Diagnóstico de síndrome de Peutz-Jeghers / The diagnosis of Peutz-Jeghers syndrome

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Study of the efficacy of Coated VICRYL Plus Antibacterial suture (coated Polyglactin 910 suture with Triclosan) in two animal models of general surgery.

OBJECTIVES: To evaluate the efficacy in vitro and in vivo of a new antibacterial suture (PGAB) compared with a traditional braided suture (PG). Our primary goals were to study microbiological effectiveness and impact on wound healing of PGAB vs PG. Secondary goal was to analyze influence on inflammatory response. METHODS: In vitro study: clinical samples of Staphylococcus epidermidis, Staphylococcus aureus, S. hominis, Staphylococcus haemolyticus, Staphylococcus auricularis, Enterococcus faecalis, Corynebacterium spp. and Escherichia coli were studied. We also implanted a flat mesh in 10 minipigs, four incisions each (two PG and two PGAB) two contaminated with S. epidermidis and two not contaminated. Finally, we performed four colic anastomosis in each of 10 minipigs, two contaminated with E. coli and two not contaminated (two PG and two PGAB). We studied the inflammatory and wound healing processes in both models. RESULTS: We observed a bactericidal efficacy of PGAB against grampositive, and bacteriostatic effect against E. coli. Mesh study: recovered CFU were lower in the group PGAB vs PG. In the group PGAB, inflammatory mediators' concentrations were lower. In the group PGAB, concentrations of wound healing mediators were normal. Colic anastomosis: recovered CFU were lower in the group PGAB vs the group PG. In the group PGAB we observed a reduction of inflammatory mediators. In the group PGAB we observed normalized concentrations of wound healing mediators. CONCLUSIONS: This study demonstrates microbiological efficacy of PGAB, that normalizes wound healing process, and an anti-inflammatory effect.

[Enteral nutrition with peri-surgery immunomodulating diet]. / Nutrición enteral con dieta inmunomoduladora perioperatoria.

OBJECTIVE: To assess the nutritional peri-surgical status of patients suffering from esophageal or gastric cancer, treated with esophagectomy and total gastrectomy, respectively, and to analyze the impact of an enteral immunomodulating diet on postsurgical complications. SETTING: Patients admitted to the Surgery Department of Hospital Clinico Universitario of Salamanca. PATIENTS AND METHODS: Patients submitted to esophagectomy and/or total gastrectomy to whom early enteral nutrition (EN) is provided with an immunomodulating diet. INTERVENTIONS: All patients were prescribed an immunomodulating diet of 1000 Kcal/day p.o. plus a normal grinded diet that they started on the 5th presurgical day and pursued during the immediate postsurgical period (within the first 24 hours) with EN through a jejunostomy catheter, in a progressive way until reaching 25 kcal/kg/day at days 4-5. EN was kept in place for at least the first 10 days after surgery and laboratory checkups were done before surgery and at days 5 and 10 after surgery. We also performed a prediction equation, with morbidity as the dependent variable and the remaining as independent variables. RESULTS: Sixty-eight patients were studied of whom 36 (35 men and 1 women) suffered from esophageal cancer and 32 (21 men and 11 women) from gastric cancer. Mean age of patients with esophageal cancer was 60 +/- 9.68 years, with a mean postsurgical stay of 36.97 +/- 62.37 days, and for gastric cancer patients mean age was 69.41 +/- 11.53 years and mean stay 24.41 +/- 13.77 days. The comparison of the means of the biochemical nutrition parameters showed a decrease in almost all values at the 5ht post-surgery day in relation to the presurgical determination, and an increase in the measurement at the 10th postsurgical day as compared to the 5th day values. In most of the cases, the differences are statistically significant. For morbimortality prediction, the variables cholesterol, related diseases, CRP, IgM, and male gender, were contributors. CONCLUSIONS: All the analyzed variables, but gender, seem to be appropriate indicators for the study of response to surgical aggression as well as of enteral nutrition. We believe that peri-surgical immunomodulating nutrition recovers the values of postsurgical nutrition parameters. Enteral nutrition through jejunostomy is well tolerated, and has a low and mild morbidity.

