Myconoside and Calceolarioside E Restrain UV-Induced Skin Photoaging by Activating NRF2-Mediated Defense Mechanisms.

Chronic and excessive ultraviolet (UVA/UVB) irradiation exposure is known as a major contributor to premature skin aging, which leads to excessive reactive oxygen species generation, disturbed extracellular matrix homeostasis, DNA damage, and chronic inflammation. Sunscreen products are the major preventive option against UVR-induced photodamage, mostly counteracting the acute skin effects and only mildly counteracting accelerated aging. Therefore, novel anti-photoaging and photopreventive compounds are a subject of increased scientific interest. Our previous investigations revealed that the endemic plant Haberlea rhodopensis Friv. (HRE) activates the antioxidant defense through an NRF2-mediated mechanism in neutrophiles. In the present study, we aimed to investigate the photoprotective potential of HRE and two of its specialized compounds-the phenylethanoid glycosides myconoside (MYC) and calceolarioside E (CAL)-in UVA/UVB-stimulated human keratinocytes in an in vitro model of photoaging. The obtained data demonstrated that the application of HRE, MYC, and CAL significantly reduced intracellular ROS formation in UVR-exposed HaCaT cells. The NRF2/PGC-1α and TGF-1ß/Smad/Wnt signaling pathways were pointed out as having a critical role in the observed CAL- and MYC-induced photoprotective effect. Collectively, CAL is worth further evaluation as a potent natural NRF2 activator and a promising photoprotective agent that leads to the prevention of UVA/UVB-induced premature skin aging.

DBT-PAHSE Intervention for Reduce Emotion Dysregulation and Suicide Behavior in Mexican Early Adolescents: A Longitudinal Study.

This study aimed to evaluate the effect of time on suicidal behavior, associated risk factors, and protective factors in early Mexican adolescents. Method: With a two-year longitudinal design, which included 18 of 34 adolescents who had previously participated in a DBT skills training program (DBT-PAHSE). The study evaluated ideation, suicide attempt, depression, emotional dysregulation, and psychological resources. Results: We observed differentiating significant differences over time in emotional dysregulation (F = 2.36 p = 0.04, η2= 0.12, ß = 0.72), affective resources (F = 3.94, p = 0.01, η2 = 0.18, ß = 0.82), and suicidal ideation. (F = 2.55, p = 0.03, η2= 0.13, ß = 0.77). In conclusion, the DBT-PAHSE program prevented deaths by suicide. It showed a reduction in emotional dysregulation up to two years after the end of treatment and maintained an increase in emotional and social resources. However, improvements are required to reduce depression over time and strengthen psychological resources.

Biotechnologically-Produced Myconoside and Calceolarioside E Induce Nrf2 Expression in Neutrophils.

The pathological manifestation of various diseases can be suppressed by the activation of nuclear factor erythroid 2 p45-related factor 2 (Nrf2), a transcriptional regulator of the cellular redox balance. Haberlea rhodopensis Friv. is a resurrection plant species endemic for Bulgaria, containing biologically active phenylethanoid glycosides that might possess antioxidant or redox activity. This study aimed to analyze the metabolic profile of in vitro cultured H. rhodopensis and to identify molecules that increase Nrf2 expression in bone marrow neutrophils. Fractions B, D, and E containing myconoside, or myconoside and calceolarioside E in ratios 1:0.6 and 0.25:1 were found to be the most active ones. Fraction B (200 µg/mL) improved neutrophil survival and strongly increased the Nrf2 intracellular level, while D and E, as well as, myconoside and calceolarioside E at the same ratios had a superior effect. Calceolarioside E (32 µg/mL) had stronger activity than myconoside, the effect of which was very similar to that of 2-cyano-3,12-dioxo-oleana-1,9(11)-dien-28-oic acid methyl ester (CDDO-Me), used as a positive control. These data indicate that both molecules, used alone or in combination have stimulatory activity on the endogenous Nrf2 level, indicating their therapeutic potential to regulate the cellular redox homeostasis oxidative stress-associated pathologies.

Prevalence of 12-month mental and substance use disorders in sexual minority college students in Mexico.

