Identificación de biomarcadores durante la vigilancia de la salud en profesionales expuestos a Xileno y Metanol. Revisión sistemática / Identification of biomarkers during health surveillance in professionals exposed to xylene and methanol. Systematic review

Introducción: El uso de xileno y metanol es habitual para el procesado de muestras ginecológicas en los laboratorios de Anatomía Patológica. Resulta necesario valorar la exposición en el personal expuesto. Material y Métodos: Se realizó una búsqueda bibliográfica por pares en las bases de datos del ámbito de la medicina: MEDLINE, IBECS, LILACS, REDALYC, RED SCIELO, COCHRANE LIBRARY Y SCOPUS. Resultados: Se encontraron 64 artículos que cumplían criterios de inclusión y 16 se seleccionaron para el estudio. La exposición profesional a xileno y metanol puede tener un impacto negativo a nivel pulmonar, auditivo, alteraciones visuales y neurológicas. Existen biomarcadores relacionados con estas exposiciones. Discusión: Los hallazgos justifican realizar mediciones periódicas en el lugar de trabajo para controlar las condiciones ambientales, incorporar pruebas específicas dentro de la vigilancia de la salud para detectar afecciones, así como realizar análisis biológicos para detectar la presencia de los contaminantes químicos, o sus marcadores biológicos (AU)

Introduction: The use of xylene and methanol is common for processing gynecological samples in Pathology Anatomy laboratories. It is necessary to assess the exposure in the exposed personnel. Material and Method: A literature search was conducted in medical databases: MEDLINE, IBECS, LILACS, REDALYC, RED SCIELO, COCHRANE LIBRARY, and SCOPUS. Results: 64 articles that met the inclusion criteria were found, and 16 were selected for the study. Occupational exposure to xylene and methanol can have a negative impact on the lungs, hearing, visual and neurological functions. There are biomarkers associated with these exposures. Discussion: The findings justify conducting periodic measurements in the workplace to monitor environmental conditions, incorporating specific tests into health surveillance to detect conditions, as well as performing biological analyses to detect the presence of chemical contaminants or their biological markers (AU)

Simultaneous Study of Analysis of Anti-inflammatory Potential of Dryopteris ramosa (C. Hope) C. Chr. using GC-Mass and Computational Modeling on the Xylene-induced Ear Oedema in Mouse Model.

INTRODUCTION: In the present study, we aimed to investigate the extraction and identification of the potential phytochemicals from the Methanolic Extract of Dryopteris ramosa (MEDR) using GC-MS profiling for validating the traditional uses of MEDR its efficacy in inflammations by using in-vitro, in-vivo and in silico approaches in anti-inflammatory models. METHODS: GC-MS analysis confirmed the presence of a total of 59 phytochemical compounds. The human red blood cells (HRBC) membrane stabilization assay and heat-induced hemolysis method were used as in-vitro anti-inflammatory activity of the extract. The in-vivo analysis was carried out through the Xylene-induced mice ear oedema method. It was found that MEDR at a concentration of 20 µg, 30 µg, and 40 µg showed 35.45%, 36.01%, and 36.33% protection to HRBC in a hypotonic solution, respectively. At the same time, standard Diclofenac at 30 µg showed 45.31% protection of HRBC in a hypotonic solution. RESULTS: The extract showed inhibition of 25.32%, 26.53%, and 33.31% cell membrane lysis at heating at 20 µg, 30 µg, and 40 µg, respectively. In comparison, standard Diclofenac at 30 µg showed 50.49% inhibition of denaturation to heat. Methanolic extract of the plant exhibited momentous inhibition in xylene-induced ear oedema in mice treated with 30 µg extract were 47.2%, 63.4%, and 78.8%, while inhibition in mice ear oedema treated with 60 µg extract was 34.7%, 43.05%, 63.21% and reduction in ear thickness of standard drug were 57.3%, 59.54%, 60.42% recorded at the duration of 1, 4 and 24 hours of inflammation. Molecular docking and simulations were performed to validate the anti-inflammatory role of the phytochemicals that revealed five potential phytochemicals i.e. Stigmasterol,22,23dihydro, Heptadecane,8methyl, Pimaricacid, Germacrene and 1,3Cyclohexadiene,_5(1,5dimethyl4hexenyl)-2methyl which revealed potential or significant inhibitory effects on cyclooxygenase-2 (COX-2), tumour necrosis factor (TNF-α), and interleukin (IL-6) in the docking analysis. CONCLUSION: The outcome of the study signifies that MEDR can offer a new prospect in the discovery of a harmonizing and alternative therapy for inflammatory disease conditions.