Nutrición enteral con dieta inmunomoduladora perioperatoria / Enteral nutrition with peri-surgery immunomodulating diet

Objetivo: Valorar el estado nutricional en el perioperatorio, de pacientes afectos de cáncer esofágico o gástrico, tratados mediante esofaguectomía y gastrectomía total respectivamente, y analizar la repercusión de la dieta enteral inmunomoduladora con las complicaciones postquirúrgicas. Ámbito: Pacientes ingresados en el Servicio de Cirugía del Hospital Clínico Universitario de Salamanca. Pacientes y métodos: Pacientes sometidos a esofaguectomía yo gastrectomía total a los que se le aporta nutrición enteral (NE) precoz con una dieta inmunomoduladora. Intervenciones: A todos los pacientes se les pautaba una dieta inmunomoduladora de 1000 kcal/día por vía oral más dieta normal por turmix que iniciaban en el 5º día preoperatorio y continuando en el postoperatorio inmediato (en las primeras 24 h) con NE por catéter de yeyunostomía, de forma progresiva hasta conseguir 25Kcal/Kg/día al 4º-5º día. La NE se mantuvo al menos los primeros diez días del postoperatorio y se realizaron controles analíticos en el preoperatorio en el quinto y décimo días postoperatorios. También realizamos una ecuación de predicción con la variable dependiente morbi-mortalidad y como independientes con el resto de las variables. Resultados: Se estudiaron 68 pacientes de los cuales 36 (35 varones y 1 mujer) padecían cáncer esofágico y 32 (21 varones y 11 mujeres) que padecían cáncer gástrico. La media de edad de los pacientes con cáncer esofágico era de 60 ± 9,68 años con una estancia media postoperatoria de 36,97 ± 62,37 días y las cifras de pacientes con cáncer gástrico eran 69,41 ± 11,53 años y 24,41 ± 13,77 días respectivamente. La comparación de medias de los parámetros nutricionales bioquímicos, puso de manifiesto una disminución de las cifras de casi todas las variables, en la determinación del 5º día postoperatorio respecto de la determinación preoperatoria y posterior aumento en la determinación del 10º día postoperatorio respecto del 5º día. Las diferencias son en la mayoría de los casos estadísticamente significativas. Resultaron ser partícipes en la ecuación de predicción de la morbimortalidad las variables, colesterol, enfermedades asociadas, PCR, IgM y sexo varón. Conclusiones: Las variables analizadas, excepto el sexo, parecen ser indicadores adecuados para el estudio de la respuesta a la agresión quirúrgica y así mismo a la nutrición enteral. La nutrición perioperatoria inmunomoduladora creemos que recupera las cifras de parámetros nutricionales postoperatorios.La nutrición enteral por yeyunostomía es bien tolerada y con morbilidad baja y poco severa (AU)

