Prioritizing pharmaceutically active compounds (PhACs) based on occurrence-persistency-mobility-toxicity (OPMT) criteria: an application to the Brazilian scenario.

A study of Quantitative Structure Activity Relationship (QSAR) was performed to assess the possible adverse effects of 25 pharmaceuticals commonly found in the Brazilian water compartments and to establish a ranking of environmental concern. The occurrence (O), the persistence (P), the mobility (M), and the toxicity (T) of these compounds in the Brazilian drinking water reservoirs were evaluated. Moreover, to verify the predicted OPMT dataset outcomes, a quality index (QI) was also developed and applied. The main results showed that: (i) after in silico predictions through VEGA QSAR, 19 from 25 pharmaceuticals consumed in Brazil were classified as persistent; (ii) moreover, after in silico predictions through OPERA QSAR, 15 among those 19 compounds considered persistent, were also classified as mobile or very mobile. On the other hand, the results of toxicity indicate that only 9 pharmaceuticals were classified with the highest toxicity level. Ultimately, the QI of 7 from 25 pharmaceuticals were categorized as 'optimal'; 15 pharmaceuticals were categorized as 'good'; and only 3 pharmaceuticals were categorized as 'regular'. Therefore, based on the QI criteria used, it is possible to assume that this OPMT prediction dataset had a good reliability. Efforts to reduce emissions of OPMT-pharmaceuticals in Brazilian drinking water reservoirs are encouraged.

Acute and chronic effects of environmental realistic concentrations of simvastatin in danio rerio: evidences of oxidative alterations and endocrine disruptive activity.

Due to their wide use, pharmaceuticals can be discarded, metabolized and excreted into the environment, potentially affecting aquatic organisms. Lipid-regulating drugs are among the most prescribed medications around the world, to control human cholesterol levels, in more than 20 million patients. Despite this massive use of lipid-regulating drugs, particularly simvastatin, the role of these drugs is not fully characterized and understood in terms of its potential toxicological effects at the environmental level. This work intended to characterize the toxicity of an acute (120 h post-fertilization) and chronic (60 days) exposure to the antihyperlipidemic drug simvastatin (in concentrations of 92.45, 184.9, 369.8, 739.6 and 1479.2 ng L-1), in the freshwater species zebrafish (Danio rerio). The concentrations hereby mentioned were implemented in both exposures, and were based on levels found in wastewater treatment plant influents (11.7 ± 3.2 µg L-1), effluents (2.65 ± 0.8 µg L-1) and Apies River (1.585 ± 0.3 µg L-1), located in Pretoria, South Africa and, particularly in the maximum levels found in effluents from wastewater treatment plants in Portugal (369.8 ng L-1). The acute effects were analysed focusing on behavioural endpoints (erratic and purposeful swimming), total distance travelled and swimming time), biomarkers of oxidative stress (the activities of the enzymes superoxide dismutase, catalase, glutathione peroxidase), biotransformation (the activity of glutathione S-transferases) and lipid peroxidation (levels of thiobarbituric acid reactive substances). Animals chronically exposed were also histologically analysed for sex determination and gonadal developmental stages identification. In terms of acute exposure, significant alterations were reported in terms of behavioural alterations (hyperactivity), followed by a general reduction in all tested biomarkers. Also, the analysis of chronically exposed fish evidenced no alterations in sex ratio and maturation stages. In addition, the analysis of chronically exposed fish evidenced no alterations in terms of sexual characteristics, suggesting that the chronic exposure of Danio rerio to simvastatin does not alter the sex ratio and maturation stages of individuals. This assumption suggests that simvastatin did not act as an endocrine disruptor. Moreover, the metabolism, neuronal interactions and the antioxidant properties of SIM seem to have modulated the hereby-mentioned results of toxicity. Results from this assay allow inferring that simvastatin can have an ecologically relevant impact in living organisms.

