Phenotype-specific melanoma uptake of fatty acid from human adipocytes activates AXL and CAV1-dependent ß-catenin nuclear accumulation.

Phenotypic diversity of cancer cells within tumors generated through bi-directional interactions with the tumor microenvironment has emerged as a major driver of disease progression and therapy resistance. Nutrient availability plays a critical role in determining phenotype, but whether specific nutrients elicit different responses on distinct phenotypes is poorly understood. Here we show, using melanoma as a model, that only MITF Low undifferentiated cells, but not MITF High cells, are competent to drive lipolysis in human adipocytes. In contrast to MITF High melanomas, adipocyte-derived free fatty acids are taken up by undifferentiated MITF Low cells via a fatty acid transporter (FATP)-independent mechanism. Importantly, oleic acid (OA), a monounsaturated long chain fatty acid abundant in adipose tissue and lymph, reprograms MITF Low undifferentiated melanoma cells to a highly invasive state by ligand-independent activation of AXL, a receptor tyrosine kinase associated with therapy resistance in a wide range of cancers. AXL activation by OA then drives SRC-dependent formation and nuclear translocation of a ß-catenin-CAV1 complex. The results highlight how a specific nutritional input drives phenotype-specific activation of a pro-metastasis program with implications for FATP-targeted therapies.

Vitamin D induces SIRT1 activation through K610 deacetylation in colon cancer.

Posttranslational modifications of epigenetic modifiers provide a flexible and timely mechanism for rapid adaptations to the dynamic environment of cancer cells. SIRT1 is an NAD+-dependent epigenetic modifier whose activity is classically associated with healthy aging and longevity, but its function in cancer is not well understood. Here, we reveal that 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3, calcitriol), the active metabolite of vitamin D (VD), promotes SIRT1 activation through auto-deacetylation in human colon carcinoma cells, and identify lysine 610 as an essential driver of SIRT1 activity. Remarkably, our data show that the post-translational control of SIRT1 activity mediates the antiproliferative action of 1,25(OH)2D3. This effect is reproduced by the SIRT1 activator SRT1720, suggesting that SIRT1 activators may offer new therapeutic possibilities for colon cancer patients who are VD deficient or unresponsive. Moreover, this might be extrapolated to inflammation and other VD deficiency-associated and highly prevalent diseases in which SIRT1 plays a prominent role.

Plasma lipoproteins in visceral leishmaniasis and their effect on Leishmania-infected macrophages.

This work aimed at investigating the lipid profile of zoonotic visceral leishmaniasis (VL) patients' sera and the effect of lipoproteins on the in vitro production of tumour necrosis factor-alpha (TNF-alpha), interleukin (IL)-6, IL-10 and IL-12 by Leishmania infantum-infected and uninfected macrophages. Lipids were quantified in 26 VL patients' sera and 26 healthy controls from a VL endemic area. The patients' sera had higher triglyceride and very low density lipoprotein (VLDL) levels, and much lower apolipoprotein A1, total cholesterol, low density lipoprotein (LDL) and high density lipoprotein (HDL) levels than the control sera. Lipoprotein fractions were obtained by ultracentrifugation of sera. The addition of LDL and HDL to Leishmania-infected and uninfected macrophages, in physiological concentrations, enhanced the production of IL-6 and IL-10, but not of IL-12. LDL stimulated the production of TNF-alpha only in infected macrophages, whereas HDL stimulated the production of lower amounts of TNF-alpha in both infected and uninfected macrophages. VLDL stimulated only the production of IL-10. It is proposed herein that LDL may influence the development of VL by promoting the production of TNF-alpha by infected macrophages. A decrease in plasma LDL in some VL patients (to 20 mg/mL or less); however, would tend to reduce the production of TNF-alpha and therefore to limit the development of immune-mediated pathology, not withstanding the fact that it would perhaps increase the permissiveness of macrophages to Leishmania growth.

Genetic variability in the severity and outcome of community-acquired pneumonia.

