Queilite actínica: expressão imuno-histoquímica da cox-2 e avaliação do diclofenaco sódico gel como uma terapia alternativa

Actinic cheilitis (AC) is a potentially malignant disorder which affects the lip vermilion and results from chronic exposure to sunlight. Currently, it is not possible to predict which cases of AC may progress to squamous cell carcinoma, and therefore, some biomolecular markers have been researched. Cyclooxygenase 2 (COX-2) is an enzyme associated with inflammatory response which is overexpressed in oral cancer; however, little is known about the role of this protein in actinic cheilitis. About the treatment of this lesion, currently available therapeutic modalities to AC may cause cytotoxic effects and deleterious results to patients. Therefore, the aim of this study was to evaluate the immunoexpression of COX-2 in AC of different risks of malignant transformation and analyse, through clinical follow-up, the efficacy of diclofenac sodium 3% gel in the treatment of this condition. Epithelial immunoexpression of COX-2 was analysed semi-quantitatively in 90 cases of AC classified as low risk (n = 55) and high risk (n = 35) of malignant transformation, in which the scores were assigned: (0) 0 to 5% of positive cells - Negative; (1) 6 to 30% of positive cells - Low expression; (2) 31 to 100% of positive cells - High expression. The chi-square test of Pearson was conducted to verify possible associations between immunoexpression of COX-2 and histologic grade of actinic cheilitis. The weighted kappa coefficient denoted a good interobserver agreement (0.677). Nineteen patients diagnosed with AC were instructed to perform topical application of the gel three times a day for a period of 90 days. In each biweekly visit, a follow-up record was accomplished through digital photographs and after treatment was completed, two researchers analysed all the images to assess clinical aspects of the lip. Furthermore, tolerability to the drug and patient satisfaction after treatment were evaluated. COX-2 was overexpressed in 74.4% of AC cases. Both low and high-risk groups revealed predominance of score 3, followed by scores 2 and 1. There was no significant association (p = 0.315) between COX-2 expression and histological grading. Among the total number of participants of this clinical study, ten showed total remission of all clinical features of the lesion and three had partial improvement of these characteristics. One participant presented worsening of the clinical condition. In five cases, the treatment was discontinued due to development of mild adverse effects at the site of gel application. Regarding analysis of satisfaction and tolerability to the drug, most patients were fully satisfied with the therapy (n = 11) and reported that the drug was not irritating to the lips (n = 9). Our study demonstrates that high expression of COX-2 is common in AC; however, this protein was not associated with malignant transformation risk of the analysed cases. Topical application of diclofenac sodium 3% gel provided a convenient and well tolerated approach in most cases, and may be a promising alternative for the treatment of actinic cheilitis.

Elevated CO2 affects predator-prey interactions through altered performance

Recent research has shown that exposure to elevated carbon dioxide (CO2) affects how fishes perceive their environment, affecting behavioral and cognitive processes leading to increased prey mortality. However, it is unclear if increased mortality results from changes in the dynamics of predator-prey interactions or due to prey increasing activity levels. Here we demonstrate that ocean pCO2 projected to occur by 2100 significantly effects the interactions of a predator-prey pair of common reef fish: the planktivorous damselfish Pomacentrus amboinensis and the piscivorous dottyback Pseudochromis fuscus. Prey exposed to elevated CO2 (880 µatm) or a present-day control (440 µatm) interacted with similarly exposed predators in a cross-factored design. Predators had the lowest capture success when exposed to elevated CO2 and interacting with prey exposed to present-day CO2. Prey exposed to elevated CO2 had reduced escape distances and longer reaction distances compared to prey exposed to present-day CO2 conditions, but this was dependent on whether the prey was paired with a CO2 exposed predator or not. This suggests that the dynamics of predator-prey interactions under future CO2 environments will depend on the extent to which the interacting species are affected and can adapt to the adverse effects of elevated CO2.

Thyroid hormone and gland status of Greenland sledge dogs (Canis lupus familiaris) exposed to contaminated blubber

As a model of high trophic level carnivores, sledge dogs were fed from 2 to 18 months of age with minke whale blubber containing organohalogen compounds (OHC) corresponding to 128 µg PCB/day. Controls were fed uncontaminated porcine fat. Thyroid hormone levels were assessed in 7 exposed and 7 control sister bitches (sampled at age 6-18 months) and 4 exposed and 4 control pups, fed the same diet as their mothers (sampled age 3-12 months). Lower free and total T3 and T4 were seen in exposed vs. control bitches beyond 10 months of age, and total T3 was lower through 3-12 months of age in exposed pups. A negative correlation with thyroid gland weight was significant for SumDDT, as was a positive association with total T3 for dieldrin. This study therefore supports observational data that OHCs may adversely affect thyroid functions, and it suggests that OHC exposure duration of 10 months or more may be required for current OHC contamination levels to result in detectable adverse effects on thyroid hormone dynamics.

