Marjoram extract prevents ischemia reperfusion-induced myocardial damage and exerts anti-contractile effects in aorta segments of male wistar rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Marjoram (Origanum majorana L.) is an herb traditionally used as a medicine in different countries, as Morocco and Iran, because of its beneficial cardiovascular effects. Some studies suggest that these effects are due, at least in part, to the presence of phenolic compounds such as rosmarinic acid (RA) and luteolin. AIM OF THE STUDY: To analyze the possible cardiprotective effects of a marjoram extract (ME) reducing myocardial damage after coronary ischemia-reperfusion (IR) and its possible antihypertensive effects reducing the response of aorta segments to the vasoconstrictors noradrenaline (NA) and endothelin-1 (ET-1). MATERIALS AND METHODS: Male Wistar rats (300g) were used. After sacrifice, the heart was immediately removed and mounted in a perfusion system (Langendorff). The aorta was carefully dissected and cut in 2 mm segments to perform vascular reactivity experiments. RESULTS: In the heart, ME perfusion after IR reduced heart rate and prevented IR-induced decrease of cardiac contractility, possibly through vasodilation of coronary arteries and through the upregulation of antioxidant markers in the myocardium that led to reduced apoptosis of cardiomyocytes. In the aorta, ME decreased the vasoconstrictor response to NA and ET-1 and exerted a potent anti-inflammatory and antioxidant effect. Neither RA nor 6-hydroxi-luteolin-O-glucoside, major compounds of this ME, were effective in improving cardiac contractility after IR or attenuating vasoconstriction to NA and ET-1 in aorta segments. CONCLUSION: In conclusion, ME reduces the myocardial damage induced by IR and the contractile response to vasoconstrictors in the aorta. Thus, it may be useful for the treatment of cardiovascular diseases such as myocardial infarction and hypertension.

Role of hormones in sarcopenia.

Aging involves numerous changes in body composition that include a decrease in skeletal muscle mass. The gradual reduction in muscle mass is associated with a simultaneous decrease in muscle strength, which leads to reduced mobility, fragility and loss of independence. This process called sarcopenia is secondary to several factors such as sedentary lifestyle, inadequate nutrition, chronic inflammatory state and neurological alterations. However, the endocrine changes associated with aging seem to be of special importance in the development of sarcopenia. On one hand, advancing age is associated with a decreased secretion of the main hormones that stimulate skeletal muscle mass and function (growth hormone, insulin-like growth factor 1 (IGFI), testosterone and estradiol). On the other hand, the alteration of the IGF-I signaling along with decreased insulin sensitivity also have an important impact on myogenesis. Other hormones that decline with aging such as the adrenal-derived dehydroepiandrosterone, thyroid hormones and vitamin D seem to also be involved in sarcopenia. Adipokines released by adipose tissue show important changes during aging and can affect muscle physiology and metabolism. In addition, catabolic hormones such as cortisol and angiotensin II can accelerate aged-induced muscle atrophy, as they are involved in muscle wasting and their levels increase with age. The role played by all of these hormones and the possible use of some of them as therapeutic tools for treating sarcopenia will be discussed.

Caloric restriction attenuates aging-induced cardiac insulin resistance in male Wistar rats through activation of PI3K/Akt pathway.

BACKGROUND AND AIM: Caloric restriction (CR) improves insulin sensitivity and is one of the dietetic strategies most commonly used to enlarge life and to prevent aging-induced cardiovascular alterations. The aim of this study was to analyze the possible beneficial effects of caloric restriction (CR) preventing the aging-induced insulin resistance in the heart of male Wistar rats. METHODS AND RESULTS: Three experimental groups were used: 3 months old rats (3m), 24 months old rats (24m) and 24 months old rats subjected to 20% CR during their three last months of life (24m-CR). After sacrifice hearts were mounted in a perfusion system (Langendorff) and heart function in basal conditions and in response to accumulative doses of insulin (10-9-10-7 M), in the presence or absence of Wortmannin (10-6 M), was recorded. CR did not attenuate the aging-induced decrease in coronary artery vasodilation in response to insulin administration, but it prevented the aging-induced downregulation of cardiac contractility (dp/dt) through activation of the PI3K/Akt intracellular pathway. Insulin stimulated in a greater extent the PI3K/Akt pathway vs the activation of the MAPK pathway and increased the protein expression of IR, GLUT-4 and eNOS in the hearts of 3m and 24m-CR rats, but not in the hearts of 24m rats. Furthermore, CR prevented the aging induced increase in endothelin-1 protein expression in myocardial tissue. CONCLUSION: In conclusion CR partially improves cardiac insulin sensitivity and prevents the aging induced decrease in myocardial contractility in response to insulin administration through activation of PI3K/Akt pathway.

