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PURPOSEAs the fifth international consensus on advanced breast cancer (ABC5) established guidelines for the management of this disease, the aim of this article was to present the applicability of the consensus recommendations and to generate knowledge to improve access.METHODSSixty-one recommendation statements were selected and discussed by 15 breast cancer experts from Latin America (LA). After the discussion, the level of consensus was determined through a vote. In addition to this, the level of access to each of the recommendations presented, according to the country and health system, was exposed.RESULTSLatin American experts had a high level of agreement with the ABC5 consensus recommendations (range, 83%-100%). Twelve of 61 statements are not available for all patients in LA. Among the limitations to access, the following ones are described: limited access to certain technologies (stereotactic body radiotherapy, positron emission tomography-computed tomography), the high costs of drugs that limits access to treatment with CDK4/6 inhibitors, pertuzumab, or poly(ADP-ribose) polymerase inhibitors, and the lack of molecular tests for access to therapeutic targets, as well as the difficult geography and cultural diversity of our continent.CONCLUSIONDespite the great relevance of the recommendations of the ABC5 consensus guidelines, we highlight that we still need to improve access for all patients, regardless of the country or health system they are in, for which we call to action to policy makers and patient groups to improve clinical outcomes of patients with advanced breast cancer in our region.

AbstractA new public policy was instituted in Argentina for free distribution of subdermal contraceptive implants to women aged 15–24 years old in the public healthcare system. The objective of this study is to determine the extent to which this population adhered to the implant, as well as predictors of continuation. The retrospective cohort study was based on a telephone survey of a random sample of 1101 Ministry of Health-registered implant users concerning the continuation of use, satisfaction with the method and side-effects, and reasons for removal. Descriptive statistics and multivariate regression analysis were used to explore the association between adherence and having received contraceptive counselling, satisfaction, and side effects. We found high levels of adherence (87%) and satisfaction (94%). Common reported side effects were amenorrhoea or infrequent bleeding, perceived weight gain, increased menstrual bleeding and headaches. Multivariate regression analysis indicates that, among adolescents, having received contraceptive counselling increased comfort, while frequent bleeding at six months hindered trust. Participants who had a history of a prior delivery or who had themselves primarily chosen the method were less likely to request the removal of the implant. Our results support the public policy of free implant distribution in the public health sector. This is a sustainable public policy that contributes to equity and access to effective contraception. It is appropriate for adolescents and young women and will also reduce unintended pregnancies. Our results suggest that counselling patients is key prior to insertion of the implant, as it improves acceptability and continuation.

AbstractPregnancy-related complications are a substantial source of morbidity and mortality among adolescents in low- and middle-income countries. While the youngest adolescents (those aged 10–14) are considered to be at particularly high risk of adverse outcomes, there is little empirical data available on their sexual and reproductive health. Using a unique dataset of clinical records drawn from a regional network of sentinel centres providing legal abortion and comprehensive post-abortion care in 12 Latin American and Caribbean countries, we described the population of adolescents aged 10–14 seeking legal abortion and post-abortion care and calculated institutional rates of complications, using older adolescents (aged 15–19) and young adults (aged 20–24) as comparator groups. We also assessed the quality of care provided as compared to WHO recommendations. Nearly 17% (89 out of 533) of young adolescents sought care when they were already at 15 or more weeks’ gestation. Young adolescents were at higher risk of pre-procedure and intra-operative complications than older adolescents and young adults, though the trend is less clear for the most severe complications. In general, the quality of care provided by centres in the network was aligned with WHO recommendations for safe abortion and comprehensive post-abortion care. Taken together, these findings provide insight into the challenges facing the global health community in assuring the sexual and reproductive health and rights of the youngest adolescents, and outline avenues for future research, advocacy, and evidence-based policymaking.

Abstract Background Knowledge about regulating transcription factors (TFs) for osteoblastogenesis from mesenchymal stem cells (MSCs) is limited. Therefore, we investigated the relationship between genomic regions subject to DNA-methylation changes during osteoblastogenesis and the TFs known to directly interact with these regulatory regions. Results The genome-wide DNA-methylation signature of MSCs differentiated to osteoblasts and adipocytes was determined using the Illumina HumanMethylation450 BeadChip array. During adipogenesis no CpGs passed our test for significant methylation changes. Oppositely, during osteoblastogenesis we identified 2462 differently significantly methylated CpGs (adj. p