BACKGROUND: Several studies have investigated single nucleotide polymorphisms (SNP) in candidate genes associated with susceptibility, severity or outcome in patients with community-acquired pneumonia (CAP) with conflicting results. METHODS: Multi-centre, prospective observational study. We studied 1162 white Spanish patients with CAP and 1413 controls. Severe forms of sepsis were recorded in 325 patients. Subjects were genotyped for the following polymorphisms: TNF -238 and -308, LTA +252, IL6 -174, IL1RN 86bp variable number of tandem repeats and TNFRSF1B+676 (TNFR2 M196R). RESULTS: No significant differences in genotype or allele frequencies were seen among patients and controls. We did not find any association between TNF, LTA, IL6 and IL1RN polymorphisms with disease severity or outcome. Analysis of 28-day mortality showed a significant difference in the distribution of TNFRSF1B+676 G/T genotypes (p=0.0129). Sequential Kaplan-Meier survival analysis of TNFRSF1B+676 G/T polymorphism showed a protective role of the GT genotype. Cox regression analysis adjusted for age, gender, hospital of origin and comorbidities showed that patients with GT genotypes had lower mortality rates compared to patients with GG or TT genotypes (p=0.02; HR 0.53; 95% CI 0.31-0.90 for 90-day survival; p=0.01; HR 0.41; 95% CI 0.21-0.81 for 28-day survival and p=0.049; HR 0.48; 95% CI 0.23-0.997 for 15-day survival). CONCLUSIONS: Our study does not support a role for the controversial studied polymorphisms of the TNF, LTA, IL6 and IL1RN genes in the susceptibility or outcome of CAP. A protective role of heterozygosity for the functionally relevant TNFRSF1B+676 polymorphism in the outcome of CAP was observed.

Retention of arsenate using genetically modified coryneform bacteria and determination of arsenic in solid samples by ICP-MS.

A novel method for the retention of arsenate [As(V)] combining time-controlled solid-phase extraction with living bacterial biomass is presented. As(V) retention was carried out by exposing the extractant, consisting of a living double-mutant of Corynebacterium glutamicum strain ArsC1-C2, to the sample for a retention time of 1-7min, before the arsenic distribution equilibrium between the sample solution and the extractant was established. The amount of As(V) retained in the biomass was measured by inductively coupled plasma-mass spectrometry (ICP-MS) after the sample had been treated with nitric acid. A theoretical model of the retention process was developed to describe the experimental retention-time profiles obtained with the bacterial cells. This relationship provided a feasible quantification of the retention process before steady-state was reached, providing that the agitation conditions and the retention time had been controlled. An analytical procedure for the retention/quantification of As(V) was then developed; the detection limit was 0.1 ng As(V)mL(-1) and the relative standard deviation 2.4-3.0%. The maximum effective retention capacity for As(V) was about 12.5mgAs(g biomass)(-1). The developed procedure was applied to the determination of total arsenic in coal fly ash, using a sample that had undergone oxidative pre-treatment.

Efeito do nível de ácido linoléico na ração de matrizes pesadas sobre o peso, composição e eclosão dos ovos / Effect of linoleic acid level in the diets on the weight, composition and eclodibility of broiler breeders eggs

Avaliaram-se os efeitos dos níveis de ácido linoléico na dieta de matrizes pesadas, de 27 a 40 semanas de idade, sobre o peso e composição dos ovos, porcentagem de eclosão, peso do pinto, porcentagem de saco vitelino em relação ao peso do pinto e composição de ácidos graxos da gema. Os tratamentos foram definidos pelo nível de ácido linoléico na dieta. O peso dos ovos e a composição de ácidos linoléico na gema foram mais altos com a inclusão de 1,93 por cento de ácido linoléico que a de 1,48 por cento (59,5g vs 59,0g e 19,5 por cento vs 15,5 por cento, respectivamente). Não houve diferença entre os tratamentos quanto às porcentagens de gema, albúmen, casca, saco vitelino, eclosão e peso do pinto.

