Influencia de la edad en el contenido de fenoles y ligninas en Gmelina arborea (Lamiaceae) / The influence of age on the phenolic contents and lignins of Gmelina arborea (Lamiaceae)

Resumen Introducción: La melina (Gmelina arborea), es una especie de gran interés por su madera y propiedades medicinales. En Costa Rica, existen clones genéticamente superiores que se propagan sin el conocimiento de la edad ontogénica y fisiológica de los materiales. Objetivo: Evaluar la relación del contenido de fenoles y ligninas en hojas, peciolos, tallos y raíces de plantas con diferentes edades. Métodos: Los contenidos de fenoles y ligninas totales se determinaron mediante el método colorimétrico de Folin-Ciocalteu y el método de extracción alcalina, respectivamente. Para la investigación se eligieron plantas in vitro "año cero" y árboles de año y medio, cuatro, siete y 20 años. El muestreo se realizó en marzo y abril del 2021. Resultados: Se demostró que todas las partes de la planta analizadas contienen compuestos fenólicos y ligninas, independientemente de su edad. No hubo una correlación positiva entre la edad con el contenido de fenoles y ligninas para ninguna condición de desarrollo, pues los valores más altos no se obtuvieron en los árboles más longevos. Los extractos de hojas de las plantas in vitro y los árboles de siete años mostraron, respectivamente, los contenidos más altos de fenoles y ligninas para todas las condiciones (P < 0.05). Los valores promedio más bajos de compuestos fenólicos para todas las condiciones se obtuvieron en los árboles de cuatro años. Respecto a las ligninas, el contenido más bajo se presentó en las raíces más longevas, aunque la tendencia no se mantuvo para el resto de las partes de la planta. Conclusiones: La investigación muestra los primeros resultados del contenido de compuestos fenólicos y ligninas presentes en diferentes tejidos de una especie forestal de edades diferentes. Por lo tanto, son los primeros valores de referencia acerca del compromiso bioquímico para la síntesis fenólica según la edad y el estado de desarrollo específico de una planta leñosa.

Abstract Introduction: Melina (Gmelina arborea) is a tree species of great interest for its wood and medicinal properties. In Costa Rica, there are genetically superior clones that are propagated without knowledge of the ontogenic and physiological age of the materials. Objective: To evaluate how age influences the content of phenols and lignins in leaves, petioles, stems, and roots of melina plants. Methods: The total phenolic and lignins contents were determined using Folin-Ciocalteu colorimetric method and alkaline extraction method, respectively. Plants of five different ages were chosen for the investigation (in vitro plants "year 0" and trees of a year and a half, four, seven and 20 years). Sampling was done in March and April 2021. Results: All parts of the plant analyzed contain phenolic compounds and lignins, regardless of their age. There was no positive correlation between age and phenol and lignin content for any development condition, since the highest values were not obtained in the oldest trees. Leaf extracts from in vitro plants and seven-year-old trees showed, respectively, the highest phenol and lignin contents for all conditions (P < 0.05). The lowest average values of phenolic compounds for all conditions were obtained in four-year-old trees. Regarding lignins, the lowest content occurred in the oldest roots, although the trend was not maintained for the rest of the plant parts. Conclusions: This study provides the first results of the content of phenolic compounds and lignins present in different tissues of a forest species of different ages. Therefore, they are the first reference values about the biochemical commitment for phenolic synthesis according to the age and the specific developmental stage of a woody plant.

Fatal acute undifferentiated febrile illness among clinically suspected leptospirosis cases in Colombia, 2016-2019.

BACKGROUND: Acute undifferentiated febrile illness is a common challenge for clinicians, especially in tropical and subtropical countries. Incorrect or delayed diagnosis of febrile patients may result in medical complications or preventable deaths. Common causes of acute undifferentiated febrile illness in Colombia include leptospirosis, rickettsioses, dengue fever, malaria, chikungunya, and Zika virus infection. In this study, we described the acute undifferentiated febrile illness in postmortem patients reported as suspected cases of leptospirosis through the national leptospirosis surveillance in Colombia, 2016-2019. METHODOLOGY/PRINCIPAL FINDINGS: We retrospectively analyze human fresh and formalin-fixed tissue samples from fatal suspected leptospirosis cases reported by the Public Health Laboratories in Colombia. Leptospirosis confirmation was made by immunohistochemistry, real-time polymerase chain reaction (PCR) in the tissue samples. In some cases, the serum sample was used for confirmation by Microagglutination test (MAT). Simultaneously, tissue samples were tested by PCR for the most common viral (dengue, Zika, and chikungunya), bacterial (Brucella spp., and Rickettsia spp.), and parasitic (malaria). Fresh tissue samples from 92 fatal suspected leptospirosis cases were reported to the National Reference Laboratory from 22/32 departments in Colombia. We confirmed leptospirosis in 27% (25/92) of cases. Other pathogens identified by real-time PCR were Brucella spp. (10.9%), Rickettsia spp. (14.1%), and dengue (2.2%). Dengue (6.9%), hepatitis (3.5%), and Yellow Fever cases (2.2%) were detected by the pathology. All patients were negative for chikungunya and Plasmodium spp. Most cases were classified as undifferentiated febrile illnesses (45.7%; 42/92). CONCLUSIONS/SIGNIFICANCE: This study underscores the importance of early and accurate recognition of leptospirosis to prevent mortalities. Moreover, it draws attention to the existence of other febrile syndromes in Colombia, including rickettsiosis and brucellosis, that currently lack sufficient human surveillance and regular reporting. Expanding laboratory surveillance to include viruses such as Hantavirus, Mayaro virus, Oropouche virus, and West Nile virus is crucial.

