Adolescent Mental Health and Family Economic Hardships: The Roles of Adverse Childhood Experiences and Family Conflict.

Rising and economically disproportionate rates of adverse mental health outcomes among children and youth warrant research investigating the complex pathways stemming from socioeconomic status. While adverse childhood experiences (ACEs) have been considered a possible mechanism linking socioeconomic status (SES) and child and youth psychopathology in previous studies, less is understood about how family environments might condition these pathways. Using data from a longitudinal, multiple-wave study, the present study addresses this gap by examining the direct relationships between family economic status and youth internalizing and externalizing symptoms, if ACEs mediate these relationships, and if conflictual family environments moderate these direct and indirect relationships. The data were obtained from 5510 youth participants [mean age at baseline = 9.52 (SD = 0.50), 47.7% female, 2.1% Asian, 10.3% Black, 17.6% Hispanic, 9.8% Multiracial/Multiethnic, 60.2% White] and their caretakers from the baseline, 1-year, and 2-year follow up waves. Conditional process analysis assessed the direct, indirect, and moderated relationships in separate, equivalent models based on youth- versus caregiver-raters of ACEs and youth psychopathology to capture potential differences based on the rater. The results of both the youth- and caregiver-rated models indicated that lower family economic status directly predicted higher levels of externalizing symptoms, and ACEs indirectly accounted for higher levels of internalizing and externalizing symptoms. Additionally, family conflict moderated some, but not all, of these relationships. The study's findings highlight that lower family economic status and ACEs, directly and indirectly, contribute to early adolescent psychopathology, and conflictual family environments can further intensify these relationships. Implementing empirically supported policies and interventions that target ACEs and family environments may disrupt deleterious pathways between SES and youth psychopathology.

Socio-contextual Determinants of Research Evidence Use in Public-Youth Systems of Care.

Recent efforts have been devoted to understanding the conditions by which research evidence use (REU) is facilitated from the perspective of system leaders in the context of implementing evidence-based child mental health interventions. However, we have limited understanding of the extent to which outer contextual factors influence REU. Outer contextual factors for 37 counties in California were gathered from public records in 2008; and child welfare, juvenile justice, and mental health system leaders' perceptions of their REU were measured via a web-based survey from 2010 to 2012. Results showed that leaders with higher educational attainment and in counties with lower expenditures on inpatient mental health services were significantly associated with higher REU. Positive relationships between gathering research evidence and racial minority concentration and poverty at the county level were also detected. Results underscore the need to identify the organizational and socio-political factors by which mental health services and resources meet client demands that influence REU, and to recruit and retain providers with a graduate degree to negotiate work demands and interpret research evidence.

Measuring Use of Research Evidence: The Structured Interview for Evidence Use.

OBJECTIVES: This article describes the Standard Interview for Evidence Use (SIEU), a measure to assess the level of engagement in acquiring, evaluating, and applying research evidence in health and social service settings. METHOD: Three scales measuring input, process, and output of research evidence and eight subscales were identified using principal axis factor analysis and parallel analysis of data collected from 202 state and county child welfare, mental health, and juvenile justice systems leaders. RESULTS: The SIEU scales and subscales demonstrate strong internal consistency as well as convergent and discriminant validity. CONCLUSIONS: The SIEU is easy to use and can be administered as a complete scale or as three smaller scales to separately examine evidence in acquisition, evaluation, or application. The measure demonstrates potential in understanding the role of research evidence in service settings and in monitoring the process of evidence-based practice and application of scientific principles in social work practice.

From placement to prison revisited: Do mental health services disrupt the delinquency pipeline among Latino, African American and Caucasian youth in the child welfare system?

Racial and ethnic disparities in delinquency among child welfare-involved youth are well documented. However, less is known about the mechanisms through which these disparities occur. This study explores the extent to which sets of variables predict the occurrence of juvenile delinquency and whether race/ethnicity moderates the strength of the relationships between (1) social, emotional, and behavioral (SEB) problems and delinquency and (2) mental health service use and delinquency. We used a nationally representative sample of 727 African American, Caucasian, and Latino youth between the ages of 12-17 who were referred to the child welfare system. Controlling for age, gender, placement instability, maltreatment history, poverty, and urbanicity, linear regression analyses revealed that African American and Latino youth engaged in more delinquent acts than Caucasian youth did. However, service use decreased the likelihood of engaging in more delinquent acts for African Americans. Additional efforts are needed to illuminate and address the contextual and organizational barriers to delivering effective mental health services as a strategy to reduce racial disparities in delinquent behavior.