Current lifestyle and environmental factors contribute to obesity development, leading to low-grade chronic inflammation (LGCI). Apart from obesity, LGCI is also related to rheumatic diseases such as osteoporosis (OP) and osteoarthritis (OA). In these, an excessive accumulation of adipose tissue has been linked to an excessive production of proinflammatory factors, such as adipokines. This work’s aim is to stablish the effect of obesity-associated LGCI in major rheumatic diseases and to determine optimal strategies to reduce it. Obesity is a risk factor for developing OA, where a systemic LGCI state has been found. Concretely, obesity-associated LGCI has been described as an OA instauration and progression promoter. To avoid this, several therapeutical approaches (diet control, physical exercise, or nutraceuticals) have been tested. OP is another major rheumatic disease where a basal LGCI has been described, being worsened by obesity. As in OA, diet management and supplementation with vitamin D or probiotics have been proposed as approaches to treat obesity-associated LGCI in this pathology. Currently, the increase in the prevalence of rheumatic diseases is unstoppable. Nonetheless, obesity is a risk factor that can be controlled. Thus, the study of new interventions to control the impact of obesity-associated LGCI is a challenge for the management of patients with rheumatic diseases.

Objectives: This study investigates the role of retinol binding protein 4 (RBP4) in an articular context. RBP4, a vitamin A transporter, is linked to various metabolic diseases. Methods: Synovial fluid RBP4 levels were assessed in crystalline arthritis (CA) patients using ELISA. RBP4’s impact on articular cell types was analysed in vitro through RT-PCR and flow cytometry. Proteomic analysis was conducted on primary human osteoarthritis chondrocytes (hOACs). Results: Synovial fluid RBP4 concentrations in CA patients correlated positively with glucose levels and negatively with synovial leukocyte count and were elevated in hypertensive patients. In vitro, these RBP4 concentrations activated neutrophils, induced the expression of inflammatory factors in hOACs as well as synoviocytes, and triggered proteomic changes consistent with inflammation. Moreover, they increased catabolism and decreased anabolism, mitochondrial dysfunction, and glycolysis promotion. Both in silico and in vitro experiments suggested that RBP4 acts through TLR4. Conclusions: This study identifies relevant RBP4 concentrations in CA patients’ synovial fluids, linking them to hypertensive patients with a metabolic disruption. Evidence is provided that RBP4 acts as a DAMP at these concentrations, inducing robust inflammatory, catabolic, chemotactic, and metabolic responses in chondrocytes, synoviocytes, and neutrophils. These effects may explain RBP4-related metabolic diseases’ contribution to joint destruction in various rheumatic conditions like CA.

Objectives. To estimate inequalities in demand for family planning satisfied with modern methods among women in Latin America and the Caribbean, with an emphasis on Brazil and Mexico, and to calculate the scenario for recovery of modern contraceptive coverage by expanding access to long-acting contraceptives (LARC) after the COVID-19 pandemic. Methods. National health surveys from 2006 to 2018 were used to estimate the demand for family planning satisfied with modern methods and how it was affected by the COVID-19 pandemic. The scenario included three variables: coverage, health outcomes, and costs. Considering coverage, United Nations Population Fund data were used to estimate the impact of COVID-19 on access to contraception in Latin America and the Caribbean. Health outcomes were assessed with the Impact 2 tool. Direct investment was used to evaluate cost-effectiveness. Results. Substantial inequalities were found in the use of modern contraceptive methods before the pandemic. We showed the potential cost-effectiveness of avoiding maternal deaths by introducing LARCs. Conclusions. In the scenario predicted for Brazil and Mexico, the costs of modern family planning and averted disability-adjusted life years are modest. Governments in Latin America and the Caribbean should consider promoting LARCs as a highly efficient and cost-effective intervention.

Osteoarthritis (OA) affects more than 300 million people worldwide and it is about to become the first disabling disease. OA is characterized by the progressive degradation of the articular cartilage but is a disease of the whole joint. Articular innate immune responses (IIR) associated with tissue degradation contribute to its progression. However, no treatment is available to block these IIRs. Through data text mining and computational pharmacology, we identified two clinical available drugs, naloxone, and thalidomide, with potential inhibitory properties on toll-like receptor 4 (TLR4), a major activator of these IIR. Proteome analysis confirmed that activation of this receptor or the IL1 receptor generated OA-like and gout-like proteomic changes in human primary chondrocytes. Both compounds were found to block TLR4 complex and inhibit TLR4 and IL1R-mediated IIR in OA chondrocytes, osteoblasts, and synoviocytes. Furthermore, naloxone and thalidomide inhibitory effects involved the downregulation of the NLRP3 inflammasome pathway, which is downstream of TLR4/IL1R signaling. We demonstrated that these compounds, within a therapeutic range of concentrations, exhibited anti-inflammatory and anti-catabolic properties in joint primary OA cells without any toxic effect. This data underpins naloxone & thalidomide repurpose to treat OA-associated inflammatory responses.

