Alberto Gómez-Alonso

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.

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.

Evaluation of Multiparameter Flow Cytometry for the Detection of Breast Cancer Tumor Cells in Blood Samples

We comparatively evaluated different cytokeratin (CK) reagents analyzed by flow cytometry (FCM) for the identification of the best combination of DNA/CK staining for detecting minimal numbers of breast cancer cells in peripheral blood (PB). In 59 primary breast cancer tumors, we comparatively analyzed the reactivity for up to 6 different anti-CK reagents using multiparameter FCM: anti-CK7, anti-CK20, anti-pan-CK, anti-CK8/CK18, anti-CK8, and anti-CK18. Afterward, dilutional experiments of Michigan Cancer Foundation (MCF)7 breast cancer cells in PB were performed, and the sensitivity of a DNA/CK18 staining was evaluated. Our results showed that anti-CK18 reagents were those providing the brightest and more sensitive staining for primary breast cancer tumor cells by FCM. Dilutional experiments of MCF cells in PB showed that the DNA/anti-CK18 double staining was highly specific for the identification of epithelial cells; its sensitivity ranged between 10(-6) and 10(-7) (detection of 1 tumor cell among 10(6) to 10(7) nucleated blood cells). Combined assessment of DNA cell contents and reactivity for CK18 by FCM is a sensitive method for the specific identification of breast cancer cells in PB.

Postoperative Evolution of Inflammatory Response in a Model of Suprarenal Aortic Cross-clamping with and without Hemorrhagic Shock. Systemic and Local Reactions

Surgery of the abdominal aorta generates a systemic inflammatory response (SIR), a source of operative morbidity-mortality. In the present work we attempted to evaluate the evolution of SIR in an experimental model that simulates elective and urgent surgery on the abdominal aorta. Fifteen mini-pigs divided into three groups were used. The animals were subjected to suprarenal aortic/iliac clamping and bypass with a Dacron-collagen prosthetic graft. Groups were as follows: (1) sham (only aortic dissection); (2) clamping and bypass; (3) hemorrhage of 40%, pre-clamping, and bypass. Determinations included (1) tumor necrosis factor-alpha (TNF-α) interleukin (IL)-1β, IL-6, IL-10, interferon-gamma; (2) myeloperoxidase (MPO), superoxide anion (SOA), superoxide dismutase (SOD), and malondialdehyde (MDA); (3) nitrites; (4) iNOS, (5) cell adhesion molecules (ICAM-1, VCAM-1) at 24 hours, 48 hours, and on day 7; and (6) NFκB at 48 hours. Our results point to an increase in all inflammatory variables, corroborated by their molecular regulators such as the expression of CAMs, iNOS, and NFκB. The alterations tended to normalize by day 7, after reperfusion. The results point to the great importance of SIR at all levels (molecular, nuclear, cellular, and systemic) in situations such as elective and urgent abdominal aorta surgery and the role that control of this response could represent for the future of vascular surgery.

Numerical abnormalities of chromosomes 17 and 18 in sporadic colorectal cancer: Incidence and correlation with clinical and biological findings and the prognosis of the disease

In recent years important information has accumulated on the genetic alterations present in colorectal tumors. However, thus far few studies have analyzed the impact of numerical abnormalities of chromosomes 17 and 18, which carry the p53 and DCC plus SHAD4/DPC4 genes involved in colorectal cancer, on the clinical and biological behaviors of the disease.

Empleo de los documentos de consentimiento informado por los servicios de cirugía españoles

Resumen Objetivo Conocer la opinion de los cirujanos sobre el uso de los documentos de consentimiento informado (CI) y la utilizacion e implantacion de los documentos editados por la Asociacion Espanola de Cirujanos (AEC). Metodo Se envio una encuesta a los jefes de servicio de cirugia (anexo I) y se realizo un analisis descriptivo de los resultados Resultado Un total de 91 encuestas. Usan documento de CI el 98,9%, siendo especifico en el 75,82%. Un total de 23 (27,27%) hospitales son de nivel I, 35 (38,46%) de nivel II y 30 (32,96%) de nivel III. El numero medio (media [DE]) de consentimientos es mayor en los hospitales de nivel I (28,78 [14,15]), que en los de nivel II (27,36 [13,9]) y en los de nivel III (26,78 [15,72]). El 92% conoce los documentos de CI de la AEC. El 69,23% los usa. La puntuacion media (DE) de los documentos de CI de la AEC es 7,84 (1,35). Conclusiones Esta muy extendido el uso de documentos de CI en los hospitales espanoles, sobre todo en los hospitales de menor nivel. Donde se usan documentos especificos el numero de procedimientos que tiene documento de CI es muy alto. La aceptacion de los documentos realizados por la asociacion ha sido muy buena y su uso muy extendido.

