E-waste dismantling as a source of personal exposure and environmental release of fine and ultrafine particles.

Electronic waste (WEEE; from TV screens to electric toothbrushes) is one of the fastest growing waste streams in the world. Prior to recycling, e-waste components (metals, wood, glass, etc.) are processed by shredding, grinding and chainsaw cutting. These activities generate fine and ultrafine particle emissions, containing metals as well as organics (e.g., flame retardants), which have high potential for human health impacts as well as for environmental release. In this work, release of fine and ultrafine particles, and their exposure impacts, was assessed in an e-waste recycling facility under real-world operating conditions. Parameters monitored were black carbon, particle mass concentrations, ultrafine particles, and aerosol morphology and chemical composition. Potential health impacts were assessed in terms of cytotoxicity (cell viability) and oxidative stress (ROS) on <2 µm particles collected in liquid suspension. Environmental release of WEEE aerosols was evidenced by the higher particle concentrations monitored outside the facility when compared to the urban background (43 vs.11 µgPM2.5/m3, respectively, or 2.4 vs. 0.2 µgCa/m3). Inside the facility, concentrations were higher in the top than on the ground floor (PM2.5 = 147 vs. 78 µg/m3, N = 15.4 ∗ 104 vs. 8.7 ∗ 104/cm3, BC = 12.4 vs. 7.2 µg/m3). Ventilation was a key driver of human exposure, in combination with particle emissions. Key chemical tracers were Ca (from plastic fillers) and Fe (from wiring and other metal components). Y, Zr, Cd, Pb, P and Bi were markers of cathode TV recycling, and Li and Cr of grinding activities. While aerosols did not evidence cytotoxic effects, ROS generation was detected in 4 out of the 12 samples collected, associated to the ultrafine fraction. We conclude on the need for studies on aerosol emissions from WEEE facilities, especially in Europe, due to their demonstrable environmental and human health impacts and the rapidly growing generation of this type of waste.

A drug interaction study investigating the effect of Rifabutin on the pharmacokinetics of Maraviroc in healthy subjects.

Effects of steady-state rifabutin on the pharmacokinetics of steady-state maraviroc were investigated in fourteen healthy adult female and male volunteers. Maraviroc 300 mg twice daily (BID) was given orally with food for fifteen days. On day six, rifabutin 300 mg once daily (QD, P.O.) was added to the regimen. Formal pharmacokinetic (PK) sampling was performed on days five and fifteen. Individual plasma drug concentration-time data for maraviroc, and rifabutin on day fifteen, were obtained using validated High Performance Liquid Chromatography (HPLC) tandem Mass Spectrometry (MS/MS). Rifabutin steady state exposure was comparable to data in the literature. Maraviroc area under the curve (AUC) and minimum plasma concentration (Clast or Cmin) were reduced by 17% and 30% respectively when co-administered with rifabutin. No unexpected or serious adverse eventsoccurred. Based on the reduced exposure of maraviroc observed in this study, increasing the dose of maraviroc may be studied to normalize its moderately reduced exposure following rifabutin co-administration, a moderate inducer of CYP3A4.

[Functional or aesthetic labia minora reduction: Complications, revision surgeries and results - a comparative study]. / Nymphoplasties de réduction fonctionnelle ou esthétique. Complications, réinterventions, résultats : étude comparative.

