Dose-dependent effects of Allopurinol on human foreskin fibroblast cell and human umbilical vein endothelial cell under hypoxia

Allopurinol, an inhibitor of xanthine oxidase, has been used in clinical trials of patients with cardiovascular and chronic kidney disease. These are two pathologies with extensive links to hypoxia and activation of the transcription factor hypoxia inducible factor (HIF) family. Here we analysed the effects of allopurinol treatment in two different cellular models, and their response to hypoxia. We explored the dose-dependent effect of allopurinol on Human Foreskin Fibroblasts (HFF) and Human Umbilical Vein Endothelial Cells (HUVEC) under hypoxia and normoxia. Under normoxia and hypoxia, high dose allopurinol reduced the accumulation of HIF-1α protein in HFF and HUVEC cells. Allopurinol had only marginal effects on HIF-1α mRNA level in both cellular systems. Interestingly, allopurinol effects over the HIF system were independent of prolyl-hydroxylase activity. Finally, allopurinol treatment reduced angiogenesis traits in HUVEC cells in an in vitro model. Taken together these results indicate that high doses of allopurinol inhibits the HIF system and pro-angiogenic traits in cells

Economic Issues in Tariffication: An Overview

Tariffication is an effort to convert all existing agricultural nontariff barriers (NTBs) to trade into bound tariffs and to reduce these tariffs over time. The main economic issues that arise with tariffication stem from the nonequivalence of tariffs in NTBs in a number of scenarios. This paper analyzes nonequivalence arising from the existence of imperfect competition in importing countries, price instability in importing and exporting countries, and inefficient allocation of quantitative restrictions. It is shown that in all these cases the definition of an appropriate equivalent tariff to be used in tariffication is not straightforward, and that in general this equivalent tariff cannot be computed on the basis of only observed price differences between countries

Elevated Incidence of Dental Caries in a Mouse Model of Cystic Fibrosis

Saliva bicarbonate constitutes the main buffering system which neutralizes the pH fall generated by the plaque bacteria during sugar metabolism. We found that the saliva pH is severely decreased in a mouse model of cystic fibrosis disease (CF). Given the close relationship between pH and caries development, we hypothesized that caries incidence might be elevated in the mouse CF model.). are enhanced at low pH values, we speculate that the decrease in the bicarbonate content and pH buffering of the saliva is at least partially responsible for the increased severity of lesions observed in the CF mouse

Hemocompatibility of Silicon-Based Substrates for Biomedical Implant Applications

Silicon membranes with highly uniform nanopore sizes fabricated using microelectromechanical systems (MEMS) technology allow for the development of miniaturized implants such as those needed for renal replacement therapies. However, the blood compatibility of silicon has thus far been an unresolved issue in the use of these substrates in implantable biomedical devices. We report the results of hemocompatibility studies using bare silicon, polysilicon, and modified silicon substrates. The surface modifications tested have been shown to reduce protein and/or platelet adhesion, thus potentially improving biocompatibility of silicon. Hemocompatibility was evaluated under four categories—coagulation (thrombin–antithrombin complex, TAT generation), complement activation (complement protein, C3a production), platelet activation (P-selectin, CD62P expression), and platelet adhesion. Our tests revealed that all silicon substrates display low coagulation and complement activation, comparable to that of Teflon and stainless steel, two materials commonly used in medical implants, and significantly lower than that of diethylaminoethyl (DEAE) cellulose, a polymer used in dialysis membranes. Unmodified silicon and polysilicon showed significant platelet attachment; however, the surface modifications on silicon reduced platelet adhesion and activation to levels comparable to that on Teflon. These results suggest that surface-modified silicon substrates are viable for the development of miniaturized renal replacement systems

Active pharmaceutical ingredients entering the aquatic environment from wastewater treatment works: A cause for concern?

publisher: Elsevier articletitle: Active pharmaceutical ingredients entering the aquatic environment from wastewater treatment works: A cause for concern? journaltitle: Science of The Total Environment articlelink: http://dx.doi.org/10.1016/j.scitotenv.2017.09.101 content_type: article copyright: © 2017 Elsevier B.V. All rights reserved

International Consensus Statement on Rhinology and Allergy: Rhinosinusitis

Background: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR‐RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR‐RS‐2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence‐based findings of the document. Methods: ICAR‐RS presents over 180 topics in the forms of evidence‐based reviews with recommendations (EBRRs), evidence‐based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. Results: ICAR‐RS‐2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence‐based management algorithm is provided. Conclusion: This ICAR‐RS‐2021 executive summary provides a compilation of the evidence‐based recommendations for medical and surgical treatment of the most common forms of RS