Malaria in populations with mining occupation, Colombia, 2012-2018 / [Malaria en poblaciones con ocupación minera, Colombia, 2012-2018].

Introduction: Malaria represents one of the biggest public health challenges, mainly in poor countries. Colombia has social characteristics such as migration, informal work, and economic shortages that favor illegal mining activities. The study of the malaria situation in these areas would allow establishing the bases for its prevention, control, and treatment in the existing public health programs. Objective: To describe the malaria situation in Colombian mining populations between 2012 and 2018. Materials and methods. We conducted a retrospective descriptive study with graphs and maps. For the statistical analysis, we used Pearson´s correlation and Moran's index. Results. From 2012 to 2018, 44,032 cases of malaria were reported in the mining population, 43,900 of uncomplicated malaria and 132 of complicated malaria, and three deaths, two due to Plasmodium vivax and one due to mixed infection. During this period, there was a decrease of 44.7% in cases. The risk rate in 2012 was 2.5 cases x 1000 inhabitants; 87.3% of cases were in men, and 37.9% corresponded to the 20 to 29-year-old age group while 46.7% were AfroColombians. We found a possible moderate positive linear correlation: The greater the mining activity, the greater the number of malaria cases. The global Moran index indicated a significant spatial grouping of cases in mining activities in Colombian Pacific municipalities. Conclusions. The case notification decrease during this period could be attributed to an underreporting of the public health surveillance system (Sivigila) system, as most miners do not have formal jobs, which prevents them from accessing health services. A cohort study is recommended in endemic areas to establish a direct relationship between mining exploitation and the occurrence of malaria cases.

Introducción. La malaria representa uno de los mayores desafíos de salud pública, principalmente en los países pobres. Ciertas características sociales de Colombia, como la migración, el trabajo informal y la escasez económica, favorecen la minería ilegal. El análisis de la situación de la malaria en estas áreas permite establecer una guía para la prevención, el control y el tratamiento de la enfermedad en los programas de salud pública existentes. Objetivo. Describir la situación de la malaria en las poblaciones mineras colombianas entre el 2012 y el 2018. Materiales y métodos. Se hizo un estudio descriptivo y retrospectivo que incluyó la creación de gráficos y mapas. Para el análisis estadístico se utilizaron la correlación de Pearson y el índice de Moran. Resultados. Entre el 2012 y el 2018, se notificaron 44.032 casos de malaria en la población minera, 43.900 de malaria no complicada y 132 de malaria complicada, así como tres muertes, dos por Plasmodium vivax y una por infección mixta. Hubo una disminución del 44,7 % de los casos en el período evaluado. La tasa de riesgo en el 2012 fue de 2,5 casos por 1.000 habitantes; el 87,3 % de los casos se presentó en hombres y el 37,9 % en personas entre los 20 y los 29 años, en tanto que el 46,7 % de la población estudiada estaba conformada por afrocolombianos. Se encontró una posible correlación lineal positiva moderada entre mayor la actividad minera, mayor el número de casos de malaria en mineros. El índice de Moran global evidenció una agrupación espacial significativa de los casos de malaria en zonas con industria minera en los municipios del Pacífico colombiano. Conclusiones. La disminución en la notificación de casos durante el período evaluado podría atribuirse a un subregistro del Sistema de Vigilancia en Salud Pública (Sivigila), ya que la mayoría de los mineros no tienen trabajos formales, lo que dificulta su acceso a los servicios de salud. Se recomienda un estudio de cohorte en áreas endémicas para establecer una relación directa entre la explotación minera y la presencia de casos de malaria.

Malaria en poblaciones con ocupación minera, Colombia, 2012-2018 / Malaria in populations with mining occupation, Colombia, 2012-2018

Resumen | Introducción. La malaria representa uno de los mayores desafíos de salud pública, principalmente en los países pobres. Ciertas características sociales de Colombia, como la migración, el trabajo informal y la escasez económica, favorecen la minería ilegal. El análisis de la situación de la malaria en estas áreas permite establecer una guía para la prevención, el control y el tratamiento de la enfermedad en los programas de salud pública existentes. Objetivo. Describir la situación de la malaria en las poblaciones mineras colombianas entre el 2012 y el 2018. Materiales y métodos. Se hizo un estudio descriptivo y retrospectivo que incluyó la creación de gráficos y mapas. Para el análisis estadístico se utilizaron la correlación de Pearson y el índice de Moran. Resultados. Entre el 2012 y el 2018, se notificaron 44.032 casos de malaria en la población minera, 43.900 de malaria no complicada y 132 de malaria complicada, así como tres muertes, dos por Plasmodium vivax y una por infección mixta. Hubo una disminución del 44,7 % de los casos en el período evaluado. La tasa de riesgo en el 2012 fue de 2,5 casos por 1.000 habitantes; el 87,3 % de los casos se presentó en hombres y el 37,9 % en personas entre los 20 y los 29 años, en tanto que el 46,7 % de la población estudiada estaba conformada por afrocolombianos. Se encontró una posible correlación lineal positiva moderada entre mayor la actividad minera, mayor el número de casos de malaria en mineros. El índice de Moran global evidenció una agrupación espacial significativa de los casos de malaria en zonas con industria minera en los municipios del Pacífico colombiano. Conclusiones. La disminución en la notificación de casos durante el período evaluado podría atribuirse a un subregistro del Sistema de Vigilancia en Salud Pública (Sivigila), ya que la mayoría de los mineros no tienen trabajos formales, lo que dificulta su acceso a los servicios de salud. Se recomienda un estudio de cohorte en áreas endémicas para establecer una relación directa entre la explotación minera y la presencia de casos de malaria.