OBJECTIVE: To evaluate and compare the complications, the rate of revision surgeries and the long-term patient postoperative satisfaction level for the two main indications of labia minora reduction: aesthetic or functional. METHODS: A comparative, retrospective and multicentered study was carried out in Belfort and Montbéliard hospitals between January 2010 and January 2017. Ninety-two primary labia minora reductions for labia minora hypertrophy have been listed. Each patient has been requested to fill in a questionnaire about the main indication of labiaplasty, any potential complication, a revision surgery and her level of the satisfaction. Patients who had agreed to respond were divided into two groups: a "functional indication" group (FI) and an "aesthetic indication" group (AI). RESULTS: Thirty-seven patients (40%) answered the survey: 19 (51%) have been included in the FI group and the remaining 18 (49%) in the AI group. The mean postoperative follow-up duration was 3.2 years. We identified 13 patients (35%) who encountered a postoperative complication. It predominates in the FI group (53% versus 17%, P=0.04). Seven patients (19%) were treated by revision surgeries. All of them belonged to the IF group. Whatever the indication of the labiaplasty, 86% of the patients have been satisfied by the outcomes. CONCLUSION: A labia minora reduction is a highly appreciated surgical treatment on the long term whatever the initial surgical indication. However, postoperative complications and revision surgeries are not negligible especially when the main indication is functional.

Effects of an environmentally relevant concentration of diuron on oyster genitors during gametogenesis: responses of early molecular and cellular markers and physiological impacts.

Genitors of the Pacific oyster Crassostrea gigas were submitted during gametogenesis to a short pulse exposure to the herbicide diuron at a realistic environmental concentration. Histological analysis showed no effect of diuron on gametogenesis course, sex ratio and reproductive effort. A non-significant increase in testosterone and progesterone levels was observed in genitors exposed to the herbicide. At cell level, diuron exposure was shown to modulate the phagocytic activity of circulating hemocytes. The results of a transcriptional analysis showed that diuron affected the expression of genes belonging to functions known to play a major role during oyster gametogenesis such as gene transcription regulation, DNA replication and repair, DNA methylation and cytokinesis. Taking into account the results we previously obtained on the same genitors, this study showed a negative effect of diuron on oyster reproduction by inducing both structural and functional modifications of the DNA.

Evidence of altered fertility in female roach (Rutilus rutilus) from the River Seine (France).

A large variety of anthropogenic chemicals present in the aquatic environment have been shown to be able to alter the endocrine system of exposed organisms, potentially impacting their reproductive function. The aim of this study was to assess the effects of environmental pollution on the reproductive system of wild female roach (Rutilus rutilus) from the Seine River (Normandy, France). A suite of biomarkers of endocrine disruption including gonado-somatic index, plasmatic vitellogenin, gonadal aromatase activity and histological parameters (oocyte diameter and gonad maturation) were studied. Female fish from the polluted sites showed a number of reproductive alterations, including inhibited gonad maturation, reduced oocyte growth, reduced levels of plasmatic vitellogenin and 3-fold lower gonadal aromatase activity than females collected in the reference site. Overall, these results highlight the presence of endocrine disruption in female roach from the Seine River.

[Optic nerve trauma: case report of partial optic nerve avulsion]. / Papillopathie traumatique: à propos d'un cas d'arrachement partiel du nerf optique.

INTRODUCTION: Partial avulsion of the optic nerve head is a rare and severe complication of ocular blunt trauma. OBSERVATION: We report the case of a 28-year-old man presenting to the emergency department for blunt trauma to his right eye with a basketball. Visual acuity was decreased to hand motion, and fundus examination showed a prepapillary hemorrhage. After five days, the preretinal hematoma spontaneously dispersed into the vitreous cavity. Because of the persistence of an intravitreal hemorrhage and the lack of visual recovery, a vitrectomy was performed 2 months later, leading to the diagnosis of a partial optic nerve avulsion with cicatricial gliosis on fundus exam and angiography. Six months after vitrectomy, the visual acuity was 4/10 P4 in the right eye and the visual field showed an absolute infero-nasal scotoma corresponding to the temporal injury. Seven months later, the visual acuity had decreased progressively, secondary to the development of a macular epiretinal membrane. A membrane peel was performed with a visual acuity recovery to 3/10 P4 after a 3-year follow-up. DISCUSSION: Through a complete literature review, we describe the clinical signs, the mechanism, the treatment and the natural history of this poorly known disease. CONCLUSION: Optic nerve avulsion must be considered in cases of trauma with forced rotation of the eye. Individualized management and monitoring of complications are essential to the preservation of residual visual acuity, especially in case of partial avulsion.