Consistency with evidence-based treatments and perceived effectiveness of children's community-based care.

This study examined whether delivery of psychotherapeutic strategies consistent with common elements of evidence-based (EB) treatments for child disruptive behavior problems was associated with parents' report of treatment effectiveness. The intensity of delivery of practice elements consistent with EB treatments was coded from a random sample of 538 videotaped psychotherapy sessions with 157 children/families and 75 therapists from six community-based clinics. Multilevel regression analyses tested whether intensity of EB practice elements was associated with parents' report of treatment effectiveness after 4 months, controlling for intensity of other practice elements. Results indicate parents reported greater perceived treatment effectiveness when community-based treatment included more intensive delivery of practice elements consistent with EB treatments to children. These findings may reassure providers about the acceptability of EB practice elements and may motivate efforts to integrate EB practice elements more intensively into community-based care.

Inter-organizational collaboration in the implementation of evidence-based practices among public agencies serving abused and neglected youth.

This study examined the role of inter-organizational collaboration in implementing new evidence-based practices for addressing problem behaviors in at-risk youth. Semi-structured interviews were conducted with 38 systems leaders of probation, mental health, and child welfare departments of 12 California counties participating in a large randomized controlled trial to scale-up the use of Multidimensional Treatment Foster Care. Three sets of collaboration characteristics were identified: (1) characteristics of collaboration process, (2) characteristics of the external environment, and (3) characteristics of participating organizations and individuals. Inter-organizational collaboration enables an exchange of information and advice and a pooling of resources individual agencies may require for successful implementation.

Do Ethnic Identity, Familial, and Community Contexts Impact the Association Between Adverse Life Events and Psychopathology Among Latinx Adolescents?

OBJECTIVE: Few studies have explored the interplay of how individual identity, parental, familial, and contextual factors impact associations between Latinx adolescent adversities and psychopathology. This study aimed to examine whether these factors mediate the relationship between adversities and psychopathology in Latinx youth. METHOD: Latinx youth (n = 2,411) data from the Adolescent Brain Cognitive Development (ABCD) Study were used to examine path models with adverse childhood experiences (ACEs) as the predictor and either youth- or caregiver-rated internalizing/externalizing scores over 4 timepoints as the outcome (ages 9-13 years). Models examined 3 potential mediators: (1) ethnic identity, (2) familial context (comprising parental monitoring, family conflict, and caregiver acceptance), and (3) community cohesion. Models were conducted separately for internalizing and externalizing symptoms. RESULTS: Greater adversity was associated with greater youth- and caregiver-rated internalizing/externalizing psychopathology over time. Greater adversity was associated with lower family functioning and lower ethnic identity, and greater family functioning was associated with lower psychopathology. Family functioning mediated associations between adversity and psychopathology over time (youth-reported internalizing: 95% CI = 0.012-0.019; youth-reported externalizing: 95% CI = 0.020-0.028). In contrast, there was not strong evidence for ethnic identity and community cohesion mediating associations between adversities and psychopathology over time. CONCLUSION: Unlike previous studies, ethnic identity did not influence the relationship between ACEs and psychopathology over time. Additional research is needed to identify whether possible tensions rise as Latinx youth acculturate into US culture and achieve optimal levels of ethnic identity formation. Providers need to assess specific Latinx parental and familial contexts that may interfere with youth identity formation.

Tobacco use behavior among adults exposed to cumulative adverse childhood experiences: A systematic review and meta analysis.