PURPOSE: Mental health disparities have been documented among sexual minority college students, but there is a dearth of evidence from developing countries. The aim is to estimate the prevalence of 12-month mental and substance use disorders across a range of sexual identities among first-year college students in Mexican universities, and test whether there is an association between sexual identity and disorders and whether the association is moderated by gender. METHOD: The University Project for Healthy Students, a web-based survey conducted as part of the World Health Organization's World Mental Health International College Student initiative, recruited 7874 students from nine Mexican universities in 2016 and 2017. Logistic regressions estimated the association of sexual identity with 12-month major depressive episode, generalized anxiety disorder, panic disorder, alcohol abuse/dependence, and drug abuse/dependence, with interaction terms for gender. RESULTS: Compared to heterosexual students reporting no same-sex attraction (SSA), heterosexual students with SSA (AORs range 1.77-3.67) and lesbian/gay and bisexual students (AORs range 2.22-5.32) were at a higher risk for several disorders. Asexual students were at higher risk for drug abuse/dependence (AOR = 3.64). Students unsure of their sexual identity were at a higher risk for major depressive episode, panic disorder, and drug abuse/dependence (AORs range 2.25-3.82). Gender differences varied across sexual identity and disorder. CONCLUSION: These findings are the first empirical report of sexual minority psychiatric disparities among a college student population from a developing nation and underscore the importance of clinical interventions that address mental health needs among sexual minority college students.

(Internet) Gaming Disorder in DSM-5 and ICD-11: A Case of the Glass Half Empty or Half Full: (Internet) Le trouble du jeu dans le DSM-5 et la CIM-11: Un cas de verre à moitié vide et à moitié plein.

BACKGROUND: Diagnostic and Statistical Manual of Mental Disorders (DSM-5) included in 2013 Internet gaming disorder (IGD) as a condition for further study, and in 2018, the World Health Organization included gaming disorder (GD) as a mental disorder in the International Classification of Disease (ICD-11). We aim to compare disorders of gaming in both diagnostic systems using a sample of young adults in Mexico. METHODS: Self-administered survey to estimate the prevalence of DSM-5 IGD and ICD-11 GD in 5 Mexican universities; 7,022 first-year students who participated in the University Project for Healthy Students, part of the World Health Organization World Mental Health International College Student Initiative. Cross-tabulation, logistic regression, and item response theory were used to inform on 12- month prevalence of DSM-5 IGD and ICD-11 GD, without and with impairment. RESULTS: The 12-month prevalence of DSM-5 IGD was 5.2% (95% CI, 4.7 to 5.8), almost twice as high as the prevalence using the ICD-11 GD criteria (2.7%; 95% CI, 2.4 to 3.1), and while adding an impairment requirement diminishes both estimates, prevalence remains larger in DSM-5. We found that DSM-5 cases detected and undetected by ICD-11 criteria were similar in demographics, comorbid mental disorders, service use, and impairment variables with the exception that cases detected by ICD-11 had a larger number of symptoms and were more likely to have probable drug dependence than undetected DSM-5 cases. CONCLUSION: DSM-5 cases detected by ICD-11 are mostly similar to cases undetected by ICD-11. By using ICD-11 instead of DSM-5, we may be leaving (similarly) affected people underserved. It is unlikely that purely epidemiological studies can solve this discrepancy and clinical validity studies maybe needed.

Suicide thought and behaviors, non-suicidal self-injury, and perceived life stress among sexual minority Mexican college students.

BACKGROUND: Sexual minority college students are at a higher risk for suicidal thoughts and self-injurious behaviors compared to heterosexual students. Minority stress theory proposes sexual minority individuals experience higher stress due to stigma. Using a sample of Mexican college students, this study tested perceived life stress as a mediator of suicide and self-injury outcomes across various sexual orientation groups. METHODS: The sample of college students (N=7882) was recruited from nine Mexican universities as part of the WHO World Mental Health International College Student (WMH-ICS) initiative. Participants completed an online survey including demographic questions, measure of perceived life stress, suicide outcomes, and non-suicidal self-injury (NSSI) in the past 12 months. RESULTS: Logistic regression analyses revealed identifying as a sexual minority significantly predicted a higher likelihood of suicide ideation (ORs 2.05-3.00), suicide attempts (ORs 2.48-8.73), and NSSI (ORs 2.92-4.18) compared to heterosexual students reporting no same-gender attraction. Significant indirect effects from mediation path analyses showed perceived life stress mediated the relationship between a sexual minority identity and suicide ideation (range of proportion mediated 10.48-31.48%), attempts (10.48-31.48%), and NSSI (7.69-20.09%) across each group except among asexual students. LIMITATIONS: The cross-sectional nature of the survey design precludes drawing causal inferences. CONCLUSION: Findings from this study contribute to minority stress theory by elucidating the role of perceived life stress as a mediator of suicide ideation and attempts and NSSI among sexual minority college students. Clinical interventions may benefit in focusing on experiences of stress across various life areas when supporting sexual minority college students.