Acute and chronic effects of environmental realistic concentrations of clofibric acid in Danio rerio: Behaviour, oxidative stress, biotransformation and lipid peroxidation endpoints.

Due to their widespread use, pharmaceuticals can be metabolized, excreted and ultimately discarded in the environment, thereby affecting aquatic organisms. Lipid-regulating drugs are among the most prescribed medications around the world, controlling human cholesterol levels, in more than 20 million patients. Despite this growing use of lipid-regulating drugs, particularly those whose active metabolite is clofibric acid, the potential toxicological effects of these pharmaceuticals in the environment is not fully characterized. This work intended to characterize the toxicity of an acute (120 hours post-fertilization) and chronic (60 days post-fertilization) exposures to clofibric acid in concentrations of 10.35, 20.7, 41.4, 82.8, and 165.6 µg L-1 in zebrafish (Danio rerio). The concentrations which were implemented in both exposures were based on predicted environmental concentrations for Portuguese surface waters. The acute effects were analysed focusing on behavioural endpoints (small and large distance travelled, swimming time and total distance travelled), biomarkers of oxidative stress (activity of the enzymes superoxide dismutase, Cu/Zn- and Mn SOD; catalase, CAT; glutathione peroxidase, Se- and total GPx), biotransformation (activity of glutathione S-transferases, GSTs) and lipid peroxidation (thiobarbituric acid reactive substances, TBARS). Chronically exposed individuals were also histologically analysed for sex determination and gonadal developmental stages. In terms of acute exposure, significant alterations were reported, in terms of behavioural alterations (hypoactivity), followed by an overall increase in all tested biomarkers. Chronically exposed organisms did not show alterations in terms of sex ratio and maturation stages, suggesting that clofibric acid did not act as an endocrine disruptor. Moreover, the metabolism of clofibric acid resulted in increased levels of both forms of SOD activity, especially for animals exposed to higher levels of this drug. An increase of CAT activity was observed in fish exposed to low levels, and a decrease in those exposed to higher amounts of clofibric acid. Both GPx forms had their activities increased. The enzyme of biotransformation GSTs were increased at low levels of clofibric acid but inhibited at higher amounts of this substance. Lipid peroxidation levels were also changed, with an induction of this parameter with increasing amounts of clofibric acid. Changes also occurred in behavioural endpoints and patterns for control organisms and for those exposed to clofibric acid were significantly distinct, for all types (light and darkness) of exposure, and for the two analysed endpoints (small and large distance). Results from this assay allow inferring that clofibric acid can have an ecologically relevant impact in living organisms exposed to this substance, with putative effects on the metabolism of individuals, affecting their behaviour and ultimately their survival.

Evaluation of a Physical-Chemical Protocol for Porcine Tracheal Decellularization.

INTRODUCTION/OBJECTIVE: Tracheal resection with primary reconstruction is the definitive treatment for many tracheal benign and malignant diseases. When primary resection is not deemed feasible as a result of the length of the stenosis, airway transplantation may become a solution. Tissue engineering offers an alternative way for creating tracheal substitutes. The development of tracheal allograft transplantation includes the decellularized tracheal scaffolds made of extracellular matrix that are seeded with the receptor's cells. Many protocols are used to obtain a decellularized scaffold. Most of them consist of cyclical physical-chemical steps with enzymes. This study proposes a protocol for decellularization based only in physical-chemical steps. METHODS: Decellularization of pig tracheal segments was carried out using a standardized protocol consisting of freezing and thawing, 10 cycles of agitation, exposure to sodium deoxycholate, and washing. The degree of decellularization was determined by quantifying residual DNA. We also analyzed the morphology under hematoxylin and eosin staining. RESULTS: Fourteen porcine tracheal segments were decellularized. All scaffolds obtained showed less than 2% of residual DNA (mean 20 ± 8 ng/mg) when compared to the fresh samples (mean 850 ± 123 ng/mg), P = .001. Morphological analysis showed that the epithelium and mixed glands were completely removed. It was possible to identify residual nuclei inside the cartilaginous rings (73.7 ± 12 × 26 ± 8 nuclei/field, P < .001). CONCLUSION: The protocol tested was able to provide effective decellularization of porcine tracheas.

