The struggle of neglected scientific groups: ten years of NeTropica efforts to promote research in tropical diseases in Central America

artículo (arbitrado) -- Universidad de Costa Rica, 2011The general strategy used by high-income countries to address global health challenges in low- and middle-income countries (LMICs) relies heavily on short-term strategies designed to diminish the burden of diseases afflicting the populations of those countries. Thanks to the support and funding of international agencies, in many cases these initiatives have resulted in health improvements. However, in order to have a sustainable impact on the public health of LMICs, “vibrant local scientific communities” need to be implemented in parallel efforts [1]. In this article we describe 10 years of activities of the Network for Research and Training in Tropical Diseases in Central America (NeTropica), aimed to develop a competitive Central American scientific community in the field of tropical diseases, with the assistance of the Swedish International Development Cooperation Agency (SIDA) and the participation of the public universities of Central America (CA).Universidad de Costa RicaUCR::Vicerrectoría de Docencia::Salud::Facultad de Microbiologí

Índices bibliométricos y revistas de ‘corriente central’: implicaciones para el desarrollo de las ciencias naturales en Costa Rica

Dada esta amplia variación en la calidad de las publicaciones en ciencias naturales, es esencial para la comunidad científica tener una perspectiva clara de dicha heterogeneidad y de sus implicaciones en la generación y transmisión del conocimiento. La pregunta obvia entonces es: ¿cómo identificar las revistas con mayor impacto y pertinencia en las diversas ramas de las ciencias naturales?UCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Instituto Clodomiro Picado (ICP

Neurobrucellosis in Stranded Dolphins, Costa Rica

Ten striped dolphins, Stenella coeruleoalba, stranded along the Costa Rican Pacific coast, had meningoencephalitis and antibodies against Brucella spp. Brucella ceti was isolated from cerebrospinal fluid of 6 dolphins and 1 fetus. S. coeruleoalba constitutes a highly susceptible host and a potential reservoir for B. ceti transmission

The Haemophilus ducreyi cytolethal distending toxin induces DNA double-strand breaks and promotes ATM-dependent activation of RhoA

Artículo científico -- Universidad de Costa Rica. Instituto de Investigaciones en Salud, 2003. Este documento es privado debido a limitaciones de derechos de autor.Among bacterial protein toxins, the cytolethal distending toxins (CDTs) are unique in their ability to activate the DNA damage checkpoint responses, causing cell cycle arrest or apoptosis in intoxicated cells. We provide direct evidence that natural intoxication of cells with the Haemophilus ducreyi CDT (HdCDT) holotoxin induces DNA double-strand breaks similarly to ionizing radiation. Upon DNA damage, epithelial cells and fibroblasts promote the formation of actin stress fibres via activation of the small GTPase RhoA. This phenomenon is not toxin specific, but is part of the ATM-induced cellular responses to genotoxic stresses, including ionizing radiation. Activation of RhoA is associated with prolonged cell survival, as HdCDT-treated epithelial cells expressing a dominant-negative form of RhoA detach and consequently die faster than cells expressing a functional RhoA. Our data highlight several novel aspects of CDT biology: (i) we show that a member of the CDT family causes DNA double-strand breaks in naturally intoxicated cells, acting as a true genotoxic agent; and (ii) we disclose the existence of a novel signalling pathway for intracellularly triggered activation of the RhoA GTPase via the ATM kinase in response to DNA damage, possibly required to prolong cell survival.Universidad de Costa Rica. Instituto de Investigaciones en SaludUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Instituto de Investigaciones en Salud (INISA

Obligatory amino acid exchange via systems b0,+ like and y+L-like. A tertiary active transport mechanism for renal re-absorption of cystine and diabsic amino acids