BACKGROUND: Tobacco use remains one of the most used substances among adults globally and substantially impacts individuals and society. Adverse childhood experiences (ACEs) contribute to tobacco use. However, the association between cumulative ACEs and tobacco use behaviors (TUB) has not been established in the literature. In this review, we aimed to estimate the prevalence of ACEs among adult tobacco users and evaluated the relationship between cumulative ACEs and TUB. METHODS: We identified original articles published before October 2022 by searching PubMed, CINAHL, and Psych INFO databases. Inclusion criteria were: English language, adults and used instruments assessing for cumulative ACEs defined as four or more ACEs. RESULTS: Forty-two studies, totaling 674,087 participants; predominantly cohort and cross-sectional in study design (n = 33). Exposure to 4 ≥ ACEs was significantly associated with increasing the odds of current tobacco use (n = 35), ever or former tobacco use (n = 13), tobacco use initiation, (n = 3) nicotine dependence (n = 1), and ever using electronic cigarettes (n = 1). In the meta-analysis, as compared to those without ACEs, those with 4 ≥ ACEs were twice as likely to have ever used tobacco (OR = 2.16, 95 %CI:1.73-2.70) and approximately four times more likely to have used tobacco currently (OR = 3.73, 95 %CI:2.69-5.18). CONCLUSION: The cumulative ACEs exposure can increase the risk for TUB. However, the evidence is limited primarily to cigarette use. Ongoing research into the effects of cumulative ACEs on TUB is needed to integrate trauma-informed intervention in treating tobacco use and guide public health initiatives aimed to reduce the prevalence of ACEs and TUB among adults.

A qualitative study of end-stage liver disease and liver transplant referral practices among primary care providers in nonurban America.

PURPOSE: In rural America, the road to obtaining a liver transplant (LTX) often starts at the primary care provider's (PCP's) office. Patients with end-stage liver disease (ESLD) in rural communities experience lower rates of wait-listing and higher mortality. This study identifies issues related to the knowledge and perceptions of ESLD and LTX referral among PCPs in rural Kentucky (KY). METHODS: The study protocol involved relying upon a semistructured outline to explore the knowledge, attitude, and perceptions of PCPs toward ESLD and LTX referral among PCPs in rural KY. Inductive thematic analysis was utilized to identify, analyze, and report themes. FINDINGS: From the focus group interviews, three themes were identified: medical culture, gaps in knowledge, and bias against those with self-induced causes of ESLD. Each theme illuminated barriers to referral for transplant evaluation. CONCLUSIONS: Knowledge gaps, attitudes in medical culture, and biases surrounding ESLD and LTX referral exist in community medicine practice. This highlights the importance of education, resources, and facilitation of LTX referral processes for PCPs.

Leaving no-one behind in the workplace health promotion: towards regulatory equity in the Ecuadorian micro-enterprises.

The purpose of workplace public health programmes and regulations is to promote safety and health for the entire working population nationwide. Some countries limit the scope of such programmes to medium or big-sized companies, leaving out small and micro-enterprises, thus discriminating against many workers exposed to risks. This Viewpoint aims to identify inequalities in occupational health generated by the new Regulation for Workplace Health Promotion (WHP) in Ecuador. We showed how the regulation excludes all micro-enterprises and displayed the essential role of micro-enterprises in the business fabric and the Ecuadorian labour market. More than 93% of the registered companies are micro-enterprises and these include more than 25% of the employees in the formal economy. Integrating occupational health into the public health system will require deep analysis to improve protection for the working population.

Fatal work accidents in Ecuador from 2014 to 2020: How the age of the deceased worker relates to the accidents' temporal and geographical characteristics.

This article analyzes the relationship between the age of male workers deceased in work accidents and temporal (year, month, day of the week, working shifts), geographic (provinces), and economic sector characteristics in which the accidents occurred in Ecuador between 2014 and 2020. Available data on fatal accidents from the Ecuadorian Social Security Institute (IESS) were collected. The results, which report both frequencies and proportions (rates), indicate that fatal accidents have decreased in the period, although the average age of deceased workers has increased. No significant differences were found regarding the month, day of the week, and work shift, nor in the frequency of accidents or the age of the deceased workers. However, differences were found in terms of geographical areas and sectors of economic activity. This study contributes to the literature as it is the first to analyze the temporal and geographical characteristics of fatal accidents about the age of the deceased worker.

Area-socioeconomic disparities in mental health service use among children involved in the child welfare system.

Relying on data from a nationally representative sample of youth involved in the child welfare system (CWS) in 1999-2000 (the National Survey of Child and Adolescent Well-Being, Cohort 1) and 2008-2009 (Cohort 2), this study implemented a diverse set of disparity indicators to estimate area-socioeconomic disparities in mental health (MH) services use and changes in area-socioeconomic disparities between the two cohorts. Our study found that there are area-socioeconomic disparities in MH service use, indicating that the rates of MH service use among youth referred to the CWS differ by area-socioeconomic positions defined by county-level poverty rates. We also found that area-socioeconomic disparities increased over time. However, the magnitude of the increase varied widely across disparity measures, suggesting that there are different conclusions about the trend and magnitude of area-socioeconomic disparities, depending upon which disparity measures are implemented. A greater understanding of the methodological differences among disparity measures is warranted, which will in turn impact how interventions are designed to reduce socioeconomic disparities among children in the CWS.