Effects of the chronic exposure to cerium dioxide nanoparticles in Oncorhynchus mykiss: Assessment of oxidative stress, neurotoxicity and histological alterations.

Cerium dioxide nanoparticles (CeO2-NPs) have a variety of uses, especially in the production of solar panels, oxygen pumps, gas sensors, computer chips and catalytic converters. Despite their worldwide use, the few published studies demonstrate that metallic nanoparticles, in general, are still not properly characterized in terms of their potencial ecotoxicological effects. CeO2-NPs, in particular, have demonstrated extreme antioxidant activity, but their in vivo toxicity is still unknown. This work intended to characterize the chronic toxicity (28 days) of three different ecologically relevant concentrations (0.1, 0.01, and 0.001 µg/L) of CeO2-NPs in the rainbow trout (Oncorhynchus mykiss), in terms of biomarkers of oxidative stress [activity of the enzymes glutathione S-transferases (GSTs) and catalase (CAT)] and neurotoxicity [activity of the enzyme acetylcholinesterase (AChE)], as well as histological alterations in liver and gills. In the hereby study, GSTs activity was increased in gills of fish exposed to the highest CeO2-NPs level. Moreover, a potential anti-oxidant response was also reported, with a significant increase of CAT activity observed in livers of the same fish. AChE, however, was not significantly altered in fish eyes. Individuals exposed to CeO2-NPs also presented marked changes in the gills (e.g. epithelial lifting, intercellular edema, lamellar hypertrophy and hyperplasia, secondary lamella fusion and aneurysms) and liver (e.g. hepatocyte vacuolization, pyknotic nucleus, enlargement of sinusoids and hyperemia). The semi-quantitative analysis (organs pathological index) also showed the establishment of a dose-effect relationship. Further studies about the ecotoxicological effects of the CeO2-NPs have yet to be conducted, considering their properties, as the aggregation chemistry and the ratio of its redox state, which may affect their availability to the organism and their toxicity in the environment and biota.

Ecotoxicological evaluation of gilthead seabream (Sparus aurata) exposed to the antibiotic oxytetracycline using a multibiomarker approach.

Oxytetracycline (OTC) is an antibiotic widely used in human and veterinary medicines. Since the primary toxicity occurs mainly at molecular/biochemical levels, the study of different biological responses corresponds to a sensitive and crucial approach. The aim of the present study was to assess the toxic effects of OTC in gilthead seabream (Sparus aurata) through the use of multibiomarkers and elucidate about the possible toxicological mechanisms involved. S. aurata were acutely (96 h: 0.04-400 µg/L) and chronically (28 days: 0.0004-4 µg/L) exposed to OTC. Detoxification, antioxidant defense, lipid peroxidation, genotoxicity, neurotransmission and energy metabolism biomarkers were evaluated. OTC impaired the detoxification pathways and caused peroxidative damage and genotoxicity. The relevance of the here-obtained data is high, since significant effects were recorded for levels already reported to occur in the wild, meaning that environmentally-exposed marine organisms (including those cultured at fish farms) are not completely exempt of risks posed by OTC.

Oxytetracycline effects in specific biochemical pathways of detoxification, neurotransmission and energy production in Oncorhynchus mykiss.