Mucosal correlates of isolated HIV semen shedding during effective antiretroviral therapy.

Effective antiretroviral therapy (ART) suppresses the blood HIV RNA viral load (VL) below the level of detection. However, some individuals intermittently shed HIV RNA in semen despite suppression of viremia, a phenomenon termed "isolated HIV semen shedding (IHS)". In a previously reported clinical study, we collected blood and semen samples from HIV-infected men for 6 months after ART initiation, and documented IHS at ≥1 visit in almost half of the participants, independent of ART regimen or semen drug levels. We now report the mucosal immune associations of IHS in these men. Blood and semen plasma cytokine levels were assayed by multiplex enzyme-linked immunosorbent assay, T-cell populations were evaluated by flow cytometry in freshly isolated blood and semen mononuclear cells, and semen cytomegalovirus (CMV) DNA levels were measured by PCR. Although IHS was not associated with altered blood or semen cytokine levels, the phenomenon was associated with a transient, dramatic increase in CD4+ and CD8+ T-cell activation that was restricted to the semen compartment. All participants were CMV infected, and although semen CMV reactivation was common despite ART, this was not associated with T-cell activation or IHS. Further elucidation of the causes of compartmentalized mucosal T-cell activation and IHS may have important public health implications.

Lack of effect of efavirenz on the pharmacokinetics of tipranavir-ritonavir in healthy volunteers.

Previously it has been shown that tipranavir-ritonavir (TPV/r) does not affect efavirenz (EFV) plasma concentrations. This study investigates the effect of steady-state EFV on steady-state TPV/r pharmacokinetics. This was a single-center, open-label, multiple-dose study of healthy adult female and male volunteers. TPV/r 500/200 mg twice a day (BID) was given with food for 24 days. After dosing with TPV/r for 10 days, EFV 600 mg once a day was added to the regimen. Intensive pharmacokinetic (PK) sampling was done on days 10 and 24. Validated bioanalytical high-pressure liquid chromatography-tandem mass spectrometry methods were used to determine plasma tipranavir (TPV), ritonavir (RTV), and EFV concentrations. Thirty-four subjects were entered into the study, and 16 subjects completed it. The geometric mean ratios (90% confidence intervals) for TPV and RTV area under the curves, C(max)s, and C(min)s comparing TPV/r alone and in combination with EFV were 0.97 (0.87 to 1.09), 0.92 (0.81 to 1.03), and 1.19 (0.93 to 1.54) for TPV and 1.03 (0.78 to 1.38), 0.92 (0.65 to 1.30), and 1.04 (0.72 to 1.48) for RTV. Frequently observed adverse events were diarrhea, headache, dizziness, abnormal dreams, and rash. EFV had no effect on the steady-state PK of TPV or RTV, with the exception of a 19% increase in the TPV C(min), which is not clinically relevant. TPV/r can be safely coadministered with EFV and without the need for a dose adjustment.

Differential effects of tipranavir plus ritonavir on atorvastatin or rosuvastatin pharmacokinetics in healthy volunteers.

To identify pharmacokinetic (PK) drug-drug interactions between tipranavir-ritonavir (TPV/r) and rosuvastatin and atorvastatin, we conducted two prospective, open-label, single-arm, two-period studies. The geometric mean (GM) ratio was 1.37 (90% confidence interval [CI], 1.15 to 1.62) for the area under the concentration-time curve (AUC) for rosuvastatin and 2.23 (90% CI, 1.83 to 2.72) for the maximum concentration of drug in serum (Cmax) for rosuvastatin with TPV/r at steady state versus alone. The GM ratio was 9.36 (90% CI, 8.02 to 10.94) for the AUC of atorvastatin and 8.61 (90% CI, 7.25 to 10.21) for the Cmax of atorvastatin with TPV/r at steady state versus alone. Tipranavir PK parameters were not affected by single-dose rosuvastatin or atorvastatin. Mild gastrointestinal intolerance, headache, and mild reversible liver enzyme elevations (grade 1 and 2) were the most commonly reported adverse drug reactions. Based on these interactions, we recommend low initial doses of rosuvastatin (5 mg) and atorvastatin (10 mg), with careful clinical monitoring of rosuvastatin- or atorvastatin-related adverse events when combined with TPV/r.

