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Boischio A.,Toxicology
Revista Panamericana de Salud Publica/Pan American Journal of Public Health | Year: 2015

Mercury is a global pollutant of public environmental health concern due to its long-range atmospheric distribution, environmental distribution, and neurotoxic effects. Following biological methylation, methylmercury (MeHg) can be un-evenly bioaccumulated within aquatic food chains. Fish consumption can be a significant route of human exposure to MeHg. MeHg exposure in the prenatal stage, at relatively low levels, has recently been established as harmful during neurological development, potentially leading to intellectual disability. The Minamata Convention on Mercury is a global agreement, currently under ratification, to protect human health and the environment from anthropogenic emissions and releases of mercury and mercury compounds. The resolution regarding the role of the World Health Organization and ministries of health in the implementation of the Convention includes protection of human health from critical exposures to MeHg. Riverside populations living in areas with artisanal small-scale gold mining, and relying heavily on fish consumption, have been identified as the most vulnerable population in terms of MeHg exposure and developmental neurotoxicity. This article focuses on the proper design and dissemination of fish advisories within the context of implementation of the Convention.

Prelle K.,Toxicology | Igl B.-W.,Bayer AG | Obendorf M.,Health Discovery | Girbig D.,Bayer AG | And 2 more authors.
Menopause | Year: 2012

OBJECTIVE: Estrogen supplementation is considered a reliable therapeutic approach to symptoms of vasomotor dysregulation (hot flashes) associated with the menopausal transition and sex hormone deprivation. Implication of changes in central neurotransmission in the pathogenesis of hot flashes has prompted the off-label use of serotonergic and γ-aminobutyric acid-ergic drugs as a therapeutic alternative, claiming similarity of outcomes to those of estrogen treatment. METHODS: Using telemetric recordings in a rat model of estrogen deficit-induced vasomotor dysregulation, we compared the long- and short-term effects of estrogen supplementation and treatment with neuropharmaceuticals (venlafaxine, desvenlafaxine, fluoxetine, agomelatine, gabapentin) on endpoints of thermoregulation. RESULTS: Among the tested drugs, only fluoxetine was capable to emulate the restorative action of estradiol on the diurnal oscillations in skin temperature and control of heat dissipation. Unlike estradiol, several of the tested compounds produced marked transient decreases in skin temperature within the first 2 hours of application while being unable to restore physiological diurnal patterns of thermoregulation. CONCLUSIONS: Our findings suggest that in this animal model of impaired thermoregulation, neuropharmaceuticals may simulate therapeutic effects by eliciting immediate but transient hypothermia, which is not associated with the recovery of physiological control of heat dissipation. Therefore, short-term monitoring of drug actions in this disease model may considerably bias readouts of drug discovery for menopausal vasomotor symptoms. © 2012 by The North American Menopause Society.

Argudo A.,Toxicology | Gonzalez De Aledo J.M.,University of Barcelona | Alia P.,University of Barcelona | Ramirez P.,University of Murcia | And 3 more authors.
Transplantation Proceedings | Year: 2015

Background The aim of this work was to evaluate the CYP3A5:CYP3A5∗1/CYP3A5∗3 (6986A>G) polymorphism related to the pharmacokinetic characteristics of tacrolimus during the first 3 months after transplantation, analyzing both donor and recipient genotype, in liver transplant patients. Methods This retrospective, single-center, cohort study included patients who had been treated with tacrolimus monotherapy with or without corticoids (n = 67). Donors and recipients were genotyped for the CYP3A5∗3 allele polymorphism (6986A>G) by use of a TaqMan polymerase chain reaction technique. The presence or absence of the∗1 allele ("minor-allele") was analyzed for correlation with the tacrolimus dose-normalized ratio during the 3 months after transplantation. Results The following observations were obtained in the population studied: (1) Frequency of the minor allele∗1 was much lower both in recipients (11.9% versus 88.1%) and donors (19.4% versus 80.6%), with no statistically significant differences between both distributions. (2) Recipient genotype for CYP3A5∗1/∗3-polymorphism had no influence in tacrolimus pharmacokinetics, with no differences between carriers and non-carriers of the minor-allele∗1. (3) However, from the first month after transplantation, patients with grafts from donor carriers of minor allele∗1 had lower concentration-dose ratios compared with patients with grafts from donor non-carriers of that allele (71.1 versus 119.3 and 90.5 versus 126.3, for 30 and 90 days after transplantation, respectively; P <.05). Conclusions The presence of the CYP3A5-6986A>G-polymorphism in the donor affects tacrolimus pharmacokinetics in the recipient, although the difference was statistically significant only for the first month after transplantation. This means that in liver transplant patients receiving grafts from donors carrying the CYP3A5∗1-polymorphism, a larger dose of tacrolimus from the first month after transplantation would be needed. The evidence provided in this study showed no effect of the recipient genotype. © 2015 by Elsevier Inc. All rights reserved.

Pauluhn J.,Toxicology
Regulatory Toxicology and Pharmacology | Year: 2014

Convincing evidence suggests that high-surface-activity nano-materials, such as MWCNT, exert two modes of action (MoA), in which one appears to be related to surface activity/area and occurs concurrent with deposition, and the other is related to cumulative lung burden. Pulmonary inflammation induced by the latter mode appears to be dependent on cumulative volumetric lung burden and on whether the accumulated particle displacement volume within the pool of alveolar macrophages is above or below the kinetic lung overload threshold. However, the relative importance and effect of each MoA are still controversial. In addition, the test protocol variables, which may predetermine the leading MoA, have not yet received increased attention. This study compares the respective outcome of previously published repeated-exposure inhalation studies with MWCNT (Nanocyl and Baytube) in rats. Modeling procedures were performed to compare post hoc the equivalence of empirical and modeled outcomes, including critical protocol variables. This comparison provided compelling evidence that the accumulated retained particle displacement volume was the most prominent unifying denominator linking the pulmonary retained volumetric particle dose to inflammogenicity and toxicity. However, conventional study designs may not always be appropriate to unequivocally dissociate the surface area/activity-related acute adversity from the cumulative retention volume-related adversity. Thus, in the absence of adequately designed studies, it may become increasingly challenging to differentiate substance-specific deposition-related acute effects from the more chronic retained cumulative dose-related effects. In summary, this analysis of existing data supports the conclusion that both the deposition and retention-related effects need to be judiciously dissociated to better understand the MoA of heightened concern. This exercise supports the conclusion that hypothesis-based computational study design delivers the highest degree of scientifically important information and may further reduce the number of experimental animals in repeated-exposure inhalation studies with low-toxicity, biopersistent, poorly soluble granular particles. © 2014 Elsevier Inc.

Kozlovic G.,Kozlovic Winery | Jeromel A.,University of Zagreb | Maslov L.,University of Zagreb | Pollnitz A.,Toxicology | Orlic S.,University of Zagreb
Food Chemistry | Year: 2010

In order to improve Malvazija from Istria wine quality, we used two types of barrels: oak (of French and Croatian origin) and acacia (of Croatian origin). After 12 months ageing period all of the wines were analysed chemically and sensorially. Results showed marked differences between oak and acacia aged wines, especially in simple volatile phenol and oak lactones concentrations. During the ageing period a significant increase in furfural, 5-methylfurfural, guaiacol, eugenol and trans-eugenol was noticed. Results pointed out the importance of choosing the right barrels (oak or acacia) and time of leaving the wine in the barrels to achieve the desired goal. The highest rated wines were made in acacia barrels. © 2009 Elsevier Ltd. All rights reserved.

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