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No description available.

Lymphocytes from patients with B-chronic lymphocytic leukemia (B-CLL) express large numbers of P2X7 receptors for extracellular adenosine triphosphate (ATP). Activation of P2X7 receptors induces multiple downstream effects, of which the best documented is the opening of an ionic channel that is selective for divalent cations. Another effect of ATP is to induce the shedding of L-selectin (CD62L), a molecule which is involved in the adhesive interactions of lymphocytes on endothelial cells. High levels of soluble L-selectin and CD23 are found in the serum of patients with B-CLL, although the mechanisms involved in their production are poorly characterized. Because extracellular ATP causes shedding of L-selectin, we studied the effect of ATP on shedding of CD23, an adhesion molecule expressed on the surface of B-CLL lymphocytes. ATP induced the shedding of CD23 at an initial rate of 12% of that for L-selectin, while the EC50 of ATP (35 uM) and BzATP (10 uM) was identical for shedding of both molecules. Inactivation of the P2X7 receptor by pre-incubation with OxATP, an irreversible inhibitor of P2X7 purinoceptor, abolished ATP-induced shedding of both molecules. Moreover, KN-62, the most potent inhibitor for the P2X7 receptor inhibited ATP-induced shedding of both CD23 and L-selectin with the same IC50 (12 nM). Ro 31-9790, a membrane permeant zinc chelator which inhibits the phorbol-ester stimulated shedding of L-selectin also inhibited shedding of CD23 from B-CLL lymphocytes, but the IC50 was different for the two shed molecules (25 versus 1 ug/ml respectively). Although L-selectin was completely shed by incubation of cells with phorbol-ester no CD23 was lost under these conditions. Also, Ca2+ inhibits ATP-induced CD23 shedding but not L-selectin shedding. Since soluble CD23 and L-selectin are found in the serum of normal subjects and B-CLL patients, the expression of these two adhesion molecules on lymphocytes before and after transendothelial migration was studied in an in vitro model of this process. In normal and B-CLL subjects, 71�b5% of L-selectin from both T and B cells and 90% of CD23 from B cells was lost following transmigration, while the expression of a range of other adhesion molecules such as VLA-4, ICAM-1, LFA-1 and CD44 was unchanged. Lymphocytes incubated with OxATP retained their capacity for transendothelial migration and showed the same loss of L-selectin as control leukaemic lymphocytes. Ro 31-9790, which can protect ATP-induced both L-selectin and CD23 shedding, had no effect on inhibiting L-selectin and CD23 lost during transmigration. These data show the presence of a second pathway for the downregulation of L-selectin and CD23 from the lymphocyte surface. Data in vivo from 'knock-out' mice show that L-selectin is essential for the emigration of lymphocytes through high endothelial venules into lymph nodes. The migration of normal and B-CLL lymphocytes across confluent human umbilical vein endothelial monolayers was studied in an in vitro model of this process. Lymphocytes treated with ATP or BzATP showed 56�b25% or 67�b16% loss of L-selectin on the surface and 36�b24% or 64�b19% decrease of transmigration, respectively, while OxATP, which does not alter the L-selectin level, had no effect on lymphocyte transmigration. Further experiments examined this correlation between L-selectin expression and lymphocyte transendothelial migration in this model system. A quantitative assay for cell surface L-selectin showed that expression of L-selectin was lower on B-CLL lymphocytes (8,880�b5,700 molecules/cell) than on normal lymphocytes (29,500�b7,500 molecules/cell, p less than 0.001). Also the rate of transmigration of B-CLL lymphocytes (1.5�b0.9 migrated cells/HUVEC) was lower than normal peripheral lymphocytes (2.4�b0.9 migrated cells/HUVEC, p=0.04). Incubation of lymphocytes in complete medium for 24 hrs increased the expression of L-selectin on B-CLL lymphocytes by 1.5 to 2 fold while the normal lymphocyte L-selectin remained at the initial level. This upregulation of B-CLL L-selectin correlated with a 2 fold increased rate of transendothelial migration. A correlation was found between L-selectin expression on lymphocytes and their ability for transendothelial migration (r^2=0.6). This study shows that the adhesion molecules L-selectin and CD23 can be lost from lymphocytes by two different physiological pathways. One is by P2X7 receptor activation by extracellular ATP while the second is activated by transendothelial migration of these cells. A second finding is that B-CLL lymphocytes have lower level of L-selectin expression and an impaired ability for transendothelial migration compared with normal peripheral blood lymphocytes. Do these results explain the high serum levels of soluble L-selectin and CD23 observed in B-CLL? Although B-CLL lymphocytes do not recirculate as rapidly as normal peripheral blood lymphocytes, the greatly increased number of leukaemic cells in B-CLL ensures that much more soluble L-selectin and CD23 is generated during the recirculation of these cells through the body.