The effect of diet linoleic acid level on egg weight, egg composition, hatchability, chick weight, yolk sac percentage relative to chick weight and yolk fatty acid composition of broiler breeders Ross 305, from 27 to 40 weeks of age, were evaluated using two diets with two levels of linoleic acid. Egg weight and linoleic acid yolk composition were higher for diet with 1.93 percent of linoleic acid than for diet with 1.48 percent (59.5g vs 59.0g and 19.5 percent vs 15.5 percent, respectively). No linoleic acid effects on yolk, albumen, egg shell, yolk sac percentage and hatchability and chick weight were observed.

Nutritional determinants of plasma total homocysteine distribution in the Canary Islands.

OBJECTIVE: We sought to define plasma homocysteine reference values in healthy individuals in the Canary Islands and to determine its relations to folate and vitamin B12 intakes and concentrations. DESIGN: Cross-sectional study. SETTING: Population-based representative sample of 557 participants, aged 18-65 years, from the Canary Islands Nutrition Survey (ENCA). SUBJECTS: All participants completed two 24-h dietary recalls and a general questionnaire collecting socio-demographic and health-related lifestyle information. INTERVENTIONS: Plasma homocysteine and serum vitamin B12 levels were measured by immunoassay, whereas folate levels through an automated ionic capturing method. RESULTS: Median plasma homocysteine was 11.9 micromol/l, higher in men (13.1 micromol/l) than in women (10.9 micromol/l) (P<0.001) and positively associated with age in both sexes (P<0.001). The prevalence of hyperhomocysteinaemia (> or = 15 micromol/l), 21.4%, was also greater in men (32.2%) than in women (13.4%). There were significant negative correlations between plasma homocysteine and serum (r=-0.32, P<0.001) and erythrocyte (r=-0.26, P<0.001) folate, as well as serum vitamin B12 (r=-0.28, P<0.001) concentrations. When divided in quartiles of vitamin intakes or concentrations, men with the lowest vitamin B12 and folate serum values had significantly higher plasma homocysteine concentrations than those in the other three quartiles. In women, hyperhomocysteinaemia was higher in the lowest quartiles of folate intake and serum and erythrocyte folate concentrations. CONCLUSIONS: These data provide further evidence that hyperhomocysteinaemia is a sensitive marker of inadequate folate and vitamin B12 status, allowing for the identification of those with greatest need for nutritional interventions.

Efeitos das condições ambientais no período entre a postura e o armazenamento de ovos de matrizes pesadas sobre o rendimento de incubação / Effect on time between oviposition and the beginning of cool storage on hatchability of broiler breeder eggs

Avaliou-se o efeito das condições ambientais no período entre a postura e o armazenamento de ovos sobre o rendimento de incubação de 2.742 ovos de matrizes pesadas da linhagem Ross com 31 semanas de idade. Os tratamentos foram definidos pelo período de permanência dos ovos sob temperatura ambiente do galpão antes do armazenamento. Para cada tratamento foram utilizados 860 ovos, distribuídos em 10 repetições de 86 ovos cada. No tratamento A, os ovos foram enviados para a sala fria imediatamente após a coleta; no B, foram enviados para a sala fria após cinco horas de permanência no galpão; e, no C, permaneceram no galpão por 10 horas, antes de serem enviados para a sala fria. As condições ambientais da sala fria foram: temperatura 18,2 a 21,0 °C e umidade relativa do ar de 72,8 a 76,8 por cento. O período de armazenamento dos ovos foi de quatro dias. A mortalidade embrionária no tratamento A foi maior que no tratamento B (P<0,05). A eclosão dos ovos do tratamento B foi maior que aquela do tratamento A (P<0,05). O peso dos pintos do tratamento A foi maior que aqueles do tratamento C (P<0,05). O melhor rendimento de incubação foi obtido quando os ovos foram resfriados cinco horas após a postura.

