Consenso intersocietario* sobre tratamiento y seguimiento de pacientes con cáncer diferenciado de tiroides / Inter Society Consensus for the Management of Patients with Differentiated Thyroid Cancer

La incidencia del cáncer diferenciado de tiroides se incrementó exponencialmente en todo el mundo. Aunque estos tumores presentan un pronóstico excelente, se produjeron múltiples cambios en el enfoque terapéutico y de seguimiento en los últimos años. Esta situación, vinculada principalmente con la estadificación por riesgos de recurrencia de la enfermedad, determinó la necesidad de generar un consenso entre representantes de las 3 sociedades argentinas que habitualmente se encuentran involucradas en el manejo de estos pacientes, (Sociedad Argentina de Endocrinología y Metabolismo, Asociación Argentina de Cirugía de Cabeza y Cuello y Asociación Argentina de Biología y Medicina Nuclear). Las recomendaciones se realizaron de acuerdo a la experiencia de los participantes y a la revisión de la literatura. Rev Argent Endocrinol Metab 52:85-118, 2014 Conflictos de interés: Pitoia F: Consultoría, Advisory Board, Speaker Genzyme-Sanofi; Consultoría, Advi­sory Board, Speaker, Steering Committee Bayer; Consultoría, Advisory Board, Speaker Astra Zeneca. Califano I: Speaker Genzyme-Sanofi; Consultoría, Advisory Board, Speaker AstraZeneca. Faure E: Consultoría, Advisory Board, Speaker Genzyme-Sanofi; Consultoría, Advisory Board, Speaker AstraZeneca. Gauna A: Advisory Board Genzyme-Sanofi.; Advisory Board Bayer. Mollerach A: Advisory Board Genzyme-Sanofi. Orlandi A: Advisory Board, Speaker Genzyme-Sanofi. El resto de los autores no declaran conflictos de intereses.

The incidence of differentiated thyroid cancer increased exponentially worldwide. Although these tumors usually have an excellent prognosis, multiple changes occurred in the therapeutic approach and follow-up in recent years. This situation, mainly related to the stratification by the risk of recurrence of the disease, made it necessary to build a consensus among representative members from the three Argentinean societies that are usually involved in the management of these patients, (Argentinean Society of Endocrinology and Metabo lism, Argentinean Association of Head and Neck Surgery and Argentinean Association of Biology and Nuclear Medicine). The recommendations were done according to personal experiences and review of bibliography. Rev Argent Endocrinol Metab 52:85-118, 2014 Conflicts of interest: Pitoia F: Consultancy, Advisory Board, Speaker Genzyme-Sanofi; Consultancy, Advisory Board, Speaker, Steering Committee Bayer; Consultancy, Advisory Board, Speaker AstraZeneca. Califano I: Speaker Genzyme-Sanofi; Consultancy, Advisory Board, Speaker AstraZeneca. Faure E: Consultancy, Advisory Board, Speaker Genzyme-Sanofi; Consultancy, Advisory Board, Speaker AstraZeneca. Gauna A: Advisory Board Genzyme-Sanofi.; Advisory Board Bayer. Mollerach A: Advisory Board Genzyme-Sanofi.Orlandi A: Advisory Board, Speaker Genzyme-Sanofi. No other financial conflicts of interest exist.

Small is fast: astrocytic glucose and lactate metabolism at cellular resolution.

Brain tissue is highly dynamic in terms of electrical activity and energy demand. Relevant energy metabolites have turnover times ranging from milliseconds to seconds and are rapidly exchanged between cells and within cells. Until recently these fast metabolic events were inaccessible, because standard isotopic techniques require use of populations of cells and/or involve integration times of tens of minutes. Thanks to fluorescent probes and recently available genetically-encoded optical nanosensors, this Technology Report shows how it is now possible to monitor the concentration of metabolites in real-time and in single cells. In combination with ad hoc inhibitor-stop protocols, these probes have revealed a key role for K(+) in the acute stimulation of astrocytic glycolysis by synaptic activity. They have also permitted detection of the Warburg effect in single cancer cells. Genetically-encoded nanosensors currently exist for glucose, lactate, NADH and ATP, and it is envisaged that other metabolite nanosensors will soon be available. These optical tools together with improved expression systems and in vivo imaging, herald an exciting era of single-cell metabolic analysis.