Lymphocytes from patients with B-chronic lymphocytic leukemia (B-CLL) express large numbers of P2X7 receptors for extracellular adenosine triphosphate (ATP). Activation of P2X7 receptors induces multiple downstream effects, of which the best documented is the opening of an ionic channel that is selective for divalent cations. Another effect of ATP is to induce the shedding of L-selectin (CD62L), a molecule which is involved in the adhesive interactions of lymphocytes on endothelial cells. High levels of soluble L-selectin and CD23 are found in the serum of patients with B-CLL, although the mechanisms involved in their production are poorly characterized. Because extracellular ATP causes shedding of L-selectin, we studied the effect of ATP on shedding of CD23, an adhesion molecule expressed on the surface of B-CLL lymphocytes. ATP induced the shedding of CD23 at an initial rate of 12% of that for L-selectin, while the EC50 of ATP (35 uM) and BzATP (10 uM) was identical for shedding of both molecules. Inactivation of the P2X7 receptor by pre-incubation with OxATP, an irreversible inhibitor of P2X7 purinoceptor, abolished ATP-induced shedding of both molecules. Moreover, KN-62, the most potent inhibitor for the P2X7 receptor inhibited ATP-induced shedding of both CD23 and L-selectin with the same IC50 (12 nM). Ro 31-9790, a membrane permeant zinc chelator which inhibits the phorbol-ester stimulated shedding of L-selectin also inhibited shedding of CD23 from B-CLL lymphocytes, but the IC50 was different for the two shed molecules (25 versus 1 ug/ml respectively). Although L-selectin was completely shed by incubation of cells with phorbol-ester no CD23 was lost under these conditions. Also, Ca2+ inhibits ATP-induced CD23 shedding but not L-selectin shedding. Since soluble CD23 and L-selectin are found in the serum of normal subjects and B-CLL patients, the expression of these two adhesion molecules on lymphocytes before and after transendothelial migration was studied in an in vitro model of this process. In normal and B-CLL subjects, 71�b5% of L-selectin from both T and B cells and 90% of CD23 from B cells was lost following transmigration, while the expression of a range of other adhesion molecules such as VLA-4, ICAM-1, LFA-1 and CD44 was unchanged. Lymphocytes incubated with OxATP retained their capacity for transendothelial migration and showed the same loss of L-selectin as control leukaemic lymphocytes. Ro 31-9790, which can protect ATP-induced both L-selectin and CD23 shedding, had no effect on inhibiting L-selectin and CD23 lost during transmigration. These data show the presence of a second pathway for the downregulation of L-selectin and CD23 from the lymphocyte surface. Data in vivo from 'knock-out' mice show that L-selectin is essential for the emigration of lymphocytes through high endothelial venules into lymph nodes. The migration of normal and B-CLL lymphocytes across confluent human umbilical vein endothelial monolayers was studied in an in vitro model of this process. Lymphocytes treated with ATP or BzATP showed 56�b25% or 67�b16% loss of L-selectin on the surface and 36�b24% or 64�b19% decrease of transmigration, respectively, while OxATP, which does not alter the L-selectin level, had no effect on lymphocyte transmigration. Further experiments examined this correlation between L-selectin expression and lymphocyte transendothelial migration in this model system. A quantitative assay for cell surface L-selectin showed that expression of L-selectin was lower on B-CLL lymphocytes (8,880�b5,700 molecules/cell) than on normal lymphocytes (29,500�b7,500 molecules/cell, p less than 0.001). Also the rate of transmigration of B-CLL lymphocytes (1.5�b0.9 migrated cells/HUVEC) was lower than normal peripheral lymphocytes (2.4�b0.9 migrated cells/HUVEC, p=0.04). Incubation of lymphocytes in complete medium for 24 hrs increased the expression of L-selectin on B-CLL lymphocytes by 1.5 to 2 fold while the normal lymphocyte L-selectin remained at the initial level. This upregulation of B-CLL L-selectin correlated with a 2 fold increased rate of transendothelial migration. A correlation was found between L-selectin expression on lymphocytes and their ability for transendothelial migration (r^2=0.6). This study shows that the adhesion molecules L-selectin and CD23 can be lost from lymphocytes by two different physiological pathways. One is by P2X7 receptor activation by extracellular ATP while the second is activated by transendothelial migration of these cells. A second finding is that B-CLL lymphocytes have lower level of L-selectin expression and an impaired ability for transendothelial migration compared with normal peripheral blood lymphocytes. Do these results explain the high serum levels of soluble L-selectin and CD23 observed in B-CLL? Although B-CLL lymphocytes do not recirculate as rapidly as normal peripheral blood lymphocytes, the greatly increased number of leukaemic cells in B-CLL ensures that much more soluble L-selectin and CD23 is generated during the recirculation of these cells through the body.