Objective: To assess the nutritional peri-surgical status of patients suffering from esophageal or gastric cancer, treated with esophagectomy and total gastrectomy, respectively, and to analyze the impact of an enteral immunomodulating diet on postsurgical complications. Setting: Patients admitted to the Surgery Department of Hospital Clínico Universitario of Salamanca. Patients and methods: Patients submitted to esophagectomy and/or total gastrectomy to whom early enteral nutrition (EN) is provided with an immunomodulating diet. Interventions: All patients were prescribed an immunomodulating diet of 1000 Kcal/day p.o. plus a normal grinded diet that they started on the 5th presurgical day and pursued during the immediate postsurgical period (within the first 24 hours) with EN through a jejunostomy catheter, in a progressive way until reaching 25 kcal/kg/day at days 4-5. EN was kept in place for at least the first 10 days after surgery and laboratory checkups were done before surgery and at days 5 and 10 after surgery. We also performed a prediction equation, with morbidity as the dependent variable and the remaining as independent variables. Results: Sixty-eight patients were studied of whom 36 (35 men and 1 women) suffered from esophageal cancer and 32 (21 men and 11 women) from gastric cancer. Mean age of patients with esophageal cancer was 60 ± 9.68 years, with a mean postsurgical stay of 36.97 ± 62.37 days, and for gastric cancer patients mean age was 69.41 ± 11.53 years and mean stay 24.41 ± 13.77 days. The comparison of the means of the biochemical nutrition parameters showed a decrease in almostall values at the 5ht post-surgery day in relation to the presurgical determination, and an increase in the measurement at the 10th postsurgical day as compared to the 5th day values. In most of the cases, the differences are statistically significant. For morbimortality prediction, the variables cholesterol, related diseases, CRP, IgM, and male gender, were contributors. Conclusions: All the analyzed variables, but gender, seem to be appropriate indicators for the study of response to surgical aggression as well as of enteral nutrition. We believe that peri-surgical immunomodulating nutrition recovers the values of postsurgical nutrition parameters. Enteral nutrition through jejunostomy is well tolerated, and has a low and mild morbidity (AU)

Nitric oxide prevents the bacterial translocation and inhibits the systemic inflammatory response produced by implantation of a vascular prosthesis followed by Zymosan A.

OBJECTIVE AND DESIGN: To evaluate the beneficial effects of exogenous NO and its levels of action in a model of SIRS/Bacterial Translocation (BT) induced by two sequential insults. MATERIAL OR SUBJECTS: Eighty-six Wistar rats were submitted to different treatments and their tissue and blood samples were accessed at the end of the experiment. TREATMENT: Nitric Oxide was compared to Gentamicin as the tested guideline for our study. METHODS: Dacron graft implantation (first insult) and subsequent administration of Zymosan A((R)) (second insult) were performed in Wistar rats. The animals were divided into 6 groups: I) No manipulation (BASAL: ); II) Laparotomy (L) + mineral oil (SHAM: ); III) L + Graft-Zymosan (GZ) (CONTROL: ); IV) L + GZ + Antibiotic (A) (ASSAY: I); V) L + GZ + NO (ASSAY: II) and VI) L + GZ + A + NO (ASSAY: III). Determinations: Survival, Bacterial Translocation, myeloperoxidase (MPO), Cytokines (TNF-alpha, IL-1beta, IFN-gamma), Oxygen Free Radical (OFR) SOA and detoxifying enzymes (SOD, Superoxide Dismutase, CAT, Catalase and GPX, Glutathione Peroxidase), Cell Adhesion Molecules, CAMs (ICAM-1, VCAM-1 and PECAM-1) and Nuclear Transcription Factor, NFkappaB. RESULTS: The model established induced a mortality rate of 20% and generated BT in all samples. It also significantly increased all variables, with P < 0.001 for MPO and all Cytokines; P < 0.01 for all OFR, and P < 0.05 for CAMs and for NFkappaB. Treatment with A reduced mortality to 0%, significantly decreased BT, MPO, Cytokines and OFR (P < 0.05), but did not reduce CAMs or NFkappaB. NO, either alone or associated, reduced mortality to 0% and abolished BT, significantly decreasing nearly all the variables studied (P < 0.001 for MPO and all Cytokines; P < 0.01 for OFR, and P < 0.05 for CAMs and for NFkappaB). CONCLUSIONS: The exogenous administration of NO before the two sequential insults prevented BT and controlled SIRS peripherally and at both cellular and transcriptional level in a lasting manner. In contrast, antibiotic treatment only exerted its action at peripheral level. The association of both treatments did not provide any important advantages.