Impactación recurrente de cerumen. ¿Qué se esconde detrás? / Earwax recurrent impaction. What lies behind it?

Se presentan los casos de dos niños de diez años con historia de impactación recurrente de cera en conductos auditivos, con hipoacusia leve ocasional. En la exploración otoscópica se apreció una estrechez de conductos auditivos externos que imposibilitaba la visualización de los tímpanos, incluso tras la limpieza de cerumen. Dicha estenosis no había sido evidente en las otoscopias previas a esta edad

We present the cases of two 10 year-old kids with recurrent earwax impaction in ear canals, with occasional mild hearing loss. Otoscopic examination revealed a narrowing of the external auditory canals, which made it impossible to visualize the tympana, even after the cleaning of the cerumen. This stenosis had not been noticeable in previous otoscopies

Población y metodología del estudio SIMETAP: Prevalencia de factores de riesgo cardiovascular, enfermedades cardiovasculares y enfermedades metabólicas relacionadas / Population and methodology of the SIMETAP study: Prevalence of cardiovascular risk factors, cardiovascular diseases, and related metabolic diseases

La prevención de la enfermedad cardiovascular se fundamenta en la detección y control de los factores de riesgo cardiovascular (FRCV). En España existen importantes diferencias territoriales tanto en la prevalencia como en el grado de control de los FRCV. En la última década ha habido una mejora del control de la hipertensión y la dislipidemia, pero un empeoramiento de los factores de riesgo cardiometabólicos relacionados con la obesidad y la diabetes. El estudio SIMETAP es un estudio observacional descriptivo transversal realizado en 64 centros de atención primaria de la Comunidad de Madrid. El objetivo principal es determinar las tasas de prevalencia de FRCV, de las enfermedades cardiovasculares y de las enfermedades metabólicas relacionadas con el riesgo cardiovascular. El presente artículo informa sobre las características basales de la población, la metodología del estudio, y las definiciones de los parámetros y enfermedades en estudio. Se seleccionaron 6.631 sujetos de estudio mediante una muestra aleatoria base poblacional. Se determinaron variables antropométricas, estilos de vida, presión arterial, parámetros bioquímicos, y tratamientos farmacológicos. Las prevalencias crudas más elevadas se detectaron en tabaquismo, inactividad física, obesidad, prediabetes, diabetes, hipertensión, dislipidemias y síndrome metabólico. Para valorar la verdadera dimensión epidemiológica de estas enfermedades y FRCV, es necesario realizar un análisis pormenorizado de tasas de prevalencia estratificadas por grupos etarios y de las tasas de prevalencia ajustadas por edad y sexo

The prevention of cardiovascular disease is based on the detection and control of cardiovascular risk factors (CVRF). In Spain there are important geographical differences both in the prevalence and in the level of control of the CVRF. In the last decade there has been an improvement in the control of hypertension and dyslipidaemia, but a worsening of cardio-metabolic risk factors related to obesity and diabetes. The SIMETAP study is a cross-sectional descriptive, observational study being conducted in 64 Primary Care Centres located at the Community of Madrid. The main objective is to determine the prevalence rates of CVRF, cardiovascular diseases, and metabolic diseases related to cardiovascular risk. A report is presented on the baseline characteristics of the population, the study methodology, and the definitions of the parameters and diseases under study. A total of 6,631 study subjects were selected using a population-based random sample. The anthropometric variables, lifestyles, blood pressure, biochemical parameters, and pharmacological treatments were determined. The highest crude prevalences were detected in smoking, physical inactivity, obesity, prediabetes, diabetes, hypertension, dyslipidaemias, and metabolic syndrome. A detailed analysis needs to be performed on the prevalence rates, stratified by age groups, and prevalence rates adjusted for age and sex to assess the true epidemiological dimension of these CVRF and diseases

Population and methodology of the SIMETAP study: Prevalence of cardiovascular risk factors, cardiovascular diseases, and related metabolic diseases. / Población y metodología del estudio SIMETAP: Prevalencia de factores de riesgo cardiovascular, enfermedades cardiovasculares y enfermedades metabólicas relacionadas.