Radical Scavenging, Anti-Inflammatory, and Hepatoprotective Activities of Pentacyclic Triterpene isolated from Rosa webbiana.

INTRODUCTION: Rosa webbiana (RW) Wall Ex. Royle is used in traditional medicine in Pakistan for the treatment of several diseases including jaundice. To date, only neuroprotective potential of the plant has been evaluated. OBJECTIVE: The current study was designed to isolate bioactive compound(s) and investigate its possible radical scavenging, anti-inflammatory and hepatoprotective activities. METHODS: Column chromatography was done to isolate compounds from the chloroform fraction of RW. The compound was characterized by mass spectrometry, 1H-NMR, and 2D-NMR spectroscopy. Radical scavenging activity was assessed by 2,2-diphenyl-1-picrylhydrazyl (DPPH) and hydrogen peroxide (H2O2) assays, while anti-inflammatory potential was evaluated via xylene-induced ear edema and carrageenan-induced paw edema models. For hepatoprotection, CCl4-induced model in mice was used. RESULTS: A triterpene compound (3α, 21ß-dihydroxy-olean-12-ene) was isolated from RW fruits (ARW1). The compound exhibited DPPH and H2O2 scavenging activities 61 ± 1.31% and 66 ± 0.48% respectively at 500 µg/ml. ARW1 (at 50 mg/kg) exhibited 62.9 ± 0.15% inhibition of xylene-induced ear edema and 66.6 ± 0.17% carrageenan-induced paw edema in mice. In CCl4-induced hepatotoxic mice, ARW1 significantly countered elevation in alanine transaminase (ALT), alkaline phosphatase (ALP), total bilirubin (T.B), and reduction in total protein (T.P) levels. Liver histomorphological study supported the serum biochemical profile for hepatoprotection. Moreover, ARW1 significantly attenuated the toxic changes in body and liver weight induced by CCl4. CONCLUSION: The compound ARW1 exhibited anti-radical, anti-inflammatory and hepatoprotective effects. The anti-inflammatory and hepatoprotective activities may be attributed to anti-oxidant potential of the compound.

Ambient BTEX exposure and mid-pregnancy inflammatory biomarkers in pregnant African American women.

Air pollution is associated with preterm birth (PTB), potentially via inflammation. We recently showed the mixture benzene, toluene, ethylbenzene, and xylene (BTEX) is associated with PTB. We examined if ambient BTEX exposure is associated with mid-pregnancy inflammation in a sample of 140 African-American women residing in Detroit, Michigan. The Geospatial Determinants of Health Outcomes Consortium study collected outdoor air pollution measurements in Detroit; these data were coupled with Michigan Air Sampling Network measurements to develop monthly BTEX concentration estimates at a spatial density of 300 m2. First trimester and mid-pregnancy BTEX exposure estimates were assigned to maternal address. Mid-pregnancy (mean 21.3 ± 3.7 weeks gestation) inflammatory biomarkers (high-sensitivity C-reactive protein, interleukin [IL]-6, IL-10, IL-1ß, and tumor necrosis factor-α) were measured with enzyme immunoassays. After covariate adjustment, for every 1-unit increase in first trimester BTEX, there was an expected mean increase in log-transformed IL-1ß of 0.05 ± 0.02 units (P = 0.014) and an expected mean increase in log-transformed tumor necrosis factor-α of 0.07 ± 0.02 units (P = 0.006). Similarly, for every 1-unit increase in mid-pregnancy BTEX, there was a mean increase in log IL-1ß of 0.06 ± 0.03 units (P = 0.027). There was no association of either first trimester or mid-pregnancy BTEX with high-sensitivity C-reactive protein, IL-10, or IL-6 (all P > 0.05). Ambient BTEX exposure is associated with inflammation in mid-pregnancy in African-American women. Future studies examining if inflammation mediates associations between BTEX exposure and PTB are needed.