Beer consumption has been identified as a risk factor for osteoarthritis (OA), a rheumatic disease characterised by cartilage degradation, joint inflammation, and eventual joint failure. One of the main isoflavonoids in beer is formononetin (FNT), an estrogenic compound also found in multiple plants and herbs. In this study, we aimed to investigate the effect of FNT on chondrocyte viability, inflammation, and metabolism. Cells were treated with FNT with or without IL-1β for 48 h and during 7 days of differentiation. Cell viability was determined via MTT assay. Nitrite accumulation was determined by Griess reaction. The expression of genes involved in inflammation and metabolism was determined by RT-PCR. The results revealed that a low concentration of FNT had no deleterious effect on cell viability and decreased the expression of inflammation-related genes. However, our results suggest that FNT overexposure negatively impacts on chondrocytes by promoting catabolic responses. Finally, these effects were not mediated by estrogen receptors (ERs) or aryl hydrocarbon receptor (AhR). In conclusion, factors that favour FNT accumulation, such as long exposure times or metabolic disorders, can promote chondrocyte catabolism. These data may partially explain why beer consumption increases the risk of OA.

It is well known that patients with attention deficit hyperactivity disorder treated with stimulants, such as methylphenidate hydrochloride (MPH), have reduced height and weight. Even though MPH has an anorexigenic effect, an additional impact of this drug on the growth plate cannot be discarded. In this study, we aimed to determine the cellular effect of MPH on an in vitro growth plate model. We tested the effects of MPH on the viability and proliferation of a prechondrogenic cell line via an MTT assay. In vitro differentiation of this cell line was performed, and cell differentiation was evaluated through the expression of cartilage- and bone-related genes as measured via RT-PCR. MPH did not alter the viability or proliferation of prechondrogenic cells. However, it reduced the expression of cartilage extracellular matrix-related genes (type II collagen and aggrecan) and increased the expression of genes involved in growth plate calcification (Runx2, type I collagen, and osteocalcin) at different phases of their differentiation process. Our results evidence that MPH upregulates genes associated with growth plate hypertrophic differentiation. This may induce premature closure of the growth plate, which would contribute to the growth retardation that has been described to be induced by this drug.

Osteoarthritis (OA) is hallmarked as a silent progressive rheumatic disease of the whole joint. The accumulation of inflammatory and catabolic factors such as IL6, TNFα, and COX2 drives the OA pathophysiology into cartilage degradation, synovia inflammation, and bone destruction. There is no clinical available OA treatment. Although traditional ayurvedic medicine has been using Boswellia serrata extracts (BSE) as an antirheumatic treatment for a millennium, none of the BSE components have been clinically approved. Recently, β boswellic acid (BBA) has been shown to reduce in vivo OA-cartilage loss through an unknown mechanism. We used computational pharmacology, proteomics, transcriptomics, and metabolomics to present solid evidence of BBA therapeutic properties in mouse and primary human OA joint cells. Specifically, BBA binds to the innate immune receptor Toll-like Receptor 4 (TLR4) complex and inhibits both TLR4 and Interleukin 1 Receptor (IL1R) signaling in OA chondrocytes, osteoblasts, and synoviocytes. Moreover, BBA inhibition of TLR4/IL1R downregulated reactive oxygen species (ROS) synthesis and MAPK p38/NFκB, NLRP3, IFNαβ, TNF, and ECM-related pathways. Altogether, we present a solid bulk of evidence that BBA blocks OA innate immune responses and could be transferred into the clinic as an alimentary supplement or as a therapeutic tool after clinical trial evaluations.

Adipogenesis-osteoblastogenesis balance-rupture is relevant in multiple diseases. Current human mesenchymal stem cells (hMSCs) in vitro differentiation models are expensive, and are hardly reproducible. Their scarcity and variability make an affordable and reliable method to study adipocyte-osteoblast-equilibrium difficult. Moreover, media composition has been inconstant throughout the literature. Our aims were to compare improved differentiation lab-made media with consensus/commercial media, and to identify a cell-line to simultaneously evaluate both MSCs differentiations. Lab-made media were compared with consensus and commercial media in C3H10T1/2 and hMSC, respectively. Lab-made media were tested on aged women primary pre-osteoblast-like cells. To determine the optimum cell line, C3H10T1/2 and hMSC-TERT cells were differentiated to both cell fates. Differentiation processes were evaluated by adipocytic and osteoblastic gene-markers expression and staining. Lab-made media significantly increased consensus medium induction and overcame commercial media in hMSCs differentiation to adipocytes and osteoblasts. Pre-osteoblast-like cells only properly differentiate to adipocyte. Lab-made media promoted adipocyte gene-markers expression in C3H10T1/2 and hMSC-TERT, and osteoblast gene-markers in C3H10T1/2. Oil Red O and Alizarin Red staining supported these findings. Optimized lab-made media were better at differentiating MSCs compared to consensus/commercial media, and evidenced the adipogenic commitment of pre-osteoblast-like cells from aged-women. C3H10T1/2 is an optimum MSC line by which to study adipocyte-osteoblast differentiation balance.

