 CLL cells express more Prostate apoptosis response-4 protein (Par-4), a known pro-apoptotic tumor suppressor protein, than normal B-1 or B-2 cells in mice. Par-4 is silenced by promoter methylation in more than 30% of all cancers and has been shown to be secreted and to induce apoptosis selectively in various types of cancer cells but not in normal cells. We found that CLL cells have constitutively active B-cell receptor signaling (BCR) and that inhibition of BCR signaling with FDA approved drugs causes a decrease in Par-4 protein, mRNA levels, and an increase in apoptosis. In particular, activities of Src family kinases, spleen tyrosine kinase and Bruton’s tyrosine kinase are required for Par-4 expression in CLL cells, suggesting a novel regulation of Par-4 through BCR signaling in both Eµ-Tcl1 CLL cells and primary human CLL samples. Consistent with this, lenti-viral shRNA mediated knockdown of Lyn kinase leads to a decrease in Par-4 expression in MEC-1 cells, a human CLL derived cell line. Igα (CD79a) silencing in primary human CLL cells also results in down regulation of Par-4 expression. Additionally, we knocked down expression of Par-4 in MEC-1 cells which resulted in a decrease in cell growth that could be attributed to an increase in p21 expression and a reduction in the G1/S cell cycle transition. We have also observed this phenomenon by crossing mice deficient in Par-4 with the Eµ-Tcl1 mouse where lack of Par-4 delays CLL growth in the mouse significantly (time to euthanization due to poor body condition - Eµ-Tcl1: 8.9mo vs Par4-/-EµTcl1: 11.97 mo, p = 0.0472) and splenic B-CLL cells from these mice also have increased expression of p21. Since mice in this cohort are whole body knockout for Par-4, the difference in survival times between the Par-4 +ve and Par-4 –ve EµTcl1 mice could be due to the influence of Par-4 on CLL cells as well as the effect of Par-4 secreted by the CLL cells on the microenvironment. There could be other potential roles for Par-4 in the context of CLL which are under further investigation. We have also investigated the site of CLL growth in mouse models to determine that the spleen is the primary organ to accumulate the CLL tumor burden. We have found that splenectomy significantly delays the development of CLL in the primary Eμ-Tcl1 mouse model and prevents growth and development in the adoptive transfer model. Interestingly, splenectomy did not delay CLL development as significantly in animals deficient for Par-4 compared to C57BL/6 wild type mice. Par-4 appears to regulate a specific microenvironment required for CLL growth. Current studies are investigating the role of Par-4 in the microenvironment and the cell types that are critical for CLL growth within the splenic niche.

Thesis (Ph. D.)--University of Washington, 2006. / Vita. Includes bibliographical references (leaves 64-71).

A vascularização arterial do baço do eqüino foi estudada por meio de radiografias contrastadas, cintilografias, dissecações e moldes. O baço está situado no antímero esquerdo e a sua posição na cavidade abdominal determina uma face parietal lisa e levemente convexa, enquanto que a face intestinal, onde estão localizados os vasos, nervos e ligamentos, é levemente côncava determinando uma área com menor espessura. O estudo da vascularização arterial demonstrou uma área paucivascular que coincide justamente com a área côncava onde a espessura é menor. Este comportamento foi observado tanto nos adultos como nos fetos. Baseado na distribuição dos vasos arteriais a região onde a espessura é menor foi indicada como local de eleição para a incisão no caso de esplenectomias parciais, dividindo o baço do eqüino em dois segmentos anátomo-cirúrgicos. A cirurgia de ressecção parcial do baço não foi descrita, no cavalo, conforme atesta a literatura atual. Duas cirurgias experimentais foram realizadas para comprovar a indicação, demonstrando que a proposta é exeqüível. A análise proporcional da área mostrou que a ressecção parcial na região indicada preserva em média 50% do parênquima. / Observation on the mode of parenchymal distribution of equine splenic artery was studied using arteriography, scintigraphy, dissection and corrosion cast. The spleen is situated in the left region of the abdomen. The parietal surface is convex and the visceral surface, where the blood vessels, nerves and ligaments are situated, is concave. The vascular arrangement may lead to division the organ into two anatomicosurgical segments. No literature is available on partial splenectomy in horses. Two partial resection was performed successfully by the method described, this partial resection preserve 50% of spleen parenchyma.