Enfermedades hereditarias de la dermis: revisión de la literatura / Hereditary diseases of the dermis: literature review

Nuestra piel tiene propiedades de elasticidad y firmeza, dada por las fibras del tejido conectivo ubicadas en la dermis. La elasticidad está dada principalmente por pequeñas fibraselásticas compuestas de elastina, mientras que la firmeza se explica por las redes de fibrillas de colágeno tipo I, III y V. La relevancia de estos componentes de la matriz extracelular, junto con otras fibras, como fibrilina y fibulina, se ha reflejado en el reconocimiento de diferentes enfermedades hereditarias causadas por mutaciones en estas proteínas. Muchas de éstas pueden tener características comunes, constituyendo un espectro de alteraciones, dependiendo de la proteína alterada, dando un pronóstico particular tanto en morbilidad y mortalidad. En esta revisión se desarrollarán las principales patologías de la dermis de importancia en dermatología.

Our skin is flexible and firm due to the fibers of the connective tissue in the dermis. Flexibility is mainly given by little elastic elastine fibers, meanwhile firmness is expressed by fibers networks made of collagen type I, III and V. The importance given to these components, including other fibers like fibrillin and fibulin in the extracellular matrix has been displayed in the recognition of different hereditary diseases caused by mutations in these proteins. Many of them have common characteristics, that build a wide spectrum of disorders depending on the altered protein, and give a particular prognostic in morbidity as well as in mortality. The main pathologies of the dermis with an importance in dermatology will be considered in this review.

Hantavirus ecology in rodent populations in three protected areas of Argentina.

In this study, we identified hantavirus genotypes and their reservoirs and evaluated the spatial and temporal distribution of the virus in rodent population in three protected areas of Argentina over 3 years (2007-2010). A total of 837 rodents were captured with an effort of 22 117 trap-nights. We detected the genotype Lechiguanas in Oligoryzomys nigripes and O. flavescens and Pergamino in Akodon azarae. There was no correlation between seroprevalence and trap success of the host. The proportion of seropositive males was significantly higher than the proportion of seropositive females. The total length of seropositives was higher than that of seronegatives in each host species. Seropositive individuals were observed in warm months and not in cold months, which suggests an infection cycle. This investigation confirms that protected areas of central east Argentina are places with a variety of sylvan rodents species associated with different hantavirus genotypes where reservoirs are numerically dominant. Although there was more than one known reservoir of hantavirus, only one species had antibodies in each area. This can be explained because the transmission of the virus does need not only the presence of a rodent species but also a threshold density. Longevity of even a small proportion of the host population in cold months may provide a trans-seasonal mechanism for virus persistence. The seroprevalence detected was higher than the one found before in rodent populations of Argentina, and this explains the appearance of human cases in two of these three areas.

Tacrolimus causes a blockage of protein secretion which reinforces its immunosuppressive activity and also explains some of its toxic side-effects.

BACKGROUND: Tacrolimus (FK506) is a macrolide immunosuppressant drug from the calcineurin inhibitor family, widely used in solid organ and islet cell transplantation, but produces significant side-effects. OBJECTIVE: This study examined the effect of FK506 on interleukin-2 (IL-2) and insulin secretion, establishing a novel characteristic of this drug that could explain its diverse adverse effects, and developed an experimental model for the simultaneous analysis of mRNA expression and protein secretion affected by this drug. METHODS: The IL-2 levels when tacrolimus was administered were analysed by Western blot, immunocytochemistry and RT-PCR in a T lymphocyte cellular line (Jurkat) 24 h post-stimulation. The insulin levels when tacrolimus was administered were analysed 4 h after stimulation of glucose-induced insulin secretion in a pancreatic cellular line (MIN6). RESULTS: The previously published information describes tacrolimus as only capable of partially blocking IL-2 mRNA expression. In our hands, the cellular content of IL-2 is almost undetectable in stimulated Jurkat cells and can be detected in cellular extracts only when the secretory pathway is blocked by brefeldin A (BFA). BFA added 2 h after the beginning of stimulation was able to inhibit IL-2 secretion, without affecting IL-2 mRNA expression. Therefore BFA utilization allowed us to establish a model to analyze the effect on IL-2 secretion, separately from its expression. Tacrolimus added before stimulation inhibits only IL-2 synthesis, but blocks IL-2 protein secretion when added 2 h after stimulation. Similarly, tacrolimus is also capable of blocking the glucose-stimulated secretion of insulin by MIN6 cells. An increase of the intracellular content can be detected concomitantly with a decrease of the hormone measured in the culture medium. CONCLUSIONS: Results of this study indicate that tacrolimus possesses another important effect in addition to the inhibition of IL-2 gene transcription, namely the ability to act as a general inhibitor of the protein secretory pathway. These results strongly suggest that the diabetogenic effect of the immune suppressant FK506 could be caused by the blockade of insulin secretion. This novel effect also provides an explanation for other side-effects observed in immunosuppressive treatment.