Abstract | Introduction: Malaria represents one of the biggest public health challenges, mainly in poor countries. Colombia has social characteristics such as migration, informal work, and economic shortages that favor illegal mining activities. The study of the malaria situation in these areas would allow establishing the bases for its prevention, control, and treatment in the existing public health programs. Objective: To describe the malaria situation in Colombian mining populations between 2012 and 2018. Materials and methods. We conducted a retrospective descriptive study with graphs and maps. For the statistical analysis, we used Pearson's correlation and Moran's index. Results. From 2012 to 2018, 44,032 cases of malaria were reported in the mining population, 43,900 of uncomplicated malaria and 132 of complicated malaria, and three deaths, two due to Plasmodium vivax and one due to mixed infection. During this period, there was a decrease of 44.7% in cases. The risk rate in 2012 was 2.5 cases x 1000 inhabitants; 87.3% of cases were in men, and 37.9% corresponded to the 20 to 29-year-old age group while 46.7% were AfroColombians. We found a possible moderate positive linear correlation: The greater the mining activity, the greater the number of malaria cases. The global Moran index indicated a significant spatial grouping of cases in mining activities in Colombian Pacific municipalities. Conclusions. The case notification decrease during this period could be attributed to an underreporting of the public health surveillance system (Sivigila) system, as most miners do not have formal jobs, which prevents them from accessing health services. A cohort study is recommended in endemic areas to establish a direct relationship between mining exploitation and the occurrence of malaria cases.

Tandem Bioorthogonal Labeling Uncovers Endogenous Cotranslationally O-GlcNAc Modified Nascent Proteins.

Hundreds of nuclear, cytoplasmic, and mitochondrial proteins within multicellular eukaryotes have hydroxyl groups of specific serine and threonine residues modified by the monosaccharide N-acetylglucosamine (GlcNAc). This modification, known as O-GlcNAc, has emerged as a central regulator of both cell physiology and human health. A key emerging function of O-GlcNAc appears to be to regulate cellular protein homeostasis. We previously showed, using overexpressed model proteins, that O-GlcNAc modification can occur cotranslationally and that this process prevents premature degradation of such nascent polypeptide chains. Here, we use tandem metabolic engineering strategies to label endogenously occurring nascent polypeptide chains within cells using O-propargyl-puromycin (OPP) and target the specific subset of nascent chains that are cotranslationally glycosylated with O-GlcNAc by metabolic saccharide engineering using tetra-O-acetyl-2-N-azidoacetyl-2-deoxy-d-galactopyranose (Ac4GalNAz). Using various combinations of sequential chemoselective ligation strategies, we go on to tag these analytes with a series of labels, allowing us to define conditions that enable their robust labeling. Two-step enrichment of these glycosylated nascent chains, combined with shotgun proteomics, allows us to identify a set of endogenous cotranslationally O-GlcNAc modified proteins. Using alternative targeted methods, we examine three of these identified proteins and further validate their cotranslational O-GlcNAcylation. These findings detail strategies to enable isolation and identification of extremely low abundance endogenous analytes present within complex protein mixtures. Moreover, this work opens the way to studies directed at understanding the roles of O-GlcNAc and other cotranslational protein modifications and should stimulate an improved understanding of the role of O-GlcNAc in cytoplasmic protein quality control and proteostasis.

Microporous polymer microspheres with amphoteric character for the solid-phase extraction of acidic and basic analytes.

Solid-phase extraction (SPE) is a widely-used and very well-established sample preparation technique for liquid samples. An area of on-going focus for innovation in this field concerns the development of new and improved SPE sorbents that can enhance the sensitivity and/or the selectivity of SPE processes. In this context, mixed-mode ion-exchange sorbents have been developed and commercialised, thereby allowing enhanced capacity and selectivity to be offered by one single material. The ion-selectivity of these materials is such that either anion-exchange or cation-exchange is possible, however one limitation to their use is that more than one sorbent type is required to capture both anions and cations. In this paper, we disclose the design, synthesis and exploitation of a novel SPE sorbent based on microporous polymer microspheres with amphoteric character. We show that it is possible to switch the ion-exchange retention mechanism of the sorbent simply by changing the pH of the loading solution; anion-exchange dominates at low pH, cation-exchange dominates at high pH, and both mechanisms can contribute to retention when the polymer-bound amphoteric species, which are based on the α-amino acid sarcosine (N-methylglycine), are in a zwitterionic state. This is an interesting and useful feature, since it allows distinctly different groups of analytes (acids and bases) to be fractionated using one single amphoteric sorbent with dual-functionality. The sarcosine-based sorbent was applied to the SPE of acidic, basic and amphoteric analytes from ultrapure water, river water and effluent wastewater samples. Under optimised conditions (loading 100 mL of sample at pH 6, washing with 1 mL of MeOH and eluting with an acidic or basic additive in MeOH) the recoveries for most of the compounds were from 57% to 87% for river water and from 61% to 88% for effluent wastewater. We anticipate that these results will lay the basis for the development of a new family of multifunctional sorbents, where two or more separation mechanisms can be embedded within one single, bespoke material optimised for application to challenging chemical separations to give significant selectivity advantages over essentially all other state-of-the-art SPE sorbents.