Background High doses of ethylenebisdithiocarbamate (EBDC) are used in banana production, and unused pesticide mixture (solution) is often disposed of improperly. This can result in soil and water contamination and present an undue risk to rural communities and the environment. An alternative to reduce the environmental impacts caused by pesticide residues is the biobeds treatment. It is necessary to establish if the composition of the proposed biomixtures supports microbial activity to degrade pesticides in biobeds. This research aimed to evaluate the EBDC effect on the distribution and abundance of microbial populations in polluted biomixtures . Methods For this purpose, a biomixture based on banana stem, mulch, and Fluvisol soil (50:25:25% v/v) was prepared and polluted with 1,000 mg L−1 EBDC. The response variables kinetics were determined every 14 days for three months, such as pH, organic matter, moisture, cation exchange capacity, microbial colonies, and cell counts at three depths within the experimental units. Results EBDC reduced the number of microbial colonies by 72%. Bacterial cells rapidly decreased by 69% and fungi 89% on the surface, while the decrease was gradual and steady at the middle and bottom of the biobed. The microbial populations stabilized at day 42, and the bacteria showed a total recovery on day 84, but the fungi slightly less. At the end of the experiment, the concentration of EBDC in the biomixture was 1.3–4.1 mg L−1. A correlation was found between fungal count (colonies and cells) with EBDC concentration. A replacement of the biomixture is suggested if the bacterial population becomes less than 40 × 106 CFU mL−1 and the fungal population less than 8 × 104 CFU mL−1 or if the direct cell count becomes lower than 50 × 104 cells mL−1 in bacteria and 8 × 102 cells mL−1 in fungi. Conclusion The biomixture based on banana stem supports the microbial activity necessary for the degradation of the EBDC pesticide. It was found that fungi could be used as indicators of the pollutant degradation process in the biomixtures. Microbial counts were useful to establish the mobility and degradation time of the pesticide and the effectiveness of the biomixture. Based on the results, it is appropriate to include the quantification of microbial populations to assess the effectiveness of pesticide degradation and the maturity level of the biomixture.

Objetivo. Esta revisión sintetiza la evidencia cuantitativa, general y desglosada por categorías tipológicas de la falta de respeto y maltrato en la atención institucional del parto y el aborto en América Latina y el Caribe. Métodos. Mediante búsquedas sistemáticas se identificaron 18 estudios primarios. Se calcularon Q e I2 y se realizaron metaanálisis, metarregresiones y análisis de subgrupos con la aplicación de un modelo de Der Simonian-Laird de efectos aleatorios agrupados con varianza inversa y la transformación arco-seno doble de Freeman-Tukey. Resultados. Se identificaron estudios realizados en cinco países de América Latina. No se identificaron estudios del Caribe. La prevalencia agregada de falta de respeto y maltrato durante el parto y el aborto fue de 39%. La medida agregada para este fenómeno durante el parto fue de 43% y la medida agregada en los casos de aborto fue de 29%. La heterogeneidad elevada no permitió generar medidas agregadas según categorías tipológicas. No obstante, se presentan las frecuencias de formas específicas del fenómeno agrupadas tipológicamente. Conclusiones. La evidencia sugiere que la falta de respeto y maltrato durante la atención del parto y el aborto son problemas de derechos humanos y salud pública prevalentes en algunos países de la Región. Es necesario lograr consenso internacional sobre la definición y operacionalización de este problema y desarrollar métodos estandarizados para su medición. Lo anterior es imprescindible para el alcance de las metas de la Agenda 2030 relacionadas con la reducción de la morbimortalidad maternoperinatal y la eliminación de todas las formas de violencia y discriminación contra la mujer.

Abstract Background Although there are public policies for eradicating congenital syphilis, they do not seem to be a routine in most health services. The objective of this study was to evaluate the management of sexual partners of pregnant women with syphilis in primary health care in northeastern Brazil. Methods This is a qualitative assessment carried out from February to October 2014 in the city of Fortaleza, Ceará, northeastern region of Brazil, through the observation of six primary health care centers and interviews with 21 professionals, six coordinators, nine women diagnosed with syphilis during antenatal care and four sexual partners. The data were submitted to thematic content analysis. Results Important flaws were identified at the primary health centers studied regarding the management of syphilis during pregnancy. Accessing testing and treatment is difficult, and there are no standardized strategies to notify the partner. The responsibility for notifying them is transferred to the women, and counseling does not offer proper guidance nor sufficient emotional support to help them. Conclusion The management of pregnant women and their sexual partners in our region does not comply with global recommendations. Professional qualification, sensitization, and standardization of health professionals’ conduct are necessary. Offering support to health professionals on their clinical practices by means of a supervision process may contribute to the adoption of the recommended guidelines and to the promotion of care based on privacy, respect, confidentiality of information, and awareness of the problems faced by women as a result of syphilis diagnosis.