The prevention of cardiovascular disease is based on the detection and control of cardiovascular risk factors (CVRF). In Spain there are important geographical differences both in the prevalence and in the level of control of the CVRF. In the last decade there has been an improvement in the control of hypertension and dyslipidaemia, but a worsening of cardio-metabolic risk factors related to obesity and diabetes. The SIMETAP study is a cross-sectional descriptive, observational study being conducted in 64 Primary Care Centres located at the Community of Madrid. The main objective is to determine the prevalence rates of CVRF, cardiovascular diseases, and metabolic diseases related to cardiovascular risk. A report is presented on the baseline characteristics of the population, the study methodology, and the definitions of the parameters and diseases under study. A total of 6,631 study subjects were selected using a population-based random sample. The anthropometric variables, lifestyles, blood pressure, biochemical parameters, and pharmacological treatments were determined. The highest crude prevalences were detected in smoking, physical inactivity, obesity, prediabetes, diabetes, hypertension, dyslipidaemias, and metabolic syndrome. A detailed analysis needs to be performed on the prevalence rates, stratified by age groups, and prevalence rates adjusted for age and sex to assess the true epidemiological dimension of these CVRF and diseases.

Study of insulin vascular sensitivity in aortic rings and endothelial cells from aged rats subjected to caloric restriction: Role of perivascular adipose tissue.

The prevalence of metabolic syndrome is dramatically increasing among elderly population. Metabolic syndrome in aged individuals is associated with hyperinsulinemia and insulin resistance both in metabolic tissues and in the cardiovascular system, with this fact being associated with the cardiometabolic alterations associated to this condition. Caloric restriction (CR) improves insulin sensitivity and is one of the dietetic strategies most commonly used to enlarge life and to prevent aging induced cardiovascular alterations. The aim of this study was to analyze the possible beneficial effects of CR in aging-induced vascular insulin resistance both in aortic rings and in primary culture of endothelial cells. In addition, the inflammatory profile of perivascular adipose tissue (PVAT) and its possible role in the impairment of vascular insulin sensitivity associated with aging was also assessed. Three experimental groups of male Wistar rats were used: 3 (3m), 24 (24m) fed ad libitum and 24months old rats subjected to 20% CR during their three last months of life (24m-CR). Aorta rings surrounded or not by PVAT were mounted in an organ bath and precontracted with phenylephrine (10-7.5M). Changes in isometric tension were recorded in response to cumulative insulin concentrations (10-8-10-5.5M) in the presence or absence of L-NAME (10-4M). Aortic rings and primary aortic endothelial cells were incubated in presence/absence of insulin (10-7M) and the activation of the PI3K/Akt and MAPK pathways as well as nitrite and nitrates concentrations and the mRNA levels of eNOS, insulin receptor, and GLUT-4 were assessed. CR prevented the aging-induced decrease in the vasodilator response to insulin and the aging-induced increase in the vasoconstrictor response to high insulin concentrations. Changes between 24m and 24m-CR aorta rings were abolished in the presence of L-NAME. CR induced-improvement in insulin vascular sensitivity was related with activation of the PI3K/Akt both in aortic rings and in aortic endothelial cells in response to insulin. CR attenuated the overexpression of iNOS, TNF-α and IL-1ß in the PVAT of aged rats although aortic rings surrounded by PVAT from 24m rats showed and increased vasorelaxation in response to insulin compared to aortic rings from 3m and 24m-CR rats. In conclusion, a moderate protocol of CR improves insulin vascular sensitivity and prevents the aging induced overexpression of pro-inflammatory cytokines in PVAT.

Effects of early overnutrition on the renal response to Ang II and expression of RAAS components in rat renal tissue.