Necrotising fasciitis following accidental injection of intraoral xylene: a preventable medication error.

The most common cause of preventable mortality and morbidity to the patient in a healthcare system is medication error. Medication errors have got a significant impact on the patient health and healthcare system. These errors are multidisciplinary and can occur at various stages of drug therapy. Physicians, nursing staff, pharmacists, hospital administration all have an important role in preventing medication errors from recurring. The most common causes include wrong patient, wrong drug prescription, look-alike sound-alike drugs, faulty drug administration, wrong dosage, drug storage, delivery problem, lack of staff, patient and physician education and failure to monitor closely. This case illustrates the importance of incorporating protocol and cross-checking before administering a drug during the procedure. Here, we discuss a case of accidental intraoral injection of xylene instead of xylocaine (local anaesthetic agent), which was a sound-alike drug that resulted in significant morbidity to the patient.

Hypermethylation in Gene Promoters Are Induced by Chronic Exposure to Benzene, Toluene, Ethylbenzene and Xylenes.

BACKGROUND AND OBJECTIVE: Gas station attendants are occupationally exposed to benzene, toluene, ethylbenzene and xylene (BTEX) compounds and thus more susceptible to the biological effects of this mixture present in gasoline, especially due to the carcinogenicity of benzene. Furthermore, the harmful effects of BTEX exposure may be potentiated by genetic and epigenetic inactivation of critical genes. The objective was to evaluate such gene-BTEX interactions accessing the promoter methylation status of p14ARF, p16INK4A and GSTP1 in peripheral blood leukocyte samples. MATERIALS AND METHODS: The 59 exposed and 68 unexposed participants from Rio de Janeiro, Brazil, were included. The promoter methylation status was accessed by methylation-specific PCR (MSP) and GSTP1 Ile105Val polymorphism was investigated by PCR-restriction fragment length polymorphism (PCR-RFLP) technique. RESULTS: Both p14ARF and p16INK4A were significantly hypermethylated in exposed subjects compared to unexposed (p = 0.004 and p<0.001, respectively). Additionally, p16INK4A hypermethylation in the exposed group was correlated with chromosomal abnormalities (CAs) (p = 0.018), thus highlighting the influence of the gene-environment interactions on genome instability. Noteworthy, p16INK4A methylation was significantly associated with miscarriage among female attendants (p = 0.047), in which those who reported miscarriage exhibited hypermethylation in at least 2 of the 3 genes analyzed. The GSTP1 heterozygote genotype, which could affect the metabolism of benzene detoxification, was found in both groups but was more frequent in those occupationally exposed. No significant association was observed between GSTP1 genotypes and methylation status. CONCLUSION: Together, these findings indicate that gas station attendants with the aforementioned epigenetic and genetic profiles may be at greater risk of occupational BTEX exposure-induced genome instability, which could require concerted efforts to establish more preventive actions and constant biomonitoring in gas station attendants.

Scrophularia Tenuipes Coss and Durieu: Phytochemical Composition and Biological Activities.