Background/Aims: Osteoarthritis (OA) is a joint degenerative biomechanical disorder involving immunity, metabolic alterations, inflammation, and cartilage degradation, where chondrocytes play a pivotal role. OA has not effective pharmacological treatments and new therapeutic targets are needed. Adipokines contribute to the low-grade systemic inflammation in OA. Here, we explored novel molecular mechanisms of sodium butyrate (BuNa) in modulating inflammation and chemotaxis in chondrocytes, demonstrating the direct involvement of its G protein-coupled receptor (GPR)-43. Methods: ATDC5 murine chondrocytes were stimulated with interleukin (IL)-1β, in the presence or not of BuNa, for 24 h. RT-PCR and Western blot analysis was performed to evaluate the expression of inflammatory mediators and structural proteins. Results: Butyrate reduced the expression of canonic pro-inflammatory mediators (Nos2, COX-2, IL-6), pro-inflammatory adipokines (lipocalin-2 and nesfatin-1) and adhesion molecule (VCAM-1 and ICAM-1) in IL-1β-stimulated chondrocytes, inhibiting several inflammatory signalling pathways (NFκB, MAPKinase, AMPK-α, PI3K/Akt). Butyrate also reduced metalloproteinase production and limited the loss of type II collagen in IL-1β-inflamed chondrocytes. The chemoattractant effect of butyrate, after different inflammatory challenges, was revealed by increased annexin (AnxA)1 levels and chemokines expression. The chemoattractant and anti-inflammatory activities of butyrate were completely blunted by GPR43 silencing using RNA interference. Conclusion: Taken together, our data suggest the potential application of sodium butyrate as a novel candidate in a multi-target approach for the treatment of chondrocyte inflammation and cartilage degenerative process.

Maternal mortality is unacceptably high in our region. In 2015, the Latin American Center for Perinatology and Women´s Reproductive Health (CLAP) created a regional network of institutions including 16 countries, committed to improving epidemiological surveillance and healthcare of women in a situation of abortion or near miss event, using a common platform, the Perinatal Information System (SIP). The objective of the current pilot project was to test a new method of study called EviSIP (Evidence from SIP), a method of generating information on maternal near miss and abortion for the region. We describe the implementation of this initiative in reproductive healthcare facilities using SIP. Junior researchers/clinicians from these countries were included, along with expert researchers in reproductive health from across the world. Articles were produced with data on maternal near miss and abortion gathered from the SIP of each participating sentinel center; and recommendations from experts. EviSIP was the first joint workspace to discuss patient outcomes after treatment of abortion or near miss cases, with data analysis of each Sentinel Center; discuss and analyze data among centers, at a country and regional level; discuss the main outcomes and their impact on changing procedures and policies; strengthen the operational research capacity of the centers; develop and encourage the publication of scientific articles. The EviSIP initiative also promoted training of healthcare professionals in research. EviSIP provided a unique opportunity to train for research and mentorship and was pivotal to the production of scientific knowledge of reproductive health in the region.

Con el propósito de identificar los sectores más atractivos para la inversión en el mercado bursátil durante la pandemia por COVID-19, se hace un análisis de las denominadas empresas “FAANG” observando el comportamiento del valor de sus acciones bajo la metodología revisión documental de tipo descriptivo apoyándose en fuentes de información secundaria como la página web de la Bolsa de valores de Colombia (BVC), y la base de datos de visualización financiera de FINVIZ, además de recurrir a conceptos necesarios de autores como Roldán, García y Rey (2020) y Şenol y Zeren (2020). Se concluye que las empresas con mayor inyección de capital por parte de inversionistas son las que desde sus inicios tienen como insumo principal el internet.