Acquired Cold Urticaria: Clinical Features, Particular Phenotypes, and Disease Course in a Tertiary Care Center Cohort

BACKGROUND: Data about special phenotypes, natural course, and prognostic variables of patients with acquired cold urticaria (ACU) are scarce. OBJECTIVES: We sought to describe the clinical features and disease course of patients with ACU, with special attention paid to particular phenotypes, and to examine possible parameters that could predict the evolution of the disease. METHODS: This study was a retrospective chart review of 74 patients with ACU who visited a tertiary referral center of urticaria between 2005 and 2015. RESULTS: Fourteen patients (18.9%) presented with life-threatening reactions after cold exposure, and 21 (28.4%) showed negative results after cold stimulation tests (classified as atypical ACU). Nineteen patients (25.7%) achieved complete symptoms resolution at the end of the surveillance period and had no subsequent recurrences. Higher rates of atypical ACU along with a lower likelihood of achieving complete symptom resolution was observed in patients who had an onset of symptoms during childhood (P < .05). In patients with atypical ACU, shorter disease duration and lower doses of antihistamines required for achieving disease control were detected (P < .05). Age at disease onset, symptom severity, and cold urticaria threshold values were found to be related to disease evolution (P < .05). LIMITATIONS: This study was limited by its retrospective nature. CONCLUSIONS: The knowledge of the clinical predictors of the disease evolution along with the clinical features of ACU phenotypes would allow for the establishment of an early and proper therapeutic strategy.

Self-titration by experienced e-cigarette users: blood nicotine delivery and subjective effects

Rationale Self-titration is well documented in the tobacco literature. The extent to which ecigarette users (vapers) self-titrate is unknown. Objective This study explored the effects of high and low nicotine strength liquid on puffing topography, nicotine delivery and subjective effects in experienced vapers. Methods Eleven experienced male vapers completed 60 minutes of ad libitum vaping under low (6 mg/mL) and high (24 mg/mL) nicotine liquid conditions in two separate sessions. Measurements included: puffing topography (puff number, puff duration, volume of liquid consumed); and changes in: plasma nicotine levels, craving, withdrawal symptoms, selfreported hit, satisfaction and adverse effects. Results Liquid consumption and puff number were higher, and puff duration longer, in the low nicotine strength condition (all ps < 0.01). The mean difference in nicotine boost from baseline in the low condition was 8.59 (7.52) ng/mL, 16.99 (11.72) ng/mL and 22.03 (16.19) ng/mL at 10, 30 and 60 minutes respectively. Corresponding values for the high condition were 33.77 (34.88) ng/mL, 35.48 (28.31) ng/mL and 43.57 (34.78) ng/mL (ps < 0.05). There were no statistically significant differences between conditions in self-reported craving, withdrawal symptoms, satisfaction, hit or adverse effects. Conclusions Vapers engaged in compensatory puffing with lower nicotine strength liquid, doubling their consumption. Whilst compensatory puffing was sufficient to reduce craving and withdrawal discomfort, self-titration was incomplete with significantly higher plasma nicotine levels in the high condition.

Aplicação de células estaminais dentárias na Medicina e na Medicina Dentária

A temática relativa às células estaminais inicia-se na década de 60 com a descoberta da primeira fonte viável destas células: a medula óssea. Diversos estudos permitiram definir a sua função de renovação tecidular e regeneração pós-dano, assim como a sua caraterização num grupo heterogéneo de células indiferenciadas, clonogénicas, definidas pela capacidade de auto-renovação e diferenciação em células maduras. Nos últimos anos, estas células ganharam popularidade face à alternativa terapêutica que representam para muitas doenças, tais como: diabetes, anomalias congénitas, danos do tecido nervoso, Parkinson, Alzheimer e outras alterações degenerativas, exposições pulpares, defeitos periodontais e perda do órgão dentário. Apesar do seu potencial terapêutico, apresentam vários efeitos adversos, especialmente em relação ao seu envolvimento direto (via transformação maligna das MSCs) e indireto (via efeito modulatório das MSCs) no desenvolvimento do cancro. Preconiza-se o seu uso no âmbito da Engenharia Tecidular, introduzindo o processo de regeneração tecidular através da utilização combinada de biomateriais e mediadores biológicos, a fim de proporcionar novas ferramentas para a medicina regenerativa. Mais tarde, tornou-se possível identificar cinco populações de células estaminais de origem dentária (DPSCs, SHEDs, DFPCs, SCAPs e PDLCs) que, para além da sua multipotência e capacidade de diferenciação, constituem fontes acessíveis para recolha. O isolamento destas células constitui ainda uma prática relativamente recente, na qual se torna preponderante isolar células com fenótipo pré-determinado e cultivá-las em meios de cultura adequados. Estudos comprovam que o método de isolamento e as condições de cultura utilizados podem dar origem a diferentes linhas celulares. A conservação é uma prática baseada na convicção de que a medicina regenerativa é o caminho mais promissor para o desenvolvimento da medicina personalizada. Informação adicional relativa à terapia com células estaminais é ainda necessária. Esta utiliza princípios de biomimética altamente desejáveis, pelo que os resultados obtidos têm vindo a despoletar grandes expetativas e a sua implementação na Engenharia Tecidular apresenta-se promissora.