Oxytetracycline (OTC) is a tetracycline antibiotic, widely used in human and veterinary medicines, including in aquaculture. Given this use, OTC has been detected in different aquatic environments. Some recent works have demonstrated unintentional biological activity of OTC in non-target aquatic organisms. This study investigated the acute and chronic effects of OTC on the physiology of the fish species Oncorhynchus mykiss (rainbow trout), namely through the quantification of the activity of enzymes involved in different biochemical pathways, such as detoxification (phase II - glutathione S-transferases - GSTs, uridine-diphosphate-glucuronosyltransferases - UGTs), neurotransmission (acetylcholinesterase - AChE) and energy production (lactate dehydrogenase - LDH). The here-obtained data demonstrated the induction of GSTs activity in gills, and inhibition of AChE activity in eyes tissue, in chronically exposed organisms, as well as alterations in LDH activity following both exposures. Considering this set of results, we can infer that OTC exposure may have induced the glutathione pathway of detoxification in gills with the involvement of GSTs, or indirectly due to the metabolites that may have been produced. In turn, these metabolites may have interfered with the mechanism of neurotransmission, also causing physiological and biochemical disturbances in rainbow trout after OTC exposure, namely disturbances in energetic metabolism. In addition, it is important to stress that such occurrences took place at low, environmentally realistic levels of OTC, suggesting that organisms exposed in the wild may be putative targets of toxic effects by commonly used drugs such as antibiotics.

Histological alterations in gills and liver of rainbow trout (Oncorhynchus mykiss) after exposure to the antibiotic oxytetracycline.

The aim of this study was to investigate the histopathological effects of oxytetracycline (OTC) on the gill and liver tissues of rainbow trouts (Oncorhynchus mykiss) following acute (96h: 0.005-50mg/L) and chronic (28days: 0.3125-5µg/L) exposures. Results suggest the existence of a cause-and-effect relationship between the exposure to OTC and tissue damage. Most predominant disorders observed in gills were progressive (e.g. hypertrophy of mucous cells and hyperplasia of epithelial cells) in acute exposure and regressive (e.g. lamellar fusion, epithelial lifting of lamellae and some changes in tissue architecture) in chronic exposure. However, only the acute exposure was responsible for a significant increase of the total gill pathological index. PAGE index, reflecting the extent of gill tissue available for gas exchanges in fish, remained unchanged for both exposures. In liver, circulatory (e.g. hemorrhage and increase of sinusoidal space), regressive (e.g. pyknotic nucleus, vacuolization and hepatocellular degenerations) and progressive (e.g. hypertrophy of hepatocytes) changes were observed, but just after acute exposure. After chronic exposure, only inflammatory changes (e.g. leucocytes infiltration) were observed. Following both exposures, a significant increase of the total liver pathological index was recorded. Despite the increase of the histological damage in individuals exposed to OTC, lesions observed were of minimal or moderate pathological importance, non-specific and reversible. The data gathered following acute and chronic exposures also suggest the onset of adaptive mechanisms of fish, namely for longer exposure periods. Furthermore the observed histological alterations appear to be result of several physio-metabolic disorders consequence of the biochemical and molecular modes of action of OTC.

Effects of chronic exposure to benzalkonium chloride in Oncorhynchus mykiss: cholinergic neurotoxicity, oxidative stress, peroxidative damage and genotoxicity.

Benzalkonium chloride (BAC) is one of the most used conservatives in pharmaceutical preparations. However, its use is limited to a small set of external use formulations, due to its high toxicity. Benzalkonium chloride effects are related to the potential exertion of deleterious effects, mediated via oxidative stress and through interaction with membrane enzymes, leading to cellular damage. To address the ecotoxicity of this specific compound rainbow trouts were chronically exposed to BAC at environmental relevant concentrations (ranging from 0.100 to 1.050mg/L), and the biological response of cholinergic neurotoxicity, modulation of the antioxidant defense, phase II metabolism, lipid peroxidation and genotoxicity was studied. The obtained results showed a dual pattern of antioxidant response, with significant alterations in catalase activity (starting at 0.180mg/L), and lipid peroxidation, for intermediate (0.180 and 0.324mg/L) concentrations. No significant alterations occurred for glutathione-S-transferases activity. An unexpected increased of the acetylcholinesterase activity was also recorded for the individuals exposed to higher concentrations of BAC (starting at 0.180mg/L). Furthermore, exposure to BAC resulted in the establishment of genotoxic alterations, observable (for the specific case of the comet assay results) for all tested BAC concentrations. However, and considering that the oxidative response was not devisable, other mechanisms may be involved in the genotoxic effects reported here.

