Growth, Survival, and Intestinal Health Alterations in Mediterranean Yellowtail (Seriola dumerili) Due to Alternatives to Fishmeal and Fish Oil.

Fishmeal and fish oil substitution in aquafeeds might have adverse effects on fish growth and health, mainly in carnivorous species, such as Mediterranean yellowtail (Seriola dumerili). Mediterranean yellowtail shows great potential as an alternative aquaculture species due to its fast growth and high price on the market, but the need for high-quality protein and fatty acid content in its diets is limiting its production. In order to improve the sustainability of its production, this study was conducted with 360 fish of 35 g to evaluate the effects on fish growth and health. Six diets were used: one control diet without replacement, three with FM replacement (FM66, FM33, and FM0) (33%, 66%, and 100% FM replacement), and two with FO replacement (FO50 and FO0) (50% and 100% FO replacement). The substitution of FM was with vegetable (VM) (corn gluten) and animal (AM) (krill and meat meal) meals. The reductions in FM and FO of up to 33 and 0%, respectively, did not affect the growth and survival of S. dumerili at the intestinal morphology level, except for the anterior intestine regarding the lower villi length and width and the posterior intestine regarding the lower width of the lamina propria. On the other hand, the substitution of fish ingredients in the diet affects liver morphology, indicating alterations in the major diameter of hepatocytes or their nuclei. Finally, diet did not affect the gut microbiota with respect to the control, but significant differences were found in alpha and beta diversity when FO and FM microbiota were compared. A 66% FM replacement and total FO replacement would be possible without causing major alterations in the fish.

Hepatic, Muscle and Intestinal Oxidative Status and Plasmatic Parameters of Greater Amberjack (Seriola dumerili, Risso, 1810) Fed Diets with Fish Oil Replacement and Probiotic Addition.

The present study was conducted to investigate the effects of dietary fish oil replacement with a mixture of vegetable oils and probiotic supplementation on plasma biochemical parameters, oxidative stress, and antioxidant ability of Seriola dumerili. Specimens with an initial weight of 175 g were used. Four feeds were formulated with 0% (FO-100), 75% (FO-25), and 100% (FO-0 and FO-0+ with the addition of Lactobacillus probiotics) substitution of fish oil with a mixture of linseed, sunflower, and palm oils. After 109 days, no significant differences were observed in the activity of antioxidant enzymes in the liver, foregut, and hindgut, only glucose-6-phosphate dehydrogenase activity in the liver was higher in the fish fed the FO-100 diet than in those fed the FO-0 diet. No significant differences were observed in the total, reduced, and oxidized glutathione and the oxidative stress index in the liver. In addition, lipid peroxidation in the liver and red muscle values were higher in the fish fed the FO-100 diet than in the fish fed the FO-0+ diet, however, the foregut of the fish fed the FO-100 diet presented lower values than that of the fish fed the FO replacement diet, with and without probiotics. There were significant differences in cholesterol levels in the FO-100 group; they were significantly higher than those observed with the fish diets without fish oil. To sum up, fish oil can be replaced by up to 25% with vegetable oils in diets for Seriola dumerili juveniles, but total fish oil substitution is not feasible because it causes poor survival. The inclusion of probiotics in the FO-0+ diet had no effects on the parameters measured.

Imágenes en la amiloidosis cardíaca / Imaging in Cardiac Amyloidosis

RESUMEN La amiloidosis es un desorden sistémico producido por el depósito de fibrillas de proteínas insolubles que se pliegan y depositan en el miocardio. Los pacientes con amiloidosis y compromiso cardíaco tienen mayor mortalidad respecto a pacientes sin compromiso cardíaco. Las dos formas de amiloidosis más prevalentes que se asocian con compromiso cardíaco son la amiloidosis AL, por el depósito de las cadenas livianas de las inmunoglobulinas, y la amiloidosis ATTR, por el depósito de la proteína transtiretina (TTR) en forma mutada o senil. Este artículo tiene el objetivo de revisar las diferentes modalidades de imágenes cardíacas (ecocardiografía, resonancia magnética cardiaca, medicina nuclear y tomografía) que permiten determinar la severidad del compromiso cardíaco en pacientes con amiloidosis, el tipo de amiloidosis y su pronóstico. Finalmente, se sugiere un algoritmo diagnóstico para determinar el compromiso cardíaco en la amiloidosis adaptado a las herramientas diagnósticas disponibles localmente, con un enfoque práctico y clínico.