A rapid bioassay is presented for determining acute toxicity directly in soil. Modifying the Organisation for Economic Cooperation and Development (OECD) protocol 207, it uses a thin layer of moistened soil laid directly in the bottom of the bioassay jar into which the earthworms are placed and incubated. Examples are presented in comparisons between the soil contact bioassay vs. the filter paper bioassay run on Toxicity Characteristic Leaching Procedure (TCLP) extracts of pesticide contaminated soil and petroleum drilling cuttings. In 2,4-dichlorophenoxyacetic acid (2,4-D) contaminated soil (300mg/Kg), no mortality was found in soil extracts, but 100% mortality was found when exposed directly to soil. Treatment with the Daremend® product in five anaerobic/aerobic cycles slowly reduced the 24 h mortality (0%) but still showed 100% mortality at 48 h. However, severe sub-lethal effects (expulsion of celomic/bloody fluids) were reduced from 50% to 37%, and further treatment may reduce the toxicity to acceptable levels. The petroleum drilling cuttings treated by chemical oxidation (1.3% H2O2, w/w) and bioremediation (simulation of biopiles), showed a similar response, where 0% mortality in soil extracts was found, but 100% mortality with soil contact. Post-treatment with chemical oxidation resulted in a reduction in the soil contact bioassay to 3% and 13% mortality, within the accepted range (≤10%) of the OECD protocol. Observations are presented with respect to moisture control to prevent earthworm desiccation and recommendation for confirmation using the sub-chronic test in the OECD protocol but by testing the contaminated/treated soil itself rather than artificial soil.

Background/Aims: The E74-like factor 3 (ELF3) is an inflammatory mediator that participates in cartilage destruction in osteoarthritis. Leptin and other adipokines negatively impact articular cartilage, triggering catabolic and inflammatory responses in chondrocytes. Here, we investigated whether leptin induces ELF3 expression in chondrocytes and the signaling pathway involved in this process. Methods: We determined mRNA and protein levels of ELF3 by RT-qPCR and Western blotting using cultured human primary chondrocytes and the human T/C-28a2 chondrocyte cell line. Further, we measured luciferase activities of different reporter constructs, and we assessed the contribution of leptin to the induction of ELF3 mRNA by knocking down hLEPR gene expression using siRNA technology. Results: Leptin synergizes with IL-1β in inducing ELF3 expression in chondrocytes. We also found that PI3K, p38, and JAK2 signaling pathways are at play in the leptin-driven induction of ELF3. Moreover, we confirm the participation of NFΚB in the leptin/IL-1β synergistic induction of ELF3. Conclusion: Here we show, for the first time, the regulation of ELF3 expression by leptin, suggesting that this transcription factor likely mediates the inflammatory responses triggered by leptin in articular chondrocytes.

Since its discovery in 1994, leptin has been considered as an adipokine with pleiotropic effects. In this review, we summarize the actual information about the impact of this hormone on cartilage metabolism and pathology. Leptin signalling depends on the interaction with leptin receptor LEPR, being the long isoform of the receptor (LEPRb) the one with more efficient intracellular signalling. Chondrocytes express the long isoform of the leptin receptor and in these cells, leptin signalling, alone or in combination with other molecules, induces the expression of pro-inflammatory molecules and cartilage degenerative enzymes. Leptin has been shown to increase the proliferation and activation of immune cells, increasing the severity of immune degenerative cartilage diseases. Leptin expression in serum and synovial fluid are related to degenerative diseases such as osteoarthritis (OA), rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Inhibition of leptin signalling showed to have protective effects in these diseases showing the key role of leptin in cartilage degeneration.

Obesity is an epidemic disease characterized by chronic low-grade inflammation associated with a dysfunctional fat mass. Adipose tissue is now considered an extremely active endocrine organ that secretes cytokine-like hormones, called adipokines, either pro- or anti-inflammatory factors bridging metabolism to the immune system. Leptin is historically one of most relevant adipokines, with important physiological roles in the central control of energy metabolism and in the regulation of metabolism-immune system interplay, being a cornerstone of the emerging field of immunometabolism. Indeed, leptin receptor is expressed throughout the immune system and leptin has been shown to regulate both innate and adaptive immune responses. This review discusses the latest data regarding the role of leptin as a mediator of immune system and metabolism, with particular emphasis on its effects on obesity-associated metabolic disorders and autoimmune and/or inflammatory rheumatic diseases.

Inflammation is a process whose main function is to fight against invading pathogens or foreign agents. Nonetheless, it is widely accepted that inflammation takes part in multiple processes in a physiological or pathophysiological context. Among these processes the inflammation has been closely related to bone metabolism. It is well-known that in systemic inflammatory diseases such as rheumatoid arthritis the inflammatory environment contributes to the reduction of the bone mineral density. This has been further evidenced in different animals models of osteoporosis where the deletion of key inflammatory molecules dramatically reduced the bone loss. On the contrary, it is also well-known that certain degree of inflammation is required to allow bone fractures healing. In fact, excessive use of anti-inflammatory drugs inhibits bone fracture consolidation. The innate immune responses (IIRs) contribute to the development and maintenance of the inflammation. These responses have been observed in cells of the musculoskeletal system. Chondrocytes and osteoblasts are equipped with the molecular repertoire necessary to setting up these IIR, including the expression of several toll-like receptors. Specifically, toll-like receptor 4 (TLR4) activation in mesenchymal stem cells, osteoblasts, and osteocytes has been involved in catabolic and anabolic process. Accordingly, in this review we have summarized the current knowledge about the physiology of TLR4, including its signaling, and its endogenous agonists. In addition we have focused on its role on osteoblast metabolism and function.