DSM-5 Internet gaming disorder among a sample of Mexican first-year college students.

BACKGROUND AND AIMS: DSM-5 includes Internet gaming disorder (IGD) as a condition for further study. While online and offline gaming may produce undesired negative effects on players, we know little about the nosology of IGD and its prevalence, especially in countries with emerging economies. METHODS: A self-administered survey has been employed to estimate prevalence of DSM-5 IGD and study the structure and performance of an instrument in Spanish to measure DSM-5 IGD among 7,022 first-year students in 5 Mexican universities that participated in the University Project for Healthy Students (PUERTAS), part of the World Health Organization's World Mental Health International College Student Initiative. RESULTS: The scale for IGD showed unidimensionality with factor loadings between 0.694 and 0.838 and a Cronbach's α = .816. Items derived from gaming and from substance disorders symptoms mixed together. We found a 12-month prevalence of IGD of 5.2% in the total sample; prevalence was different for males (10.2%) and females (1.2%), but similar for ages 18-19 years (5.0%) and age 20+ (5.8%) years. Among gamers, the prevalence was 8.6%. Students with IGD were more likely to report lifetime psychological or medical treatment [OR = 1.8 (1.4-2.4)] and any severe role impairment [OR = 2.4 (1.7-3.3)]. Adding any severe role impairment to the diagnostic criteria decreased the 12-month prevalence of IGD to 0.7%. DISCUSSION AND CONCLUSIONS: Prevalence of DSM-5 IGD and the performance of diagnostic criteria in this Mexican sample were within the bounds of what is reported elsewhere. Importantly, about one in every seven students with IGD showed levels of impairment that would qualify them for treatment under DSM-5.

Barriers of mental health treatment utilization among first-year college students: First cross-national results from the WHO World Mental Health International College Student Initiative.

BACKGROUND: Although mental disorders and suicidal thoughts-behaviors (suicidal thoughts and behaviors) are common among university students, the majority of students with these problems remain untreated. It is unclear what the barriers are to these students seeking treatment. AIMS: The aim of this study is to examine the barriers to future help-seeking and the associations of clinical characteristics with these barriers in a cross-national sample of first-year college students. METHOD: As part of the World Mental Health International College Student (WMH-ICS) initiative, web-based self-report surveys were obtained from 13,984 first-year students in eight countries across the world. Clinical characteristics examined included screens for common mental disorders and reports about suicidal thoughts and behaviors. Multivariate regression models adjusted for socio-demographic, college-, and treatment-related variables were used to examine correlates of help-seeking intention and barriers to seeking treatment. RESULTS: Only 24.6% of students reported that they would definitely seek treatment if they had a future emotional problem. The most commonly reported reasons not to seek treatment among students who failed to report that they would definitely seek help were the preference to handle the problem alone (56.4%) and wanting to talk with friends or relatives instead (48.0%). Preference to handle the problem alone and feeling too embarrassed were also associated with significantly reduced odds of having at least some intention to seek help among students who failed to report that they would definitely seek help. Having 12-month major depression, alcohol use disorder, and suicidal thoughts and behaviors were also associated with significantly reduced reported odds of the latter outcome. CONCLUSIONS: The majority of first-year college students in the WMH-ICS surveys report that they would be hesitant to seek help in case of future emotional problems. Attitudinal barriers and not structural barriers were found to be the most important reported reasons for this hesitation. Experimental research is needed to determine whether intention to seek help and, more importantly, actual help-seeking behavior could be increased with the extent to which intervention strategies need to be tailored to particular student characteristics. Given that the preference to handle problems alone and stigma and appear to be critical, there could be value in determining if internet-based psychological treatments, which can be accessed privately and are often build as self-help approaches, would be more acceptable than other types of treatments to student who report hesitation about seeking treatment.

Psychopathology and self-harm among incoming first-year students in six Mexican universities.