Dietary Potassium Downregulates Angiotensin-I Converting Enzyme, Renin, and Angiotensin Converting Enzyme 2.

BACKGROUND: The importance of dietary potassium in health and disease has been underestimated compared with that placed on dietary sodium. Larger effort has been made on reduction of sodium intake and less on the adequate dietary potassium intake, although natural food contains much more potassium than sodium. The benefits of a potassium-rich diet are known, however, the mechanism by which it exerts its preventive action, remains to be elucidated. With the hypothesis that dietary potassium reduces renal vasoconstrictor components of the renin-angiotensin system in the long-term, we studied the effect of high potassium diet on angiotensin-I converting enzyme, renin, and angiotensin converting enzyme 2. METHODS: Sprague Dawley male rats on a normal sodium diet received normal potassium (0.9%, NK) or high potassium diet (3%, HK) for 4 weeks. Urine was collected in metabolic cages for electrolytes and urinary volume measurement. Renal tissue was used to analyze angiotensin-I converting enzyme, renin, and angiotensin converting enzyme 2 expression. Protein abundance analysis was done by Western blot; gene expression by mRNA levels by RT-qPCR. Renal distribution of angiotensin-I converting enzyme and renin was done by immunohistochemistry and morphometric analysis in coded samples. RESULTS: High potassium diet (4 weeks) reduced the levels of renin, angiotensin-I converting enzyme, and angiotensin converting enzyme 2. Angiotensin-I converting enzyme was located in the brush border of proximal tubules and with HK diet decreased the immunostaining intensity (P < 0.05), decreased the mRNA (P < 0.01) and the protein levels (P < 0.01). Renin localization was restricted to granular cells of the afferent arteriole and HK diet decreased the number of renin positive cells (P < 0.01) and renin mRNA levels (P < 0.01). High potassium intake decreased angiotensin converting enzyme 2 gene expression and protein levels (P < 0.01).No morphological abnormalities were observed in renal tissue during high potassium diet.The reduced expression of angiotensin-I converting enzyme, renin, and angiotensin converting enzyme 2 during potassium supplementation suggest that high dietary potassium intake could modulate these vasoactive enzymes and this effects can contribute to the preventive and antihypertensive effect of potassium.

Early Long-Term Memory Impairment and Changes in the Expression of Synaptic Plasticity-Associated Genes, in the McGill-R-Thy1-APP Rat Model of Alzheimer's-Like Brain Amyloidosis.

Accruing evidence supports the hypothesis that memory deficits in early Alzheimer Disease (AD) might be due to synaptic failure caused by accumulation of intracellular amyloid beta (Aß) oligomers, then secreted to the extracellular media. Transgenic mouse AD models provide valuable information on AD pathology. However, the failure to translate these findings to humans calls for models that better recapitulate the human pathology. McGill-R-Thy1-APP transgenic (Tg) rat expresses the human amyloid precursor protein (APP751) with the Swedish and Indiana mutations (of familial AD), leading to an AD-like slow-progressing brain amyloid pathology. Therefore, it offers a unique opportunity to investigate learning and memory abilities at early stages of AD, when Aß accumulation is restricted to the intracellular compartment, prior to plaque deposition. Our goal was to further investigate early deficits in memory, particularly long-term memory in McGill-R-Thy1-APP heterozygous (Tg+/-) rats. Short-term- and long-term habituation to an open field were preserved in 3-, 4-, and 6-month-old (Tg+/-). However, long-term memory of inhibitory avoidance to a foot-shock, novel object-recognition and social approaching behavior were seriously impaired in 4-month-old (Tg+/-) male rats, suggesting that they are unable to either consolidate and/or evoke such associative and discriminative memories with aversive, emotional and spatial components. The long-term memory deficits were accompanied by increased transcript levels of genes relevant to synaptic plasticity, learning and memory processing in the hippocampus, such as Grin2b, Dlg4, Camk2b, and Syn1. Our findings indicate that in addition to the previously well-documented deficits in learning and memory, McGill-R-Thy1-APP rats display particular long-term-memory deficits and deep social behavior alterations at pre-plaque early stages of the pathology. This highlights the importance of Aß oligomers and emphasizes the validity of the model to study AD-like early processes, with potentially predictive value.

Next-generation Interactomics: Considerations for the Use of Co-elution to Measure Protein Interaction Networks.

Understanding how proteins interact is crucial to understanding cellular processes. Among the available interactome mapping methods, co-elution stands out as a method that is simultaneous in nature and capable of identifying interactions between all the proteins detected in a sample. The general workflow in co-elution methods involves the mild extraction of protein complexes and their separation into several fractions, across which proteins bound together in the same complex will show similar co-elution profiles when analyzed appropriately. In this review we discuss the different separation, quantification and bioinformatic strategies used in co-elution studies, and the important considerations in designing these studies. The benefits of co-elution versus other methods makes it a valuable starting point when asking questions that involve the perturbation of the interactome.

Local and regional dynamics of chikungunya virus transmission in Colombia: the role of mismatched spatial heterogeneity.

