Search

Widespread occurrence of pharmaceuticals is reported in aquatic systems, posing concerns for the health of aquatic wildlife and a theoretical risk to humans. A recent concept was developed for the identification of highly active compounds amongst the environmental pharmaceuticals, based on their mode of action, the homology between human targets and possible targets in the environment, and the importance of the affected pathway for the target species. In line with this approach, this study investigated whether propranolol (PROP) affects the cAMP-dependent pathway in Mediterranean mussels, Mytilus galloprovincialis. PROP is a prototypical β-adrenoceptor antagonist, and these receptors exist in bivalves and show gross pharmacological properties similar to their mammalian counterparts. PROP also acts as a 5-HT1 receptor antagonist, which is the sole 5-HT receptor reported in bivalves to date. Importantly, β-adrenoceptor and 5HT-1 receptor subtypes are positively and negatively coupled to cAMP-mediated signaling, respectively. PROP was administered as either l-PROP or dl-PROP. A wide range of concentrations was tested including low (0.3, 3 and 30ng/L) and high (300ng/L) environmental ranges, and a concentration 5-fold above the maximum reported environmental level (30,000ng/L). After a 7-day exposure, mussel cAMP levels and PKA activities were significantly reduced in digestive gland, increased in mantle/gonads and unaffected in gills. Similar patterns were observed for the mRNA expression of the ABCB1 gene encoding the membrane transporter P-glycoprotein, hypothesised to be under PKA modulation. The effects on the digestive gland are consistent with PROP blocking β-adrenoceptors. The observed increased cAMP levels in the mantle/gonad tissue support PROP blocking 5-HT1 receptors. Catalase and glutathione-S tranferase were differently affected by PROP in the two tissues. Mussel haemocyte lysosome membrane stability, a sensitive biomarker of animal health status, was concentration-dependently reduced following PROP exposure. Our observations provide evidence for PROP affecting cell signaling in M. galloprovincialis. Moreover, the chemical interacts with specific and evolutionally conserved biochemical pathways for which it was designed. The mode of action of PROP in mussels is related with its therapeutic properties in humans, based upon these conserved human targets. It also induced a stress response, and all these effects were displayed at the lowest concentrations tested., (2010 Elsevier B.V. All rights reserved.)

This work aimed to develop a fast-dissolving film made of low dextrose equivalent maltodextrins (MDX) containing nicotine hydrogen tartrate salt (NHT). Particular attention was given to the selection of the suitable taste-masking agent (TMA) and the characterisation of the ductility and flexibility under different mechanical stresses. MDX with two different dextrose equivalents (DEs), namely DE 6 and DE 12, were selected in order to evaluate the effect of polymer molecular weight on film tensile properties. The bitterness and astringency intensity of NHT and the suppression effect of several TMA were evaluated by a Taste-Sensing System. The films were characterised in term of NHT content, tensile properties, disintegration time and drug dissolution test. As expected, placebo films made of MDX DE 6 appeared stiffer and less ductile than film prepared using MDX DE 12. The films disintegrated within 10 s. Among the tested TMA, the milk and mint flavours resulted particularly suitable to mask the taste of NHT. The addition of NHT and taste-masking agents affected film tensile properties; however, the effect of the addition of these components can be counterweighted by modulating the glycerine content and/or the MDX molecular weight. The feasibility of NHT loaded fast-dissolving films was demonstrated.

Coastal environments are often subjected to contamination, whose biological impact is profitably evaluated through sentinel organisms and biomarkers. mRNA profiling was also proposed as a potential biomarker, whose relevance is still under discussion. Indeed, correlation between molecular and cell-organism responses need further investigations, especially under field conditions. In this study, we followed the development of physiological alterations in Mytilus galloprovincialis transplanted into a polluted coastal lagoon for 2, 4, 7, 14 and 30 days. Three consolidated biomarkers were measured, i.e. lysosomal membrane stability, lipofuscin and metallothionein contents. In parallel, the expressions of stress-related genes encoding metallothioneins (mt10 and mt20), 70-kDa heat shock proteins (MgHSC70 and MgHSP70), and Multi Xenobiotic Resistance-related transporters (MgPgp, MgMrp2, and MgMvp) were analyzed, to have a greater insight into the time-related evolution of the response. Significant (p<0.05) biomarker responses were induced after 7 days of exposure and further increased with time, whereas gene expression profiles were dramatically altered 2 days after transplanting. Biomarkers and gene expression profiles indicated a stress syndrome development in mussels, although with different temporal patterns. Their combined application provided insights into the molecular and cellular basis of mussel responses to challenging environments, and may have far-reaching implications for monitoring environmental health., (Copyright 2010 Elsevier Inc. All rights reserved.)