BACKGROUND AND AIMS: The aim of this study was to analyze the effects of early overnutrition (EON) on the expression of the renin angiotensin aldosterone system (RAAS) components in renal cortex, renal arteries and renal perivascular adipose tissue (PVAT), as well as the vascular response of renal arteries to Angiotensin II (Ang II). METHODS AND RESULTS: On birth day litters were adjusted to twelve (L12-control) or three (L3-overfed) pups per mother. Half of the animals were sacrificed at weaning (21 days old) and the other half at 5 months of age. Ang II-induced vasoconstriction of renal artery segments increased in young overfed rats and decreased in adult overfed rats. EON decreased the gene expression of angiotensinogen (Agt), Ang II receptors AT1 and AT2 and eNOS in renal arteries of young rats, while it increased the mRNA levels of AT-2 and ET-1 in adult rats. In renal PVAT EON up-regulated the gene expression of COX-2 and TNF-α in young rats and the mRNA levels of renin receptor both in young and in adult rats. On the contrary, Ang II receptors mRNA levels were downregulated at both ages. Renal cortex of overfed rats showed increased gene expression of Agt in adult rats and of AT1 in young rats. However the mRNA levels of AT1 were decreased in the renal cortex of overfed adult rats. CONCLUSION: EON is associated with alterations in the vascular response of renal arteries to Ang II and changes in the gene expression of RAAS components in renal tissue.

Programa de cribado para el déficit De alfa 1-antitripsina en el servicio de neumonología del Hospital Tránsito Cáceres de Allende / Alpha-1-antitrypsin deficiency screening program at the Pneumonology Department of Hospital Tránsito Cáceres de Allende

El déficit de alfa -1 Antitripsina (DAAT) es una enfermedad genética rara, asociada a un incremento a padecer enfisema pulmonar y hepatopatía crónicas en niños y adultos, frecuentemente subdiagnosticada, con largos retrasos entre el inicio de los síntomas y el diagnóstico definitivo. La alfa 1-antitripsina (AAT) es el inhibidor de proteasas más abundante en el organismo humano. Se considera déficit grave y es a lo que habitualmente se refiere la literatura científica a los siguientes fenotipos: SZ, ZZ y Null. Es necesario programas de cribado para su detección precoz, por lo que se ha descripto y validado un método sencillo y específico, mediante el cual se cuantifica el valor de AAT por nefelometría en muestras de gota de sangre en papel secante y se realiza genotipificación rápida de las variantes Z y S. Objetivos: Determinar la proporción de individuos con DAAT en una población de pacientes con enfermedades respiratorias crónicas. Identificar y caracterizar a aquellos con déficit de AAT. Materiales y Método: Estudio Observacional, Descriptivo de corte Transversal de cribado de déficit de AAT, entre el 2 de enero de 2014 a 30 de marzo de 2015. De 80 personas que cumplieron con los criterios de inclusión y que concurrieron de forma espontánea o por derivación al Servicio de Neumonología del Hospital Tránsito Cáceres de Allende, Córdoba, Argentina, se analizaron 62 pacientes que aceptaron realizarse el estudio. Se realizó dosaje de alfa1-antitripsina mediante gota de sangre en papel secante a los pacientes que cumplieron los criterios de inclusión. Se solicitó espirometría, Tomografía Computada de Tórax de Alta Resolución y genotipificación rápida solo a aquellos pacientes con valores de alfa 1-antitripsina < 1,8 mg/dL. Resultados: En el presente trabajo se estudió un total de 62 pacientes, 28 (45,2%) fueron de sexo femenino y 34 (54,8%) de sexo masculino, 37 (59,7%) tuvieron valores de alfa 1-antitripsina ≥ 1,8 mg/dL y 25 (40,3%) < 1,8 mg/dL. La obtención del genotipo por la técnica de gota seca a 25 (40,3%; 25:62) pacientes con valores < 1,8 mg/dL mostró que: 22 (88%; 22:25) fueron NoS NoZ, 2 (8%; 2:25) Heterocigoto para Z y 1 (4%; 1:25) Heterocigoto para S. El patrón espirométrico predominante según criterio de ATS/ERS fue el obstructivo (88%). El patrón en TCAR fue de enfisema en 22 pacientes (88%): 7 (31,8%) centrolobulillar, 8 (36,4%) paraseptal, 7 (31,8%) panlobulillar. Hubo 2 pacientes (8%) con bronquiectasias, y 1 (4%) fue normal. Conclusión: En una población seleccionada por síntomas y/o antecedentes se pueden identificar con el cribado con técnica de gota seca a pacientes con DAAT, que en su expresión grave es poco frecuente en la Argentina, probablemente subdiagnosticado, siendo superior el número de portadores heterocigotos PIS y PIZ. El diagnóstico precoz de DAAT es poco frecuente. Es difícil establecer conclusiones sobre el grupo de alfa 1-antitripsina <1,8 mg/dL sin ser deficiencias graves, en relación a las variables estudiadas en la muestra debido a la escases de estudios y bibliografía encontradas sobre el tema. Consideramos que los pacientes que presentan un genotipo No S No Z y los que presentan discordancia deben ser confirmados cuantitativamente y tener una caracterización del fenotipo en muestras de suero por Isoelectoenfoque y ocasionalmente el análisis molecular del gen para variantes alélicas poco frecuentes, nuevas o nulas.