Scrophularia tenuipes is an Algerian-Tunisian endemic species, which has not been studied yet. Ethyl acetate (EA) and n-butanol (Bu) fractions obtained from Scrophularia tenuipes were investigated for their health benefit properties, in particular with respect to in vivo/in vitro anti-inflammatory and antioxidant activities, as well as their potential to inhibit key enzymes with impact in diabetes (α-glucosidase and α-amylase). The fractions had a distinct phytochemical composition, of which EA was richer in total phenolic compounds (225 mg GAE/g) and mostly composed of the phenylethanoid acetyl martynoside. Compared to EA, Bu had higher amounts of total flavonoids, and according to the result obtained from UHPLC-DAD-ESI-MSn analysis, harpagoside (iridoid) was its major phytochemical. EA fraction was quite promising with regard to the in vivo (at 200 mg/kg, po) anti-inflammatory effect (62% and 52% for carrageenan-induced rat paw edema and xylene-induced ear edema tests, respectively), while Bu fraction exhibited a stronger antioxidant capacity in all tests (IC50 = 68 µg/mL, IC50 = 18 µg/mL, IC50 = 18 µg/mL and A0.50 = 43 µg/mL for DPPH●, ABTS•+, O2•- scavenging assays and cupric-reducing antioxidant capacity method, respectively). Both fractions also showed a strong effect against α-amylase enzyme (IC50 = 8 µg/mL and 10 µg/mL for EA and Bu fraction, respectively).

Triclosen and Its Alternatives in Antibacterial Soaps.

BACKGROUND: In 2017, the Food and Drug Administration banned the marketing of triclosan and triclocarban in antibacterial soaps, citing inefficacy and concerns of systemic absorption and antibacterial resistance. As a result, there is an anticipated decrease in the number of triclosan-containing products on the market with an associated increase in antibacterial alternatives (eg, benzalkonium chloride, benzethonium chloride, chloroxylenol, chlorhexidine) and cases of allergic and irritant contact dermatitis. OBJECTIVES: The aims of the study were to determine the extent that triclosan and triclocarban are being used in the consumer and medical industries after the Food and Drug Administration marketing ban and to appraise the risk of allergic contact dermatitis to triclosan alternatives. METHODS: The National Drug Code Directory (NDCD), Google, Amazon, Target, Walgreens, Walmart, CVS, and Colorado hospitals were surveyed for antibacterial soap use. Antibiotics surveyed include triclosan, triclocarban, benzalkonium chloride, benzethonium chloride, chloroxylenol, and chlorhexidine. RESULTS: The most common antibiotics reported by the NDCD, consumer sites, and Colorado hospitals were benzalkonium chloride, chloroxylenol, and triclosan, respectively. Triclosan accounted for the second most prevalent antibacterial in the NDCD- and consumer site-surveyed products. CONCLUSIONS: The triclosan marketing ban may instigate increased exposure to triclosan alternatives. The addition of antibacterial products to hand soaps does not improve soap effectiveness and may cause harm by contributing to antibiotic resistance and the development of allergic conditions. Additional studies are needed to elucidate the benefits and harms of antibacterial soaps.

Allergic Contact Dermatitis to Operating Room Scrubs and Disinfectants.

BACKGROUND: Both surgical personnel and patients undergoing procedures are exposed regularly to different antiseptic chemicals in various forms. Little is known about the ingredients in these antiseptics and the risk these products may provoke allergic contact dermatitis. OBJECTIVE: The aim of the study was to identify and characterize common allergens in surgical scrubs and patient surgical cleansers that health care workers and surgical patients may encounter in the perioperative period. METHODS: DailyMed website was searched using numerous terms for surgical disinfectants. Products used for health care worker handwashing/scrubbing or patient surgical cleansing/disinfecting were included. Each product's ingredients were recorded; those found on the 2017 American Contact Dermatitis Society (ACDS) Core Allergen Series were noted from each product. CONCLUSIONS: A total of 1940 products were identified, of which 267 were included in the analysis. A total of 66.3% contained iodine, 25.8% contained chlorhexidine digluconate, and 2.6% contained chloroxylenol. Within the group analyzed, 1586 ingredients were identified. Of these, 241 were ACDS Core Series allergens. Most products contained a single ACDS allergen. There were significant differences in allergens based on product type and active ingredient, with iodine-containing products having the fewest number of allergens. The most common ACDS allergens found were cocamide diethanolamide (22.5%), fragrance (21.7%), lanolin (19.5%), propylene glycol (6.7%), alkyl glucosides (6.0%), and sorbic acid derivatives (5.6%).