Absence of effects of different types of detergents on the cholinesterasic activity and histological markers of mosquitofish (Gambusia holbrooki) after a sub-lethal chronic exposure.

The release of anthropogenic compounds into the aquatic environment has been a particular concern, since some of these substances exhibit biologic activity of different types in non-target species. Among anthropogenic compounds present in the aquatic compartment, detergents are commonly found and may be responsible for physiological modifications in exposed organisms. The impairment of key physiological functions, such as neurotransmission, and tissue damage in some important organs, has been used to assess the effects of several classes of xenobiotics, including detergents, in aquatic organisms. The present study intended to assess the effect of three types of detersive compounds (sodium dodecylsulfate (SDS), benzalkonium chloride (BZC), and Triton X-100 (TX100)) in the acetylcholinesterase activity (AChE) and tissue damage (gills and liver) of Gambusia holbrooki after a chronic exposure to realistic levels of these compounds. SDS, BZC, and TX100 did not cause any significant alteration in AChE. Furthermore, no specific gross morphological changes were also observed in the gills and liver of the exposed individuals. It is possible to conclude that, under ecologically relevant conditions of exposure, both tissue damage and cholinesterasic impairment are not toxicological pathways affected by detergents in G. holbrooki.

Habitat residency and movement patterns of Centropomus parallelus juveniles in a subtropical estuarine complex.

Sixty Centropomus parallelus juveniles were collected in March 2013 in two locations (Tromomó and Guaraguaçu) inside the Paranaguá estuarine complex, southern Brazil. The habitat residency and movement patterns of the individuals were inferred from Sr:Ca ratios and age recorded in the otoliths. Data suggest that the species spawns preferentially in brackish areas mainly from October to January, and that growth rate during the early juvenile stage could be influenced by environmental salinity. Furthermore, the data also show that C. parallelus can occupy diverse salinity habitats and migrate among marine, brackish and freshwater areas within the Paranaguá estuarine complex, showing a high environmental plasticity and adaptation.

The effects of urban particulate matter on the nasal epithelium by gender: An experimental study in mice.

Nose is the first portion of the respiratory system into contact with air pollution particles, including organic compounds that could act as endocrine releasers. The objective was to identify and quantify estrogenic receptor-ß (ERß), aryl hydrocarbon receptor (AhR), the cytochrome P450 enzymes CYP1A1, 1A2, 1B1, and mucus profile in the nasal epithelium of mice. BALB/c mice male (n = 32) and female (n = 82) in proestrus, estrus and diestrus were divided into two groups: 1) exposed to ambient air; 2) concentrated ambient particles (CAPs) to achieve an accumulated dose (concentration vs. time product) of 600 µg/m(3), the time of the exposure was controlled to ensure the same concentration for all groups (5 days per week for 40-51 days). RT-PCR (Erß-1, Erß-2, Ahr, Cyp1a1, Cyp1a2, Cyp1b1), immunohistochemistry and morphometry (ERß, AhR) were used to analyze. The mucus profiles were examined using acid (Alcian Blue) and neutral (periodic acid Schiff's) stains. Exposed females had significantly lower levels of Erß-2 mRNA than exposed males (p = 0.036). Cyp1b1 mRNA in diestrus females was significantly lower in the CAP-exposed group compared with the ambient air group (p ≤ 0.05). ERß expression in the epithelium and submucosa nucleus was lower in estrus exposed to CAPs compared with ambient air. CAPs increases AhR in the epithelium (p = 0.044) and submucosa (p = 0.001) nucleus of female when compared with male mice. Exposure to CAPs, also led to relatively increased acidic content in the mucus of males (p = 0.048), but decreased acidic content in that of females (p = 0.04). This study revealed sex-dependent responses to air pollution in the nasal epithelium that may partially explain the predisposition of females to airway respiratory diseases.