The effect on hatchability of time post-oviposition until initiation of cool storage was examined using 2,742 eggs from 31-week-old Ross hens. Treatments were defined by the length of time that eggs remained at breeder house temperature, prior to cool storage. In treatments A, B and C, respectively, eggs were taken to the cooling room immediately after collection, after 5 hours in the aviary or after 10 hours in the aviary. From each treatment, 860 eggs were distributed into 10 replicates of 86 eggs each and stored for 4 days at 18.2 - 21.0°C and 75 percent humidity. After cool storage, they were incubated. Embryo mortality in treatment A was higher than in B (P<0.05). The hatchability of eggs of treatment B was higher (P<0.05) than that of treatment A. Average chick weight at hatching was higher for treatment A than for treatment C (P<0.05). Eggs that were cooled beginning five hours after oviposition produced the highest incubation yield.

Rendimento, composição e teor de ácidos graxos da carcaça de frangos de corte alimentados com diferentes fontes lipídicas / Carcass yield, composition and fat acid percentage of carcass for broiler fed on different lipid source diets

Avaliou-se o efeito de diferentes fontes de lipídios da dieta (óleo degomado de soja, óleo de vísceras de aves, óleo ácido de soja, mistura de 50 por cento de óleo de soja e 50 por cento de óleo de vísceras e mistura de 50 por cento de óleo de soja e 50 por cento de óleo ácido de soja) sobre rendimento, composição de peito, coxa e carcaça inteira e perfil de ácidos graxos da carcaça inteira de frangos de corte. O delineamento experimental foi o inteiramente ao acaso, com cinco tratamentos e seis repetições de uma ave cada. Não houve diferenças entre os tratamentos (P>0,05) para rendimentos de carcaça e cortes, composição de proteína bruta, umidade e extrato etéreo da carcaça inteira e da musculatura da coxa e do peito. As aves alimentadas com dietas com óleo de vísceras apresentaram maior percentual de ácidos graxos monoinsaturados na carcaça do que as alimentadas com dietas contendo as demais fontes lipídicas. A deposição de ácidos graxos poliinsaturados foi influenciada pela fonte lipídica das dietas. O perfil de ácidos graxos da carcaça inteira de frangos de corte foi influenciado pela fonte lipídica da dieta.

A completely randomized design, with six replicates of one bird per experimental unit was used to evaluate the effect of different fat sources of diets (soybean oil, poultry fat, acidulated soybean oil soapstock and a mix of soybean oil plus poultry fat and soybean oil plus acidulated soybean oil soapstock) on carcass yield, composition of the breast, thigh and whole chicken and fatty acid profile of the whole carcass of broilers. No effects of fat source on carcass yield and cuts, composition of crude protein, humidity and ether extract of the whole chicken, whole leg and breast were observed (P>0,05). The birds fed on poultry fat diet showed a higher percentage of monounsaturated fatty acid on the carcass than birds fed on diets with the others fat sources. The deposition of polyunsaturated fatty acids was influenced by fat source added to the diet. The fatty acid profile of the whole carcass of broilers was influenced by the fat source added to the diets.

Efeito de fontes lipídicas sobre o desempenho de frangos de corte / Effect of lipid sources of diets on broiler performance

Avaliou-se O efeito de fontes lipídicas (óleo degomado de soja, óleo de vísceras de aves, óleo ácido de soja, mistura de 50% de óleo de soja e 50% de óleo de vísceras e mistura de 50% de óleo de soja e 50% de óleo ácido de soja) adicionadas às rações sobre o desempenho de frangos de corte, machos, da linhagem Ross. Os tratamentos foram definidos de acordo com a fonte de lipídio, e o período de criação foi de 1 a 45 dias de idade. As rações, para cada fase de criação, foram isonutritivas. O delineamento experimental foi o inteiramente ao acaso, com cinco tratamentos e seis repetições com 30 aves cada. As aves que receberam óleo de soja ganharam mais peso quando comparadas com as que receberam óleo ácido de soja (P<0,05). O consumo de ração das aves alimentadas com óleo de soja foi maior em relação ao das alimentadas com rações contendo óleo ácido de soja e mistura de óleo de soja com óleo ácido de soja. Quanto à conversão alimentar e à viabilidade, não foram observadas diferenças significativas entre os tratamentos (P>0,05). A utilização do óleo de soja nas rações melhorou o desempenho de frangos de corte quando comparado com o uso do óleo ácido de soja.