Role of Th2 cytokines on the onset of asthma induced by meta-xylene in mice.

meta-Xylene (m-xylene) is one of three isomers of xylene, which is widely used as a solvent and detergent in various industries and medical technology. Exposure to volatile organic compounds, such as m-xylene, causes pulmonary inflammation and airway inflammation, thereby contributing to the onset of asthma. Exposure to m-xylene increases acute wheezing and intensity of asthma symptom. However, the mechanism of the onset of asthma by m-xylene has not been studied yet. C57BL/6 mice were sensitized and challenged by m-xylene at 100 or 300 mg/kg. The mice were then sacrificed after the last challenge. Exposure to m-xylene increased the total number of inflammatory cells and the production of interleukin (IL)-4, IL-5, IL-13, and immunoglobulin E related to the Th2 immune response. In contrast, the production of interferon-γ related to the Th1 immune response was decreased. In addition, the airway resistance increased according to the airway hyper-responsiveness measurements. Finally, a histological analysis revealed infiltration of inflammatory cells, mucus production, and lung fibrosis. These results suggest that m-xylene is a potential risk factor for asthma and the onset of asthma is caused by TH2 cytokines.

[Analysis of the cardiovascular effects on workers expose to occupational benzene-toluene-xylene and noise in a painting workshop of an automobile company].

Objective: To learn about the cardiovascular health effects of workers expose to benzene-toluene-xylene and noise in painting workshop of automobile manufacturing enterprises, and to provide intervention measures and strategies for the health of workers. Methods: The effects of noise exposure, benzene-toluene-xylene exposure and combined exposure on workers' blood pressure and electrocardiogram were analyzed through epidemiological investigation, workplace monitoring and occupational health examination in several automobile enterprises which had carried out occupational hazard factors monitoring and occupational health examination in our hospital from April to October 2017. Results: There were differences in age, sex, working years, smoking, drinking and physical exercise among workers in different exposure groups (P<0.05) . The systolic blood pressure level of workers in benzene-toluene-xylene exposure group and combined exposure group was significantly different comparing with control group (P< 0.05) , After the factors of age and working years were adjusted. The abnormity rate of electrocardiogram in workers were not statistically significant in all groups (P>0.05) . Conclusion: The benzene-toluene-xylene exposure and noise combined with benzene-toluene-xylene exposure in painting workshop of automobile manufacturing enterprises has positive influence on the systolic blood pressure of workers. Regular physical examination and health intervention measures should be strengthened to improve health.

Blood BTEX levels and neurologic symptoms in Gulf states residents.