Trombofilias y trombosis venosa profunda / Thrombophilia and Jeep vein thrombosis

En esta publicación los autores presentan: primero, una actualización del tema. Después de una introducción, se expone el concepto y las características de las trombofilias, una clasificación de las mismas y se pormenoriza el estudio de la antitrombina III y del sistema de la proteína C, de los factores V y 11, la hiperhomocistenemia y del síndrome antifosfolipido. Asimismo se presentan las asociaciones posibles de diversas situaciones trombofílicas. El segundo apartado destacado son las consideraciones prácticas del tema expuesto. Y finalmente, se expone la experiencia de los autores. (AU)

Consecuencias del precondicionamiento sobre los efectos de la isquemia intestinal en un modelo experimental en ratas / Consequences of preconditioning on the effects of intestinal ischemia in a rat experimental model

Introducción. El precondicionamiento isquémico se define como el efecto protector frente a la isquemia de larga duración experimentado por un órgano si previamente ha sido sometido a cortos períodos de isquemia. El fenómeno no es bien conocido y su duración y el grado de protección que proporciona varía según el tipo de tejido y modelo experimental utilizado. El objetivo de la presente publicación es estudiar el efecto del precondicionamiento en un modelo de isquemia/reperfusión intestinal en la rata evaluando los valores de superóxido dismutasa (SOD), principal enzima detoxificante, frente a los radicales libres del oxígeno, la lesión histológica y la mortalidad.Material y métodos. Se han utilizado ratas adultas, aleatoriamente asignadas a tres grupos: grupo simulado, grupo control en el que se provocó isquemia intestinal y grupo de estudio en el que, antes de la isquemia, los animales fueron sometidos a precondicionamiento. La isquemia se realizó por pinzamiento de la arteria mesentérica en su origen durante 90 min. El precondicionamiento consistió en 5 min de isquemia seguidos de 10 min de reperfusión previos a la isquemia de 90 min. Estudiamos la supervivencia a las 24 y 72 h, los niveles de SOD en la pared intestinal y los cambios morfológicos de la mucosa intestinal.Resultados. En los animales sometidos a precondicionamiento, se evidencian mayores valores de SOD y un incremento de la supervivencia con respecto a los grupos sin precondicionamiento, tanto a las 24 h (el 84 frente al 73 por ciento) como a las 72 h (el 83 frente al 53 por ciento) aunque estas diferencias no resultan significativas. El estudio histológico objetiva un menor grado de lesión de la pared intestinal en los animales sometidos a precondicionamiento (predominio de lesiones de los grados I y II de Chiu).Conclusiones. La realización de cortos períodos de isquemia intestinal provoca aumento de la resistencia del intestino a isquemias posteriores de mayor duración. Este efecto beneficioso se objetiva por un incremento de la supervivencia y un menor grado de lesión histológica del intestino, y se asocia con valores significativamente más elevados de SOD en la pared intestinal. (AU)

Ruptured aneurysm of the deep femoral artery. Case report and historical review.

The exceptional characteristics of the case are put forward and commented on. The patient was a 96-year-old man with an arteriosclerotic aneurysm of the deep femoral artery, which became urgently apparent on bursting. The surgical resolution was simple and satisfactory. Later investigation showed that the aneurysm was unilateral and only in the deep femoral artery. Deep femoral artery continues to be an exceptional location of true arteriosclerotic aneurysms, above all when they arise in an isolated fashion. However, in recent years the available information has changed two substantial aspects: 1) these peripheral aneurysms have the greatest risk of rupture, and 2) on many occasions it is possible, when the superficial femoral artery is permeable, to give simple and satisfactory treatment (exclusion of the aneurysms without revascularization).