Während die zellulären Mechanismen der Pathogenese der Arteriosklerose intensiv untersucht worden sind, ist über die Mechanismen, die zu einer bevorzugten Lokalisation arteriosklerotischer Läsionen in bestimmten Gefäßarealen führen, weniger bekannt. Zur Untersuchung dieser Mechanismen wurden Endothelzellen aus menschlichen Koronararterien, einem Gefäßbereich, in dem häufig arteriosklerotische Läsionen beobachtete werden, isoliert und kultiviert. Endothelzellen der Mikrozirkulation menschlicher Herzen wurden unter gleichen Bedingungen kultiviert und die Reaktionen beider Zellarten verglichen. Inkubation der Zellen mit den in Bezug auf die Bildung arteriosklerotischer Plaques besonders pathogenen oxidierten LDL induzierte in makrovaskulären koronaren Endothelzellen eine stärkere Zunahme der PAI-1 Aktivität (182%, p / While the cellular mechanisms of atherosclerosis have been intensively studied, the mechanisms leading to preferential localization of atherosclerotic lesions are less well understood. To further define these mechanisms, endothelial cells from coronary arteries, i.e. vessels with frequent atherosclerotic lesions, were isolated and grown in vitro. In order to compare the reactions of both cell types, endothelial cells derived from microvessels of human hearts were isolated and cultured under identical conditions. Incubation of endothelial cells with oxidized LDL (75 µg/ml protein) induced a significant increase in PAI-1 activity (182 %, p

Ischemia followed by reperfusion, as happens in myocardial infarction, or the development of acute respiratory distress syndrome, are associated with a exaggerated extravasation of leukocytes into the surrounding tissue , which may cause severe bystander damage. In animal models of these diseases, pharmacological blockage of the leukocyte adhesion molecule, L-selectin (CD62L), has been shown to be partially protective by reduction or inhibition of leukocyte-mediated secondary tissue damage. The aim of this project was the development of an in vitro assay to investigate the relative effectiveness of potential L-selectin antagonists. Ideally, the assay should require low sample volumes and allow for measurements of larger series of reagents. The assay system investigated was based on the homotypic granulocyte aggregation under shear stress, which mimicks the L-selectin-dependent adhesion of leukocytes to previously arrested neutrophils on vascular endothelium. After optimizing numerous variables of the aggregation assay, the requirement of L-selectin for the homotypic granulocyte aggregation induced was demonstrated by inhibition experiments using soluble L-selectin or monoclonal antibodies directed against the lectin domain of L-selectin. Several carbohydrate polymers with L-selectin binding properties, such as the seaweed-derived fucose polymer fucoidin, high-molecular-weight dextran sulfate or heparin, also inhibited neutrophil aggregation in a dose-dependent fashion. However, despite employing a flow cytometry-based read-out technique, the assay remained extremely labor intensive, precluding investigations of extended series. Therefore, the homotypic aggregation experiments with freshly isolated human granulocytes remains a useful tool to further evaluate specific questions of L-selectin dependent adhesion processes, but it is not apt for transfer into routine laboratories.