Comparison of six methods for the extraction of lipids from serum in terms of effectiveness and protein preservation.

The present work compares six biochemical methods for extraction of lipids from human serum. Although some organic solvents were good lipid extractors, they precipitated most of the total proteins and albumin. On the other hand, methodologies using Triton X-114 and silica were efficient for extraction of lipids, while sparing the protein fraction.

La regresión logística: una herramienta versátil / Logistic regression: a valuable tool

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Rentabilidad de la información de la alfa fetoproteí na (AFP). Utilización de bases de datos relacionales / Profitabldity of the information of alpha fetoprotein (AFP). Utilization of data base related with

El carcinoma hepatocelular (CHC) es el más frecuente de los cánceres primitivos de hígado y desde su descubrimiento, la alfa fetoproteína (AFP) ha sido el marcador de elección para su diagnóstico y seguimiento. En base a obtener información valiosa sobre la rentabilidad diagnóstica del marcador, en cuanto a sus niveles y circunstancias de comorbilidad, se realizó un estudio de tipo retrospectivo en el área de referencia del Hospital Nuestra Señora del Pino de Las Palmas de Gran Canaria. Para ello se utilizaron los datos del laboratorio, exportados en un fichero en código ASCII, e implementados con datos demográficos y clínicos obtenidos del fichero maestro de pacientes del Hospital.Se realizaron 346 determinaciones a 159 pacientes. De ellos, 11 presentaban CHC (6 asociados con cirrosis y 4 con hepatitis), 75 cirrosis hepática (4 asociados con hepatitis), 64 presentaban otros procesos tumorales, 2 cáncer secundario de hígado y 7 otros diagnósticos. El 45 por ciento de los casos de CHC tenían niveles de AFP > 50 ng/ml y el 36.5 por ciento AFP > 500 ng/ml, frente al 5.2 por ciento y 1.3 por ciento respectivamente para los casos de cirrosis hepática. La utilización de bases de datos relacionales constituye un método eficaz, rápido y rentable en términos económicos para obtener información sobre problemas clínicos seleccionados. Abreviaturas: CHC, carcinoma hepatocelular; AFP, alfa fetoproteína; VHB, virus de la hepatitis B; VHC, virus de la hepatitis C; CH, cirrosis hepática; CEA, antígeno carcinoembrionario. (AU)

[Epidemiologic study of infection by hepatitis C virus in a hemodialysis unit]. / Estudio epidemiológico de la infección por el virus de la hepatitis C en una Unidad de Hemodiálisis.

OBJECTIVE: To analyze the prevalence of infection, the frequency of HCV genotypes and the epidemiology characteristics among the patients in hemodialysis treatment in one 25 years old hospital hemodialysis center and one 15 years old secondary unit by a transversal cross-section study in 1998. PATIENTS AND METHODS: 171 hemodialyzed-patients were studied. Patients sera were analyzed by the presence of HCV antibodies anti-VHC by a enzymoimmunoassay (Abbott Cientifica) and the presence of antibodies was confirmed by a line immunoassay (Inno-LIA HCV AbIII) and by the presence of VHC-RNA by reverse transcriptase PCR (Cobas Amplicor HCV). Genotypes were determinate by reverse hybridization (Inno-LIA HCV III). RESULTS: Fifty (29.2%) of the patients were HCV antibody positive. Forty-five (26.3%) were HCV-RNA positive, all of them with antibodies positive. The distribution of genotypes was: 1b, 34 (75.5%); 4f, 4 (8.9%); 1a, 3 (6.7%); 1, 3 (6.7%) and 1 case could not be typed (2.2%). In 14 patients (28.0%), seroconversions were documented Twenty-one patients (42.0%) were diagnosed when the routine tests were available and 15 patients (30.0%) were diagnosed pre-dialysis. The multivariate analysis showed that the risk of HCV infection was greater for patients who had been more 8 years on dialysis (OR: 6.22; 95% CI: 1.24-31.07). CONCLUSIONS: Data presented indicate that the prevalence of HCV infections in our hemodialysis units and the number of seroconversions were high and the HCV subtype 1b was more frequent; because of this, the screening by both serological and molecular methods is necessary, at least twice a year, to identify all the infected patients. Besides, we think that is necessary to increase the control of the completion of the Universal Precautions.