BACKGROUND: The chemicals benzene, toluene, ethylbenzene, and xylenes (BTEX) are neuroactive. Exposures often co-occur because they share common sources. We examined neurologic effects of environmental BTEX exposure among U.S. Gulf coast residents taking into account concomitant exposures. METHODS: We measured blood concentrations of BTEX in 690 Gulf state residents. Neurologic symptoms were ascertained via telephone interview. We used log-binomial regression to estimate associations between blood BTEX levels and self-reported neurologic symptoms independently for the presence of any neurologic, central (CNS), or peripheral nervous system (PNS) symptoms. We estimated associations in single chemical models mutually adjusted for co-occurring BTEX and used weighted quantile sum regression to model associations between the combined BTEX mixture and neurologic symptoms. RESULTS: Half (49%) of participants reported at least one neurologic symptom. Each BTEX chemical was associated with increased CNS and PNS symptoms in single-chemical models comparing the highest to lowest quartile of exposure. After adjusting for coexposures, benzene was associated with CNS symptoms among all participants (PR = 2.13, 95% CI: 1.27, 3.57) and among nonsmokers (PR = 2.30, 95% CI: 1.35, 3.91). After adjusting for coexposures, associations with toluene were apparent only for reporting multiple PNS symptoms (PR = 2.00, 95% CI: 0.96, 4.16). In mixture analyses, a one-quartile increase in BTEX exposure was associated with neurologic symptoms (OR = 1.47, 95% CI: 1.11, 1.98). The weighted quantile sum index weighted benzene most heavily, which was consistent with single chemical analyses. CONCLUSIONS: Increasing blood benzene concentration was associated with increased prevalence of CNS symptoms. In this sample, BTEX-associated neurologic effects are likely driven by exposure to benzene and, to a lesser extent, toluene.

Evaluation of Anti-Inflammatory Activities of a Triterpene ß-Elemonic Acid in Frankincense In Vivo and In Vitro.

The purpose of this research was to extract and separate the compounds from frankincense, and then evaluate their anti-inflammatory effects. The isolated compound was a representative tetracyclic triterpenes of glycine structure according to ¹H-NMR and 13C-NMR spectra, which is ß-elemonic acid (ß-EA). We determined the content of six different localities of frankincense; the average content of ß-EA was 41.96 mg/g. The toxic effects of ß-EA administration (400, 200, 100 mg/kg) for four weeks in Kunming (KM) mice were observed. Compared with the control group, the body weight of mice, the visceral coefficients and serum indicators in the ß-EA groups showed no systematic variations. The anti-inflammatory effects of ß-EA were evaluated in LPS-induced RAW264.7 cells, xylene-induced induced ear inflammation in mice, carrageenin-induced paw edema in mice, and cotton pellet induced granuloma formation in rats. ß-EA inhibited overproduction of tumor necrosis factor-α(TNF-α), interleukin-6 (IL-6), monocyte chemotactic protein 1 (MCP-1), soluble TNF receptor 1 (sTNF R1), Eotaxin-2, Interleukin 10 (IL-10) and granulocyte colony-stimulating factor (GCSF) in the RAW264.7 cells. Intragastric administration with ß-EA (300, 200, and 100 mg/kg in mice, and 210, 140, and 70 mg/kg in rats) all produced distinct anti-inflammatory effects in vivo in a dose-dependent manner. Following treatment with ß-EA (300 mg/kg, i.g.), the NO level in mice ears and PGE2 in mice paws both decreased (p < 0.01). In conclusion, our study indicates that ß-EA could be a potential anti-inflammatory agent for the treatment of inflammatory diseases.

Potential Health Risks of Chemicals in Car Colorant Products.

Public concern regarding the use of products with chemicals has increased in Korea, following reports indicating that hazardous chemicals in products, such as disinfectants, can cause fatal lung disease. Despite the widespread use of car colorant products, little is known regarding their potential health risks. The purpose of this study was to determine the potential health risks of substances that exist in car colorant products. Thirteen car colorant products were purchased from the Korean market and 15 commonly used chemicals were analyzed. Exposure and risk assessments were conducted in two assessment stages (screening and refined). The analysis showed that all of the examined products contained toluene, ethylbenzene, and xylene. The maximum concentration of toluene was 52.5%, with a median concentration of 10.8%. Tier 1 (screening) assessment showed that four chemicals (toluene, ethylbenzene, xylene, and 2-butoxyethanol) may pose health risks, but tier 2 (refined) assessment showed that these chemicals do not pose any risk. However, these chemicals were present in all of the examined products, and government regulations did not control their concentrations in these products. Therefore, we suggest that levels of toluene, ethylbenzene, and xylene in car colorant products should be regulated to protect public health.