Discordance in HIV-1 viral loads and antiretroviral drug concentrations comparing semen and blood plasma.

OBJECTIVES: For individuals not on antiretroviral therapy, the risk of heterosexual transmission of HIV appears negligible when blood plasma (BP) viral loads are <1500 HIV-1 RNA copies/mL. It is not clear whether this observation can be extrapolated to individuals on highly active antiretroviral therapy (HAART). Because of differential tissue penetration, antiretroviral drug concentrations may be sufficient to maintain an undetectable viral load in the BP yet not achieve adequate levels to suppress HIV in the genital tract. Therefore, we wanted to correlate HIV viral loads and drug concentrations in semen plasma (SP) and BP. METHODS: Thirty-three men were included. All were on combination antiretroviral therapy with an undetectable BP viral load for at least 1 year. Blood and semen samples were collected within 2 h of each other and tested for HIV RNA by the NucliSens QT (bioMerieux, St Laurent, QC, Canada) method; drug concentrations were determined by liquid chromatography tandem mass spectrometry. RESULTS: Two of the 33 patients (6.1%) with BP viral loads below detection had time-matched HIV viral loads in SP > or =700 copies/mL. Both patients were on efavirenz, the SP concentrations of which were < or =10% of the levels in BP and well below the minimal therapeutic drug monitoring target concentration required to suppress HIV. CONCLUSIONS: Because, at least in part, of poor drug penetration into the genital tract, an undetectable HIV viral load in the BP does not guarantee an undetectable viral load in semen. In view of this, caution should be taken in concluding that patients on HAART with suppressed viraemia are sexually non-infectious.

Short-term exposure to the organotin compound triphenyltin modulates esterified steroid levels in females of Marisa cornuarietis.

Long-term exposures to organotin compounds have shown alterations on endogenous steroid levels in gastropods together with the development of imposex. However, information regarding short-term effects of these compounds on the endocrine system of gastropods is lacking. This work aimed at investigating those responses in the ramshorn snail Marisa cornuarietis by looking at both endogenous levels of free and esterified steroids and the metabolism of the androgen precursor androstenedione by digestive gland/gonad microsomal fractions. One-week exposure to the organotin compound triphenyltin (TPT) led to a significant increase in esterified testosterone (60-85%) and a decrease in esterified estradiol (50-84%) in females, but had no effect on males. The observed alterations in esterified steroids were not directly related to changes in P450 aromatase activity that remained unchanged in exposed females. The enzymes involved in the metabolism of the androgen precursor androstenedione, namely 17beta-hydroxysteroid dehydrogenases and 5alpha-reductases, were not significantly altered by TPT exposure, suggesting that such enzymes are not primary targets of TPT in M. cornuarietis. Additional studies are needed to fully understand the significance of the observed alterations in females and their potential relationship with the development of imposex.

Interactions between protease inhibitors and acid-reducing agents: a systematic review.

OBJECTIVE: The purpose of this article is to provide a systematic review of the available pharmacokinetic and clinical data on drug interactions between protease inhibitors (PIs) and acid-reducing agents, and their clinical relevance. METHODS: A literature search was performed using Medline and EMBASE, abstracts of the previous 2 years of major conferences were searched and the drug information service of the manufacturer of every currently available PI was contacted. All data were summarized, and verified by at least two authors. RESULTS: A total of 1231 references were identified, 22 of which were studies of pharmacokinetic interactions between PIs and acid-suppressive agents and a further 12 of which provided pharmacokinetic and/or clinical data. CONCLUSIONS: Many pharmacokinetic studies show a lack of a drug interaction between at least one acid-reducing agent and most PIs. Little clinical information is available, except on interactions between atazanavir and acid-reducing agents. This is probably a consequence of the complexity of the interaction.