Adverse childhood experiences among youth reported to child welfare: Results from the national survey of child & adolescent wellbeing.

The negative influence of adverse childhood experiences (ACEs) on social, emotional, and behavioral (SEB) outcomes are well documented. However, no research to date has examined the effect of ACEs on SEB outcomes in youth who received mental health services after reporting to the child welfare system. This study's analyses of data from the National Survey of Child and Adolescent Well-Being II revealed that the most prevalent ACEs included hospitalization for a medical condition, neglect, and exposures to domestic and community violence. Logistic regression of this data showed that the odds of being diagnosed with internalizing problems increased with age and when sexual abuse was reported. The results also showed that compared to Caucasian youth, Latinos were less likely to be diagnosed with externalizing behaviors, even when sexual abuse had been reported. Contrary to one of this study's hypotheses, mental health service use within the past 18 months increased the odds of being diagnosed with SEB problems. These findings highlight the persistence of SEB problems despite receipt of mental health services. Future research should assess the impact of interventions that aim to mitigate poor SEB outcomes due to ACEs, especially sexual abuse.

Measuring Racial/Ethnic Disparities in Mental Health Service Use Among Children Referred to the Child Welfare System.

This study aims to compare different approaches to measuring racial/ethnic disparities in mental health (MH) service use among a nationwide representative sample of children referred to the child welfare system and compare the magnitude and direction of potential disparities in MH service use over time. Using data from the National Survey of Child and Adolescent Well-Being, six summary measures of disparity were implemented to quantify racial/ethnic disparities in MH service use. This study found that youth of color were less likely than their White counterparts to receive MH services. This racial/ethnic disparity was found to increase over time; however, the magnitude of the increase varied considerably across disparity measures. In addition, the estimated increases in disparity were even greater when the sample was limited to youth in need of MH services. This study shows that the same data may produce different magnitudes of disparity, depending on which metric is implemented and whether MH need is accounted for. A greater understanding of and justification for selection of methods to examine MH disparities among child welfare researchers and policy makers is warranted.

Pérdidas laborales asociadas a la mortalidad por lesiones en accidentes de tránsito: estimaciones provinciales de ecuador / Labor productivity losses associated with road traffic injury fatalities: Provincial estimates of Ecuador

RESUMEN Objetivo Estimar los años potenciales de vida perdidos (APVP) y los años potenciales de vida laboral perdidos (APVLP) en la población en edad laboral asociados a los fallecimientos prematuros por lesiones en accidentes de tránsito para las 24 provincias de Ecuador. Métodos Se emplearon fuentes de información estadística (registro de defunciones CIE-10 V01 a V89 y censo poblacional) para estimar los APVP y APVLP en edades laborales (15 a 64 años de edad) por sexo y provincias. Además, se calcularon la tasa cruda y específica (edades laborales) y la edad media (IC95%). Resultados La mayoría de las muertes en edad laboral por lesiones en accidentes tránsito estuvo en hombres con edades jóvenes y en las provincias de las regiones amazónica (Orellana y Sucumbíos) y la costa del Pacífico del país (Los Ríos). El número de APVLP se estima en 69 314 años, mientras que los APVP asciende a 94 567 años, las provincias de Guayas y Pichincha acumulan la mayor cantidad de APVP y APVLP. Conclusiones Los años perdidos estimados por muertes prematuras por esta causa representan un problema de salud pública y un importante coste laboral para el desarrollo del país. Los resultados encontrados refuerzan la necesidad de intensificar la mejora de programas y actuaciones públicas en seguridad vial.

ABSTRACT Objetive To estimate the potential years of life lost (YPLL) and the potential years of wor-king life lost (YPPLL) in the working-age population associated with premature deaths from injuries in traffic accidents for the 24 provinces of Ecuador. Methods Statistical information sources (ICD-10 V01 to V89 death registry and population census) were used to estimate the YPLL and YPPLL for working ages (15 to 64 years of age) by sex and provinces. Additionally, the crude and specific rate (working ages) and the mean age (95% CI) were calculated. Results Most deaths of working age for injuries in traffic accidents was in men younger ages and in the provinces of the Amazon regions (Orellana and Sucumbíos) and the Pacific coast of the country (Los Ríos). The number of YPLL is estimated at 69,314 years, while the YPPLL amounts to 94,567 years, the provinces of Guayas and Pichincha accumulate the highest amount of YPLL and YPPLL. Conclusions Estimated lost years for this cause premature deaths represent a public health problem and a major labor cost for the development of the country. The results reinforce the need to strengthen public programs and improve road safety performances.