BACKGROUND: Mathematical models of transmission dynamics are routinely fitted to epidemiological time series, which must inevitably be aggregated at some spatial scale. Weekly case reports of chikungunya have been made available nationally for numerous countries in the Western Hemisphere since late 2013, and numerous models have made use of this data set for forecasting and inferential purposes. Motivated by an abundance of literature suggesting that the transmission of this mosquito-borne pathogen is localized at scales much finer than nationally, we fitted models at three different spatial scales to weekly case reports from Colombia to explore limitations of analyses of nationally aggregated time series data. METHODS: We adapted the recently developed Disease Transmission Kernel (DTK)-Dengue model for modeling chikungunya virus (CHIKV) transmission, given the numerous similarities of these viruses vectored by a common mosquito vector. We fitted versions of this model specified at different spatial scales to weekly case reports aggregated at different spatial scales: (1) single-patch national model fitted to national data; (2) single-patch departmental models fitted to departmental data; and (3) multi-patch departmental models fitted to departmental data, where the multiple patches refer to municipalities within a department. We compared the consistency of simulations from fitted models with empirical data. RESULTS: We found that model consistency with epidemic dynamics improved with increasing spatial granularity of the model. Specifically, the sum of single-patch departmental model fits better captured national-level temporal patterns than did a single-patch national model. Likewise, multi-patch departmental model fits better captured department-level temporal patterns than did single-patch departmental model fits. Furthermore, inferences about municipal-level incidence based on multi-patch departmental models fitted to department-level data were positively correlated with municipal-level data that were withheld from model fitting. CONCLUSIONS: Our model performed better when posed at finer spatial scales, due to better matching between human populations with locally relevant risk. Confronting spatially aggregated models with spatially aggregated data imposes a serious structural constraint on model behavior by averaging over epidemiologically meaningful spatial variation in drivers of transmission, impairing the ability of models to reproduce empirical patterns.

Imbalance in Renal Vasoactive Enzymes Induced by Mild Hypoxia: Angiotensin-Converting Enzyme Increases While Neutral Endopeptidase Decreases.

Chronic hypoxia has been postulated as one of the mechanisms involved in salt-sensitive hypertension and chronic kidney disease (CKD). Kidneys have a critical role in the regulation of arterial blood pressure through vasoactive systems, such as the renin-angiotensin and the kallikrein-kinin systems, with the angiotensin-converting enzyme (ACE) and kallikrein being two of the main enzymes that produce angiotensin II and bradykinin, respectively. Neutral endopeptidase 24.11 or neprilysin is another enzyme that among its functions degrade vasoactive peptides including angiotensin II and bradykinin, and generate angiotensin 1-7. On the other hand, the kidneys are vulnerable to hypoxic injury due to the active electrolyte transportation that requires a high oxygen consumption; however, the oxygen supply is limited in the medullary regions for anatomical reasons. With the hypothesis that the chronic reduction of oxygen under normobaric conditions would impact renal vasoactive enzyme components and, therefore; alter the normal balance of the vasoactive systems, we exposed male Sprague-Dawley rats to normobaric hypoxia (10% O2) for 2 weeks. We then processed renal tissue to identify the expression and distribution of kallikrein, ACE and neutral endopeptidase 24.11 as well as markers of kidney damage. We found that chronic hypoxia produced focal damage in the kidney, mainly in the cortico-medullary region, and increased the expression of osteopontin. Moreover, we observed an increase of ACE protein in the brush border of proximal tubules at the outer medullary region, with increased mRNA levels. Kallikrein abundance did not change significantly with hypoxia, but a tendency toward reduction was observed at protein and mRNA levels. Neutral endopeptidase 24.11 was localized in proximal tubules, and was abundantly expressed under normoxic conditions, which markedly decreased both at protein and mRNA levels with chronic hypoxia. Taken together, our results suggest that chronic hypoxia produces focal kidney damage along with an imbalance of key components of the renal vasoactive system, which could be the initial steps for a long-term contribution to salt-sensitive hypertension and CKD.

Blockade of Bradykinin receptors worsens the dystrophic phenotype of mdx mice: differential effects for B1 and B2 receptors.

The Kallikrein Kinin System (KKS) is a vasoactive peptide system with known functions in the maintenance of tissue homeostasis, renal function and blood pressure. The main effector peptide of KKS is Bradykinin (BK). This ligand has two receptors: a constitutive B2 receptor (B2R), which has been suggested to have anti-fibrotic effects in renal and cardiac models of fibrosis; and the inducible B1 receptor (B1R), whose expression is induced by damage and inflammation. Inflammation and fibrosis are hallmarks of Duchenne muscular dystrophy (DMD), therefore we hypothesized that the KKS may play a role in this disease. To evaluate this hypothesis we used the mdx mouse a model for DMD. We blocked the endogenous activity of the KKS by treating mdx mice with B2R antagonist (HOE-140) or B1R antagonist (DesArgLeu8BK (DALBK)) for four weeks. Both antagonists increased damage, fibrosis, TGF-ß and Smad-dependent signaling, CTGF/CCN-2 levels as well as the number of CD68 positive inflammatory cells. B2R blockade also reduced isolated muscle contraction force. These results indicate that the endogenous KKS has a protective role in the dystrophic muscle. The KKS may be a new target for future therapies to reduce inflammation and fibrosis in dystrophic muscle.

Combining cationic and anionic mixed-mode sorbents in a single cartridge to extract basic and acidic pharmaceuticals simultaneously from environmental waters.

The aim of the present study is to broaden the applications of mixed-mode ion-exchange solid-phase extraction sorbents to extract both basic and acidic compounds simultaneously by combining the sorbents in a single cartridge and developing a simplified extraction procedure. Four different cartridges containing negative and positive charges in the same configuration were evaluated and compared to extract a group of basic, neutral, and acidic pharmaceuticals selected as model compounds. After a thorough optimization of the extraction conditions, the four different cartridges showed to be capable of retaining basic and acidic pharmaceuticals simultaneously through ionic interactions, allowing the introduction of a washing step with 15 mL methanol to eliminate interferences retained by hydrophobic interactions. Using the best combined cartridge, a method was developed, validated, and further applied to environmental waters to demonstrate that the method is promising for the extraction of basic and acidic compounds from very complex samples.

