Recalcitrant Pharmaceuticals in the Aquatic Environment: A Comparative Screening Study of Their Occurrence, Formation of Phototransformation Products and Their in Vitro Toxicity

Data allowing for a complete environmental risk assessment of pharmaceuticals and their photoderatives in the environment are still scarce. In the present study, in vitro toxicity and both bio- and photopersistence of various pharmaceuticals (aciclovir, allopurinol, cetirizine, cimetidine, fluconazole, hydrochlorothiazide, lisinopril, phenytoin, primidone, ranitidine, sotalol, sulpiride, tramadol and valsartane) as well as their phototransformation products were evaluated in order to fill data gaps and to help prioritise them for further testing. Twelve out of the fourteen compounds investigated were found to be neither readily nor inherently biodegradable in the Organisation of Economic Cooperation and Development-biodegradability tests. The study further demonstrates that the photo-induced transformation of the pharmaceuticals was faster upon irradiation with a Hg lamp (UV light) than with a Xe lamp emitting a spectrum that mimics sunlight. Comparing the non-irradiated with the respective irradiated solutions, a higher acute and chronic toxicity against bacteria was found for the irradiated solutions of seven compounds (cetirizine, cimetidine, hydrochlorothiazide, ranitidine, sulpiride, tramadol and valsartane). No cyto- and genotoxic effects were found in human cervical (HeLa) and liver (Hep-G2) cells for any of the investigated compounds or their phototransformation products. This comparative study documents that phototransformation products can arise as a result of UV treatment of wastewater containing these pharmaceuticals. It further demonstrates that some phototransformation products may have a higher environmental risk potential than the respective parent compounds because some phototransformation products exhibited a higher bacterial toxicity

Determinación de daño genético en comerciantes de plaguicidas en el departamento de Matagalpa

EL DAÑO CITOGENÉTICO ASOCIADO CON PLAGUICIDAS POR PARTE de comerciantes de agroquímicos fue evaluado en el departamento de Matagalpa analizando micronúcleos en células bucales (MNBC). Así mismo, fue evaluada la exposición crónica a plaguicidas usando la prueba de acetilcolinesterasa y adicionalmente se identificaron mutaciones de manera exploratoria en el gen CYP2D6, implicado en el metabolismo de plaguicidas. La comparación entre comerciantes de plaguicidas y controles reveló diferencias significativas en las frecuencias de MNBC (6.23±2.2 vs. 3.63±1.3 MN/2000 MNBC, P<0.001, t de student). Niveles de colinesterasa indican efecto neurotóxico crónico en los comerciantes de plaguicidas. Estos comerciantes utilizan poco o ningún equipo de protección personal así como medidas de seguridad. Este es el primer estudio a nivel nacional que reporta efecto citogenético de exposición crónica a plaguicidas en comerciantes expuestos

Nanoparticle Release from Thermal Decomposition of Polymer Nanocomposites and the Biological Potential of the Emissions

Adding nanoparticles to polymers improves the properties significantly, such as UV resistance or even electrical conductivity. The growing use of these composite materials leads to a higher amount in disposals eventually. Within the circular economy there are two ways of handling: the recycling by shredding and reuse and the thermal treatment by combustion in municipal waste incinerators. In both cases there is nearly no information about the behavior of the nanoparticles and possible release scenarios. In this study a laboratory burner is used as a flexible set up to incinerate the polymer nanocomposites. The flue gas containing a complex mixture of combustion gases and particles is characterized by different particle analysers, PAH analysis, VOC analysis and TEM. The biological impact is studied by using a VITROCELL Automated ALI exposure station. Hereby, cells of the adenocarcino cell line A549 as well as a reconstituted bronchial epithelium (MucilAir, Epithelix) were exposed for 4 hours to the aerosols emitted from the combustion process. Within the exposure process, cells were exposed to the native aerosol, an aerosol under conditions to increase particle deposition via high voltage as well as a filtered aerosol, and therefore the sole gaseous phase. Furthermore, each exposure included a so-called clean air control, where cells where exposed to filtered air. The exposure was followed by a 21 h post-incubation before the cytotoxic effects were determined via LDH-release. To reveal if possible adverse effects are caused by the used nano-scaled filling material, all used nanomaterials did also undergo the same combustion process as a single material. Cytotoxicity studies showed no increased cytotoxic effects after the combustion of the sole nano-scaled filling materials. However, combustion of PE containing materials resulted in an enhanced LDH-release, and therefore cytotoxicity, in both cell culture models. Since no difference between exposures of unfiltered and filtered aerosols was apparent, it suggested that the observed cytotoxicity is due to the combustion induced gaseous phase

Impact of Nanocomposite Combustion Aerosols on A549 Cells and a 3D Airway Model

The use of nanomaterials incorporated into plastic products is increasing steadily. By using nano-scaled filling materials, thermoplastics, such as polyethylene (PE), take advantage of the unique properties of nanomaterials (NM). The life cycle of these so-called nanocomposites (NC) usually ends with energetic recovery. However, the toxicity of these aerosols, which may consist of released NM as well as combustion-generated volatile compounds, is not fully understood. Within this study, model nanocomposites consisting of a PE matrix and nano-scaled filling material (TiO$_{2}$, CuO, carbon nano tubes (CNT)) were produced and subsequently incinerated using a lab-scale model burner. The combustion-generated aerosols were characterized with regard to particle release as well as compound composition. Subsequently, A549 cells and a reconstituted 3D lung cell culture model (MucilAir™, Epithelix) were exposed for 4 h to the respective aerosols. This approach enabled the parallel application of a complete aerosol, an aerosol under conditions of enhanced particle deposition using high voltage, and a filtered aerosol resulting in the sole gaseous phase. After 20 h post-incubation, cytotoxicity, inflammatory response (IL-8), transcriptional toxicity profiling, and genotoxicity were determined. Only the exposure toward combustion aerosols originated from PE-based materials induced cytotoxicity, genotoxicity, and transcriptional alterations in both cell models. In contrast, an inflammatory response in A549 cells was more evident after exposure toward aerosols of nano-scaled filler combustion, whereas the thermal decomposition of PE-based materials revealed an impaired IL-8 secretion. MucilAir™ tissue showed a pronounced inflammatory response after exposure to either combustion aerosols, except for nanocomposite combustion. In conclusion, this study supports the present knowledge on the release of nanomaterials after incineration of nano-enabled thermoplastics. Since in the case of PE-based combustion aerosols no major differences were evident between exposure to the complete aerosol and to the gaseous phase, adverse cellular effects could be deduced to the volatile organic compounds that are generated during incomplete combustion of NC