Complicaciones de la esplenectomía. Análisis de nuestra casuística / Complications in splenectomy. An analisys of our case history

La esplenectomía es una técnica quirúrgica común en los servicios de cirugía general, y sus indicaciones habituales son médicas, traumáticas e iatrogénicas. Las correspondientes al primer grupo han aumentado a pesar de la mejora de los medios diagnósticos. Las segundas han disminuido con el control en los servicios de cuidados intensivos y el uso de técnicas conservadoras. Se ha revisado la casuística de nuestro hospital, comparándola con la del resto de la bibliografía, y se ha comprobado que las complicaciones postoperatorias fundamentalmente han sido las respiratorias y el absceso subfrénico. Se corrobora, también, cómo esta última ha tenido gran incidencia en las esplenectomías iatrogénicas, siendo un factor esencial en la morbimortalidad, de tal modo que muchos autores llevan a contraindicar la esplenectomía en el transcurso de cirugía contaminada. Nuestros resultados han sido escasos en relación con la infección grave postesplenectomía, al igual que en otras series; por tanto, la profilaxis correcta (inmunoterapia y antibioterapia) ejerce un papel esencial en la disminución de su incidencia (AU)

Participación de los radicales libres del oxígeno en el proceso de cicatrización de las anastomosis cólicas isquémicas / Role of oxygen free radicals in healing of ischemic colonic anastomosis

Introducción. Se estudia la participación de los radicales libres del oxígeno en la cicatrización de las anastomosis cólicas realizadas en condiciones de isquemia. Métodos. Se han utilizado ratas adultas a las que se realizó una anastomosis en colon normal y en colon previamente desvascularizado (anastomosis isquémica).Se han cuantificado las concentraciones de radicales super óxido (medida de los aniones superóxido y de la mieloperoxidasa), las principales enzimas desintoxicantes (superóxido-dismutasa y glutatión-peroxidasa), la producción de colágeno (OH-prolina) y la tensión de rotura. Resultados. En las anastomosis realizadas en condiciones de isquemia se observa una menor síntesis de colágeno y, por consiguiente, su tensión de rotura es significativamente menor. Las concentraciones detectadas de radicales libres de oxígeno (mayores valores de anión superóxido y mayor grado de infiltración leucocitaria) son significativamente más elevadas que en las anastomosis realizadas en condiciones normales. Conclusión. Nuestros resultados demuestran que los radicales libres de oxígeno están aumentados en las anastomosis con deficiente perfusión sanguínea de los extremos anastomosad (AU)

Diarrea crónica por fístula biliocolónica posperitonitis biliar / Chronic diarrhea secondary to biliary-enteric fistula developing after bile peritonitis

La fístula biliocolónica posperitonitis biliar es muy infrecuente. Su sintomatología dominante es la diarrea crónica y las consecuencias derivadas de la misma. El diagnóstico es dificultoso porque las pequeñas comunicaciones entre el árbol biliar y el colon no son fáciles de demostrar. Se comenta la historia clínica de una paciente de 84 años de edad que, tras múltiples exploraciones, fue diagnosticada por colangiografía transparietohepática (CTPH) y la reintervención quirúrgica solucionó la afección. Se aclaran los mecanismos de producción de la fuga, así como la fisiopatología de la esteatorrea. A la luz de la bibliografía se hace hincapié en la conveniencia de la colecistectomía precoz en los casos de colecistitis aguda como medio para evitar ésta y otras complicaciones (AU)

The sialyl Lewis X analogue, CY-1503, down-regulates leucocyte-endothelium interactions and the inflammatory response.

OBJECTIVE: To elucidate mechanisms of protection of ischaemic liver with the sialyl Lewis X analogue CY-1503 by regulation of inflammatory mediators such as oxygen free radicals and cytokines as well as blocking the migration of leucocytes. DESIGN: Laboratory study. SETTING: Teaching hospital, Spain. ANIMALS: 122 male Sprague-Dawley rats divided into four groups: normal (n = 18), sham-operated (n = 28), ischaemic controls (n = 38), and CY-1503 (n = 38). INTERVENTIONS: Warm total hepatic ischaemia for 90 minutes followed by various periods of reperfusion. MAIN OUTCOME MEASURES: Survival, liver histology, liver function, neutrophil infiltration, and free radical and cytokine concentrations. RESULTS: 2/20 ischaemic controls survived, compared with 14/20 given CY-1503. Liver function was better, as was histological appearance judged by the Suzuki score); myeloperoxidase activity was significantly decreased (n = 6 in each group, p<0.01) as were concentrations of free radicals (n = 12 in each group, p<0.05) in the group given CY-1503. CY-1503 had no effect on concentrations of the cytokines tumour necrosis factor-alpha or interleukin 1-alpha. CONCLUSIONS: CY-1503 exerts a protective effect in that it able to down-regulate concentrations of free radicals in our rat model. It is a potent inhibitor of neutrophil migration, but has no effect on cytokine concentrations.