IntroduÃÃo â AlteraÃÃes na expressÃo ou funÃÃo das molÃculas de adesÃo (MA) nas cÃlulas leucÃmicas podem contribuir para a evoluÃÃo e no comportamento biolÃgico das leucemias agudas. A expressÃo aumentada nas LLAs parece relacionar-se aos mecanismos de disseminaÃÃo extramedular dos linfoblastos, infiltraÃÃo do SNC e formaÃÃo de massas tumorais. Objetivos â Analisar a expressÃo da L-selectina e do CD44 nas LLAs em crianÃas e adolescentes. Avaliar os fatores prognÃsticos (idade, sexo, leucometria ao diagnÃstico, imunofenÃtipo, classificaÃÃo FAB, EGIL, Ãndice de DNA e resposta ao tratamento de induÃÃo) e as apresentaÃÃes extramedulares das LLAs e correlacionÃ-los com essas MA. Pacientes e MÃtodos â Foram avaliados 76 pacientes com LLA, tratados com o Protocolo GBTLI-LLA. O diagnÃstico foi baseado em critÃrios FAB, imunofenotÃpicos (EGIL) e citogenÃticos. A expressÃo das MA foi avaliada por citometria de fluxo, utilizando tripla marcaÃÃo. O anticorpo monoclonal CD45-PerCP (ImmunotechÂ) foi utlizado como marcador dos linfoblastos. O CD44-PE (Clone HP2/9 - ImmunostepÂ) e o CD62L-FITC (Clone HI62L - ImmunostepÂ) foram utilizados para a marcaÃÃo das MA. Para a anÃlise das amostras e o cÃlculo da intensidade mÃdia de fluorescÃncia foi utilizado o programa Cell Quest. Na anÃlise estatÃstica utilizou-se o software SPSS 16.0. A associaÃÃo entre as variÃveis, os fatores prognÃsticos e resposta foi realizada com os testes de Qui-quadrado, exato de Fisher e Mann-Whitney. Sobrevida global foi determinada por curvas Kaplan-Meier e teste log-rank. AnÃlise multivariada por modelo proporcional de Cox foi utilizada para assegurar a independÃncia dos fatores prognÃsticos. Resultados â A mÃdia de idade foi 6,3Â0,5 anos (5m -17a) e predominou o sexo masculino (65%). Ao diagnÃstico os achados clÃnicos foram: hepatomegalia (63%), esplenomegalia (58%) e linfadenomegalia (44%). A infiltraÃÃo SNC ocorreu em 6,6% dos casos e o alargamento de mediastino em 11,8%. Quanto ao risco, 54% eram baixo risco e 46% alto risco. A classificaÃÃo FAB determinou 83% como L1 e 17% L2. DiagnÃstico de LLA-B foi mais frequente (89,5%) e o da LLA-T em 10,5% dos pacientes. O subtipo EGIL mais prevalente foi B II e B III, 51,5% e 45% respectivamente. O IDNA &#8805; 1.16 foi encontrado em 19% dos pacientes e associou-se a bom prognÃstico. Na avaliaÃÃo do D8, 95% dos pacientes apresentaram contagem de blastos <1000/mm3 e leucÃcitos < 5.000/mm3. A taxa de remissÃo de induÃÃo foi de 95% e ocorreram 2,6% de Ãbitos na induÃÃo. Observou-se uma maior expressÃo do CD44 na LLA-T (87,5%/ IMF=150,44Â20,29), porÃm sem significÃncia estatÃstica. LLAs com massa tumoral apresentaram 84% de expressÃo do CD44, quando comparada a 52% das LLAs sem massa tumoral (p=0.01; OR=4,8). ExpressÃo aumentada da L-selectina na LLA-T (87,5%/IMF=272,33Â52,72) foi estatisticamente significante (p=0,004), comparado a LLA-B (54,5%/ IMF= 115,90Â12,75). NÃo houve correlaÃÃo entre os outros fatores prognÃsticos e essas MA. Na anÃlise multivariada as variÃveis de maior impacto para a sobrevida foram: a leucometria ao diagnÃstico, sexo, imunofenÃtipo T e a L-selectina. ConclusÃo â A expressÃo da L-selectina e do CD44 estÃo aumentadas nas LLAs estudadas, principalmente na LLA-T. O CD44 correlacionou-se com LLAs com massas tumorais e parece estar relacionado aos mecanismos de disseminaÃÃo extramedular dos linfoblastos / Introduction â Altered expression or function of adhesion molecules on leukemic blasts may contribute to the evolution of acute leukemia and its biological behavior. The elevated expression of adhesion molecules in ALL might be correlated with the extramedullary dissemination of blast cells, CNS involvement and leukemia tumor burden. Purpose â To analyze the expression of L-selectin and CD44 in ALL in children and adolescents. As well as to evaluate the prognostic factors (age, gender, initial leukocyte count, immunophenotype, FAB and EGIL classification, DNA index and early response to treatment) and the extramedullary presentation of ALL, to finally correlate the prognostic factors with these adhesion molecules. Patients and Methods â From November 2007 to November 2008, 76 patients with newly diagnosed ALL started on