Investigation of Complement Activation Product C4d as a Diagnostic and Prognostic Biomarker for Lung Cancer

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3776260/[EN] Background There is a medical need for diagnostic biomarkers in lung cancer. We evaluated the diagnostic performance of complement activation fragments. Methods We assessed complement activation in four bronchial epithelial and seven lung cancer cell lines. C4d, a degradation product of complement activation, was determined in 90 primary lung tumors; bronchoalveolar lavage supernatants from patients with lung cancer (n = 50) and nonmalignant respiratory diseases (n = 22); and plasma samples from advanced (n = 50) and early lung cancer patients (n = 84) subjects with inflammatory lung diseases (n = 133), and asymptomatic individuals enrolled in a lung cancer computed tomography screening program (n = 190). Two-sided P values were calculated by Mann-Whitney U test. Results Lung cancer cells activated the classical complement pathway mediated by C1q binding that was inhibited by phosphomonoesters. Survival was decreased in patients with high C4d deposition in tumors (hazard ratio [HR] = 3.06; 95% confidence interval [CI] = 1.18 to 7.91). C4d levels were increased in bronchoalveolar lavage fluid from lung cancer patients compared with patients with nonmalignant respiratory diseases (0.61 +/- 0.87 vs 0.16 +/- 0.11 mu g/mL; P < .001). C4d levels in plasma samples from lung cancer patients at both advanced and early stages were also increased compared with control subjects (4.13 +/- 2.02 vs 1.86 +/- 0.95 mu g/mL, P < 0.001; 3.18 +/- 3.20 vs 1.13 +/- 0.69 mu g/mL, P < .001, respectively). C4d plasma levels were associated with shorter survival in patients at advanced (HR = 1.59; 95% CI = 0.97 to 2.60) and early stages (HR = 5.57; 95% CI = 1.60 to 19.39). Plasma C4d levels were reduced after surgical removal of lung tumors (P < .001) and were associated with increased lung cancer risk in asymptomatic individuals with (n = 32) or without lung cancer (n = 158) (odds ratio = 4.38; 95% CI = 1.61 to 11.93). Conclusions Complement fragment C4d may serve as a biomarker for early diagnosis and prognosis of lung cancer.This work was supported by UTE project CIMA; the Spanish Government (grant numbers ISCIII-RTICC RD06/0020/0066, RD06/0020/1024, RD12/0036/0025, RD12/0036/0040, RD12/0036/0062, PI08/0923, PI10/01652, PI10/00166, and PI11/00618); the European Regional Development Fund; the European Community’s Seventh Framework Programme (HEALTH-F2-2010-258677- CURELUNG); and the Early Detection Research Network from the National Cancer Institute (grant number U01 CA152662). This work was supported (in part) by a grant (RD12/0036/XXXX) from Red Temática de Investigación Cooperativa en Cáncer, Instituto de Salud Carlos III, Spanish Ministry of Economy and Competitiveness & European Regional Development Fund “Una manera de hacer Europa”.Jantus Lewintre, E. (2013). Investigation of Complement Activation Product C4d as a Diagnostic and Prognostic Biomarker for Lung Cancer. JNCI: Journal of the National Cancer Institute. 105:1385-1393. https://doi.org/10.1093/jnci/djt205S1385139310

Barriers to Screening, Diagnosis, and Treatment of Type 2 Diabetes in the Pediatric Population within a Military Treatment Facility

Type 2 Diabetes Mellitus (T2DM) was once a disease process found only in the adult population. However, incidence rates of T2DM in children and adolescents are increasing at alarming rates and becoming a grave public health concern. As many as 5,089 individuals under the age of 20 are newly diagnosed with T2DM each year. The military community is not immune to these national trends and T2DM among military dependents is growing at similar rates to that of the civilian population. The primary aim of this DNP project was to investigate if barriers exist with regard to pediatric military dependents, ages 10-17 years, receiving appropriate diagnosis, and treatment of T2DM. Previously published literature has identified health disparities exist within the Military Health System (MHS), despite beneficiaries having equal access to care. This project also sought to assess providers' use of Evidence Based Practice (EBP) and Clinical Practice Guidelines (CPGs) in the treatment of pediatric patients' ages 10-17 with T2DM, as it has been indicated that use of evidence based guidelines for management of T2DM vary among military treatment facilities. Results of the DNP Project reflected information found in previous evidence based literature. Fifty percent of providers felt there is "probably" a health disparity among Type 2 Diabetic youth who seek care at a Military Treatment Facility (MTF). Diverse responses were received regarding applicable health disparity indicators among MHS beneficiaries, indicating these disparities may be multifactorial. Routine incorporation of EBP and CPGs into clinical practice also appeared to vary among participants. It is evident that further research may positively contribute to current understanding of health disparities among MHS beneficiaries