Levels of serum cathepsin L and several glycosidases in patients operated for colorectal cancer.

The activities of several glycosidases and cathepsin L were determined in the blood serum of a control group of ten healthy humans in comparison with a group (group I: 32 subjects) of preoperative colorectal cancer patients (1 week before surgical exeresis) and with another two groups: group II, comprising 18 operated subjects (1 week after surgery), and group III, of 15 operated subjects (4 months after surgery). All subjects were 48-88 years old. Both 'enzyme activity' and 'specific activity' determinations of serum beta-galactosidase, alpha-L-fucosidase and cathepsin L revealed peculiar profiles that differed from one another. Control values differed from those of some stages of the pathological groups, but not of others. These values were compared also with the levels of total, lipid- and glycoprotein-associated serum sialic acid. The usefulness of some assays (especially cathepsin L activity measurement) in the follow-up of the health status of humans operated for colorectal cancer is discussed.

Protective effect of exogenous nitric oxide on the renal function and inflammatory response in a model of ischemia-reperfusion.

BACKGROUND: Tissue subjected to a period of ischemia undergoes morphological and functional damage that increases during the reperfusion phase. The aim of the present work was to assess the possible improvement induced by exogenous administration of nitric oxide (NO) on renal injury and inflammatory reaction in an experimental animal model of renal ischemia-reperfusion (I-R). METHODS: Ischemia was achieved by ligation of the left arteria and vein for 60 min, followed first by contralateral nephrectomy and then reestablishment of blood flow. Molsidomine, used as an NO donor, was administered by systemic injection 30 min before reperfusion. The effect of molsidomine was compared with the effect of hydralazine, a non-NO donor hypotensive agent. RESULTS: Treatment with molsidomine improved the renal dysfunction (increase in plasma creatinine and urea levels) caused by I-R. Moreover, molsidomine blunted the enhanced production of proinflammatory cytokines (tumor necrosis factor [TNF]-alpha and interleukin [IL] 1alpha), the increase in tissular levels of superoxide anions and oxygen free radical scavengers, and the neutrophilic infiltration observed in the ischemic kidney. One hundred percent survival was achieved in the group of animals treated with the NO donor, whereas the groups of animals undergoing I-R that did not receive molsidomine showed a 40% mortality from the second day after reperfusion. CONCLUSIONS: The present work demonstrated that systemic treatment with an NO donor before reperfusion improved renal function and diminished inflammatory responses in a kidney subjected to an I-R process.

Multicriteria decision analysis for determining drug therapy for intermittent claudication.

Drugs of various classes are prescribed for intermittent claudication. However, there is some discrepancy between medical practice and the scientific basis for drug selection. We have developed a quantitative criteria-based decision analysis to evaluate all implications of drug treatment choices for intermittent claudication. Pentoxifylline, buflomedil, naftidrofuryl and ticlopidine were the drugs selected for analysis. The evaluation criteria were 1) therapeutic efficacy, 2) safety, 3) patient acceptance and 4) cost. A review panel of experts determined the relative importance of each criterion by assigning points (or utility values) to each one. The points were 48, 20, 14 and 18, respectively, for criteria 1, 2, 3 and 4. A probability value, or numerical estimate of how well a drug meets a criterion, was assigned to each drug for each of the 4 criteria. The probability value was multiplied by the utility value to determine the score for each drug and criterion. The criteria points for each drug were added for a total score for the drug. The drug with the highest overall score was pentoxifylline, with 69 points out of an ideal score of 100. The rank order for the other drugs was buflomedil, ticlopidine and naftidrofuryl. A sensitive analysis showed that the relative ranking of the drugs remained unchanged over a series of data modifications.