Alpha-1-antitrypsin deficiency screening program at the Pneumonology Department of Hospital Tránsito Cáceres de Allende

Alpha-1-antitrypsin deficiency (AATD) is a rare genetic disease associated with an increased risk of suffering from pulmonary emphysema and chronic hepatopathy in children and adults alike. It is often underdiagnosed, with long periods elapsing between the onset of symptoms and a definite diagnosis. Alpha-1-antitrypsin (AAT) is the most abundant protease inhibitor in the human body. Scientific literature considers severe deficiency to be associated with the following phenotypes: SZ, ZZ and Null. Screening programs are required for early detection, this is why an easy and specific method has been described and validated. Through this method, AAT values are quantified using nephelometry in blood drop samples on blotting paper, then genotyping of the Z and S variants is quickly performed. Objectives: To determine the number of individuals with AATD within a population of patients with chronic respiratory diseases. To identify and define those with AAT deficiency. Materials and Method: Observational, descriptive and cross-sectional study of AAT deficiency screening, between January 2nd, 2014 and March 30th, 2015. Out of 80 individuals who fulfilled the inclusion criteria and who spontaneously attended or were referred to the Pneumonology Department of Hospital Tránsito Cáceres de Allende, Córdoba, Argentina, 62 patients who agreed to the study were analyzed. A test to determine the concentration of alpha-1-antitrypsin was performed to the patients who met all the inclusion criteria using blood drops on blotting paper. Only patients with alpha-1-antitrypsin levels < 1.8 mg/dL were requested a spirometry, a high-resolution computed tomography of the chest and quick genotyping tests. Results: A total of 62 patients was evaluated in this study, 28 (45.2%) were females and 34 (54.8%) were males, 37 (59.7%) had alpha-1-antitrypsin levels ≥ 1.8 mg/dL and 25 (40.3%) < 1.8 mg/dL. Genotype elicitation using the dried-droplet method in 25 (40.3%; 25:62) patients with values < 1.8 mg/dL showed that: 22 (88%; 22:25) were Non-S Non-Z, 2 (8%; 2:25) were heterozygote for Z and 1 (4%; 1:25) was heterozygote for S. According to ATS/ERS criteria, the predominant spirometric pattern was obstructive (88%). The HRCT pattern corresponded to emphysema in 22 patients (88%): 7 (31.8%) centrilobular, 8 (36.4%) paraseptal, 7 (31.8%) panlobular. There were 2 patients (8%) with bronchiectasis and 1 (4%) was normal. Conclusion: In a population selected by symptoms and/or history, patients with AATD can be identified using the dried-droplet method. Severe AATD is uncommon in Argentina, probably because it is underdiagnosed, and the amount of heterozygote PIS and PIZ carriers is higher. Early AATD diagnosis is uncommon. It is difficult to draw conclusions about the alpha-1-antitrypsin group below 1.8 mg/dL without severe deficiencies in connection with the variables analyzed in the sample due to the lack of studies and bibliography on this subject. We consider that patients with non-S non-Z genotypes and the ones with discrepancies must be quantitatively confirmed and their phenotype defined in serum samples using isoelectric focusing and, occasionally, they must have a molecular gene analysis to look for uncommon, new or null allelic variants.

HR007: a family of biomaterials based on glycosaminoglycans for tissue repair.