Microplastics in sediments: A review of techniques, occurrence and effects

Microplastics are omnipresent in the marine environment and sediments are hypothesized to be major sinks of these plastics. Here, over 100 articles spanning the last 50 year are reviewed with following objectives: (i) to evaluate current microplastic extraction techniques, (ii) to discuss the occurrence and worldwide distribution of microplastics in sediments, and (iii) to make a comprehensive assessment of the possible adverse effects of this type of pollution to marine organisms. Based on this review we propose future research needs and conclude that there is a clear need for a standardized techniques, unified reporting units and more realistic effect assessments.

Mineral and organic pollution in river Sabor (Northeastern Portugal): ecotoxicological effects on freshwater fauna

Aquatic ecosystems are final collectors of all kinds of pollution as an outcome of anthropogenic inputs, such us untreated industrial and municipal sewage and agricultural pollutants. There are several aquatic ecosystems that are threatened by mineral and organic pollution. In Northeastern Portugal, near Bragança, different watercourses are suffering negative impacts of human activities. It has been developed several studies in the monitoring of environmental impacts in these river basins, namely in Rio Fervença, affected by organic pollution, and in Portelo stream, affected, since 2009, by the collapse and continuous input of mining deposits. In this sense, the present study aimed to continue the monitoring study of ecological status of freshwater ecosystems of Northeastern Portugal, namely the following objectives: a) mineral pollution effects of mining deposits sudden incorporated into Portelo stream; b) organic pollution due to domestic and industrial inputs in River Fervença. Also, since fish are useful experimental models to evaluate toxicological mechanisms of contaminants, c) acute toxicity tests with Cu were conducted in laboratory conditions. During 2015/2016, it was made abiotic and biotic characterization of 16 sampling sites distributed by both Portelo and Fervença rivers, tributaries of main River Sabor (Douro Basin). Several physicochemical parameters were determined and Riparian Quality (QBR Index) and Channel Quality (GQC) Indexes were determined for habitat evaluation. Fish and invertebrate communities were sampled, according to protocols of Water Framework Directive (WFD). Several metrics were determined, with particular emphasis on the Biotic Index IBMWP and the Northern Portuguese Invertebrate Index (IPtIN). Acute toxicity tests were conducted with an Iberian fish species, common barbel (Luciobarbus bocagei) and some plasmatic electrolytes levels were evaluated, to assess their contribution to mitigate osmoregulatory adverse effects of Cu. Also, same electrolytes were measured after changing to clean water, in attempt to assess fish capacity to reverse this situation. Results obtained for both rivers showed a significant level of disturbance that affected decisively water, habitat and biological quality of aquatic ecosystems. Mineral and Organic Pollution in River Sabor (NE Portugal): Ecotoxicological Effects on Freshwater Fauna Due to this change of environmental conditions in Portelo stream (extreme pH values, high conductivity and presence of heavy metals), several biological metrics (e.g. taxonomic richness, abundance, diversity, evenness) confirmed, comparatively with reference sites, a substantial decrease on ecological integrity status. The same pattern was found for Fervença River; however other water parameters, namely the content of most limiting nutrients (e.g. N and P) seemed to have more influence in the composition and structure of macroinvertebrate and fish communities. In fact, despite the operation of the Sewage Treatment Plant of Bragança, Fervença River presented significant levels of disturbance that affected decisively the quality and ecological integrity of the aquatic ecosystem. The synergic effect of domestic and industrial pollution, intensive agriculture, regulation and degradation of aquatic and riparian habitats contributed to the decrease of ecological condition, namely in the downstream zones (after Bragança). The results for acute toxicity, showed that fish can change Na+ and K+ levels face to Cu exposition and, depending of Cu concentration tested, can also return to normal levels, providing some insights to that are believed to occurred in fish population, near the Portelo mines. The low ecological integrity status detected in the lotic ecosystems in NE Portugal as a result of mineral and organic pollution deserves the development of several measures for rehabilitation and improving of water quality. On the other hand, environmental education actions are needed to contribute to improvement of ecological integrity of the river and its conservation.