Mutations in the rBAT gene cause type I cystinuria, a common inherited aminoaciduria of cystine and dibasic amino acids due to their defective renal and intestinal reabsorption (Calonge, M. J., Gasparini, P., Chillarón, J., Chillón, M., Gallucci, M., Rousaud, F., Zelante, L., Testar, X., Dallapiccola, B., Di Silverio, F., Barceló, P., Estivill, X., Zorzano, A., Nunes, V., and Palacín, M. (1994) Nat. Genet. 6, 420-426; Calonge, M. J., Volipini, V., Bisceglia, L., Rousaud, F., De Sanctis, L., Beccia, E., Zelante, L., Testar, X., Zorzano, A., Estivill, X., Gasparini, P., Nunes, V., and Palacín, M.(1995) Proc. Natl. Acad. Sci. U. S. A. 92, 9667-9671). One important question that remains to be clarified is how the apparently non-concentrative system bo,+-like, associated with rBAT expression, participates in the active renal reabsorption of these amino acids. Several studies have demonstrated exchange of amino acids induced by rBAT in Xenopus oocytes. Here we offer evidence that system bo,+-like is an obligatory amino acid exchanger in oocytes and in the 'renal proximal tubular' cell line OK. System bo, +-like showed a 1:1 stoichiometry of exchange, and the hetero-exchange dibasic (inward) with neutral (outward) amino acids were favored in oocytes. Obligatory exchange of amino acids via system bo,+-like fully explained the amino acid-induced current in rBAT-injected oocytes. Exchange via system bo,+-like is coupled enough to ensure a specific accumulation of substrates until the complete replacement of the internal oocyte substrates. Due to structural and functional analogies of the cell surface antigen 4F2hc to rBAT, we tested for amino acid exchange via system y+L-like. 4F2hc-injected oocytes accumulated substrates to a level higher than CAT1-injected oocytes (i.e. oocytes expressing system y+) and showed exchange of amino acids with the substrate specificity of system y+L and L-leucine-induced outward currents in the absence of extracellular sodium. In contrast to L-arginine, system y+L-like did not mediate measurable L-leucine efflux from the oocyte. We propose a role of systems bo,+-like and y+L-like in the renal reabsorption of cystine and dibasic amino acids that is based on their active tertiary transport mechanism and on the apical and basolateral localization of rBAT and 4F2hc, respectively, in the epithelial cells of the proximal tubule of the nephron

Nutrição no final da vida: A perspectiva paliativa do cirurgião

The care of cancer patients at the end-of-life represents a clinical challenge and an ethical and moral dilemma. Establishing follow-up strategies for the patient and his or her family, or the nutritional strategies to undertake is not easy. The objective of this review is to analyze theoretical aspects defined in the literature on the definition of end-of-life and the nutritional management strategies for cancer patients obtained from the experience of the Hepatobiliary and Pancreatic Surgery Service at Méderi Hospital in Bogotá, Colombia.El manejo médico en el final de la vida en pacientes con cáncer representa un reto clínico y un dilema ético y moral. No resulta fácil establecer las estrategias de acompañamiento para el paciente y su familia, ni establecer las estrategias nutricionales a seguir. El objetivo de esta revisión es analizar los aspectos teóricos establecidos en la literatura sobre la definición de final de la vida y las estrategias para el manejo nutricional en pacientes con cáncer desde la experiencia del Servicio de Cirugía Hepatobiliar y Pancreática del Hospital Méderi en Bogotá, Colombia.O manejo médico do paciente no final da vida em pacientes com câncer representa um desafio clínico e um dilema ético e moral. Não é fácil estabelecer as estratégias de acompanhamento para o paciente e sua familia, assim como as estratégias nutricionais a serem seguidas. O objetivo desta revisão é analisar os aspectos teóricos estabelecidos na literatura sobre a definição de final da vida e as estratégias de manejo nutricional, em pacientes com câncer a partir da experiência do Serviço de Cirurgia Hepatobiliar e Pancreática do Hospital Mederi de Bogotá, Colômbia