ABSTRACT Cardiac amyloidosis is a systemic disorder caused by the extracellular deposition of fibrils of insoluble proteins that misfold and deposit in the myocardium. Patients with amyloidosis and cardiac involvement have higher mortality rate than those without cardiac involvement. The two most prevalent types are amyloidosis with cardiac involvement are light-chain amyloidosis (AL) due to immunoglobulin light chain deposition and transthyretin amyloidosis (ATTR) due to deposition of mutated or senile forms of the transthyretin (TTR) protein. The aim of this paper is to review the different modalities of cardiac imaging tests (echocardiography, cardiac magnetic resonance imaging, nuclear medicine images and computed tomography scan) that can determine the severity of cardiac involvement in patients with amyloidosis, the type of amyloidosis and its prognosis. Finally, a diagnostic algorithm is proposed to determine cardiac involvement in amyloidosis, tailored to the diagnostic tools locally available with a practical and clinical approach.

Intestinal Explant Cultures from Gilthead Seabream (Sparus aurata, L.) Allowed the Determination of Mucosal Sensitivity to Bacterial Pathogens and the Impact of a Plant Protein Diet.

The interaction between diet and intestinal health has been widely discussed, although in vivo approaches have reported limitations. The intestine explant culture system developed provides an advantage since it reduces the number of experimental fish and increases the time of incubation compared to similar methods, becoming a valuable tool in the study of the interactions between pathogenic bacteria, rearing conditions, or dietary components and fish gut immune response. The objective of this study was to determine the influence of the total substitution of fish meal by plants on the immune intestinal status of seabream using an ex vivo bacterial challenge. For this aim, two growth stages of fish were assayed (12 g): phase I (90 days), up to 68 g, and phase II (305 days), up to 250 g. Additionally, in phase II, the effects of long term and short term exposure (15 days) to a plant protein (PP) diet were determined. PP diet altered the mucosal immune homeostasis, the younger fish being more sensitive, and the intestine from fish fed short-term plant diets showed a higher immune response than with long-term feeding. Vibrio alginolyticus (V. alginolyticus) triggered the highest immune and inflammatory response, while COX-2 expression was significantly induced by Photobacterium damselae subsp. Piscicida (P. damselae subsp. Piscicida), showing a positive high correlation between the pro-inflammatory genes encoding interleukin 1ß (IL1-ß), interleukin 6 (IL-6) and cyclooxygenase 2(COX-2).

Recovery of Fatty Acid Composition in Mediterranean Yellowtail (Seriola dumerili, Risso 1810) fed a Fish-Oil Finishing Diet.

The present study evaluated the effects of wash-out on the fatty acid (FA) composition in the muscles of Mediterranean yellowtail. After 109 days during which fish were fed either a fish oil (FO)-based diet (FO 100) or a diet (FO 0) in which FO was completely substituted by vegetable oils, all fish were subjected to a wash-out with FO 100 diet for 90 days. The FA profile of muscles in fish fed FO 0 diet at the beginning of the experiment reflected that of dietary vegetable oils, rich in linoleic acid (LA), and α-linolenic acid (ALA), and was deficient in AA (arachidonic acid), EPA (eicosapentaenoic acid), and DHA (docosahexaenoic acid). No essential FA were fully restored in fish previously fed FO 0 diet on 45th or 90th day of wash-out. At the end of wash-out, the FA composition showed that AA, EPA, and DHA in the white muscles increased by +33%, +16%, and +43% (p < 0.001), respectively. Similarly, AA and DHA in the red muscles increased by +33% and +41% respectively, while EPA remained similar to fish fed FO 0 diet exclusively. Therefore, a 90-d wash-out can partially improve the FA profile in muscles of Mediterranean yellowtail previously fed vegetable oil-based diets.