Synthesis, characterization and antiproliferative behavior of tricarbonyl complexes of rhenium(I) with some 6-amino-5-nitrosouracil derivatives: crystal structure of fac-[ReCl(CO)3(DANU-N5,O4)] (DANU=6-amino-1,3-dimethyl-5-nitrosouracil).

New complexes of rhenium(I) with some 5-nitrosopyrimidines with general formula [ReCl(CO)3L] have been prepared and characterized by elemental analysis, conductivity measurements, IR and 1H, 13C and 15N NMR spectroscopic methods. The complexes appear to be monomeric and the pyrimidine ligands act in a neutral form. The structure of [ReCl(CO)3(DANU)].CH3CN has been solved by X-ray diffraction. The coordination environment around the Re(I) may be described as a distorted octahedron in which the ligand behaves in a bidentate fashion through N5 and O4 atoms, making a five-membered chelate ring. The coordination sphere is completed with three carbonyl groups in fac-arrangement and one chlorine atom. The evaluation of the antiproliferative behavior against five human tumor cell lines (human breast cancer MCF-7 and EVSA-T, human neuroblastoma NB69, human glioma H4 and human bladder carcinoma cell line ECV) suggested a modulator behavior of cell growth at low concentrations due to their estrogenic-like characteristics.

Structural and theoretical studies on rhodium and iridium complexes with 5-nitrosopyrimidines. Effects on the proteolytic regulatory enzymes of the renin-angiotensin system in human tumoral brain cells.

The reactions of [RhCl(CO)(PPh3)2], [RhCl(CO)2]2 and [IrCl(CO)(PPh3)2] with different 5-nitrosopyrimidines afforded sixteen complexes which have been structurally characterized by elemental analysis, IR and NMR ((1)H and (13)C) spectral methods and luminescence spectroscopy. The crystal and molecular structures of [Rh(III)Cl(VIOH-1)2(PPh3)], [Rh(III)Cl(DVIOH-1)2(PPh3)] and [Rh(II)(DVIOH-1)2(PPh3)2] have been established from single crystal x-ray structure analyses. The three complexes are six-coordinated with both violurato ligands into an equatorial N5,O4-bidentate fashion, but with different mutually arrangements. Theoretical studies were driven on the molecular structure of [Rh(III)Cl(VIOH-1)2(PPh3)] to assess the nature of the metal-ligand interaction as well as the foundations of the cis-trans (3L-2L) isomerism. An assortment of density functional (SOGGA11-X, B1LYP, B3LYP, B3LYP-D3 and wB97XD) has been used, all of them leading to a similar description of the target system. Thus, a topological analysis of the electronic density within AIM scheme and the study of the Mulliken charges yield a metal-ligand link of ionic character. Likewise, it has been proved that the cis-trans isomerism is mainly founded on that metal-ligand interaction with the relativistic effects playing a significant role. Although most of the compounds showed low direct toxicity against the human cell lines NB69 (neuroblastoma) and U373-MG (astroglioma), they differently modify in several ways the renin-angiotensin system (RAS)-regulating proteolytic regulatory enzymes aminopeptidase A (APA), aminopeptidase N (APN) and insulin-regulated aminopeptidase (IRAP). Therefore, these complexes could exert antitumor activity against both brain tumor types, acting through the paracrine regulating system mediated by tissue RAS rather than exerting a direct cytotoxic effect on tumor cells.