Eco-Pap: The Ecological Modification of the Papanicolaou Stain for Sustainable Cervical Cancer Diagnosis.

OBJECTIVES: To validate the ecological modification of the Papanicolaou stain (Eco-Pap) for the diagnosis of cervical cancer. STUDY DESIGN: A prospective study was performed at the Mother and Child "San Bartolomé" Hospital, Lima, Peru. Reagent handling strategies were divided into three phases: we used (1) Harris progressive hematoxylin (for nuclear staining), (2) a polychromatic solution (a mix of EA-36/Orange G-6 to suppress the use of several alcohol baths), and (3) direct mounting (with Entellan® solution). The cellular details were analyzed by the staining quality index, an external quality control, and the Bethesda System 2014. RESULTS: We evaluated 72,901 cervical smears stained with the Eco-Pap. The validation of the Eco-Pap against the conventional Pap stain was optimal (κ = 0.89; 95% CI: 0.87-0.92), showing a sensibility and specificity of 88.3% (95% CI: 85.1-90.0) and 98.7% (95% CI: 98-99.2), respectively. The Eco-Pap dramatically reduced the environmental pollution caused by 72 L of xylene, hydrochloric acid, and ammonia (6 L each) and mercury oxide. CONCLUSION: The Eco-Pap is an innovative and efficient staining method reducing the use of toxic reagents with carcinogenic potential during cervical cancer screening by exfoliative cytology.

Occupational exposure to benzene, toluene, xylene and styrene and risk of prostate cancer in a population-based study.

OBJECTIVES: While several monocyclic aromatic hydrocarbons are classified as definite or possible carcinogens to humans, little data exist on their role in prostate cancer (PCa). We examined occupational exposure to benzene, toluene, xylene (BTX) and styrene and PCa risk in a population-based case-control study in Montreal, Canada. METHODS: Cases aged ≤75 years diagnosed with PCa in 2005-2009 (n=1920) and population controls frequency-matched on age (n=1989) provided detailed work histories. Experts evaluated the certainty, frequency and concentration of exposure to monocyclic aromatic hydrocarbons in each job lasting ≥2 years. Logistic regression estimated OR and 95% CIs for PCa risk, adjusting for potential confounders. RESULTS: Exposures to BTX were highly intercorrelated, except for durations of exposure at substantial levels. Ever exposure to any BTX was associated with overall PCa (OR 1.27, 95% CI 1.05 to 1.53), while the OR for styrene was 1.19. However, increases in risk were largely confined to low-grade tumours, with ORs of 1.33 (95%CI 1.08 to 1.64) and 1.41 (95% CI 0.85 to 2.31) for ever exposure to any BTX and styrene, respectively, and a duration response pattern for any BTX. Risks for low-grade tumours were elevated among men exposed ≥25 years at substantial levels of benzene (OR 2.32) and styrene (OR 2.44). Some cumulative exposure categories showed increased risks but without clear trends. CONCLUSION: Exposure to any BTX was associated with higher risks of overall PCa. Prolonged exposures at the substantial level to benzene and styrene increased risks of low-grade tumours. These novel findings were independent from PCa screening.

Prenatal exposure to environmental pollutants and child development trajectories through 7 years.