Effects of dietary inclusions of red beet and betaine on the acute stress response and muscle lipid peroxidation in rainbow trout.

This study evaluates the effects of red beet (RB) and betaine on rainbow trout submitted to an acute stress challenge. A control diet was compared with four experimental diets in which red beet (14 and 28%) and betaine (0.9 and 1.63%) were incorporated in different concentrations according to a factorial design. Cortisol in plasma and fin, glucose and lactate plasma levels, and malondialdehide (MDA) in muscle were all measured before the stress challenge and 30 min and 6 and 12 h after the stress challenge as parameters to determine the diet effects. RB and betaine had no effect on cortisol, glucose, and MDA basal levels. However, lactate basal levels were significantly lower on fish fed with RB and betaine. Thirty minutes after the stress challenge, there was a significant increase in plasma and fin cortisol, glucose and lactate concentrations, although fish fed with diets containing RB and betaine showed significantly higher plasma cortisol values. MDA values of fish fed with 14% RB and 0.9% betaine were significantly higher than MDA values from fish fed with 28% RB and 1.63% betaine. After 6 and 12 h, plasma and fin cortisol and lactate levels recovered in a similar trend. Glucose plasma levels recovered in almost all groups 12 h after the stress. Also, MDA values recovered basal levels after 6 and 12 h. RB and betaine did not enhance the tolerance to the stress challenge compared to the control group, although the presence of these ingredients had no negative effect on any of the stress indicators.

Allopurinol partially prevents disuse muscle atrophy in mice and humans.

Disuse muscle wasting will likely affect everyone in his or her lifetime in response to pathologies such as joint immobilization, inactivity or bed rest. There are no good therapies to treat it. We previously found that allopurinol, a drug widely used to treat gout, protects muscle damage after exhaustive exercise and results in functional gains in old individuals. Thus, we decided to test its effect in the prevention of soleus muscle atrophy after two weeks of hindlimb unloading in mice, and lower leg immobilization following ankle sprain in humans (EudraCT: 2011-003541-17). Our results show that allopurinol partially protects against muscle atrophy in both mice and humans. The protective effect of allopurinol is similar to that of resistance exercise which is the best-known way to prevent muscle mass loss in disuse human models. We report that allopurinol protects against the loss of muscle mass by inhibiting the expression of ubiquitin ligases. Our results suggest that the ubiquitin-proteasome pathway is an appropriate therapeutic target to inhibit muscle wasting and emphasizes the role of allopurinol as a non-hormonal intervention to treat disuse muscle atrophy.

Red beet and betaine as ingredients in diets of rainbow trout (Oncorhynchus mykiss): effects on growth performance, nutrient retention and flesh quality.

The objective of the study was to evaluate the impact of different concentrations of dietary red beet and betaine on the growth performance and fish flesh quality of rainbow trout. Therefore, a control diet was compared with four diets in which two levels of red beet (14% and 28%) and betaine (0.9% and 1.63%) were incorporated in combination. The study was set up with an average body weight of 69 ± 2.2 g and finished when fish reached commercial weight (175-250 g) after 105 d. The impact of the diets was studied based on the growth performance, biometric indexes, proximal composition, protein and fat retention efficiencies and apparent nutrient digestibility by fish reared on a recirculation system. Further estimates were the effect of red beet and betaine on the flesh proximate composition and quality of the final product (water activity, colour, texture, thiobarbituric acid reactive substances and sensory characteristics). Results showed that inclusion of 14% red beet and 0.9% betaine did not affect growth, nutritive or biometric parameters and nutrient retention when compared with the control diet. However, higher levels of red beet and betaine had negative effects on growth and nutritive parameters. The tested ingredients enhanced quality parameters regardless of the concentration used. After feeding the red beet and betaine, fish flesh showed lower water activity and better textural and colour properties than the control and also a dose-dependent effect on lipid oxidation was observed.