Prevalencia de Leptospirosis en Colombia: revisión sistemática de literatura / Prevalence of leptospirosis in Colombia: systematic literature review

RESUMEN Objetivo Realizar una revisión sistemática de literatura para identificar las prevalencias de leptospirosis en Colombia en el periodo de tiempo comprendido entre los años 2000 y 2012. Materiales y Métodos Se seleccionaron estudios descriptivos, realizados y publicados durante los años 2000 y 2012 sobre prevalencias de leptospirosis en humanos, animales y medio ambiente, por métodos diagnósticos de Microaglutinación (MAT) e Inmunoensayo (ELISA). Dentro de los criterios de exclusión, se tuvieron en cuenta estudios en idiomas diferentes al español, inglés y portugués, con determinación de prevalencias de leptospirosis por Inmunofluorescenia (IFI), o sueroaglutinación (SAT). Resultados De 91 artículos revisados en las diferentes bases de datos se seleccionaron 18 que cumplieron con los criterios de inclusión, los cuales determinaron prevalencias de leptospirosis en hombres, caninos, bovinos, porcinos, primates y roedores, en los departamentos de Atlántico, Antioquia, Meta, Córdoba, Risaralda, Tolima, Boyacá, Quindío y Valle del Cauca. Conclusiones La revisión sistemática permitió determinar cuáles son los departamentos de país donde se concentra la investigación en leptospirosis y los autores que cuentan con mayor número de publicaciones sobre prevalencias. De igual manera se pudo evidenciar que las prevalencias encontradas están entre 6% y el 35% para humanos, 41% y 60,9% para bovinos, 10,3% para porcinos, 12% y 47,14% para caninos, 23,07% para primates no humanos y entre el 25% y el 82,7% en roedores, siendo las más altas. Los serovares de mayor circulación fueron Icterohaemorrhagiae, Grippotyphosa, y Canicola.(AU)

ABSTRACT Objective To conduct a systematic literature review to identify the prevalence of leptospirosis in Colombia between 2000 and 2012. Methods Descriptive studies conducted and published between 2000 and 2012 on the prevalence of leptospirosis in humans, animals and the environment using microagglutination (MAT) and immunoassay (ELISA) diagnostic methods, were selected. The exclusion criteria included studies in languages other than Spanish, English and Portuguese, in which the prevalence of leptospirosis was determined by immunofluorescence (IF), or serum agglutination test (SAT). Results Out of 91 articles reviewed in the different databases, 18 were selected since they met the inclusion criteria, which sought to determine the prevalence of leptospirosis in humans, canines, cattle, pigs, primates and rodents in the Atlántico, Antioquia, Meta, Córdoba, Risaralda, Tolima, Boyacá, Quindío and Valle del Cauca departments. Conclusions The systematic review allowed to determine the departments of the country where leptospirosis research is concentrated, as well as the authors with the highest number of publications on prevalence. The prevalence was found to be between 6% and 35% in humans, 41% and 60.9% in cattle, 10.3% in pigs, 12% and 47.14% in canines, 23.07 % in non-human primates, and the highest figure, between 25% and 82.7% in rodents, showing that the most frequent serovars were Icterohaemorrhagiae, Grippotyphosa and Canicola.(AU)

[Prevalence of leptospirosis in Colombia: systematic literature review]. / Prevalencia de Leptospirosis en Colombia: revisión sistemática de literatura.

OBJECTIVE: To conduct a systematic literature review to identify the prevalence of leptospirosis in Colombia between 2000 and 2012. METHODS: Descriptive studies conducted and published between 2000 and 2012 on the prevalence of leptospirosis in humans, animals and the environment using microagglutination (MAT) and immunoassay (ELISA) diagnostic methods, were selected. The exclusion criteria included studies in languages other than Spanish, English and Portuguese, in which the prevalence of leptospirosis was determined by immunofluorescence (IF), or serum agglutination test (SAT). RESULTS: Out of 91 articles reviewed in the different databases, 18 were selected since they met the inclusion criteria, which sought to determine the prevalence of leptospirosis in humans, canines, cattle, pigs, primates and rodents in the Atlántico, Antioquia, Meta, Córdoba, Risaralda, Tolima, Boyacá, Quindío and Valle del Cauca departments. CONCLUSIONS: The systematic review allowed to determine the departments of the country where leptospirosis research is concentrated, as well as the authors with the highest number of publications on prevalence. The prevalence was found to be between 6% and 35% in humans, 41% and 60.9% in cattle, 10.3% in pigs, 12% and 47.14% in canines, 23.07 % in non-human primates, and the highest figure, between 25% and 82.7% in rodents, showing that the most frequent serovars were Icterohaemorrhagiae, Grippotyphosa and Canicola.