OBJECTIVE: To estimate psychopathology and self-harm behavior of incoming first-year college students, sociodemographic correlates, service use and willingness to seek treatment. MATERIALS AND METHODS: 4 189 male and female incoming first-year students of six universities in four different states of Mexico responded to an online survey with a 79.3% response rate. RESULTS: Almost one in three incoming students has experienced some type of psychopathology; however, only one in five has received treatment. Female, students who are older, whose parents are not married or deceased, and who have a non-heterosexual orientation, no religion or a non-Catholic/Christian religion have greater odds (1.18 - 1.99), whereas those who attend a private university and have a parent with some college education have lower odds (0.68 - 0.75) of experiencing any probable disorder. CONCLUSIONS: Substantial unmet need for mental health services combined with reported willingness to use university services suggests an opportunity for the detection, referral, and treatment of incoming students to promote a successful transition.

OBJETIVO: Estimar psicopatologías y autolesiones en universitarios de nuevo ingreso, así como los correlatos sociodemográficos, el uso de servicios y la disposición para recibir tratamiento. MATERIAL Y MÉTODOS: 4 189 estudiantes de nuevo ingreso de seis universidades en cuatro estados contestaron una encuesta en línea con una tasa de respuesta de 79.3%. RESULTADOS: 32.5% han padecido psicopatologías en su vida, pero únicamente 19.5% han recibido tratamiento. Mujeres, estudiantes con una orientación no heterosexual, estudiantes de mayor edad, quienes tienen padres fallecidos o no casados, sin religión o con una religión no católica/cristiana tienen mayor probabilidad de presentar psicopatologías (RM= 1.18-1.99), mientras que aquellos de universidades privadas y cuyos padres tienen estudios universitarios tienen menor probabilidad (RM= 0.68-0.75). CONCLUSIONES: La alta tasa de psicopatologías no tratadas combinada con la disposición reportada de recibir servicios a través de su universidad sugiere una oportunidad para la detección, canalización y tratamiento de alumnos de nuevo ingreso para promover una transición exitosa.

Psychopathology and self-harm among incoming first-year students in six Mexican universities / Psicopatología y autolesiones en alumnos de nuevo ingreso en seis universidades mexicanas

Abstract: Objective: To estimate psychopathology and self-harm behavior of incoming first-year college students, socio-demographic correlates, service use and willingness to seek treatment. Materials and methods: 4 189 male and female incoming first-year students of six universities in four different states of Mexico responded to an online survey with a 79.3% response rate. Results: Almost one in three incoming students has experienced some type of psychopathology; however, only one in five has received treatment. Female, students who are older, whose parents are not married or deceased, and who have a non-heterosexual orientation, no religion or a non-Catholic/Christian religion have greater odds (1.18 - 1.99), whereas those who attend a private university and have a parent with some college education have lower odds (0.68 - 0.75) of experiencing any probable disorder. Conclusions: Substantial unmet need for mental health services combined with reported willingness to use university services suggests an opportunity for the detection, referral, and treatment of incoming students to promote a successful transition.

Resumen: Objetivo: Estimar psicopatologías y autolesiones en universitarios de nuevo ingreso, así como los correlatos sociodemográficos, el uso de servicios y la disposición para recibir tratamiento. Material y métodos: 4 189 estudiantes de nuevo ingreso de seis universidades en cuatro estados contestaron una encuesta en línea con una tasa de respuesta de 79.3%. Resultados: 32.5% han padecido psicopatologías en su vida, pero únicamente 19.5% han recibido tratamiento. Mujeres, estudiantes con una orientación no heterosexual, estudiantes de mayor edad, quienes tienen padres fallecidos o no casados, sin religión o con una religión no católica/cristiana tienen mayor probabilidad de presentar psicopatologías (RM= 1.18-1.99), mientras que aquellos de universidades privadas y cuyos padres tienen estudios universitarios tienen menor probabilidad (RM= 0.68-0.75). Conclusiones: La alta tasa de psicopatologías no tratadas combinada con la disposición reportada de recibir servicios a través de su universidad sugiere una oportunidad para la detección, canalización y tratamiento de alumnos de nuevo ingreso para promover una transición exitosa.

First Report of DHA-1 Producing Enterobacter cloacae Complex Isolate in Bulgaria.

THE AIM: of the present study was to reveal the characteristics of an. MATERIALS AND METHODS: Susceptibility testing, conjugation experiments, isoelectric focusing, PCR and sequencing were carrying out. RESULTS: Of 176. CONCLUSIONS: To the best of our knowledge this is the first report of DHA-1 producing isolate in Bulgaria. The emergence of DHA-1 producing.