Inteligencia emocional y lesión aterosclerótica coronaria: estudio exploratorio en base a la aplicación del test Trait Meta-Mood Scale / Emotional intelligence and coronary atherosclerosis: exploratory study using the Trait Meta-Mood Scale

Introducción No existen estudios previos que evalúen la inteligencia emocional en adultos asintomáticos con lesiones ateroscleróticas coronarias. ObjetivoEn este trabajo nos proponemos estudiar la inteligencia emocional como rasgo en adultos asintomáticos con y sin lesiones ateroscleróticas coronarias, junto con comparar los datos estadísticos de los mismos. Diseño y método Estudio de corte transversal. Participaron 100 adultos asintomáticos, entre 30 y 80 años, que cumplieron con los criterios de inclusión y exclusión, y que se realizaron una angiotomografía coronaria derivados por su médico tratante. La presencia o ausencia de lesión se determinó utilizando un tomógrafo computarizado multicorte de 64 canales. La inteligencia emocional se evaluó mediante la aplicación del test Trait Meta-Mood Scale. Resultados: La muestra fue constituida por 73 por ciento hombres y 27 por ciento mujeres. 51 por ciento tenía lesión aterosclerótica coronaria, 78 por ciento presentó puntajes inferiores a los valores de referencia tanto para el factor claridad como para el factor reparación emocional. 79 por ciento presentó puntajes superiores a los valores de referencia para el factor atención emocional. Se hallaron asociaciones estadísticamente significativas entre la presencia de lesión aterosclerótica coronaria y cada uno de los tres factores evaluados: atención emocional, Chi-cuadrado: 0,302, p=0,043; claridad emocional, Chi-cuadrado: -0,312, p=0,040; y regulación emocional, Chi-cuadrado: -0,313, p=0,040. Conclusiones: Las personas con lesiones ateroscleróticas coronarias presentaron una tendencia excesiva a centrarse en la experiencia emocional, observando y pensando sobre las propias emociones, así como una baja habilidad para identificar, distinguir y describir las emociones que experimentan. También evidenciaron habilidad disminuida para reducir o eliminar las emociones negativas e incrementar o mantener la intensidad de las emociones positivas.

Introduction There are no prior studies that assess emotional intelligence in asymptomatic adults with coronary atherosclerosis. Aim The purpose of this study is to explore associations between emotional intelligence in asymptomatic adults with and without coronary atherosclerotic lesions. Design and methodCross-sectional design. The sample consisted of 100 asymptomatic 30 to 80 year-old adults that met the inclusion and exclusion criteria and who underwent coronary multislice computed tomography. Coronary atherosclerosis was shown by 64-channel multislice computed tomography. Emotional intelligence was assessed by applying the Trait Meta-Mood Scale. Results The sample was composed of 73 percent men and 27 percent women. Fifty-one percent had coronary atherosclerotic lesions, 78 percent had scores below the reference values for both Clarity and Repair. Seventy-nine percent had scores above the reference values for Attention. Statistically significant associations were found between the presence of coronary atherosclerotic lesion and: a) emotional attention, chi-square: 0.302, p=0.043, b) emotional clarity, chi-square: -0.312, p=0.040, b) emotional regulation, chi-square: -0.313, p=0.040. Conclusions: People with coronary atherosclerotic lesions showed an excessive tendency to focus on their own feelings and higher levels of rumination, together with lower ability to identify, distinguish and describe their emotions. Likewise, they have lower ability to reduce or eliminate negative emotions and to increase or maintain the intensity of positive emotions.