Most new advances in tissue engineering (TE) focus on the creation of adequate microenvironments that may accelerate the repair processes of damaged tissues. Extracellular matrix (ECM) of Wharton's jelly (WJ) from umbilical cords is very rich in sulphated GAGs (sGAGs) and hyaluronic acid (HA), components which have special properties that could positively influence the regeneration of several types of tissue. Previously, we described the methodology for the extraction and purification of GAGs from WJ and, importantly, the separation of sGAGs and HA to develop various scaffolds for regenerative medicine. In this new study we hypothesized that the biomaterials obtained, called HR007s, would be excellent candidates for two different applications, chondral and dermal repair. First, we have confirmed that the GAGs obtained are biocompatible, as they do not cause cytotoxicity, haemolysis or an inflammatory response. Second, we have developed three-dimensional (3D) structures through the combination of different ratios of GAGs and their subsequent stabilization, which can be properly adapted to target tissues, cartilage or skin. Finally, we have combined these scaffolds with adipose mesenchymal stem cells (ASCs) or fibroblasts for application to chondral or dermal defects, respectively, with the goal of promoting fast reparative processes. The results show that HR007 scaffolds induce cell proliferation, enhance the expression of specific gene markers, increase the production of tissue ECM proteins and have chemotactic effects over the studied cells. In summary, the bioactive properties of HR007 scaffolds make them promising candidates for use in regenerative medicine, at least for chondral and dermal repair. Copyright © 2015 John Wiley & Sons, Ltd.

Policies and practices on the programmatic management of latent tuberculous infection: global survey.

SETTING: Global survey among low tuberculosis (TB) burden countries, which are primary target countries for the World Health Organization (WHO) guidelines on the programmatic management of latent tuberculous infection (LTBI). OBJECTIVE: To perform a baseline assessment of policies and practices for the programmatic management of LTBI. DESIGN: Online and paper-based pre-tested questionnaire filled out by national TB programme managers or their equivalents from 108 countries. RESULTS: Of 74 respondent countries, 75.7% (56/74) had a national policy on LTBI. The majority of the countries (67/74, 90.5%) provided LTBI testing and treatment for child contacts of TB cases, while almost two thirds (49/74, 66%) reported provision of LTBI testing and treatment to people living with the human immunodeficiency virus (PLHIV). Six countries (8.1%) did not report providing LTBI management to child contacts and PLHIV. Among countries that reported both the availability of policy and practice of testing and treatment of LTBI for at-risk populations, a system for recording and reporting data was available in 62% (33/53) for child contacts and in 53% (21/40) for PLHIV. CONCLUSION: Countries need to ensure that national LTBI policies and a standardised monitoring and evaluation system are in place to promote the programmatic management of LTBI.

Seguimiento de la fiebre chikunguña: a propósito de un caso importado / Follow up of Chikungunya virus: report of an imported case

La fiebre chikunguña es una infección vírica transmitida por artrópodos. Se caracteriza por un cuadro sistémico con una fase aguda de fiebre alta, poliartralgia, dolor de espalda, cefalea y erupciones cutáneas como síntomas comunes, a la que eventualmente pueden suceder unas fases subaguda y crónica. Las manifestaciones oculares pueden estar presentes en cualquiera de ellas, en forma de conjuntivitis, uveítis y retinitis fundamentalmente. La fotofobia aislada se describe como un síntoma frecuente en niños. Se presenta un caso de fiebre chikunguña en una niña de tres años que se contagió y cursó el cuadro agudo durante un viaje a República Dominicana, en un entorno epidémico. Semanas después, ya de vuelta en España, y tras un periodo asintomático, aparecen fotofobia y molestias oculares, así como estancamiento ponderal. Se confirmó el diagnóstico mediante serología de virus chikunguña. Se describen las principales manifestaciones clínicas de esta infección, subrayando las más características de la edad infantil, así como las oftalmológicas

Chikungunya fever is a viral infection transmitted by arthropods. It is a systemic disease characterized by these cardinal symptoms in the acute phase: polyarthralgia, back pain, headache and skin eruptions, which can sometimes be followed by subacute and chronic stages. Ophthalmological manifestations, such as uveitis, retinitis or conjunctivitis, may appear in any of these phases. Isolated photophobia has been described as a common manifestation in children. A case of chikungunya is presented in a three-year-old child who got infected and underwent the acute phase of the disease during a trip to the Dominican Republic, an epidemic environment. Weeks later, already back in Spain, and after an asymptomatic period, the child showed signs of photophobia, eye pain and ponderal stagnation. The diagnosis was confirmed through viral serology, which was positive for the chikungunya virus. The main clinical manifestations of this infection will be described in this article, highlighting the ophthalmological symptoms as well as the most common ones in the pediatric age group

Peritumoral adipose tissue as a source of inflammatory and angiogenic factors in colorectal cancer.