Prognostic value of pre-embolisation MRI features of uterine fibroids in uterine artery embolisation.

AIM: To evaluate the prognostic value of pretreatment pelvic magnetic resonance imaging (MRI) features in uterine artery embolisation (UAE) for symptomatic fibroids. MATERIALS AND METHODS: MRI characteristics of 109 fibroids (≥3 cm) in 70 patients were analysed retrospectively. Imaging was performed 1.8±1.3 (SD) months before and 6.6±1.8 months after UAE. On pretreatment images, signal intensity (SI) of fibroids was compared with that of the myometrium and skeletal muscle on T1- and T2-weighted sequences; the contrast enhancement pattern and localisation of fibroids were also analysed. Fibroid volume reduction (VR) was assessed by control imaging. The numerical analogue quality-of-life score was obtained before and after UAE. Statistical analysis was performed using the Mann-Whitney U-test, Kruskal-Wallis test, and Wilcoxon signed-rank test. RESULTS: The mean fibroid volume decreased by 51.1±30.8% during the 6.6±1.8 months (p<0.001). Mean quality-of-life score improved by 48.2±27.6 points (p<0.001). The mean VR of submucosal fibroids (82.1±18.5%) was greater than that of intramural (49.4±30.7%) and subserosal (43±28.3%) fibroids (p<0.001 for both). Fibroids that were isointense/hyperintense to myometrium on T2-weighted images showed a better response than hypointense fibroids (63.7±25.8% versus 48.6±31.3%, respectively; p=0.041). On contrast-enhanced images, isointense/hyperintense fibroids showed a better VR than hypointense fibroids (61.3±27.4% versus 47.6±31.6%, respectively; p=0.035). Baseline fibroid volume of <50 cm3 was also associated with favourable imaging outcome (p=0.021). T2 SI compared to skeletal muscle and T1 SI compared to myometrium or skeletal muscle did not show association with VR. CONCLUSIONS: Localisation, T2 SI, contrast enhancement, and <50 cm3 fibroid volume were associated with better VR; these may help with treatment decisions.

Behavior Patterns of Antisocial Teenagers Interacting with Parents and Peers: A Longitudinal Study.

Antisocial behavior may begin during childhood and if maintained during adolescence, is likely to continue and escalate during adulthood. During adolescence, in particular, it has been established that antisocial behavior may be reinforced and shaped by exchanges between the teenager and his parents and peers, although the molecular process of these relations is as yet unknown. This paper explores the patterns of social interaction established by adolescents with and without the risk of engaging in antisocial behavior in order to understand the exchanges of them with their most important social groups, during 2 years. The study involved a sample of 70 adolescents classified into these two groups (with risk of antisocial behavior and control group). They were video-recorded interacting with one of their parents and one of their peers, independently. The interaction was done about the negotiation of conflictive conversational topics. Those video-records were registered by pairs of trained observers, using an observational catalog with nineteen behavioral categories, to know about the molecular interactional patterns characteristics. Thirty participants were evaluated only once, 30 were evaluated two times, and the other 10 were evaluated three times, the evaluations were performed annually. It was found that a higher occurrence of eye contact and use of open questions and elaborate answers appears to act as a protective factor for engaging in antisocial behavior.

Hearing Loss in Patients with Shunt-Treated Hydrocephalus.

Hearing loss is a common manifestation of the long-term complications in patients with shunt treated hydrocephalus along with motor development disturbance, cognitive and visual impairment, epilepsy and endocrine disorders. The aim of the present study was to investigate the alterations of hearing in patients with shunt treated hydrocephalus of non-tumor etiology and at least one year after implantation of ventriculo-peritoneal shunt, as well as their impact on the quality of life of patients. The study included 70 patients (age range 1.25 years - 21.25 years) with shunted non-tumor hydrocephalus and at least one year after placement of the shunt system. Hearing alterations were proved by measuring the brainstem auditory evoked potentials (BAEP) for children up to 5 years of age and children with mental retardation; audiograms was used for children older than 5 years with normal neuro-psychological development (NPD). Of the 70 studied patients 17 (24%) had hearing loss (10 bilateral and 7-unilateral) and all of them had sensorineural hearing loss, which is associated with low weight at birth, posthemorrhagic hydrocephalus and brainstem symptoms at the time of diagnosis of hydrocephalus. Hearing pathology was found more often in shunt-treated patients with NPD retardation, poor functional status and low quality of life. Children with shunt-treated hydrocephalus have hearing loss of sensorineural type. Children with brain stem symptomatology at diagnosing hydrocephalus and children with post-hemorrhagic hydrocephalus show higher risk of hearing loss. Children with shunted hydrocephalus and hearing loss show lower NPD, lower quality of life and lower functional status.