Trastornos de la personalidad y placa aterosclerótica coronaria / Personality Disorders and Atherosclerotic Coronary Plaque

Introducción El sustrato esencial de las patologías cardiovasculares isquémicas, las lesiones ateroscleróticas, se ha estudiado poco en su asociación con los factores psicosociales y en la bibliografía no se encuentran estudios específicos sobre la asociación entre los trastornos de la personalidad siguiendo los criterios diagnósticos internacionales y la presencia de placas ateroscleróticas coronarias. Objetivos Investigar la asociación entre los trastornos de la personalidad y la presencia de placas ateros­cleróticas coronarias, describir la personalidad de las personas con placa y la de las personas sin placa y compararlas estadísticamente. Material y métodos Estudio descriptivo transversal. Participaron 78 personas de entre 40 y 90 años que cumplieron con los criterios de inclusión y exclusión. Para la recolección de datos se utilizaron la coronariografía mediante tomografía computarizada multicorte y se empleó el Cuestionario Salamanca para el screening de los trastornos de la personalidad. Se utilizó el programa SPSS 12.0 para describir y comparar los trastornos de la personalidad de los grupos con placa y sin placa aterosclerótica. Resultados El 77% presentó trastorno de la personalidad y placa. El 23% tenía placa y no presentaba trastorno de la personalidad. La presencia de placa se asoció de manera estadísticamente significativa, a nivel 0,05 bilateral, con: a) el trastorno de personalidad histriónico, rho de Spearman: 0,250, p = 0,027, b) el trastorno de personalidad ansioso o por evitación, rho de Spearman: 0,232, p = 0,041 y c) el número de trastornos de la personalidad, rho de Spearman: 0,286, p = 0,011. Se hallaron diferencias estadísticamente significativas entre el grupo con placa y el grupo sin placa para los trastornos de personalidad histriónico (chi cuadrado: 4,872, p = 0,027) y ansioso o por evitación (chi cuadrado: 4,181, p = 0,041). Conclusión En la muestra estudiada, el grupo con placa se diferenció de manera estadísticamente significativa del grupo sin placa por la presencia del trastorno de personalidad histriónico y por la presencia del trastorno de personalidad ansioso o por evitación.

Background The association between psychosocial factors and atheros­clerotic lesions, the essential substrate of ischemic heart disease, has been poorly studied. No specific studies have been published on the association between personality disorders, according to the international diagnostic criteria, and the presence of atherosclerotic coronary plaques. Objective To investigate the association between personality disorders and the presence of atherosclerotic coronary plaques, and to describe the personality of persons with and without plaques and make statistical comparisons between them. Methods A descriptive cross-sectional study was conducted. Seventy eight subjects between 40 and 90 years were included. All the participants underwent multislice computed tomography coronary angiography and the Salamanca screening test was used to assess personality disorders. SPSS 12.0 statistical package was used to describe and compare the personality disorders of the groups with and without atherosclerotic plaque. Results Personality disorder and plaque were present in 77% of patients; 23% had plaque but not personality disorder. The presence of plaque showed a statistically significant association (two-tailed significance level, p=0.05) with: a) histrionic personality disorder, Spearman rho coefficient: 0.250, sig 0.027, b) anxious or avoidant personality disorder, Spearman rho coefficient: 0,232, sig 0,041, and, c) the number of personality disorders, Spearman rho coefficient: 0.286, sig 0.011. There were statistically significant differences between the group with plaque and the group without plaque in the histrionic personality disorder (chi square: 4.872, sig two-sided significance level: 0.027) and anxious or avoidant personality disorder (chi square: 4.181, two-sided significance level: 0.041). Conclusion Subjects with coronary atherosclerotic plaque presented a significant association with histrionic personality disorder and anxious or avoidant personality disorder compared to subjects without plaque.

Inhibition of xanthine oxidase by allopurinol prevents skeletal muscle atrophy: role of p38 MAPKinase and E3 ubiquitin ligases.