Brote de enfermedad alimentaria en la localidad de El Huecú, provincia de Neuquén / Foodborne disease outbreak in El Huecú community, province of Neuquén

En febrero de 2006 ocurrió un brote epidémico de gastroenteritis aguda de origen alimentario, en ocasión de un festejo popular en una pequeña localidad de la provincia de Neuquén, Argentina. Aproximadamente 800 personas participaron de un almuerzo en las instalaciones del Gimnasio Municipal, y unas tres horas después de finalizado, cerca de 150 asistentes consultaron al hospital local, afectados por síndrome gastroentérico agudo. Se realizó una investigación epidemiológica caso-control a través de un muestreo representativo no probabilístico. Los resultados epidemiológicos establecieron un brote de ETA a fuente común, con una relación caso-control de 1:1,8. Los principales síntomas fueron cólicos abdominales (88%), vómitos (73,5%) y diarrea (60%). La torta que se sirvió en ese evento fue identificada como el alimento causal (OR 9,79; IC 95%; 2,66-36,00; valor p = 0,0001), sujeto a condiciones higiénico-sanitarias insatisfactorias en los diferentes procesos de elaboración, conservación y manipulación. De una porción de la torta se aisló una cepa de Staphylococcus aureus subespecie aureus, coagulasa positiva, enterotoxigénica, con un recuento de 2,4x10(6) UFC/g, y también se aisló este microorganismo de tres muestras de manos y narinas de personas involucradas en la preparación y el servicio. Las cepas aisladas de un operador y de la torta portaron el gen sea y presentaron el mismo patrón de SmaI-PFGE. Se atribuyó el brote de ETA a la contaminación durante el proceso de preparación de la torta consumida durante ese almuerzo popular, lo que podría estar relacionado con deficiencias en aspectos higiénicos y con la falta de refrigeración y de mantenimiento de la cadena de frío.

In the summer of 2006, an epidemic outbreak of acute gastrointestinal illness related to food consumption occurred in a small town in the province of Neuquén, Argentina. During a popular feast, approximately 800 local residents attended lunch held in the facilities of the Municipal Gymnasium. About three hours later, nearly 150 attendees sought medical assistance at the local hospital due to acute gastroenteritis. A case-control epidemiological investigation was conducted using representative non-probability sampling. The epidemiological investigation showed a common-source foodborne disease outbreak with a case-control ratio of 1:1.8. The main symptoms were abdominal cramps (88%), vomiting (73.5%) and diarrhea (60%). The cake was identified as the source of infection (OR 9.79; IC 95%, 2.66-36.00; p = 0.0001), and unsatisfactory hygienic conditions in food production, conservation and handling steps were identified. Coagulase positive, enterotoxigenic Staphylococcus aureus, subspecies aureus was detected in a piece of cake, with a count of 2.4x10(6) CFU/g, and in samples from the hands and nostrils of three people involved in food preparation and service. The strains isolated from both the cake and one of the food handlers carried the sea gene, and presented the same SmaI-PFGE pattern. The foodborne disease outbreak was considered to be due to contamination in the preparation process of the cake consumed at the feast, which was related to inadequate hygienic conditions, lack of refrigeration and cold chain disruption.

New diterpenes from the marine pulmonate Trimusculus peruvianus.