Resíduos de agrotóxicos em alimentos: uma preocupação ambiental global - um enfoque às maçãs.

This paper describes the use of pesticides in agriculture. Research has shown that signifcant quantities of pesticide residues have been found in many types of foods. Thus, an overview is given of pesticide residue determinations in fruits and vegetables, with special attention to apples. The toxicity and the adverse effects possibly caused by the exposure of these compounds are alerting the scientifc community to develop studies about the validation of analytical methods for multiresidue pesticide determination in these samples. This review shows that pesticide-residue determination in apples is becoming a very important and challenging issue.

The real effects of banking supervision:evidence from enforcement actions

We present a novel way to examine macro-financial linkages by focusing on the real effects of bank supervisors’ enforcement actions. Exploiting plausibly exogenous variation in supervisory monitoring intensity, we show that enforcement actions in single-market banks trigger temporarily large adverse effects for the macroeconomy by reducing personal income growth, the number of establishments, and increasing unemployment. These effects are related to contractions in bank lending and liquidity creation, and are more pronounced when we consider enforcement actions on both single-market and multi-market banks, and in counties with fewer banks and greater external financial dependence.

Transcriptional profiling in Saccharomyces cerevisiae relevant for predicting alachlor mechanisms of toxicity

Alachlor has been a commonly applied herbicide and is a substance of ecotoxicological concern. The present study aims to identify molecular biomarkers in the eukaryotic model Saccharomyces cerevisiae that can be used to predict potential cytotoxic effects of alachlor, while providing new mechanistic clues with possible relevance for experimentally less accessible eukaryotes. It focuses on genome-wide expression profiling in a yeast population in response to two exposure scenarios exerting effects from slight to moderate magnitude at phenotypic level. In particular, 100 and 264 genes, respectively, were found as differentially expressed on a 2-h exposure of yeast cells to the lowest observed effect concentration (110 mg/L) and the 20% inhibitory concentration (200 mg/L) of alachlor, in comparison with cells not exposed to the herbicide. The datasets of alachlor-responsive genes showed functional enrichment in diverse metabolic, transmembrane transport, cell defense, and detoxification categories. In general, the modifications in transcript levels of selected candidate biomarkers, assessed by quantitative reverse transcriptase polymerase chain reaction, confirmed the microarray data and varied consistently with the growth inhibitory effects of alachlor. Approximately 16% of the proteins encoded by alachlor-differentially expressed genes were found to share significant homology with proteins from ecologically relevant eukaryotic species. The biological relevance of these results is discussed in relation to new insights into the potential adverse effects of alachlor in health of organisms from ecosystems, particularly in worst-case situations such as accidental spills or careless storage, usage, and disposal.

Diaphragm muscle adaptation to sustained hypoxia: lessons from animal models with relevance to high altitude and chronic respiratory diseases

The diaphragm is the primary inspiratory pump muscle of breathing. Notwithstanding its critical role in pulmonary ventilation, the diaphragm like other striated muscles is malleable in response to physiological and pathophysiological stressors, with potential implications for the maintenance of respiratory homeostasis. This review considers hypoxic adaptation of the diaphragm muscle, with a focus on functional, structural, and metabolic remodeling relevant to conditions such as high altitude and chronic respiratory disease. On the basis of emerging data in animal models, we posit that hypoxia is a significant driver of respiratory muscle plasticity, with evidence suggestive of both compensatory and deleterious adaptations in conditions of sustained exposure to low oxygen. Cellular strategies driving diaphragm remodeling during exposure to sustained hypoxia appear to confer hypoxic tolerance at the expense of peak force-generating capacity, a key functional parameter that correlates with patient morbidity and mortality. Changes include, but are not limited to: redox-dependent activation of hypoxia-inducible factor (HIF) and MAP kinases; time-dependent carbonylation of key metabolic and functional proteins; decreased mitochondrial respiration; activation of atrophic signaling and increased proteolysis; and altered functional performance. Diaphragm muscle weakness may be a signature effect of sustained hypoxic exposure. We discuss the putative role of reactive oxygen species as mediators of both advantageous and disadvantageous adaptations of diaphragm muscle to sustained hypoxia, and the role of antioxidants in mitigating adverse effects of chronic hypoxic stress on respiratory muscle function.