Tacrolimus (FK506) down-regulates free radical tissue levels, serum cytokines, and neutrophil infiltration after severe liver ischemia.

BACKGROUND: Liver ischemia and reperfusion injury is associated with activation of multiple inflammatory pathways, including free radicals, cytokines, and neutrophil-mediated tissue damage among others. Tacrolimus (FK506) has shown important regulatory effects on some inflammatory pathways, such as cytokines, neutrophils, and adhesion molecules. In this study, we explored a new potential protective mechanism for tacrolimus in the liver inflammatory response after ischemia and reperfusion, specifically its effect on liver tissue free radicals. METHODS: Total hepatic ischemia was produced in the rat for 90 min with an extracorporeal portosystemic shunt. Animals (n=96) were divided into four groups: group 1 comprised normal rats for reference values; group 2 comprised sham operated rats; in group 3, ischemic control rats received only the vehicle; and the experimental treatment group, group 4, received tacrolimus at a dose of 0.3 mg/kg, 4 hr before ischemia. Animal survival was followed up to 7 days. Liver function tests were performed and liver tissue free radicals and myeloperoxidase, serum cytokines (interleukin 1, tumor necrosis factor-alpha), and liver histology were measured 4 hr after reperfusion. RESULTS: Seven-day survival was significantly improved from only 20% in the control group to 55% in the tacrolimus group (P<0.01). Liver function tests, histology, and myeloperoxidase tissue values were significantly improved (P<0.05) with tacrolimus pretreatment. Furthermore, a significant (P<0.05) down-regulation of serum cytokines and liver tissue free radicals was observed. CONCLUSIONS: These data indicate a new and different protective mechanism for FK506 in regard to its ability to down-regulate free radical levels in livers subjected to severe ischemia and reperfusion. Tacrolimus, also confirmed to be a potent suppressor of the cytokine response, specifically interleukin 1 and tumor necrosis, decreased neutrophil tissue migration as well.

Sulfo-Lewis(x) diminishes neutrophil infiltration and free radicals with minimal effect on serum cytokines after liver ischemia and reperfusion.

BACKGROUND: Cell adhesion plays a central role in the pathogenesis of neutrophil-induced hepatic injury after ischemia and reperfusion. Sialyl Lewis(x) binds to selectins mediating neutrophil adherence to endothelium, thereby facilitating subsequent migration and tissue damage. AIM: We studied the effect of a novel sulfo-derivative of sialyl Lewis(x), GM-1998, on the liver inflammatory response after ischemia and reperfusion. Specifically, we evaluated its impact on three key inflammatory mediators: neutrophil migration, free radicals, and serum cytokines. MATERIAL AND METHODS: Rats were subjected to total hepatic ischemia for 90 min using an extracorporeal portosystemic shunt to avoid splanchnic congestion. GM-1998 was given at a total dose of 20 mg/kg both prior to and after reperfusion. Liver function tests, liver tissue free radicals, and myeloperoxidase (MPO), serum cytokines (IL-1, TNF-alpha), and liver histology were analyzed 4 hr after reperfusion. Additionally, survival was followed for up to 7 days. RESULTS: Seven-day survival significantly increased from 20% in the control group to 65% in the sulfo-Lewis(x) treated group. Liver function tests and histological damage scores were improved in comparison to controls. We observed significant downregulation of free radicals and neutrophil migration. This compound did not significantly affect serum cytokine levels. CONCLUSIONS: GM-1998 showed a protective effect in an in vivo model of severe liver ischemia and reperfusion by decreasing tissue free radical levels and selectin-mediated neutrophil migration. This protective effect was also reflected in improved liver function tests and histological response leading to better survival. We confirmed the beneficial effect of neutrophil blockade as a key target to prevent damage after the reperfusion phenomenon by using a glycomimetic sulfo-Lewis(x).