The family Trimusculidae produce labdane diterpenes, which differ in the degree and type of esterification with acetoxy and isovaleroyl ester, predominantly. In this article, we describe the isolation from the marine pulmonate Trimusculus peruvianus, collected on intertidal rocks of Chilean coasts, of two new labdane diterpenes closely related to the above mentioned characteristics. Their structures were determined by spectroscopic data and correspond to 6beta-hydroxy-labda-8, 13-dien-15-ol and 3, 19-isovaleroyl-6beta, 9alpha-dihydroxylabda-Delta(8,17), 13-dien-15-oic acid.

[Foodborne disease outbreak in El Huecú community, province of Neuquén]. / Brote de enfermedad alimentaria en la localidad de El Huecú, provincia de Neuquén.

In the summer of 2006, an epidemic outbreak of acute gastrointestinal illness related to food consumption occurred in a small town in the province of Neuquén, Argentina. During a popular feast, approximately 800 local residents attended lunch held in the facilities of the Municipal Gymnasium. About three hours later, nearly 150 attendees sought medical assistance at the local hospital due to acute gastroenteritis. A case-control epidemiological investigation was conducted using representative non-probability sampling. The epidemiological investigation showed a common-source foodborne disease outbreak with a case-control ratio of 1:1.8. The main symptoms were abdominal cramps (88%), vomiting (73.5%) and diarrhea (60%). The cake was identified as the source of infection (OR 9.79; IC 95%, 2.66-36.00; p = 0.0001), and unsatisfactory hygienic conditions in food production, conservation and handling steps were identified. Coagulase positive, enterotoxigenic Staphylococcus aureus, subspecies aureus was detected in a piece of cake, with a count of 2.4 x 10(6) CFU/g, and in samples from the hands and nostrils of three people involved in food preparation and service. The strains isolated from both the cake and one of the food handlers carried the sea gene, and presented the same Smal-PFGE pattern. The foodborne disease outbreak was considered to be due to contamination in the preparation process of the cake consumed at the feast, which was related to inadequate hygienic conditions, lack of refrigeration and cold chain disruption.

Furoplocamioids A-C, novel polyhalogenated furanoid monoterpenes from Plocamium cartilagineum.

Three new tetrahydrofuran derivatives, marine monoterpenes, with an unusual chlorobromo vinyl functional group, have been isolated from the red alga Plocamium cartilagineum. The structure and relative stereochemistry of these compounds were determined on the basis of spectroscopic evidence and molecular mechanics (MM2) calculations. These compounds are related to pantofuranoids isolated from the antarctic Pantoneura plocamioides, which strongly suggests a close relationship between these species.

Complementary effects of Mediterranean diet and moderate red wine intake on haemostatic cardiovascular risk factors.

OBJECTIVES: To compare the effect of alcohol-free Mediterranean-type diet (MD) and high-fat diet (HFD) on plasma concentration of emergent haemostatic cardiovascular risk factors (HCVRF). Also, to test if red wine supplementation modifies HCVRF, independent of diet. DESIGN, SUBJECTS AND INTERVENTION: Controlled prospective intervention study. Two groups, each of 21 healthy male university students (22+/-3.4 y), received either MD or HFD for 90 days. Between days 30 and 60, both diets were supplemented with 240 ml/day of red wine. Baseline and T30, T60 and T90-day samples were drawn. No drop out from the study was observed. SETTING: University campus and outpatient nutrition clinic. RESULTS: Volunteers on HFD at T30 had increases in pro-coagulants fibrinogen (22%), factor VIIc (9%), and factor VIIIc (4%), and decreases in natural anticoagulants antithrombin III (3%), protein C (11%) and protein S (6%) and of 20% in plasminogen activator inhibitor-1. At the same time, individuals on MD had increases in fibrinogen (4%), antithrombin III (5%), protein C (3%), protein S (2.7%), and decreases in factor VIIIc (9%), and plasminogen activator inhibitor-1 (21%). After adjusting by baseline values, MD was associated with lower plasma fibrinogen (P=0.03), factor VIIc (P=0.034) and factor VIIIc (P=0.0057) and with higher levels of protein S (P=0.013). Red wine supplementation, in both diets, resulted in decreased plasma fibrinogen (P=0.001) and factor VIIc (P=0.05), and increased tissue plasminogen activator antigen (P=0.01) and plasminogen activator inhibitor-1 antigen (P=0.0003). Wine consumption was also associated with significantly (P=0.01) divergent effects on antithrombin III: it decreased by 10% in individuals on HFD but increased slightly in those on MD. No effects of diet or wine were detected in plasma protein C and C-reactive protein. CONCLUSION: MD and moderate consumption of red wine have complementary, mostly beneficial effects on HCVRF.