Efectividad del tratamiento de lumbalgia con acupuntura

Se realizó un estudio observacional retrospectivo longitudinal en una Institución prestadora de Servicios de Salud de la ciudad de Bogotá, con el objetivo de evaluar la efectividad en el manejo del dolor de la terapia con acupuntura en el tratamiento de lumbalgia. Se tomaron 150 historias clínicas de pacientes con lumbalgia atendidos de enero de 2014 a mayo de 2016, las cuales fueron sometidas a los criterios de inclusión definidos por los autores, arrojando 48 historias sometidas a la prueba de Friedman con el fin de identificar el impacto sobre el dolor del tratamiento con acupuntura en los pacientes seleccionados. Adicionalmente, bajo un muestreo aleatorio simple de distribución normal sobre las 48 historias clínicas evaluadas, se seleccionaron 25 casos a los cuales se les aplicó una encuesta no estructurada, con el fin de obtener información sobre el estado de la patología después de finalizar el tratamiento e identificar las posibles causas de deserción. Con este estudio se concluye que la terapia con acupuntura es efectiva en el manejo del dolor de pacientes con lumbalgia, y que es necesario realizar más estudios que puedan sustentar la inclusión de la terapéutica en el manejo de esta patología.

Effects of allelopathic compounds produced by native and invasive marine macroalgae on the associated communities

In this study, the production of bioactive secondary metabolites called "allelochemicals" by algae has been investigated, specifically focusing on polyunsaturated aldehydes (PUAs). PUAs are known to have adverse effects on planktonic grazers and on phytoplankton; however, their effect on benthic communities has been poorly studied. Macroalgae are ecosystem engineers that play an important role in the structure of the habitat and associated communities, presenting a great variability in their morphology and structural complexity, which is a primary factor in the structuring of associated communities. In recent decades, it has been seen how the introduction of invasive species can modify the benthic habitat structure, causing cascading effects on the trophic chain. The thesis includes several field and laboratory studies. Field studies examined aldehyde production by native and invasive macroalgal species (Sargassum muticum, in the Adriatic Sea, and Rugulopterix okamurae in the Strait of Gibraltar), their structural complexity, together with their associated phyto and meiobenthos. Two laboratory studies were conducted. The first one, based on microcosms experiments, evaluated the effect of PUA (produced by the diatom Skeletonema marinoi, or as decadienal analytical standard) on meiofauna. The second one evaluated the inhibitory effect of dilkamural, an allelopathic compound isolated from R. okamurae, on unicellular phototrophs. Our results showed that PUAs produced by macroalgae were species-specific and had a significant impact on the benthic community. The morphology of macroalgae was an important factor in shaping associated communities, particularly for microphytobenthos. Invasive species, such as S. muticum and R. okamurae, could reduce the biodiversity of native benthic communities and simplify the habitat. Dilkamural was hypothesized to be an allelochemical defense, and laboratory toxicity tests confirmed this hypothesis. Overall, this thesis sheds light on the importance of allelochemicals and macroalgal structural complexity in the benthic environment and highlights the potential impact of invasive species.

The Consequences Of Refractory Epilepsy And Its Treatment.

Seizures in some 30% to 40% of patients with epilepsy fail to respond to antiepileptic drugs or other treatments. While much has been made of the risks of new drug therapies, not enough attention has been given to the risks of uncontrolled and progressive epilepsy. This critical review summarizes known risks associated with refractory epilepsy, provides practical clinical recommendations, and indicates areas for future research. Eight international epilepsy experts from Europe, the United States, and South America met on May 4, 2013, to present, review, and discuss relevant concepts, data, and literature on the consequences of refractory epilepsy. While patients with refractory epilepsy represent the minority of the population with epilepsy, they require the overwhelming majority of time, effort, and focus from treating physicians. They also represent the greatest economic and psychosocial burdens. Diagnostic procedures and medical/surgical treatments are not without risks. Overlooked, however, is that these risks are usually smaller than the risks of long-term, uncontrolled seizures. Refractory epilepsy may be progressive, carrying risks of structural damage to the brain and nervous system, comorbidities (osteoporosis, fractures), and increased mortality (from suicide, accidents, sudden unexpected death in epilepsy, pneumonia, vascular disease), as well as psychological (depression, anxiety), educational, social (stigma, driving), and vocational consequences. Adding to this burden is neuropsychiatric impairment caused by underlying epileptogenic processes (essential comorbidities), which appears to be independent of the effects of ongoing seizures themselves. Tolerating persistent seizures or chronic medicinal adverse effects has risks and consequences that often outweigh risks of seemingly more aggressive treatments. Future research should focus not only on controlling seizures but also on preventing these consequences.