Brazilian GBTLI-ALL Protocol. The diagnosis was based on cytological, immunophenotypic, and cytogenetic methods. The mean fluorescence intensity (MFI) and the percentage of the adhesion molecules blasts cells was measured by flow cytometry using triple staining with McAb directly conjugated. CD45-PerCP positive cells were gated for blasts analysis. Anti-CD44-PE (Clone HP2/9 - ImmunostepÂ) and CD62L-FITC (Clone HI62L - ImmunostepÂ) were used to mark the adhesion molecules. The Cell Quest program was used for data acquisition and analysis. Statistical analysis was done by SPSS 16.0 Software. The association of features, prognosis and response to treatment was assessed by Chi-square, Fisher exact and Mann-Whitney tests. Overall survival curves were constructed by the Kaplan-Meier method and the log-rank test. Multivariate Cox regression analysis showed independent prognostic factors. Results â The mean age at diagnosis was 6.3Â0.5 years (range 9mo to 17yr) and 65% of them were boys. Clinical findings were hepatomegaly (63%), splenomegaly (58%), lymphadenopathy (44%). CNS involvement was detected in 6.6% of cases and mediastinal mass appeared in 11.8% of them. Patients were classified into low risk (54%) and high risk (46%). FAB classification identified 83% as L1 and 17% as L2. Immunophenotypically, 89.5% of patients were classified as B-lineage ALL and 10.5% as T-lineage ALL. The most frequent EGIL subtype was B common and pre-B-ALL (51.5% and 45.5%, respectively). DNA index greater than 1.16 was found in 19% of the patients and was associated with favorable prognosis. On the D8 evaluation, 95% of the patients had blast count lower than 1.000/mm3 and leukocyte count lower than 5.000/mm3. The remission induction rate was 95% and there was a rate of 2.6% of death during induction therapy. CD44 had greater expression to the rate of 87.5% in T-cell ALL (MFI=150.44Â20.29) with no statistical correlation. A significant positive correlation was demonstrated between 84% of CD44 expression and Leukemia burden tumor cases (p=0.01; OR=4.8). There was statistical correlation between L-selectin expression (87.5%/MFI=272.33Â52.72) and T-cell ALL (p=0,004). No significant correlation was detected between L-selectin and CD44 expression and other prognostic factors. Multivariate statistical analysis (adjusted for overall survival) indicated that initial leukocyte count, gender, T immunophenotype and L-selectin were independent factors. Conclusion â L-selectin and CD44 expressions were elevated in ALL studied, mainly in T-cell ALL. The research demonstrated that there is an association between CD44 expression and leukemia tumor burden, which might be involved in the dissemination of leukemic cells and the progression of the disease.

CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior / IntroduÃÃo e objetivos: Os neutrÃfilos desempenham importante papel na pancreatite aguda grave. InfiltraÃÃo de neutrÃfilos no pÃncreas à um processo complexo, coordenado por molÃculas de adesÃo especÃficas, tais como a P-selectina. Fucoidina à um polissacarÃdeo sulfatado que bloqueia a funÃÃo da L-e P-selectinas. No presente estudo avaliamos se o tratamento com fucoidina poderia impedir a infiltraÃÃo de neutrÃfilos e, assim, reverter a inflamaÃÃo sistÃmica e dismotilidades gastrintestinais associadas à pancreatite aguda grave. MÃtodos: A pancreatite aguda foi induzida em camundongos Swiss pela infusÃo retrÃgrada de Ãcido taurolitocÃlico (3,0%) (TLC-S) no ducto pancreÃtico ou por injeÃÃes intraperitoneais de ceruleÃna (50 Âg/kg/h). Os grupos experimentais receberam fucoidina (25 mg/kg, iv) antes da induÃÃo da pancreatite, e os grupos de controle receberam apenas soluÃÃo salina. ApÃs 24 horas, os nÃveis sÃricos de amilase, lipase, IL-1&#946;, TNF-&#945;, nitrito e de malondialdeÃdo (MDA) pancreÃtico foram medidos. AlÃm disso, a atividade de mieloperoxidase (MPO) (pulmÃo, pÃncreas, estÃmago e jejuno) e avaliaÃÃo histolÃgica (pÃncreas) foram determinadas. O esvaziamento gÃstrico e trÃnsito gastrintestinal foram medidos pelo mÃtodo de centro geomÃtrico. A contratilidade gastrintestinal in vitro foi registrada atravÃs de transdutores de forÃa conectados a sistema computadorizado de aquisiÃÃo