Pharmaceuticals represent a diverse collection of thousands of bioactive chemicals used in human and veterinary medicine. The increased consumption, together with the recent development of more sensitive analytical techniques, has identified these as emerging contaminants in the aquatic environment. According to many investigations pharmaceuticals do not cause acute toxic effects in organisms when released in the environment. However, many independent studies agree that chronic exposure and more specific endpoints should be used in risk assessment of these compounds. We thus investigated the effects of exposure to environmentally relevant concentrations of the antiepileptic drug carbamazepine (CBZ) on Mediterranean mussels (Mytilus galloprovincialis) by considering the existing knowledge about the therapeutic and side effects of this drug on humans. To do so we analysed: (a) six consolidated biomarkers related primarily to oxidative stress; (b) cAMP levels and protein kinase A (PKA) activities; (c) mRNA expression of MXR-related genes. MXR proteins are involved both in the cAMP pathway and in the protective response of organisms towards xenobiotics. Mussels exposed to 0.1 or 10microg CBZ per liter water for 7 days showed a 60% and 80% reduction in haemocyte lysosome membrane stability, respectively. Moreover, increased neutral lipid and lipofuscin accumulation in the digestive gland, and lipid peroxidation in gills and mantle/gonads were observed. Also glutathione S-tranferase and catalase activities were increased in digestive gland and mantle, while no increase in primary DNA damage was observed. In agreement with the mode of action of CBZ in humans, exposure resulted in a significant reduction in cAMP levels and PKA activities in digestive gland, gills and mantle/gonads of mussels, and lowered the mRNA expression of genes encoding three different MXR-related transporters in the same tissues. Our data indicate that CBZ, at concentrations found in the environment, affects the Mediterranean mussel by acting on specific biochemical pathways that are evolutionarily conserved.

Candida infections in paediatric patients are an important issue. They are associated with significant mortality, particularly in newborns and those with congenital immunodeficiencies. At present, there is limited knowledge regarding factors associated with an increased risk of developing invasive candidiasis in newborns and those with congenital immunodeficiencies, although there have been a number of studies conducted to characterize these risk factors. These studies have suggested that, in neonates, the most important of these factors is colonization, whereas in paediatric patients with congenital immunodeficiencies, risk factors may differ according to the specific deficiency present. Regarding treatment of invasive candidiasis in paediatric patients, fluconazole is considered an appropriate choice, although the method for determining treatment strategies for each patient should be the same as that used for such decisions in adult patients.

Classification and influence matrix analysis (CAIMAN) is a new classification method, recently proposed and based on the influence matrix (also called leverage matrix). Depending on the purposes of the classification analysis, CAIMAN can be used in three outlines: (1) D-CAIMAN is a discriminant classification method, (2) M-CAIMAN is a class modelling method allowing a sample to be classified, not classified at all, or assigned to more than one class (confused) and (3) A-CAIMAN deals with the asymmetric case, where only a reference class needs to be modelled. In this work, the geographic classification of samples of wine and olive oil has been carried out by means of CAIMAN and its results compared with discriminant analysis, by focusing great attention on the model predictive capabilities. The geographic characterization has been carried out on three different datasets: extra virgin olive oils produced in a small area, with a "protected denomination of origin" label, wines with different denominations of origin, but produced in enclosed geographical areas, and olive oils belonging to different production areas. Final results seem to indicate that the application of CAIMAN to the geographical origin identification offers several advantages: first, it shows--on an average basis--good performances; second, it is able to deal in a simple way classification problems related to tipicity, authenticity, and uniqueness characterization, which are of increasing interest in food quality issues.

This report describes our experience with esophagogastric disconnection and Roux-en-Y esophagojejunostomy for the treatment of gastroesophageal reflux disease (GERD) in seven neurologically impaired children as a second antireflux operation following failed Nissen fundoplication. After a mean follow-up of 3 years, three children (43%) were completely or almost completely symptom-free and had improved nutritional status. Early complications occurred in three patients (43%): small bowel obstruction, wound infection, and necrosis of the Roux-en-Y loop. Three patients (43%) presented long-term complications: jejunoesophageal bile reflux and bile reflux with gastric irritation. Two patients required reoperation (28%), and two deaths occurred in the postoperative period (28%). In three previous reports in the surgical literature, severe postoperative complications occurred in 0-44%, requiring reoperation in 0-22% of the patients, and the mortality rate was 0-11%. Esophagogastric disconnection for the treatment of GERD in neurologically impaired children is associated with major complications and should be considered after more conservative procedures fail.

Objective: To investigate the prevalence of cumulative organ damage in patients with juvenile-onset systemic lupus erythematosus (SLE) and its association with demographic and clinical variables, medication use, and quality of life., Methods: The occurrence of organ system damage, as measured by the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI), was determined for 387 patients consecutively enrolled in pediatric rheumatology centers from Europe, the US, Mexico, and Japan. Risk factors for damage included demographic variables; clinical manifestations at diagnosis; previous corticosteroid, immunosuppressive, and antimalarial therapies; disease activity; and quality of life., Results: Overall, 195 (50.5%) patients had damage within a mean of 5.7 years after disease onset. Renal (21.8%) and neuropsychiatric (15.8%) system involvement were observed most frequently, followed by musculoskeletal (11.7%), ocular (10.9%) and skin (9.6%) system involvement, with a mean SDI score of 1.1. In multivariate models, the occurrence of neuropsychiatric manifestations at diagnosis, a longer disease duration, and a greater number of intravenous cyclophosphamide pulses showed the strongest association with the presence of damage., Conclusion: We found evidence of cumulative organ damage, as measured by the SDI, in half of the patients with juvenile-onset SLE. Damage was significantly more likely in patients who had experienced neuropsychiatric manifestations at diagnosis, had a longer disease duration, and had received more intravenous pulses of cyclophosphamide.