PURPOSE: Obesity is a risk factor for the development of human colorectal cancer (CC). The aim of this work is to report the inflammatory and angiogenic scenario in lean (BMI < 25 kg/m2) and obese (BMI > 30 kg/m2) patients with and without CC and to assess the role of peritumoral adipose tissue in CC-induced inflammation. MATERIAL AND METHODS: Patients were divided in four experimental groups: obese patients with CC (OB-CC), lean patients with CC (LEAN-CC), obese patients without CC (OB), and lean patients without CC (LEAN). RESULTS: Plasma levels of pro-inflammatory cytokines (interleukin (IL)-6, IL-4, IL-8) and granulocyte-macrophage colony-stimulating factor (GM-CSF) were increased in OB-CC patients. Peritumoral adipose tissue (TF) explants and cultured mature adipocytes secreted higher amounts of nitrites and nitrates than did control and non-tumoral (NTF) adipose tissue both alone and in response to lipopolysaccharide (LPS). Nitrite and nitrate secretion was also increased in TF explants from OB-CC patients compared with that from LEAN-CC patients. Gene expression of adiponectin, tumor necrosis factor alpha (TNF-α), insulin-like growth factor type I (IGF-I), cyclooxygenase-2 (COX-2), and peroxisome proliferator-activated receptor γ (PPAR-γ) was increased in TF explants from CC patients. LPS increased the gene expression of IL-6, IL-10, TNF-α, vascular endothelial growth factor (VEGF), and COX-2 in OB and in TF explants from OB-CC patients. COX-2 and PPAR-γ inhibition further increased LPS-induced release of nitrites and nitrates in TF explants and adipocytes from OB-CC patients. CONCLUSIONS: In conclusion, OB-CC patients have increased plasma levels of pro-inflammatory and angiogenic factors. TF from OB-CC patients shows an increased secretion of inflammatory markers compared with both TF from LEAN-CC and non-tumoral adipose tissue (AT) through a COX-2- and PPAR-γ-independent mechanism.

The metabolic response to postnatal leptin in rats varies with age and may be litter dependent.

Hyperleptinemia during postnatal life induces long-term effects on metabolism. However, these effects are controversial as both increased and decreased propensity towards obesity has been reported. To further analyze the effects of chronic neonatal hyperleptinemia on the subsequent metabolic profile, male Wistar rats proceeding from 18 different litters (8 pups/litter) received a daily subcutaneous injection of either saline (10 ml/kg, n=36) or leptin (3 µg/g, n=36) from postnatal day (PND) 2 to PND9. Rats were sacrificed at 10, 40, or 150 days of age. At 10 days of age, leptin treated rats had decreased body weight (p<0.001) and body fat (p<0.05). Leptin levels and glycemia were increased (p<0.01), whereas insulin, total lipids, triglycerides and glycerol levels were decreased (p<0.05). At PND40 rats receiving leptin had increased glycemia (p<0.01) and plasma HDL and LDL levels, but decreased total lipids (p<0.05). At PND150 neonatal leptin treatment induced different effects in rats raised in different litters. Rats from litter 1 had increased body weight (p<0.05), body fat (p<0.01), and plasma leptin (p<0.001), cholesterol (p<0.001), triglyceride (p<0.001), total lipid (p<0.001), LDL (p<0.05), and glycerol (p<0.001) levels. In rats from litter 2 these parameters did not differ from controls. Rats from litter 3 had decreased body weight (p<0.05), visceral fat (p<0.01) and plasma leptin (p<0.001), cholesterol (p<0.001), triglyceride (p<0.001), glycerol (p<0.001), and HDL (p<0.001) levels. In conclusion, the metabolic response to postnatal leptin varies with age, with the response in adulthood being variable and most likely influenced by other factors, including the genetic make-up.