Brucella ceti infection in dolphins from the Western Mediterranean sea

Background: Brucella ceti infections have been increasingly reported in cetaceans. Brucellosis in these animals is associated with meningoencephalitis, abortion, discospondylitis’, subcutaneous abscesses, endometritis and other pathological conditions B. ceti infections have been frequently described in dolphins from both, the Atlantic and Pacific Oceans. In the Mediterranean Sea, only two reports have been made: one from the Italian Tyrrhenian Sea and the other from the Adriatic Sea. Results: We describe the clinical and pathological features of three cases of B. ceti infections in three dolphins stranded in the Mediterranean Catalonian coast. One striped dolphin had neurobrucellosis, showing lethargy, incoordination and lateral swimming due to meningoencephalitis, A B. ceti infected bottlenose dolphin had discospondylitis, and another striped dolphin did not show clinical signs or lesions related to Brucella infection. A detailed characterization of the three B. ceti isolates was performed by bacteriological, molecular, protein and fatty acid analyses. Conclusions: All the B. ceti strains originating from Mediterranean dolphins cluster together in a distinct phylogenetic clade, close to that formed by B. ceti isolates from dolphins inhabiting the Atlantic Ocean. Our study confirms the severity of pathological signs in stranded dolphins and the relevance of B. ceti as a pathogen in the Mediterranean Sea

Neutrophils as Trojan Horse Vehicles for Brucella abortus Macrophage Infection

Brucella abortus is a stealthy intracellular bacterial pathogen of animals and humans. This bacterium promotes the premature cell death of neutrophils (PMN) and resists the killing action of these leukocytes. B. abortus-infected PMNs presented phosphatidylserine (PS) as “eat me” signal on the cell surface. This signal promoted direct contacts between PMNs and macrophages (Mϕs) and favored the phagocytosis of the infected dying PMNs. Once inside Mϕs, B. abortus replicated within Mϕs at significantly higher numbers than when Mϕs were infected with bacteria alone. The high levels of the regulatory IL-10 and the lower levels of proinflammatory TNF-α released by the B. abortus-PMN infected Mϕs, at the initial stages of the infection, suggested a non-phlogistic phagocytosis mechanism. Thereafter, the levels of proinflammatory cytokines increased in the B. abortus-PMN-infected Mϕs. Still, the efficient bacterial replication proceeded, regardless of the cytokine levels and Mϕ type. Blockage of PS with Annexin V on the surface of B. abortus-infected PMNs hindered their contact with Mϕs and hampered the association, internalization, and replication of B. abortus within these cells. We propose that B. abortus infected PMNs serve as “Trojan horse” vehicles for the efficient dispersion and replication of the bacterium within the host

Brucella ceti infection in dolphins from the Western Mediterranean sea

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Cd98hc (slc3A2) sustains amino acid and nucleotide availability for cell cycle progression

CD98 heavy chain (CD98hc) forms heteromeric amino acid (AA) transporters by interacting with different light chains. Cancer cells overexpress CD98hc-transporters in order to meet their increased nutritional and antioxidant demands, since they provide branched-chain AA (BCAA) and aromatic AA (AAA) availability while protecting cells from oxidative stress. Here we show that BCAA and AAA shortage phenocopies the inhibition of mTORC1 signalling, protein synthesis and cell proliferation caused by CD98hc ablation. Furthermore, our data indicate that CD98hc sustains glucose uptake and glycolysis, and, as a consequence, the pentose phosphate pathway (PPP). Thus, loss of CD98hc triggers a dramatic reduction in the nucleotide pool, which leads to replicative stress in these cells, as evidenced by the enhanced DNA Damage Response (DDR), S-phase delay and diminished rate of mitosis, all recovered by nucleoside supplementation. In addition, proper BCAA and AAA availability sustains the expression of the enzyme ribonucleotide reductase. In this regard, BCAA and AAA shortage results in decreased content of deoxynucleotides that triggers replicative stress, also recovered by nucleoside supplementation. On the basis of our findings, we conclude that CD98hc plays a central role in AA and glucose cellular nutrition, redox homeostasis and nucleotide availability, all key for cell proliferation