de dados. Carbacol (0,01 ÂM - 30 ÂM), KCl 60 mM e estimulaÃÃo elÃctrica (0,5-8,0 Hz; 1ms, 40 V), foram aplicados sobre o fundo gÃstrico e jejuno dos animais 24 horas apÃs a pancreatite induzida por TLC-S. Resultados: Os nÃveis de MDA pancreÃtico, amilase, lipase, nitrito, TNF-&#945; e IL-1&#946; sÃricos, bem como MPO pancreÃtica e pulmonar estavam aumentados tanto no modelo de pancreatite aguda induzida por TLCS quanto no modelo ceruleÃna quando comparado aos grupos controle correspondentes. Fucoidina reduziu significativamente os nÃveis aumentados de amilase, lipase, MPO pancreÃtica e pulmonar, MDA, TNF-&#945;, IL-1&#946; e nitrito em ambos os modelos de pancreatite aguda. As mudanÃas histolÃgicas observadas no pÃncreas em ambos os modelos foram significativamente atenuadas pela fucoidina. O modelo de pancreatite aguda induzida por TLC-S induziu retardo no esvaziamento gÃstrico e trÃnsito gastrointestinal, aumento de MPO no estÃmago e no jejuno, alÃm de hipercontratilidade de jejuno in vitro. Fucoidina reverteu significativamente os distÃrbios gastrintestinais in vivo e in vitro e os nÃveis aumentados de MPO gÃstrica e jejunal induzidos pela injeÃÃo de TLC-S. ConclusÃo: Fucoidina reduziu a gravidade da pancreatite aguda experimental atravÃs da diminuiÃÃo da infiltraÃÃo de neutrÃfilos, inflamaÃÃo sistÃmica e dismotilidades gastrintestinais, sugerindo que a modulaÃÃo das selectinas, pode constituir uma abordagem terapÃutica promissora para pancreatite aguda. / Background & Aims: Neutrophils play a critical role in severe acute pancreatitis. Tissue infiltration of neutrophils in the pancreas is a multistep process, coordinated by specific adhesion molecules, such as P-selectin. Fucoidin is a sulphated fucosylated polysaccharide that binds to and blocks the function of L- and P-selectins, and the present study has evaluated whether fucoidin treatment could prevent neutrophil infiltration, and thereby reverse the systemic inflammation and gastrointestinal dysmotility associated with severe acute pancreatitis. Methods: Acute pancreatitis was induced in Swiss mice either by the retrograde infusion of taurolithocholic acid (3.0%) (TLC-S) into the pancreatic duct or by intraperitoneal injections of cerulein (50 Âg/kg/h). The experimental groups received fucoidan (25 mg/kg, i.v.) before pancreatitis induction whist control groups received only saline. After 24 hours, pancreatic malondialdehyde (MDA), serum amylase, lipase, IL-1&#946;, TNF-&#61537; and nitrite were measured. In addition, myeloperoxidase (MPO) activity (lung, pancreas, stomach and jejunum) and histological assessment (pancreas) were determined. Gastric emptying and gastrointestinal transit (using the geometric center method) were also measured. Gastrointestinal contractility in vitro was recorded through force transducers coupled to a computerized data acquisition system, carbachol (0,01 ÂM â 30 ÂM), KCl 60mM and electrical field stimulation (0.5-8.0 Hz; 1ms; 40 V), was applied on gastric fundus and jejunum of mice 24 hours after TLC-S induced pancreatitis. Results: Pancreatic MDA, serum amylase, lipase, nitrite, TNF-&#61537; and IL-1&#946;, pancreatic and lung MPO, were increased in both TLCS- and cerulein acute pancreatitis compared with respective control groups. Fucoidan significantly decreased the augmented levels of amylase, lipase, pancreatic and lung MPO, MDA, TNF-&#61537;, IL-1&#946; and nitrite in both acute pancreatitis models. Pancreas histological changes observed in both models were significantly attenuated by fucoidan. The acute pancreatitis model induced by TLC-S caused delayed gastric emptying and gastrointestinal transit, incresead gastric and jejunum MPO, and jejunum hypercontractility in vitro. Fucoidan significantly reversed the gastrointestinal disorders in vivo and in vitro and augmented levels of gastric and jejunum MPO induced by TLC-S. Conclusion: Fucoidan reduced the severity of acute pancreatitis in mice by decreasing neutrophil infiltration, systemic inflammation and gastrointestinal dysmotility, suggesting that modulation of selectins may constitute a promising therapeutic approach for acute pancreatitis.

No description available.

No description available.