Identifying young people's guidance needs through telephone counseling.

This study examined the needs that young people in Guadalajara, in the state of Jalisco, Mexico, expressed in phone calls to a research unit of the Mexican Social Security Institute. Three hundred forty-five calls, from individuals 11 to 24 years old who phoned from June 1995 to November 1998, were analyzed. Two hundred ninety-four of the callers were female and 51 were male. Greater percentages of females than males called to ask about sexuality and family problems. Males more than females asked about reproductive health (particularly pregnancy) and mental health. There were significant differences by gender and age, differences that were not detected in health service statistics. The findings have implications for decision makers and health and education service providers. They point to the need for programs that will reinforce young people's good health practices and help them avoid risky behaviors.

[Differences in plasma antioxidants according to socioeconomic level in Chilean women]. / Diferencias en antioxidantes plasmáticos según nivel socioeconómico en mujeres chilenas.

BACKGROUND: Free radical-mediated oxidative damage is a known initial event in atherogenesis. Cardiovascular disease is frequent in the Chilean population showing differences in the prevalence of risk factors of the disease according to socioeconomic level (SEL). AIM: To determine levels of antioxidants and lipid peroxides in Chilean women from different SEL. PATIENTS AND METHODS: Blood samples were taken from 81 women for measurements of plasma ascorbic acid, beta-carotene, alpha-tocopherol, licopene, ubiquinol, glutathione, total plasma antioxidant capacity, and lipid peroxides (TBARS). RESULTS: Individuals in the lower SEL showed reduced levels of plasma beta-carotene, ascorbic acid, alpha-tocopherol, and ubiquinol compared to women in the higher SEL. There were no differences between groups in the plasma levels of glutathione, total antioxidant capacity, or TBARS. CONCLUSIONS: The results could be explained in part by the higher consumption of fruits and vegetables in women from the upper SEL.

Diterpenoids from Azorella yareta and their trichomonicidal activities.

Diterpenoids with trichomonicidal activity were isolated from the aerial parts of Azorella yareta Hauman. One was 13beta-hydroxyazorellane, together with the known constituents mulinolic acid, mulin-11,13-dien-20-oic acid, azorellanol and 13alpha-hydroxyazorellane. Their structures were determined by spectroscopic and chemical methods.

Diferencias en antioxidantes plasmáticos según nivel socioeconómico en mujeres chilenas / Differences in plasma antioxidants according to socioeconomic level in chilean women

Background: Free radical-mediated oxidative damage is a known initial event in atherogenesis. Cardiovascular disease is frequent in the Chilean population showing differences in the prevalence of risk factors of the disease according to socioeconomic level (SEL). Aim: To determine levels of antioxidants and lipid peroxides in Chilean women from different SEL. Patients and methods: Blood samples were taken from 81 women for measurements of plasma ascorbic acid, ß-carotene, a-tocopherol, licopene, ubiquinol, glutathione, total plasma antioxidant capacity, and lipid peroxides (TBARS). Results:Individuals in the lower SEL showed reduced levels of plasma ß-carotene, ascorbic acid, a-tocopherol, and ubiquinol compared to women in the higher SEL. There were no differences between groups in the plasma levels of glutathione, total antioxidant capacity, or TBARS. Conclusions: The results could be explained in part by the higher consumption of fruits and vegetables in women from the upper SEL

Mulinane-type diterpenoids from Laretia acaulis.

In addition to the known mulinolic acid and mulin-11, 13-dien-20-oic acid, 13-epimulinolic acid has been isolated from the aerial parts of Laretia acaulis (Cav.) Gill et Hook (Umbelliferae). Its structure was based on spectroscopic comparison with mulinolic acid and by chemical characterization.

Plasma polyphenols and antioxidants, oxidative DNA damage and endothelial function in a diet and wine intervention study in humans.