Acute and chronic effects of erythromycin exposure on oxidative stress and genotoxicity parameters of Oncorhynchus mykiss.

Erythromycin (ERY) is a macrolide antibiotic used in human and veterinary medicine, and has been detected in various aquatic compartments. Recent studies have indicated that this compound can exert biological activity on non-target organisms environmentally exposed. The present study aimed to assess the toxic effects of ERY in Oncorhynchus mykiss after acute and chronic exposures. The here adopted strategy involved exposure to three levels of ERY, the first being similar to concentrations reported to occur in the wild, thus ecologically relevant. Catalase (CAT), total glutathione peroxidase (GPx), glutathione reductase (GRed) activities and lipid peroxidation (TBARS levels) were quantified as oxidative stress biomarkers in gills and liver. Genotoxic endpoints, reflecting different types of genetic damage in blood cells, were also determined, by performing analysis of genetic damage (determination of the genetic damage index, GDI, measured by comet assay) and of erythrocytic nuclear abnormalities (ENAs). The results suggest the occurrence of a mild, but significant, oxidative stress scenario in gills. For acutely exposed organisms, significant alterations were observed in CAT and GRed activities, and also in TBARS levels, which however are modifications with uncertain biological interpretation, despite indicating involvement of an oxidative effect and response. After chronic exposure, a significant decrease of CAT activity, increase of GPx activity and TBARS levels in gills was noticed. In liver, significant decrease in TBARS levels were observed in both exposures. Comet and ENAs assays indicated significant increases on genotoxic damage of O. mykiss, after erythromycin exposures. This set of data (acute and chronic) suggests that erythromycin has the potential to induce DNA strand breaks in blood cells, and demonstrate the induction of chromosome breakage and/or segregational abnormalities. Overall results indicate that both DNA damaging effects induced by erythromycin may be related to the oxidative damage observed, shown to occur at environmentally relevant concentrations of erythromycin.

Metazoan parasites of blue jack mackerel Trachurus picturatus (Perciformes: Carangidae) from Portuguese mainland waters.

Blue jack mackerel, Trachurus picturatus, is a carangid fish which constitutes an important commercial resource in the north-east Atlantic. Its metazoan parasite community from Portuguese mainland waters was investigated here for the first time. Nine parasite taxa were found, most of which are common parasites of Trachurus spp. The parasite community was broadly similar to that of the Atlantic horse mackerel, T. trachurus, from the same region, but two digenean species were detected in blue jack mackerel, Monascus filiformis and Tergestia sp., which did not occur in horse mackerel from this region. A comparison with the two previous studies of T. picturatus parasite communities shows that continental-shelf regions are characterized by higher prevalences of digenean trematodes and an absence of trypanorhynch cestodes, in contrast with oceanic regions.

Ecotoxicological effect of zinc pyrithione in the freshwater fish Gambusia holbrooki.