Management of abdominal aortic and iliac artery aneurysms by stent-graft implantation in a patient on CAPD.

We present the case of a 76-year-old male patient, who - after 2.5 years of CAPD treatment - underwent aorto-biiliac aneurysm reconstruction for aorto-biiliac aneurysm by bifurcational stent-graft implantation. To our knowledge this is the first case presentation of a stent-graft implantation and uninterrupted continuation of CAPD treatment in a patient on peritoneal dialysis.

Effect of vitamin levels on biomarkers of exposure and oxidative damage-the EXPAH study.

DNA adducts are markers of carcinogen exposure and of their biological effect; they have been shown to be related to mutagenesis, and therefore they could be a predictive biomarker of human cancer. The objective of this study was to assess if there is a relationship between vitamins A, C, and E, which are known to play a significant role as free radical scavengers and antioxidant agents, and biomarkers of genotoxicity and oxidative stress. Three hundred and fifty-six subjects from Czech Republic, Slovak Republic and Bulgaria, who completed a questionnaire on dietary information and had a measurement of plasma A, C, E vitamins, DNA adduct levels (benzo[a]pyrene (B[a]P) and bulky (DNA-Tot) DNA adducts) and oxidative damage (cyclic pyrimidopurinone N-1,N2 malondialdehyde-2 deoxyguanosine (M1dG) and 8-oxo-7,8-dihydro-2_deoxyguanosine (8-oxodG)) were analyzed. A significant inverse correlation was observed between plasma vitamin levels and both benzo[a]pyrene (B[a]P) and bulky DNA adducts. Vitamin A was also significantly inversely correlated with M1dG, a marker of oxidative damage. The associations were stronger in non-smokers than in smokers. Dietary intake of certain antioxidants such as vitamins is associated with reduced levels of markers of DNA damage (B[a]P and DNA-Tot) and oxidation (M1dG and 8-oxodG) measured in peripheral white blood cells. This could contribute to the protective role of such a dietary pattern on cancer risk. The protective effect of dietary vitamins is less evident in smokers.

An iridoid and a flavonoid from Sideritis lanata L.

A new iridoid diglucoside, 10-O-(E)-p-coumaroylmelittoside (1) and a new flavone glucoside, O-(6''-O-Acetyl-)-beta-glucopyranosylchrysoeriol (2), together with four known flavone glycosides, were isolated from the aerial parts of Sideritis lanata. The structures of the new compounds were elucidated by spectroscopic methods, 2D NMR and MS.

In vitro genotoxicity of PAH mixtures and organic extract from urban air particles part I: acellular assay.

Acellular assay of calf thymus DNA+/-rat liver microsomal S9 fraction coupled with (32)P-postlabelling was used to study the genotoxic potential of organic compounds bound onto PM10 particles collected in three European cities-Prague (CZ), Kosice (SK) and Sofia (BG) during summer and winter periods. B[a]P alone induced DNA adduct levels ranging from 4.8 to 768 adducts/10(8) nucleotides in the concentration dependent manner. However, a mixture of 8 c-PAHs with equimolar doses of B[a]P induced 3.7-757 adducts/10(8) nucleotides, thus suggesting the inhibition of DNA adduct forming activity by interaction among various PAHs. Comparison of DNA adduct levels induced by various EOMs indicates higher variability among seasons than among localities. DNA adduct levels for Prague collection site varied from 19 to 166 adducts/10(8) nucleotides, for Kosice from 22 to 85 and for Sofia from 6 to 144 adducts/10(8) nucleotides. Bioactivation with S9 microsomal fraction caused 2- to 7-fold increase in DNA adduct levels compared to -S9 samples, suggesting a crucial role of indirectly acting genotoxic EOM components, such as PAHs. We have demonstrated for the first time a significant positive correlation between B[a]P content in EOMs and total DNA adduct levels detected in the EOM treated samples (R=0.83; p=0.04). These results suggest that B[a]P content in EOM is an important factor for the total genotoxic potential of EOM and/or B[a]P is a good indicator of the presence of other genotoxic compounds causing DNA adducts. Even stronger correlation between the content of genotoxic compounds in EOMs and total DNA adduct levels detected (R=0.94; p=0.005) was found when eight c-PAHs were taken into the consideration. Our findings support a hypothesis that a relatively limited number of EOM components is responsible for a major part of its genotoxicity detectable as DNA adducts by (32)P-postlabelling.