OBJETIVO: Realizar una revisión sistemática de literatura para identificar las prevalencias de leptospirosis en Colombia en el periodo de tiempo comprendido entre los años 2000 y 2012. MATERIALES Y MÉTODOS: Se seleccionaron estudios descriptivos, realizados y publicados durante los años 2000 y 2012 sobre prevalencias de leptospirosis en humanos, animales y medio ambiente, por métodos diagnósticos de Microaglutinación (MAT) e Inmunoensayo (ELISA). Dentro de los criterios de exclusión, se tuvieron en cuenta estudios en idiomas diferentes al español, inglés y portugués, con determinación de prevalencias de leptospirosis por Inmunofluorescenia (IFI), o sueroaglutinación (SAT). RESULTADOS: De 91 artículos revisados en las diferentes bases de datos se seleccionaron 18 que cumplieron con los criterios de inclusión, los cuales determinaron prevalencias de leptospirosis en hombres, caninos, bovinos, porcinos, primates y roedores, en los departamentos de Atlántico, Antioquia, Meta, Córdoba, Risaralda, Tolima, Boyacá, Quindío y Valle del Cauca. CONCLUSIONES: La revisión sistemática permitió determinar cuáles son los departamentos de país donde se concentra la investigación en leptospirosis y los autores que cuentan con mayor número de publicaciones sobre prevalencias. De igual manera se pudo evidenciar que las prevalencias encontradas están entre 6% y el 35% para humanos, 41% y 60,9% para bovinos, 10,3% para porcinos, 12% y 47,14% para caninos, 23,07% para primates no humanos y entre el 25% y el 82,7% en roedores, siendo las más altas. Los serovares de mayor circulación fueron Icterohaemorrhagiae, Grippotyphosa, y Canicola.

[Atypical mucocutaneous manifestations in neonates and infants with chikungunya fever in the municipalities of Cúcuta, Los Patios and Villa del Rosario, Norte de Santander, Colombia, 2014].

INTRODUCTION: Atypical clinical manifestations have been observed in newborns and infants suffering from fever caused by the chikungunya virus. Objective: To describe the cases of fever caused by the chikungunya virus in newborns and infants with atypical mucocutaneous lesions. Materials and methods: We reviewed the clinical records, as well as lab tests and histopathological results, of newborns and infants diagnosed with Chikungunya virus and atypical mucocutaneous lesions in three regional hospitals. Results: Out of 18 suspected cases of chikungunya virus in newborns and infants, 11 were positive and presented atypical mucocutaneous manifestations. Six of the eleven confirmed cases corresponded to children under five months of age. The most common symptoms were fever, skin rash, irritability, and diarrhea. Three of the patients were infected with both dengue and chikungunya viruses. The ulcers occurred in the scalp, abdomen, genital and perianal region. CONCLUSIONS: We report mucocutaneous manifestations in newborns and infants diagnosed with fever caused by the chikungunya virus in Colombia. The rapid development of ulcers is most likely due to the immune response to the virus. Special attention should be given to pregnant women presenting symptoms of chikungunya virus infection prior to delivery, and their offspring should be followed-up in order to monitor possible complications.

Manifestaciones mucocutáneas atípicas por fiebre por el virus del chikungunya en neonatos y lactantes de Cúcuta, Los Patios y Villa del Rosario, Norte de Santander, Colombia, 2014 / Atypical mucocutaneous manifestations in neonates and infants with chikungunya fever in the municipalities of Cúcuta, Los Patios and Villa del Rosario, Norte de Santander, Colombia, 2014

Introducción. Se han observado manifestaciones clínicas atípicas en recién nacidos y lactantes con fiebre por el virus del chikungunya. Objetivo. Describir los casos de fiebre causada por el virus del chikungunya en recién nacidos y lactantes con lesiones mucocutáneas atípicas. Materiales y métodos. Se revisaron las historias clínicas y los resultados de laboratorio y de patología en tres hospitales regionales de los casos de recién nacidos y lactantes diagnosticados con el virus del chikungunya que presentaban lesiones mucocutáneas atípicas; se hizo una búsqueda activa comunitaria en los barrios de residencia de los pacientes. Resultados. De 18 casos sospechosos de chikungunya en recién nacidos y lactantes, 11 pacientes con diagnóstico confirmado presentaron manifestaciones mucocutáneas atípicas. Seis de los 11 casos confirmados eran niños menores de cinco meses de edad. Los síntomas más frecuentes fueron: fiebre, eritema, irritabilidad y diarrea. Tres de los pacientes estaban infectados con dengue y chikungunya. Las úlceras se presentaron en cuero cabelludo, abdomen, región genital y perianal. En la búsqueda activa comunitaria se encontraron altas tasas de ataque de la enfermedad. Conclusiones. Se presenta un informe de las manifestaciones mucocutáneas en recién nacidos y lactantes diagnosticados con fiebre por el virus del chikungunya en Colombia. El rápido desarrollo de las úlceras se debe, probablemente, a la reacción inmunitaria al virus. Es necesario priorizar la atención de las mujeres embarazadas que presenten síntomas una semana antes del parto y hacerle seguimiento a los recién nacidos, para hacer el diagnóstico temprano del chikungunya y evitar complicaciones.

Introduction: Atypical clinical manifestations have been observed in newborns and infants suffering from fever caused by the chikungunya virus. Objective: To describe the cases of fever caused by the chikungunya virus in newborns and infants with atypical mucocutaneous lesions. Materials and methods: We reviewed the clinical records, as well as lab tests and histopathological results, of newborns and infants diagnosed with Chikungunya virus and atypical mucocutaneous lesions in three regional hospitals. Results: Out of 18 suspected cases of chikungunya virus in newborns and infants, 11 were positive and presented atypical mucocutaneous manifestations. Six of the eleven confirmed cases corresponded to children under five months of age. The most common symptoms were fever, skin rash, irritability, and diarrhea. Three of the patients were infected with both dengue and chikungunya viruses. The ulcers occurred in the scalp, abdomen, genital and perianal region. Conclusions: We report mucocutaneous manifestations in newborns and infants diagnosed with fever caused by the chikungunya virus in Colombia. The rapid development of ulcers is most likely due to the immune response to the virus. Special attention should be given to pregnant women presenting symptoms of chikungunya virus infection prior to delivery, and their offspring should be followed-up in order to monitor possible complications.