BACKGROUND: Prenatal exposure to environmental pollutants such as mold, lead, pesticides, tobacco, and air pollutants has been suggested to impair cognitive development. Evidence is needed from longitudinal studies to understand their joint impact on child development across time. OBJECTIVE: To study associations between exposure to indoor environmental pollutants or outdoor air pollution during pregnancy and offspring cognitive development trajectories through 7 years. METHODS: We included 718 Mexican mother-child pairs. Prenatal exposure to indoor environmental pollutants (mold, ventilation, pesticides, tobacco smoke, and use of vidiartred clay pots) was self-reported by the mothers and integrated into an index, or objectively measured in the case of outdoor air pollutants (nitrogen oxides, benzene, toluene, and xylene). Child global cognitive development was measured at 12, 18, 60, or 84 months. Using Latent Class Growth Analysis, we identified three developmental trajectories (positive = 108, average = 362, low = 248). We used multinomial logistic models to test associations between environmental pollutant score (EPS) or outdoor air pollutants, and cognitive development trajectories. RESULTS: After adjustment for sociodemographic covariates, EPS was associated with the average (OR = 1.26 95%CI = 1.01, 1.55) and low (OR = 1.41 95%CI = 1.11, 1.79) trajectories compared to positive; where a unit increase in EPS means an additional prenatal exposure to a pollutant. There was no association between outdoor air pollutants and cognitive development trajectories. CONCLUSION: Children of women who reported higher exposure to indoor environmental pollutants during pregnancy were more likely to follow worse developmental trajectories through 7 years. These results support the development and testing of interventions to reduce exposure to environmental pollutants during pregnancy and early childhood as a potential strategy to improve long-term cognitive development.

Self-Nanoemulsifying Drug Delivery Systems Containing Plantago lanceolata-An Assessment of Their Antioxidant and Antiinflammatory Effects.

The most important components of Plantago lanceolata L. leaves are catalpol, aucubin, and acteoside (=verbascoside). These bioactive compounds possess different pharmacological effects: anti-inflammatory, antioxidant, antineoplastic, and hepatoprotective. The aim of this study was to protect Plantago lanceolata extract from hydrolysis and to improve its antioxidant effect using self-nano-emulsifying drug delivery systems (SNEDDS). Eight SNEDDS compositions were prepared, and their physical properties, in vitro cytotoxicity, and in vivo AST/ALT values were investigated. MTT cell viability assay was performed on Caco-2 cells. The well-diluted samples (200 to 1000-fold dilutions) proved to be non-cytotoxic. The acute administration of PL-SNEDDS compositions resulted in minor changes in hepatic markers (AST, ALT), except for compositions 4 and 8 due to their high Transcutol contents (80%). The non-toxic compositions showed a significant increase in free radical scavenger activity measured by the DPPH test compared to the blank SNEDDS. An indirect dissolution test was performed, based on the result of the DPPH antioxidant assay; the dissolution profiles of Plantago lancolata extract were statistically different from each SNEDDS. The anti-inflammatory effect of PL-SNEDDS compositions was confirmed by the ear inflammation test. For the complete examination period, all compositions decreased ear edema as compared to the positive (untreated) control. It can be concluded that PL-SNEDDS compositions could be used to deliver active natural compounds in a stable, efficient, and safe manner.

Microbial transformation of ginsenoside Rb1, Re and Rg1 and its contribution to the improved anti-inflammatory activity of ginseng.

Microbial transformation of ginsenosides to increase its pharmaceutical effect is gaining increasing attention in recent years. In this study, Cellulosimicrobium sp. TH-20, which was isolated from soil samples on which ginseng grown, exhibited effective ginsenoside-transforming activity. After protopanaxadiol (PPD)-type ginsenoside (Rb1) and protopanaxatriol (PPT)-type ginsenosides (Re and Rg1) were fed to C. sp. TH20, a total of 12 metabolites, including 6 new intermediate metabolites, were identified. Stepwise deglycosylation and dehydrogenation on the feeding precursors have been observed. The final products were confirmed to be rare ginsenosides Rd, GypXVII, Rg2 and PPT after 96 h transformation with 38-96% yields. The four products showed improved anti-inflammatory activities by using lipopolysaccharide (LPS)-induced murine RAW 264.7 macrophages and the xylene-induced acute inflammatory model of mouse ear edema. The results indicated that they could dramatically attenuate the production of TNF-α more effectively than the precursors. Our study would provide an example of a unique and powerful microbial cell factory for efficiently converting both PPD-type and PPT-type ginsenosides to rare natural products, which extends the drug candidates as novel anti-inflammatory remedies.