In vitro genotoxicity of PAH mixtures and organic extract from urban air particles part II: human cell lines.

Principal aims of this study were at first, to find a relevant human derived cell line to investigate the genotoxic potential of PAH-containing complex mixtures and second, to use this cell system for the analysis of DNA adduct forming activity of organic compounds bound onto PM10 particles. Particles were collected by high volume air samplers during summer and winter periods in three European cities (Prague, Kosice, and Sofia), representing different levels of air pollution. The genotoxic potential of extractable organic matter (EOM) was compared with the genotoxic potential of individual carcinogenic polycyclic aromatic hydrocarbons (c-PAHs) as well as their artificial mixtures. Metabolically competent human hepatoma HepG2 cells, confluent cultures of human diploid lung fibroblasts (HEL), and the human monocytic leukemia cell line THP-1 were used as models. DNA adducts were analyzed by (32)P-postlabeling. The total DNA adduct levels induced in HepG2 cells after exposure to EOMs were higher than in HEL cells treated under the same conditions (15-190 versus 2-15adducts/10(8) nucleotides, in HepG2 and HEL cells, respectively). THP-1 cells exhibited the lowest DNA adduct forming activity induced by EOMs (1.5-3.7adducts/10(8) nucleotides). A direct correlation between total DNA adduct levels and c-PAH content in EOM was found for all EOMs in HepG2 cells incubated with 50microg EOM/ml (R=0.88; p=0.0192). This correlation was even slightly stronger when B[a]P content in EOMs and B[a]P-like adduct spots were analyzed (R=0.90; p=0.016). As THP-1 cells possess a limited metabolic capacity for most c-PAHs to form DNA reactive intermediates and are also more susceptible to toxic effects of PAHs and various EOM components, this cell line seemed to be an inappropriate system for genotoxicity studies of PAH-containing complex mixtures. The seasonal variability of genotoxic potential of extracts was stronger than variability among the three localities studied. In HepG2 cells, the highest DNA adduct levels were induced by EOM collected in Prague in the winter period, followed by Sofia and Kosice. However, in the summer sampling period, the order was quite opposite: Kosice>Sofia>Prague. When the EOM content per m(3) of air was taken into consideration in order to compare real exposures of humans to genotoxic compounds in all three localities, extracts from respirable dust particles collected in Sofia exhibited the highest genotoxicity regardless of the sampling period. The results indicate that most of DNA adducts detected in cells incubated with EOMs have their origin in low concentrations of c-PAHs representing 0.03-0.17% of EOM total mass. Finally, our results suggest that HepG2 cells have a metabolic capacity for PAHs similar to human hepatocytes and represent therefore the best in vitro model for investigating the genotoxic potential of complex mixtures containing PAHs among the three cell lines tested in this study.

Phenylethanoids, iridoids and a spirostanol saponin from Veronica turrilliana.

From the aerial parts of Veronica turrilliana two phenylethanoid glycosides, turrilliosides A and B and a steroidal saponin, turrillianoside were isolated and their structures elucidated as beta-(3,4-dihydroxyphenyl)ethyl-4-O-E-caffeoyl-O-[beta-glucopyranosyl-(1-->4)-alpha-rhamnopyranosyl-(1-->6)]-beta-glucopyranoside, beta-(3,4-dihydroxyphenyl)ethyl-4-O-E-caffeoyl-[6-O-E-feruloyl-beta-glucopyranosyl-(1-->4)-alpha-rhamnopyranosyl-(1-->6)]-beta-glucopyranoside and (23S,25S)-12beta,23-dihydroxyspirost-5-en-3beta-yl O-alpha-rhamnopyranosyl-(1-->4)-beta-glucopyranoside, respectively. Furthermore, eight known glucosides are reported namely, catalpol, catalposide, verproside, amphicoside, isovanilloylcatalpol, aucubin, arbutin, and 6-O-E-caffeoylarbutin, the latter two for the first time in the genus Veronica. The two phenylethanoid glycosides were found to be potent DPPH radical scavengers. All of the tested compounds were inactive against the representative species of fungi and bacteria.