Age-dependent pharmacokinetics of lamivudine in HIV-infected children.

The recommended dose of lamivudine in children is higher when compared with adults: 4 mg/kg vs approximately 2 mg/kg (150 mg) and administered twice a day. Limited data are available to demonstrate that this increased dose results in adequate exposure to lamivudine in children with human immunodeficiency virus (HIV) infection. Data were selected from children who were using lamivudine for at least 2 weeks before a full pharmacokinetic (PK) study was conducted. Lamivudine PK parameters were significantly related to age. The age of 6 years appeared to be a cutoff for a change in PK parameters of lamivudine, with children <6 years of age (n=17) having a median area under the curve 43% lower and a median peak plasma concentration 47% lower (both P<0.001) than older children (n=34). In conclusion, further investigation of the relationship between decreased lamivudine exposure and treatment outcome and long-term resistance development in younger children with HIV infection is warranted.

The effect of ABCB1 polymorphism on the pharmacokinetics of saquinavir alone and in combination with ritonavir.

This genotype panel study investigated the effect of ABCB1 polymorphism in exon 26 (C3435T), exon 21 (G2677T/A), and exon 12 (C1236T) on saquinavir pharmacokinetics and on the expression and activity of P-glycoprotein (P-gp) in peripheral blood monocytic cells (PBMCs). One hundred and fifty healthy volunteers were genotyped to identify 15 TT3435 and 15 CC3435 individuals. In these individuals, saquinavir pharmacokinetics were assessed after administration of a single oral dose of saquinavir 1,000 mg and saquinavir/ritonavir 1,000/100 mg. PBMC P-gp expression and activity were assessed in 15 and 19 subjects. The co-administration of ritonavir on study day 2 caused a significant increase in saquinavir exposure, in both TT3435 and CC3435 individuals. No correlation was observed between the ABCB1 C3435T, G2677T/A, and C1236T polymorphisms, separately and in haplotypes, with saquinavir pharmacokinetics, administered with or without ritonavir and with PBMC P-gp expression and activity. In conclusion, ABCB1 polymorphism has no pronounced effect on saquinavir exposure.

Endocrine disruptors in marine organisms: approaches and perspectives.

Organic pollutants exhibiting endocrine disrupting activity (Endocrine Disruptors--EDs) are prevalent over a wide range in the aquatic ecosystems; most EDs are resistant to environmental degradation and are considered ubiquitous contaminants. The actual potency of EDs is low compared to that of natural hormones, but environmental concentrations may still be sufficiently high to produce detrimental biological effects. Most information on the biological effects and mechanisms of action of EDs has been focused on vertebrates. Here we summarize recent progress in studies on selected aspects of endocrine disruption in marine organisms that are still poorly understood and that certainly deserve further research in the near future. This review, divided in four sections, focuses mainly on invertebrates (effects of EDs and mechanisms of action) and presents data on top predators (large pelagic fish and cetaceans), a group of vertebrates that are particularly at risk due to their position in the food chain. The first section deals with basic pathways of steroid biosynthesis and metabolism as a target for endocrine disruption in invertebrates. In the second section, data on the effects and alternative mechanisms of action of estrogenic compounds in mussel immunocytes are presented, addressing to the importance of investigating full range responses to estrogenic chemicals in ecologically relevant invertebrate species. In the third section we review the potential use of vitellogenin (Vtg)-like proteins as a biomarker of endocrine disruption in marine bivalve molluscs, used worldwide as sentinels in marine biomonitoring programmes. Finally, we summarize the results of a recent survey on ED accumulation and effects on marine fish and mammals, utilizing both classical biomarkers of endocrine disruption in vertebrates and non-lethal techniques, such as non-destructive biomarkers, indicating the toxicological risk for top predator species in the Mediterranean. Overall, the reviewed data underline the potential to identify specific types of responses to specific groups of chemicals such as EDs in order to develop suitable biomarkers that could be useful as diagnostic tools for endocrine disruption in marine invertebrates and vertebrates.