Currently diverse biocidal agents can be used for distinct applications, such as personal hygiene, disinfection, antiparasitic activity, and antifouling effects. Zinc pyrithione is an organometallic biocide, with bactericidal, algicidal and fungicidal activities. It has been recently incorporated in antifouling formulas, such as paints, which prevent the establishment of a biofilm on surfaces exposed to the aquatic environment. It has also been used in cosmetics, such as anti-dandruff shampoos and soaps. Previously reported data has shown the presence of this substance in the aquatic compartment, a factor contributing to the potential exertion of toxic effects, and there is also evidence that photodegradation products of zinc pyrithione were involved in neurotoxic effects, namely by inhibiting cholinesterases in fish species. Additional evidence points to the involvement of zinc pyrithione in alterations of metal homeostasis and oxidative stress, in both aquatic organisms and human cell models. The present work assesses the potential ecotoxicity elicited by zinc pyrithione in the freshwater fish Gambusia holbrooki after an acute (96 h) exposure. The oxidative stress was assessed by the quantification of the activities of specific enzymes from the antioxidant defense system, such as catalase, and glutathione-S-transferases; and the extent of peroxidative damage was quantified by measuring the thiobarbituric acid reactive substances levels. Neurotoxicity was assessed through measurement of acetylcholinesterase activity; and a standardized method for the description and assessment of histological changes in liver and gills of was also used. Zinc pyrithione caused non-specific and reversible tissue alterations, both in liver and gills of exposed organisms. However, histopathological indices were not significantly different from the control group. In terms of oxidative stress biomarkers, none of the tested biomarkers indicated the occurrence of pro-oxidative effects, suggesting that the oxidative pathway is not the major toxicological outcome of exposure to zinc pyrithione.

Acute effects of tetracycline exposure in the freshwater fish Gambusia holbrooki: antioxidant effects, neurotoxicity and histological alterations.

A large body of evidence was compiled in the recent decades showing a noteworthy increase in the detection of pharmaceutical drugs in aquatic ecosystems. Due to its ubiquitous presence, chemical nature, and practical purpose, this type of contaminant can exert toxic effects in nontarget organisms. Exposure to pharmaceutical drugs can result in adaptive alterations, such as changes in tissues, or in key homeostatic mechanisms, such as antioxidant mechanisms, biochemical/physiological pathways, and cellular damage. These alterations can be monitored to determine the impact of these compounds on exposed aquatic organisms. Among pharmaceutical drugs in the environment, antibiotics are particularly important because they include a variety of substances widely used in medical and veterinary practice, livestock production, and aquaculture. This wide use constitutes a decisive factor contributing for their frequent detection in the aquatic environment. Tetracyclines are the individual antibiotic subclass with the second highest frequency of detection in environmental matrices. The characterization of the potential ecotoxicological effects of tetracycline is a much-required task; to attain this objective, the present study assessed the acute toxic effects of tetracycline in the freshwater fish species Gambusia holbrooki by the determination of histological changes in the gills and liver, changes in antioxidant defense [glutathione S-transferase (GST), catalase (CAT), and lipoperoxidative damage] as well as potential neurotoxicity (acetylcholinesterase activity). The obtained results suggest the existence of a cause-and-effect relationship between the exposure to tetracycline and histological alterations (more specifically in gills) and enzymatic activity (particularly the enzyme CAT in liver and GST in gills) indicating that this compound can exert a pro-oxidative activity.

Ecotoxicological effects of salicylic acid in the freshwater fish Salmo trutta fario: antioxidant mechanisms and histological alterations.

The presence of pharmaceutical drugs in aquatic ecosystems has been widely reported during the past years. Salicylic acid (SA) is mainly used in human medicine as an analgesic and antipyretic drug, being also active in preventing platelet aggregation. To study the ecotoxicological effects potentially elicited by SA in freshwater fish, brown trout individuals (Salmo trutta fario) were chronically exposed (28 days) to this drug, in order to evaluate the enzymatic and histological effects, in both gills and liver. A qualitative and semi-qualitative evaluation of the gills and liver was performed, and also a quantitative evaluation of various lamellar structures. Oxidative stress was quantified trough the determination of glutathione S-transferases (GSTs), glutathione reductase (GRed), total and selenium-dependent glutathione peroxidase (GPx) and Catalase (Cat) activities. Lipid peroxidative damage was also assessed by the quantification of thiobarbituric acid reactive substances (TBARS) in the liver. The here-obtained data showed the occurrence of oxidative stress, reflected by an increased activity of GPx and GRed in the liver; additionally, it was possible to observe non-specific histological changes in gills. The global significance of the entire set of results is discussed, giving emphasis to the ecological relevance of the responses.