Aparición temprana de varicela modificada en niños vacunados con una dosis / Early presentation of breakthrough varicella in vaccinated children

Introducción: El uso sistemático de la vacuna de la varicela en niños ha conseguido una reducción significativa de la morbimortalidad. Sin embargo, persiste la incidencia de varicela en sujetos vacunados, varicela modificada (VM), lo que ha motivado la incorporación de una segunda dosis a los calendarios vacunales, a una edad que podría ser demasiado tardía. Se pretende medir el tiempo trascurrido desde la vacunación hasta la aparición de la VM. Pacientes y métodos: Se presentan 23 casos de niños diagnosticados de VM (media de edad al diagnóstico: 4,85 años), vacunados con una dosis (media de edad de vacunación: 2,37 años). Resultados: El tiempo medio transcurrido desde la vacunación hasta la VM fue de 2,48 años y la mediana 2,0 años. El 13% de los niños diagnosticados de VM habían sido vacunados el año previo y el 52%, en los 2 previos, tiempo inferior al recomendado para recibir la segunda dosis de vacuna según los calendarios vigentes. Conclusiones: Para disminuir los fallos vacunales, podría considerarse la aproximación de las dosis de vacuna e incluso la administración consecutiva (AU)

Introduction: The introduction of a routine varicella vaccination program for children has achieved a significant reduction in morbidity and mortality due to varicella. However, there is still an incidence of chickenpox in those vaccinated, called “varicella breakthrough” (VB). This has led to the inclusion of a 2nd dose vaccination schedule, at an age which could be too late. Patients and methods: This study presents 23 cases of children diagnosed with VB (mean age at diagnosis 4.85 years) who had been vaccinated with one dose of varicella vaccine (mean age of vaccination 2.37 years). Results: The mean time between the vaccine and the disease was 2.48 years, with a median of 2.0 years. VB was diagnosed in 13% of children who had been vaccinated the previous year, and 52% diagnosed in the previous two. Therefore many of these patients had suffered the disease before the recommended time of administration of the second dose of vaccine according to the current vaccine schedules. Conclusions: To avoid these vaccine failures, it would be appropriate to bring the two doses of varicella vaccine closer, or even assess the pattern of two consecutive doses (AU)

Successful management of multidrug-resistant tuberculosis under programme conditions in the Dominican Republic.

SETTING: The Dominican Republic is a high-incidence area for multidrug-resistant tuberculosis (MDR-TB; 6.6% of initial cases). Standardised treatment regimens for MDR-TB may be a potential solution. OBJECTIVE: To present the effectiveness of standard regimens under routine national conditions. DESIGN: We reviewed all MDR-TB patients treated under routine conditions from 29 August 2006 to 30 June 2010, showing interim and final outcomes. Patients were treated with regimens that were standardised or individualised based on previously received second-line anti-tuberculosis drugs. RESULTS: Population description and culture conversion data are reported for the 289 MDR-TB patients. The median patient age was 31 years. Most had failed first-line treatment (72.6%). Culture negativity was obtained within 4 months (median 2 months) in 78.6%. Among the 150 patients treated between 2006 and 2008, 74% had favourable results on standardised and 66% on individualised regimens (P = 0.211). The efficacy of the standardised and individualised regimens was respectively 92.8% and 81% (P = 0.056). The relapse rate was approximately 1%. A median of five drug side effects occurred per patient. More than 2 months to culture conversion and bilateral cavitation on chest X-ray were found to be unfavourable outcome risk factors. CONCLUSIONS: Standardised MDR-TB regimens may be effective at the national level, even in resource-poor settings.

[Early presentation of breakthrough varicella in vaccinated children]. / Aparición temprana de varicela modificada en niños vacunados con una dosis.

INTRODUCTION: The introduction of a routine varicella vaccination program for children has achieved a significant reduction in morbidity and mortality due to varicella. However, there is still an incidence of chickenpox in those vaccinated, called "varicella breakthrough" (VB). This has led to the inclusion of a 2nd dose vaccination schedule, at an age which could be too late. PATIENTS AND METHODS: This study presents 23 cases of children diagnosed with VB (mean age at diagnosis 4.85 years) who had been vaccinated with one dose of varicella vaccine (mean age of vaccination 2.37 years). RESULTS: The mean time between the vaccine and the disease was 2.48 years, with a median of 2.0 years. VB was diagnosed in 13% of children who had been vaccinated the previous year, and 52% diagnosed in the previous two. Therefore many of these patients had suffered the disease before the recommended time of administration of the second dose of vaccine according to the current vaccine schedules. CONCLUSIONS: To avoid these vaccine failures, it would be appropriate to bring the two doses of varicella vaccine closer, or even assess the pattern of two consecutive doses.