Open and Endovascular Treatment for Pseudoaneurysms of the Superior Mesenteric Artery

BACKGROUND Pseudoaneurysms of the superior mesenteric artery are rare, and their natural history is characterized by their tendency to rupture, thereby leading to a high mortality rate. Compared with classic surgical techniques (open), in recent years the possibility of endovascular treatment has increased. RESULTS We report the cases of two patients with a pseudoaneurysm of the superior mesenteric artery. Each case was successfully treated in a different way: open and endovascular surgery. CONCLUSION Despite the advantages (less risk for the patient) and good results obtained with endovascular surgery, this cannot completely replace open surgery. The choice of the most appropriate therapeutic option for pseudoaneurysms of the superior mesenteric artery depends on the state of the patient and the characteristics of the lesion. Open and endovascular surgical techniques are complementary, not mutually exclusive, techniques.

P- and E-selectin blockade can control bacterial translocation and modulate systemic inflammatory response.

Bacterial translocation is an important phenomenon in clinical medicine and leads to an increase in patient morbidity and mortality by multiple organ failure. The selectin family plays an important role in the pathogenesis of inflammation, causing an increase in leukocyte-endothelium interactions and inducing a greater leukocytes migration. This study considered the effect of a sulfo derivative of Sialyl-Lewis(X), GM 1998-016, that will block the P- and E-selectins interaction with a ligand, the Sialyl-Lewis(X), valuing the modulation of the systemic inflammatory response and the induced translocation. Seventy-five Wistar male rats were injected intraperitoneally with Zymosan A and treated with different doses of GM 1998-016 according to study groups. Measurements of values of qualitative and quantitative microbiology, neutrophil infiltration (myeloperoxidase), oxygen free radicals (superoxide anion, superoxide dismutase, catalase, and gluthatione peroxidase), and cytokines (tumor necrosis factor-alpha and interleukin-1beta) were taken at different times after Zymosan administration. A significant decrease of bacterial translocation, both local (MLN) and systemic (p < .05), was observed, with a decrease in the neutrophil infiltration (p < .001), the oxygen free radicals production (p < .01) and the studied cytokines (p < .01). In conclusion, GM 1998-016 showed a protective effect in an in vivo experimental model of bacterial translocation, downregulating the inflammatory response and the leukocyte-endothelium interactions.

Microorganismos y cáncer: evidencias científicas y nuevas hipótesis

Microorganism involvement in cancer has been known for over a century, and different types of parasites, bacteria and viruses have been associated with oncogenic processes. Among the bacteria, the first recognised was Helicobacter pylori which causes gastric cancer and might be related to extra-gastric cancer in humans. Helicobacter hepaticus has been associated with liver cancers using animal models. Other bacteria, such as Chlamydia psitacii, Borrelia burgdorferi and Streptococcus bovis, have been associated with ocular, skin and colorectal cancers, respectively. Also, a commensal bacterium in the human intestine, Bacteroides fragilis, has been linked, very recently, with colorectal cancer using animal models.

Microorganisms and cancer: Scientific evidence and new hypotheses

Microorganism involvement in cancer has been known for over a century, and different types of parasites, bacteria and viruses have been associated with oncogenic processes. Among the bacteria, the first recognised was Helicobacter pylori which causes gastric cancer and might be related to extra-gastric cancer in humans. Helicobacter hepaticus has been associated with liver cancers using animal models. Other bacteria such as, Chlamydia psitacii, Borrelia burgdorferi and Streptococcus bovis have been associated with ocular, skin and colorectal cancers, respectively. Also, a commensal bacterium in the human intestine, Bacteroides fragilis, has been linked, very recently, with colorectal cancer using animal models.