Effect of acetaminophen exposure in Oncorhynchus mykiss gills and liver: detoxification mechanisms, oxidative defence system and peroxidative damage.

The increasing presence of pharmaceutical drugs in nature is cause of concern due to the occurrence of oxidative stress in non-target species. Acetaminophen is widely used in human medicine as an analgesic and antipyretic drug, and it is one of the most sold non-prescription drugs. The present study aimed to assess the toxic effects of acetaminophen (APAP) in Oncorhynchus mykiss following acute and chronic exposures in realistic levels. In order to evaluate the APAP effects in the rainbow trout, gills and liver were analyzed with biochemical biomarkers, such as catalase (CAT), total and selenium-dependent glutathione peroxidase (GPx), glutathione reductase (GRed) and glutathione-S-transferases (GSTs) activity and also lipid peroxidation levels (TBARS). The results obtained in all tests indicate that a significant response of oxidative stress was established, along with the increase of APAP concentrations. The establishment of an oxidative stress scenario occurred with the involvement of all tested biomarkers, sustaining a generalized set of pro-oxidative effects elicited by APAP. Additionally, the occurrence of oxidative damage strongly suggests the impairment of the antioxidant defense mechanism of O. mykiss. It is important to note that the occurrence of oxidative deleterious effects and peroxidative damages occurred for concentrations similar to those already reported for several freshwater ecosystems. The importance of these assumptions is further discussed under the scope of ecological relevance of the assessment of effects caused by pharmaceuticals in non-target organisms.

Validation of otolith daily increments in early juveniles of shanny Lipophrys pholis.

To assess the periodicity of micro-increment formation in otoliths of Lipophrys pholis, 90 early juveniles were immersed in alizarin red S or tetracycline hydrochloride for 24 h and sacrificed after 10, 20 and 30 days. The number of micro-increments viewed under light microscopy was significantly related to the duration of the experimental period, and the slopes of the linear regressions were not significantly different from 1. This study indicates that micro-increments in sagittae were deposited daily and can be used as reliable sources of age information for L. pholis.

Lung transplantation in patients with cystic fibrosis.

Cystic fibrosis (CF) an autosomal recessive genetic disorder, affects many organs. The great majority of deaths occur due to respiratory failure after many years of chronic pulmonary infection. Despite recent progress in early detection by studies of genetic mutations and better understanding to treat nutritional and infectious states, lung transplantation is the CF treatment for most advanced cases. According to the International Society for Heart and Lung Transplantation (ISHLT) data, CF is the third most common reason for lung transplantation (16.8%) showing the best survival rate (60% at 5 years). We have described our experience in lung transplantation of CF patients between January 2000 and December 2011, reviewing medical charts of these patients were for gender, age, body mass index (BMI), comorbidities, disease duration, previous sputum gram stain, ischemic time, incidence of severe primary graft dysfunction (PGD Grade 3), intensive care unit (ICU) length of stay, and Kaplan-Meier survival. Among 150 lung transplantation, the 30 CF patients (20%) represented the second most common cause. The average age was 27.4 ± 9.2 years, with a slight predominance of males (n = 16; 53.3%). The average BMI was 18.9 ± 2.6. Most patients (60%) had pancreatic exocrine dysfunction. Also, 83.3% of patients showed a positive sputum culture for Pseudomonas, while Burkholderia cepacia was identified in only 4 patients (13.3%). The average time of the disease was 20.8 ± 9.7 years. All transplantation were bilateral with an average ischemic time of 472 ± 98.3 minutes and ICU length of stay of 9.9 ± 6.3 days. The survival rates at 1 and 5 years were 92% and 77%, respectively, corresponding to the best outcomes among underlying diseases, comparable with other worldwide series and better than the ISHLT reports. CF, the second most common cause for lung transplantation among our cases, showed the best survival rate among all causes. Our survival rate was comparable with other reports.