Alterations in muscle play an important role in common diseases and conditions. Reactive oxygen species (ROS) are generated during hindlimb unloading due, at least in part, to the activation of xanthine oxidase (XO). The major aim of this study was to determine the mechanism by which XO activation causes unloading-induced muscle atrophy in rats, and its possible prevention by allopurinol, a well-known inhibitor of this enzyme. For this purpose we studied one of the main redox sensitive signalling cascades involved in skeletal muscle atrophy i.e. p38 MAPKinase, and the expression of two well known muscle specific E3 ubiquitin ligases involved in proteolysis, the Muscle atrophy F-Box (MAFbx; also known as atrogin-1) and Muscle RING (Really Interesting New Gene) Finger-1 (MuRF-1). We found that hindlimb unloading induced a significant increase in XO activity and in the protein expression of the antioxidant enzymes CuZnSOD and Catalase in skeletal muscle. The most relevant new fact reported in this paper is that inhibition of XO with allopurinol, a drug widely used in clinical practice, prevents soleus muscle atrophy by ~20% after hindlimb unloading. This was associated with the inhibition of the p38 MAPK-MAFbx pathway. Our data suggest that XO was involved in the loss of muscle mass via the activation of the p38MAPK-MAFbx pathway in unloaded muscle atrophy. Thus, allopurinol may have clinical benefits to combat skeletal muscle atrophy in bedridden, astronauts, sarcopenic, and cachexic patients.

Glutathione and Bcl-2 targeting facilitates elimination by chemoradiotherapy of human A375 melanoma xenografts overexpressing bcl-xl, bcl-2, and mcl-1.

BACKGROUND: Bcl-2 is believed to contribute to melanoma chemoresistance. However, expression of Bcl-2 proteins may be different among melanomas. Thus correlations among expression of Bcl-2-related proteins and in vivo melanoma progression, and resistance to combination therapies, was investigated. METHODS: Human A375 melanoma was injected s.c. into immunodeficient nude mice. Protein expression was studied in tumor samples obtained by laser microdisection. Transfection of siRNA or ectopic overexpression were applied to manipulate proteins which are up- or down-regulated, preferentially, during melanoma progression. Anti-bcl-2 antisense oligonucleotides and chemoradiotherapy (glutathione-depleting agents, paclitaxel protein-binding particles, daunorubicin, X rays) were administered in combination. RESULTS: In vivo A375 cells down-regulated pro-apoptotic bax expression; and up-regulated anti-apoptotic bcl-2, bcl-xl, and mcl-1, however only Bcl-2 appeared critical for long-term tumor cell survival and progression in vivo. Reduction of Bcl-2, combined with partial therapies, decreased melanoma growth. But only Bcl-2 targeting plus the full combination of chemoradiotherapy eradicated A375 melanoma, and led to long-term survival (> 120 days) without recurrence in 80% of mice. Tumor regression was not due to immune stimulation. Hematology and clinical chemistry data were within accepted clinical toxicities. CONCLUSION: Strategies to target Bcl-2, may increase the effectiveness of antitumor therapies against melanomas overexpressing Bcl-2 and likely other Bcl-2-related antiapoptotic proteins.

Utilidad de la angiotomografía computarizada multidetector en patología aórtica / Usefulness of Multi-Detector Row Computed Tomography Angiography in Aortic Diseases

El propósito de esta revisión es demostrar mediante imágenes la utilidad de la angiotomografía computarizada multidetector (angio-TCMD) en el estudio de la patología aórtica. La elevada morbimortalidad de éstas exige precisión diagnóstica y rapidez al momento de evaluar al paciente con patología conocida o sospecha clínica. Una de las principales ventajas de la angio- TCMD es su carácter de no invasiva y la velocidad con la que se realiza, lo que la convierte en un método ampliamente aceptado por los pacientes. La angio-TCMD es el estándar de referencia para la evaluación de los aneurismas aórticos caracterizando su ubicación en los planos del espacio, extensión y diámetros además de las particulares de la pared. Los síndromes aórticos agudos: el aneurisma disecante, el hematoma intramural y la úlcera arteriosclerótica penetrante son de presentación clínica similar. La angio_TCMD constituye la herramienta de mayor eficacia para confirmar o descartar lesiones. Las múltiples técnicas de visualización y la posibilidad de reconstrucciones multiplanares y tridimensionales facilitan la elección del tratamiento quirúrgico o endovascular.