An intervention study was performed to evaluate the influence of a Mediterranean diet, a high fat diet, and their supplementation with red wine in moderate amounts, on biochemical, physiological, and clinical parameters related to atherosclerosis and other chronic diseases. For 3 months two groups of 21 male volunteers each, received either a Mediterranean diet or a high fat diet; during the second month, red wine was added isocalorically, 240 ml/day. Participants were kept under close medical and nutritional surveillance. At days 0, 30, 60 and 90, clinical, physiological and biochemical evaluations were made. Plasma vitamin C was significantly decreased in the high fat diet group compared to the Mediterranean diet group. After wine supplementation to the Mediterranean diet, a significant 13.5% increase in plasma vitamin C was observed. Furthermore, when wine was added vitamin E decreased significantly in plasma, 15% in the high fat diet and 26% in the Mediterranean diet. Total plasma antioxidant capacity (total antioxidant reactivity) increased 28% above basal levels in the Mediterranean diet group, but not in the high fat diet group. In both groups, wine induced a marked increase in total antioxidant reactivity above basal levels, 56% and 23%, respectively. Oxidative DNA damage, detected as 8-hydroxydeoxyguanosine (8-OHdG) levels in blood leukocyte DNA, was markedly increased by the high fat diet; however, it was strongly reduced, to approximately 50% basal values, after wine supplementation, both in the high fat diet and Mediterranean diet groups. Endothelial function, evaluated noninvasively as flow-mediated vascular reactivity of the brachial artery, was suppressed by the high fat diet, and was normal after wine supplementation. These effects are attributed to oxidative stress associated with a high fat diet, and to the elevated plasma antioxidant capacity associated with wine consumption and the Mediterranean diet. The results presented support the following conclusions: a high fat diet induces oxidative stress; a diet rich in fruits and vegetables enhances antioxidant defenses; wine supplementation to a high fat or a Mediterranean diet increases plasma antioxidant capacity, decreases oxidative DNA damage, and normalizes endothelial function.

Tetrahydropyran monoterpenes from plocamium cartilagineum and pantoneura plocamioides

Four new marine monoterpenes have been isolated from two species of marine red algae, Plocamium cartilagineum and Pantoneura plocamioides. The structures and relative stereochemistry of these compounds were determined on the basis of spectroscopic evidence and suggest a relationship between P. cartilagineum and P. plocamioides.

The compound 14-keto-stypodiol diacetate from the algae Stypopodium flabelliforme inhibits microtubules and cell proliferation in DU-145 human prostatic cells.

We investigated the effects of the drug 14-keto-stypodiol diacetate (SDA) extracted from the seaweed product Stypopodium flabelliforme, in inhibiting the cell growth and tumor invasive behavior of DU-145 human prostate cells. In addition, the molecular action of the drug on microtubule assembly was analyzed. The effects of this diterpenoid drug in cell proliferation of DU-145 tumor cells in culture revealed that SDA at concentrations of 5 microM decreased cell growth by 14%, while at 45 microM a 61% decrease was found, as compared with control cells incubated with the solvent but in the absence of the drug. To study their effects on the cell cycle, DU-145 cells were incubated with increasing concentrations of SDA and the distribution of cell-cycle stages was analyzed by flow cytometry. Interestingly, the data showed that 14-keto-stypodiol diacetate dramatically increased the proportion of cells in the G2/M phases, and decreased the number of cells at the S phase of mitosis, as compared with appropriate controls. Studies on their action on the in vitro assembly of microtubules using purified brain tubulin, showed that SDA delayed the lag period associated to nucleation events during assembly, and decreased significantly the extent of polymerization. The studies suggest that this novel derivative from a marine natural product induces mitotic arrest of tumor cells, an effect that could be associated to alterations in the normal microtubule assembly process. On the other hand, a salient feature of this compound is that it affected protease secretion and the in vitro invasive capacity, both properties of cells from metastases. The secretion of plasminogen activator (u-PA) and the capacity of DU-145 cells to migrate through a Matrigel-coated membrane were significantly inhibited in the presence of micromolar concentrations of SDA. These results provide new keys to analyze the functional relationships between protease secretion, invasive behavior of tumor cells and the microtubule network.