The effect of organotin compounds on gender specific androstenedione metabolism in the freshwater ramshorn snail Marisa cornuarietis.

In a recent study, we demonstrated that androstenedione was mainly converted to testosterone (T) and 5alpha-dihydrotestosterone (DHT) by digestive gland/gonad complex microsomal fractions isolated from male Marisa cornuarietis, whereas it was primarily metabolized to 5alpha-dihydroandrostenedione (DHA) by females. In the present work, the sexual dimorphic metabolism of androstenedione was further investigated, and attributed to a higher 17beta-hydroxysteroid dehydrogenase activity in males than in females. Thereafter, the hypothesis was tested that the metabolism of androstenedione might be affected by exposure to tributyltin (TBT) and triphenyltin (TPT), which are known to induce the development of imposex in several gastropod species. The in vitro metabolism of androstenedione, particularly the formation of DHA and DHT, was inhibited by both compounds. However, in vivo experiments showed no significant alteration in the metabolism of androstenedione in males, but a marginal (TBT) and a significant (TPT) inhibition of the formation of DHA in females exposed for 150 days to concentrations that had significantly induced the development of imposex. The ratio DHT+T/DHA, a possible indicator of metabolic androgenization, tended to increase (0.43 versus 0.35, p=0.06) in TPT exposed females. However, this ratio never reached values comparable to those found in males (11+/-1).

Evaluación de efectos biológicos asociados al vertido del "Prestige" en poblaciones de peces de interés comercial / No disponible

No disponible

A comparative study on androgen metabolism in three invertebrate species.

A comparative approach was taken in this study to evaluate androgen (androstenedione and testosterone) metabolism in three invertebrate species: the gastropod Marisa cornuarietis, the amphipod Hyalella azteca, and the echinoderm Paracentrotus lividus. The existence of 17beta/3beta-hydroxysteroid dehydrogenase (HSD) and 5alpha-reductase catalyzed reactions was demonstrated in all three species. Androstenedione was primarily converted to 5alpha-androstanedione in M. cornuarietis, while it was primarily metabolized to testosterone in P. lividus and H. azteca. In addition, and consistent with vertebrate findings, tissue specific pathways and sexual dimorphism in androgen metabolism were observed. Namely, testosterone was metabolized to dihydrotestosterone in P. lividus gonads (via 5alpha-reductase), and metabolized to 4-androstene-3beta,17beta-diol in the digestive tube (via 3beta-hydroxysteroid dehydrogenase). Furthermore, the synthesis of 17beta-reduced metabolites of androstenedione (testosterone and dihydrotestosterone) was 3- to 4-fold higher in males of M. cornuarietis than in females. Organotin compounds, which have been shown to interfere with some aspects of androgen metabolism, had no major effect on testosterone metabolism in any of the three species. Fenarimol enhanced 5alpha-reductase-mediated catalysis in gonads of P. lividus. Overall, results demonstrate the ubiquity of some androgen biotransformation processes in invertebrates and reveals interphyla differences in androgen metabolic pathways, and different sensitivity of these pathways to some xenobiotics.

Sulfatase activity in the oyster Crassostrea virginica: its potential interference with sulfotransferase determination.

Two sulfatase isoforms, a soluble one with an optimum pH of 5.0, and a microsomal one with an optimum pH of 7.6, were observed in digestive gland, gonads, mantle and gills of the oyster C. virginica. The highest sulfatase activity was recorded in the digestive gland cytosol and is likely to interfere with the in vitro determination of sulfotransferase activity. Indeed, the sulfatase inhibitor Na(2)SO(3) led to an increase of measured sulfotransferase activity (31+/-9%), suggesting that those sulfatases might be partially responsible for the low sulfotransferase activities found in C. virginica.