Diurnal activity patterns as a sensitive behavioural outcome in fish: Effect of short-term exposure to treated sewage and a sub-lethal PPCP mixture

Fabbro, LD ORCiD: 0000-0001-8893-5115Sub-lethal toxicological responses are common occurrences in aquatic animals exposed to sewage wastewater and organic wastewater contaminants. Behavioural alterations are particularly sensitive indicators of sub-lethal toxicological stress in animals exposed to various pollutants, and often correlate with higher-level outcomes. Diurnal activity patterns in many fish species are sensitive to changes in natural biotic factors, but few studies have explored how environmental pollutants influence such rhythms. We investigated diurnal activity patterns in the mosquitofish (Gambusia holbrooki), after exposure to UV-treated sewage and a mixture of key contaminants identified through chemical analysis and subsequent risk-based prioritization of the wastewater. Exposure to 50% and 100% wastewater abolished daytime activity levels in male, but not female fish. Chemical analysis identified fluoxetine, diazinon and triclosan above their reported predicted-no-effect-concentrations (PNECs), and fish were thus exposed to a mixture of these compounds at 1, 10 and 100 μg l–1. Behavioural responses were highly consistent between fish exposed to wastewater and the contaminant mixture, indicating that these prioritized contaminants are indeed likely contributing to the observed effects. Effective concentrations of the mixture were considerably lower than those reported as eliciting behavioural effects in previous studies exploring each of these compounds alone. Results warn of the potential for negative higher-level consequences associated with exposures of fish to common organic wastewater contaminants, as altered diurnal activity patterns could conceivably scale-up to influence performance including foraging success and predator avoidance. Further research is necessary to increase our understanding of linkages between alterations to diurnal activities and effects at the population level. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd

Prevalência de defeitos de fechamento de tubo neural no Vale do Paraíba, São Paulo Prevalence of neural tube defects in Vale do Paraíba, São Paulo, Brazil

OBJETIVO: Estimar a prevalência de defeitos de fechamento do tubo neural no Vale do Paraíba paulista e identificar possíveis fatores maternos e neonatais associados a tais defeitos. MÉTODOS: Realizou-se um estudo transversal com dados secundários obtidos na Secretaria Estadual da Saúde referentes aos nascimentos ocorridos em 2004 no Vale do Paraíba paulista, que compreende 35 municípios e conta com população de 2 milhões de habitantes. Anencefalia, encefalocele e espina bífida (mielocele e mielomeningocele) foram considerados defeitos de fechamento do tubo neural. As variáveis maternas foram: idade, escolaridade, cor da pele, número de consultas no pré-natal, número de filhos vivos e relato de óbito fetal prévio. As variáveis relativas ao recém-nascido foram: peso, idade gestacional e escore de Apgar. Realizou-se comparação das médias por meio do teste t de Student e obtiveram-se os valores das razões de chance com intervalos de confiança de 95%. RESULTADOS: Foram analisados 33.653 nascidos vivos. Trinta e oito recém-nascidos com o defeito foram encontrados (1,13/1.000 nascidos vivos), sendo 23 casos de espina bífida. Houve associação com baixo peso ao nascimento, prematuridade e menores escores de Apgar de cinco minutos. CONCLUSÕES: A prevalência desta anomalia foi inferior à de outros estudos nacionais e sua presença esteve associada ao baixo peso, à prematuridade e à baixa vitalidade ao nascer.<br>OBJECTIVE: To estimate the prevalence of neural tube defects in Vale do Paraíba, São Paulo, Brazil, and to identify possible maternal and neonatal variables associated with these defects. METHODS: This cross-sectional study used secondary records of the Health Department of São Paulo State related live births during 2004 in Vale do Paraíba, São Paulo, Brazil. This region has 35 cities and 2 million inhabitants. Anencephaly, encephalocele and spina bifida (myelocele and myelomeningocele) were considered as neural tube defects. The following maternal variables were analyzed: age, educational level, race, number of born alive and stillborn infants and prenatal visits. Neonatal variables were: birth weight, gestational age and Apgar score. Numerical variables were compared by Student t test, and Odds Ratio values were obtained with the 95% confidence interval. RESULTS: The analysis was performed based on 33,653 records of born alive infants. Twenty-three infants with spina bifida were identified, with an estimated prevalence of 1.13 cases for each 1,000 live births. The presence of neural tube defects was associated to low birth weight, prematurity and low Apgar score. CONCLUSIONS: The estimated prevalence of neural tube defects in this region of São Paulo was lower than others reported in previous Brazilian studies. These defects were associated with low birth weight, prematurity and respiratory depression at birth