[The Internet as a solution facilitating the identification of patients with a suspected acute myocardial infarct]. / A Internet como solução facilitadora da identificação de doentes com suspeita de enfarte agudo do miocárdio.

The current steps for diagnosing heart disease are very time consuming, delaying the correct identification of the problem, therefore, delaying the right treatment. In this study we have developed an experimental method using e-mail in order to identify patients with "rule out myocardial" condition and reduce the time lag for thrombolysis or coronary angioplasty in this clinical setting. Three different locations linked to the Internet by ISDN lines were used. Each line was connected with a computer. A pager and a dedicated phone line were also used. The following steps were performed for each situation: filling out of a questionnaire, ECG recording, questionnaire mailing and ECG by e-mail as attachment, pager warning that an urgent cardiology consultation was requested, including the doctor and patient's phone number, time to open the message and reply by e-mail, phone call for additional comments. A total of 24 attempts of interactive communication were performed. In 22 of those, an answer was obtained in less than 30 minutes. Two failures were recorded. One was due to a delay in the pager message, which did not arrive within the first hour; the second was due to a computer break down. This report shows that it is possible to establish a fast communication between the out patient clinic and the hospital (less than 30 minutes in most cases) at a very low cost and in a simple manner.

[The digital image archive--its clinical applications and importance in cardiology consulting by telemedicine]. / Arquivo digital de imagens--aplicações clínicas e sua importância na consultoria cardiológica por telemedicina.

The revolution in digital technology is rapidly changing the world of telecommunications. Its applications to Medicine, and in particular to Cardiology, offer enormous benefits since communication is an essential part of medical practice. The need to improve the management of medical information is critical because of the explosion of medical knowledge, and the need to provide comprehensive documentation on patient care. The availability of a network offers many possibilities for clinical, research and teaching activities. Relevant, up-to-date scientific information is instantly available for analysis and interaction. The authors review the issue of digital communications as well as its potential application to Telemedicine, and present their preliminary experience with digital analysis and storage of echocardiographic images.

[Incessant atrial tachycardia and peripartum cardiomyopathy--a therapeutic challenge]. / Taquicardia auricular incessante e miocardiopatia peripartum--um desafio terapêutico.

Peripartum cardiomyopathy is an uncommon cause of heart failure but with serious prognosis. We report the case of a patient with peripartum cardiomyopathy presenting acute heart failure (severe biventricular systolic failure) and incessant atrial tachycardia, a rare arrhythmia difficult to control, that was responsible for cardiogenic shock, fetus death and multiple organ failure: renal failure (hemodialysis during 17 days), respiratory and hepatic failure and ischemic acute cholecystitis (treated surgically). After emergency cesarean section, heart rate control was obtained only after administering verapamil. Progressive clinical improvement with total recovery of hepatic and renal functions followed under treatment with vigorous multiple organ support. Six months after referral, the patients is doing well with normal daily life controlled with conventional therapy for heart failure, in stable sinus rhythm. Echocardiography shows a dilated left ventricle with partial resolution of systolic dysfunction rhythm. Echocardiography shows a dilated left ventricle with partial resolution of systolic dysfunction. The use of verapamil in severe biventricular systolic failure is discussed.