The goal of the present review is to demonstrate the usefulness of multi-detector row computed tomography (MDCT) angiography in the evaluation of diseases of the aorta. The high morbidity and mortality associated with this condition requires a rapid diagnostic tool with diagnostic accuracy at the moment of evaluating patients with known or clinically suspected disease of the aorta. The non-invasive nature of and the rapid evaluation provided by MDCT angiography are the main advantages of the method that is widely accepted by the patients. MDCT angiography is the reference-standard method for the evaluation of aneurysms of the aorta, describing its location in the spatial planes, extension, diameters and characteristics of the aortic wall. The clinical presentation of the acute aortic syndromes - aortic dissection, intramural hematoma and penetrating aortic ulcer - is similar. MDCT angiography is a diagnostic tool with the greatest efficacy to confirm or rule out aortic lesions. The multiple visualization techniques and the possibility of multiplanar and three-dimensional reconstructions make it easy to choose between surgical or endovascular treatment.

Effect of simultaneous inhibition of TNF-alpha production and xanthine oxidase in experimental acute pancreatitis: the role of mitogen activated protein kinases.

OBJECTIVE: To assess the effects of inhibiting both tumor necrosis factor (TNF)-alpha production and xanthine oxidase activity on the inflammatory response, mitogen-activated protein kinase (MAPK) activation and mortality in necrotizing acute pancreatitis in rats. SUMMARY BACKGROUND DATA: Pancreatic injury triggers 2 major pathways involved in the systemic effects of severe acute pancreatitis: pro-inflammatory cytokines and oxidative stress. METHODS: Pancreatitis was induced by intraductal infusion of 3.5% sodium taurocholate. We examined whether treatment with oxypurinol, a specific inhibitor of xanthine oxidase, and/or pentoxifylline, an inhibitor of TNF-alpha production, affects pancreatic damage, ascites, lung inflammation, and MAPK phosphorylation. RESULTS: Oxypurinol prevented p38 phosphorylation in the pancreas and partially avoided the rise in lung myeloperoxidase activity. Pentoxifylline prevented erk 1/2 and JNK phosphorylation in the pancreas, and it partially reduced ascites and the rise in lung myeloperoxidase activity. Combined treatment with oxypurinol and pentoxifylline almost completely abolished ascites, MAPK phosphorylation in the pancreas, and the increase in lung myeloperoxidase activity. Histology revealed a reduction in pancreatic and lung damage. These changes were associated with a significant improvement of survival. CONCLUSIONS: : Simultaneous inhibition of TNF-alpha production and xanthine oxidase activity greatly reduced local and systemic inflammatory response in acute pancreatitis and decreased mortality rate. These effects were associated with blockade of the 3 major MAPKs.

Ductal carcinoma in situ of the breast: a comparative analysis of histology, nuclear area, ploidy, and neovascularization provides differentiation between low- and high-grade tumors.

Ductal carcinoma in situ (DCIS) is a heterogeneous group of lesions that has been subdivided into three types: well differentiated (grade I), moderately differentiated (grade II), and poorly differentiated (grade III). Forty-five cases of DCIS were analyzed for image analysis: nuclear area, DNA ploidy, and vascularization in order to establish a more precise correlation between the histologic grade and these morphometric parameters. Our results confirm that the mean nuclear area, DNA ploidy, and microvessel density (MVD) progressively increased from DCIS grade I to DCIS grade III. The analysis of the nuclear area in relationship to DCIS grading demonstrated a progressive increase of values between grades I/II to grade III, but these data have no statistical significance. An analysis of DNA ploidy demonstrated significant differences between grades I/III (p < 0.05), but there was no statistical significance between grades I/II, grades II/III, or both (p > 0.005). The analysis of MVD was extremely significant between grades I/III (p < 0.001) and grades II/III (p < 0.001), but between grades I/II, these values showed no significant differences (p > 0.05). Based on this study, it can be concluded that image analysis techniques confirm how DCIS presents morphometric values that increase from DCIS grade I to DCIS grade III and that within this spectrum, DCIS grade III can be identified as a group of tumors presenting a large nuclear area, aneuploid DNA, and abundant vascular neogenesis, confirming that this neoplasm displays more aggressive patterns than the other two types. These criteria should justify a higher rate of tumor progression to DCIS grade III.