Análisis filogenético del virus del chikungunya en Colombia: evidencia de selección purificadora en el gen E1 / Phylogenetic analysis of Chikungunya virus in Colombia: Evidence of purifying selection in the E1 gene

Introducción. El virus del chikungunya, perteneciente al género Alphavirus de la familia Togaviridae, es un virus ARN de 11,8 kb, de cadena sencilla y polaridad positiva, transmitido por Aedes spp . Se han identificado tres genotipos a nivel mundial: el de Asia, el del este-centro-sur de África ( East/Central/South African, ECSA) y el de África occidental ( West African, WA). La fiebre del chikungunya es una enfermedad febril aguda, acompañada principalmente de inflamación en las articulaciones y erupción cutánea. Después de su aparición en las Américas en el 2013, los primeros casos en Colombia ocurrieron en septiembre de 2014 y hasta junio del 2015 se habían notificado 399.932 casos. Objetivo. Identificar el genotipo o los genotipos responsables de la primera epidemia por el virus del chikungunya en Colombia y la variabilidad genética asociada a su dispersión en el territorio nacional. Materiales y métodos. Se seleccionaron muestras de suero de pacientes con síntomas indicativos de fiebre del chikungunya durante 2014 y 2015. Se hizo una transcripción inversa seguida de reacción en cadena de la polimerasa del gen E1, así como su secuenciación, análisis filogenético y análisis de evolución adaptativa. Resultados. Se demostró la presencia exclusiva del genotipo de Asia en Colombia. Se registró un promedio de 0,001 sustituciones de bases por sitio, una identidad de 99,7 a 99,9 % en los nucleótidos y de 99,9 % en los aminoácidos entre las secuencias colombianas y las secuencias de las Américas. Los análisis de evolución adaptativa indicaron una fuerte selección purificadora en el gen E1 . Conclusiones. Se determinó la circulación del genotipo de Asia del virus del chikungunya como la causa de la primera epidemia en Colombia. Es necesario continuar con la vigilancia de genotipos, con el fin de detectar posibles cambios en la epidemiología, la eficacia ( fitness ) viral y la patogenia del virus.

Introduction: Chikungunya virus (CHIKV) is a single-stranded positive sense RNA virus that belongs to the Alphavirus genus of the family Togaviridae. Its genome is 11.8 kb in length, and three genotypes have been identified worldwide: Asian, East/Central/South African (ECSA) and West African. Chikungunya fever is an acute febrile disease transmitted by Aedes spp . that usually presents with polyarthralgia and cutaneous eruption. Following introduction of the virus to the Americas in 2013, the first cases in Colombia occurred in September of 2014, and they reached a cumulative total of 399,932 cases by June of 2015. Objective: To identify the genotype or genotypes responsible for the current epidemic in Colombia and to describe the genetic variability of the virus in the country. Materials and methods: Serum samples from patients presenting with symptoms compatible with Chikungunya fever during 2014-2015 were selected for the study. RT-PCR products of the E1 gene from these samples were used for sequencing and subsequent phylogenetic and adaptive evolution analyses. Results: The study identified only the presence of the Asian genotype in Colombia. Comparing the Colombian sequences with other sequences from the Americas revealed an average of 0.001 base substitutions per site, with 99.7% and 99.9% nucleotide identity and 99.9% amino acid identity. The adaptive evolution analysis indicated that the E1 gene is under strong purifying selection. Conclusions: The first epidemic of Chikunguya fever in Colombia was caused by the circulation of the virus Asian genotype. Further genotypic surveillance of the virus in Colombia is required to detect possible changes in its epidemiology, fitness and pathogenicity.

Study of the retention of benzotriazoles, benzothiazoles and benzenesulfonamides in mixed-mode solid-phase extraction in environmental samples.

In the present study, the capabilities of strong cation-exchange and strong anion-exchange sorbents for solid-phase extraction (SPE) have been evaluated for the selective retention of benzotriazoles (BTRs), benzothiazoles (BTs) and benzenesulfonamides (BSAs), which are a group of neutral analytes with interesting properties such as high polarity and the capability of delocalizing electron density. The retention of these analytes has been compared in both sorbents for the first time, using a SPE procedure specially designed to promote ionic retention of the analytes with the objective of including a washing step with an organic solvent to eliminate interferences retained by hydrophobic interactions. As a result, ionic interactions between the analytes and both sorbents were observed, which allowed the successful introduction of a washing step using methanol in the SPE procedure even when most of the analytes were in their neutral state under SPE conditions. Consequently, a method was developed and further validated for each sorbent using liquid chromatography coupled to high-resolution mass spectrometry (LC-HRMS). Apart from the development of an improved method, special attention was paid to the discussion of the interactions present between the sorbents and each group of analytes to explain how these analytes in their neutral state might develop ionic interactions with the sorbents. At the end, the use of these sorbents helped to simplify previous developed methods where hydrophobic/hydrophilic sorbents were used, obtaining enhanced results when evaluated in river water and effluent and influent wastewaters.