Biotransformation of drugs is one of the major functions of liver. Hepatic drug metabolism develops early in organogenesis and continues in postnatal life through puberty. Genetic and developmental studies on hepatic drug metabolism show that immaturity, polymorphisms, and altered balance of different hepatic enzymatic activities affect pharmacologic inactivation and alter the risk of toxic effects of drugs on the hepatic parenchyma. Although drug-induced liver disease is less common in children, several reports of hepatotoxicity are published every year. Furthermore, the increasing use of nonregulated remedies (eg, herbal preparations or recreational drugs) increases the risk of unpredictable and potentially severe reactions. Many significant advances in the treatment of hepatic diseases have been achieved recently. However, differences in clinical features, natural history, and response to treatment between children and adults require evaluation of new therapeutic options in focused pediatric clinical trials.

In this paper, a novel electrochemical method to evaluate the antioxidant power of lipophilic compounds present in vegetables, such as carotenoids, chlorophylls, tocopherols, and capsaicin, is reported. The method is based on a flow injection system with an electrochemical detector equipped with a glassy carbon working electrode operating amperometrically at a potential of + 0.5 V (vs Ag/AgCl). The proposed method is selective for lipophilic compounds having antioxidant power. When applied to pure compounds, the order of antioxidant power resulted as follows: lycopene > beta-carotene > zeaxanthin > alpha-carotene > beta-cryptoxanthin > lutein > alpha-tocopherol > capsaicin > chlorophyll a > chlorophyll b > astaxanthin > canthaxanthin. Results obtained on five vegetable and two fruit extracts were compared to those obtained by the 2,2'-azinobis(3-ethylbenz-thiazoline-6-sulfonic) acid (ABTS) radical cation decolorization assay, one of the most used methods to evaluate the total antioxidant capacity of foods. A good correlation between the two methods was found, except for spinach, because of the different antioxidant powers assigned by the two methods to chlorophylls. In conclusion, results suggest that the proposed electrochemical method can be successfully employed for the direct, rapid, and reliable monitoring of the antioxidant power of lipophilic food extracts.

In this paper a rapid method based on a FIA (flow injection analysis) system with amperometric detection for the evaluation of ascorbyl 6-palmitate in foods is described. The selectivity of the proposed method is related to the low anodic potential applied to the working glassy carbon electrode (+0.1 V vs. Ag/AgCl) that leaves out interferences from ascorbic acid and phenolic compounds. By flow injection analysis, under optimised conditions, the calibration curve was linear in the range 0-20 mg l(-1) and the detection limit was 0.2 mg l(-1).

Aim of this study was to evaluate the total antioxidant activity (TAA) of extra virgin olive oil (EVOO) and the effect of heating on the alpha-tocopherol content and TAA in relation to the presence of polyphenols, heating time, and temperature. Experiments included the measurement by ABTS decolorization assay of antioxidant capacity of alpha-tocopherol and 14 simple phenolic compounds present in EVOO, either dissolved in ethanol or added to refined olive oil, and the evaluation of TAA, total phenols, and alpha-tocopherol of six commercial EVOO and three olive oils. Finally, four experimental oils were prepared from refined olive oil containing a fixed amount (300 ppm) of alpha-tocopherol and increasing amounts of polyphenols (25, 125, 225, and 326 ppm) extracted from EVOO. The thermal stability of experimental oils under domestic heating conditions (heating time from 30 to 120 min, heating temperature from 160 to 190 degrees C) was studied by evaluating the loss of alpha-tocopherol and TAA according to a Latin square design. Results indicate that TAA of commercial oils is mainly due to their phenol and alpha-tocopherol content. Heating experiments suggest that polyphenols from EVOO are effective stabilizers of alpha-tocopherol during olive oil heating, thus contributing to the nutritional value of cooked foods.

A new method for the evaluation of the 'total antioxidant power' of olive oils, based on a flow injection analysis system with electrochemical detection, is described. It represents a attractive alternative to the mostly used Rancimat method since it is based on the chemical structure of antioxidants and does not require the manipulation of several parameters, such as temperature and oxygen pressure, to accelerate oil oxidation. The proposed procedure is simple, rapid, allows a throughput of 90 samples h-1 and provides a good precision: an RSD of 3.5% was obtained for caffeic acid at the concentration level of 5 mg L-1 (n = 12). A comparison of the proposed was obtained for caffeic acid at the concentration level of 5 mg L-1 (n = 12). A comparison of the proposed procedure with two other methods (Rancimat method and ABTS.+ decoloration assay) was performed to investigate the applicability and limitations of the proposed method.