Este estudio tiene como objetivo la caracterización gravimétrica del material paritculado fracción respirable (PM10) colectado en la estación de Monitoreo Atmosférico de la División Académica de Ciencias Biológicas de la UJAT. Para lograr la generación continua de datos atmosféricos confiables, se utilizaron metodologías y procedimientos estandarizados por normas nacionales (NOM-035-ECOL-1993) e internacionales (US-EPA-IO 2.1). Las PM10 fueron muestreadas de agosto 2015 a julio 2017 (n = 90), durante 24 h cada una. La máxima concentración fue de 80.59 ?g/m3 en febrero del 2017. La norma superó los límites máximos permisibles dos días durante el periodo 2016-2017. En las estaciones de primavera y principios de verano del 2016 se observaron las tendencias de concentración más alta de todo el periodo de muestreo (arriba de 50 ?g/m3). La concentración total de partículas suspendidas PM10 durante 24 h varía en un rango de 2.45 a 80.59 ?g/m3. La concentración PM10 se incrementa de dos a cuatro veces en la época de estiaje. La información generada por ésta estación permite a las autoridades estatales y municipales, conocer y evaluar la calidad del aire de una región de la ciudad de Villahermosa y vigilar el cumplimiento de la normatividad correspondiente, para de esta manera, asegurar el derecho a la salud de la población tabasqueña.

Intervertebral disc degeneration (IVDD) is a chronic, expensive, and high-incidence musculoskeletal disorder largely responsible for back/neck and radicular-related pain. It is characterized by progressive degenerative damage of intervertebral tissues along with metabolic alterations of all other vertebral tissues. Despite the high socio-economic impact of IVDD, little is known about its etiology and pathogenesis, and currently, no cure or specific treatments are available. Recent evidence indicates that besides abnormal and excessive mechanical loading, inflammation may be a crucial player in IVDD. Furthermore, obese adipose tissue is characterized by a persistent and low-grade production of systemic pro-inflammatory factors. In this context, chronic low-grade inflammation associated with obesity has been hypothesized as an important contributor to IVDD through different, but still unknown, mechanisms. Adipokines, such as leptin, produced prevalently by white adipose tissues, but also by other cells of mesenchymal origin, particularly cartilage and bone, are cytokine-like hormones involved in important physiologic and pathophysiological processes. Although initially restricted to metabolic functions, adipokines are now viewed as key players of the innate and adaptative immune system and active modulators of the acute and chronic inflammatory response. The goal of this review is to summarize the most recent findings regarding the interrelationships among inflammation, obesity and the pathogenic mechanisms involved in the IVDD, with particular emphasis on the contribution of adipokines and their potential as future therapeutic targets.

Cartilage is an avascular tissue and cartilage metabolism depends on molecule diffusion from synovial fluid and subchondral bone. Thus, nutrient availability is limited by matrix permeability according to the size and charge of the molecules. Matrix composition limits the access of molecules to chondrocytes, determining cell metabolism and cartilage maintenance. Lipids are important nutrients in chondrocyte metabolism and are available for these cells through de novo synthesis but also through diffusion from surrounding tissues. Cartilage status and osteoarthritis development depend on lipid availability. This paper reviews lipid transport and metabolism in cartilage. We also analyze signalling pathways directly mediated by lipids and those that involve mTOR pathways, both in normal and osteoarthritic cartilage.

It has been proposed that the metal-drug complexes could be in fact the active agents displaying therapeutic effects of drugs. The characterization of the global formation equilibrium of complexes formed between metal ions and species with biological activity such as nonsteroidal anti-inflammatory drugs provides essential information to understand the mechanism of action of drugs. Since equilibrium constants determine the relative predominance of species, they provide crucial information to identify what complexes are more likely to be present in the system being responsible for the therapeutic effects of the drug. In this paper, the systems formed between copper and Indomethacin of different concentrations in ethanol or water were studied by UV-Vis spectrophotometry. The stoichiometry of the complexes Cu(II)–Indomethacin and their formation constants were investigated. Moreover, molecular structures of the Cu(II)–Indomethacin complexes were explored by means of the molecular modeling within the frame of the density functional theory.

The cloning of leptin in 1994 by Zhang et al. introduced a novel concept about white adipose tissue (WAT) as a very dynamic organ that releases a plethora of immune and inflammatory mediators, such as adipokines and cytokines, which are involved in multiple diseases. Actually, adipokines exert potent modulatory actions on target tissues involved in rheumatic diseases including cartilage, synovial, bone and immune cells. The goal of this paper is to elucidate the recent findings concerning the involvement of adipokines in rheumatic diseases, such as rheumatoid arthritis (RA), osteoarthritis (OA), and systemic lupus erythematosus (SLE).

OBJECTIVES:Emerging data suggest that several metabolic factors, released mainly by white adipose tissue (WAT) and joint tissues, and collectively named adipokines, might have a role in the pathophysiology of OA. Recently, novel adipokines such as SERPINE2, WISP2, GPNMB and ITIH5 have been identified in WAT. The main goal of this study was to analyse the expression of these novel adipokines in synovium, infrapatellar fat pad and chondrocytes and to compare the expression of these molecules in healthy and OA tissues. METHODS:Synovial tissues, infrapatellar fat pad and chondrocytes were obtained from 36 OA patients (age 52-85; mean BMI 28.9) who underwent total knee replacement surgery. Healthy synovial tissues and infrapatellar fat pad were obtained from 15 traumatic knee patients (age 23-53; mean BMI 23.5). mRNA and protein expression were determined by qRT-PCR and western blot analysis respectively. RESULTS:All the novel adipokines, matter of our study, are expressed in OA synovium, infrapatellar fat pad and chondrocytes. Moreover, we detected a differential expression of SERPINE2 and ITIH5 in OA synovial tissues as compared to healthy samples. Finally, we also observed an increased expression of WISP2 in OA infrapatellar fat pad in comparison to healthy controls. CONCLUSIONS:In this study we demonstrated for the first time the expression of four novel adipokines in different joint tissues and how these molecules are differentially expressed in healthy and OA joint tissues.

La tecnología se extracción-texturación de concentrados proteicos de pescado (CPP) por etanol a baja temperatura (5-6oC) fue puesta en marcha a nivel de laboratorio en el propósito de comparar resultados obtenidos por Suzuki et al. (1982), Para obtener el articulo completo pueden contactar al Editor de la Revista Ecosistemas y Recursos Agropecuarios en el siguiente correo electrónico era@ujat.mx y se les enviará sin algún costo.

Patients with rheumatic diseases have an increased risk of mortality by cardiovascular events. In fact, several rheumatic diseases such as rheumatoid arthritis, osteoarthritis, systemic lupus erythematosus, and ankylosing spondylitis are associated with a higher prevalence of cardiovascular diseases (CVDs). Although traditional cardiovascular risk factors have been involved in the pathogenesis of cardiovascular diseases in rheumatic patients, these alterations do not completely explain the enhanced cardiovascular risk in this population. Obesity and its pathologic alteration of fat mass and dysfunction, due to an altered pattern of secretion of proinflammatory adipokines, could be one of the links between cardiovascular and rheumatic diseases. Indeed, the incidence of CVDs is augmented in obese individuals with rheumatic disorders. Thus, in this paper we explore in detail the relationships among adipokines, rheumatic diseases, and cardiovascular complications by giving to the reader a holistic vision and several suggestions for future perspectives and potential clinical implications.

BACKGROUND: Osteoarthritis (OA) and rheumatoid arthritis (RA), the most common rheumatic diseases, are characterized by irreversible degeneration of the joint tissues. There are several factors involved in the pathogenesis of these diseases including pro-inflammatory cytokines, adipokines and adhesion molecules. OBJECTIVE: Up to now, the relationship between adipokines and adhesion molecules at cartilage level was not explored. Thus, the aim of this article was to study the effect of leptin and adiponectin on the expression of VCAM-1 in human and murine chondrocytes. For completeness, intracellular signal transduction pathway was also explored. METHODS: VCAM-1 expression was assessed by quantitative RT-PCR and western blot analysis upon treatment with leptin, adiponectin and other pertinent reagents in cultured human primary chondrocytes. Signal transduction pathways have been explored by using specific pharmacological inhibitors in the adipokine-stimulated human primary chondrocytes and ATDC5 murine chondrocyte cell line. RESULTS: Herein, we demonstrate, for the first time, that leptin and adiponectin increase VCAM-1 expression in human and murine chondrocytes. In addition, both adipokines have additive effect with IL-1β. Finally, we demonstrate that several kinases, including JAK2, PI3K and AMPK are at a play in the intracellular signalling of VCAM-1 induction. CONCLUSIONS: Taken together, our results suggest that leptin and adiponectin could perpetuate cartilage-degrading processes by inducing also factors responsible of leukocyte and monocyte infiltration at inflamed joints.