Sistema de indicadores de morbilidad y mortalidad por accidentes de tráfico: una revisión sistemática / System of morbidity and mortality indicators for traffic accidents: a systematic review

RESUMEN Objetivo Elaborar un sistema de indicadores de morbilidad y mortalidad por accidentes de tráfico, con el fin de mejorar los procesos de recopilación y registro de la información de seguridad vial en el país. Materiales y Métodos Revisión sistemática cualitativa de artículos científicos publicados en revistas indexadas en las principales bases de datos (Scopus, PubMed, Lilacs, SciELO, Google Scholar), sobre accidentes de tráfico desde el año 1995 hasta el año 2015. La información recolectada pasó por 4 fases de revisión. Resultados Se seleccionaron 84 indicadores, agrupados en nueve dimensiones: accidentalidad, morbilidad, mortalidad, temporalidad, geoespacial, sociodemográfica, parque vehicular, impacto en salud pública, tipos y causas. Conclusiones Una gestión eficaz sobre seguridad vial exige que cada país cuente con un sistema de indicadores efectivo e institucionalizado que permita recolectar, analizar y gestionar la información de forma rápida y oportuna, enmarcada en el campo de la investigación científica, para difundir a la comunidad y organismos responsables de la seguridad vial, con miras a la adopción de medidas preventivas y correctivas. Por lo que, se recomienda a los organismos competentes de seguridad vial del país incorporar el sistema de indicadores elaborado en la presente investigación, lo cual permitirá contar con un sistema de registro de datos confiables.

ABSTRACT Objective Prepare a system of morbidity and mortality indicators for traffic accidents, to propose its implementation in Ecuador, in order to improve the processes for collecting and recording road safety information in the country. Materials and Methods Qualitative systematic review of scientific articles published in journals indexed in the main databases (Scopus, PubMed, Lilacs, SciELO, Google Scholer), on traffic accidents from 1995 to 2015. The information collected went through 4 phases review. Results 84 indicators were selected, grouped into nine dimensions: accident rate, morbidity, mortality, temporality, geospatial, socio-demographic, vehicle fleet, impact on public health, types and causes. Conclusions An effective management of road safety requires that each country have an effective and institutionalized system of indicators that allows the collection, analysis and management of information in a fast and timely manner, framed in the field of scientific research, to disseminate to the community and organizations. responsible for road safety, with a view to adopting preventive and corrective measures. Therefore, it is recommended that the competent road safety agencies of the country incorporate the system of indicators developed in this research, which will allow them to have a reliable data registration system.

Diseño y validación de un cuestionario para el diagnóstico de riesgos psicosociales en empresas ecuatorianas / Design and validation of a questionnaire for the diagnosis of psychosocial risks in Ecuatorian companies

OBJETIVO: presentar el diseño, construcción y validación de un cuestionario para el diagnóstico de riesgos psicosociales en Ecuador, conformado por 58 ítems que evalúan el riesgo psicosocial a través de 8 dimensiones. Diseño: estudio transversal en 2 fases: (i) diseño del marco conceptual y construcción del cuestionario y; (ii) valoración de la validez y consistencia interna aplicado en una muestra de 3.225 trabajadores de empresas ecuatorianas. Resultados: El cuestionario posee una alta fiabilidad en términos de consistencia interna (Alfa de Cronbach = 0,968) y una adecuación satisfactoria de los datos a la matriz factorial (KMO = 0,980; Bartlett = 93818,0, <0,05). Conclusiones: se recomienda el uso de este cuestionario como instrumento para el diagnóstico preliminar, permitiendo el diseño e implementación de futuros programas de prevención de riesgos psicosociales en empresas de más de 10 trabajadores en el país.

Abstract: Objective: to present the design, construction and validation of a questionnaire for the diagnosis of psychosocial risks in Ecuador, consisting of 58 items that assess psychosocial risk through 8 dimen sions. Design: cross-sectional study in 2 phases: (i) design of the conceptual framework and construction of the questionnaire and; (ii) assessment of the validity and internal consistency applied to a sample of 3.225 workers from ecuadorian companies. Results: The questionnaire has a high reliability in terms of internal consistency (Cronbach's alpha = 0,968) and a satisfactory adaptation of the data to the factorial matrix (KMO = 0,980; Bartlett = 93818,0, <0,05). Conclusions: the use of this questionnaire is recommended as an instrument for preliminary diagnosis, allowing the design and imple mentation of future psychosocial risk prevention programs in com panies with more than 10 workers in the country.

Antiproliferative effects of palladium(II) complexes of 5-nitrosopyrimidines and interactions with the proteolytic regulatory enzymes of the renin-angiotensin system in tumoral brain cells.

Seventeen new palladium(II) complexes of general formulaes PdCl2L, PdCl(LH-1)(solvent) and PdCl2(PPh3)2L containing pyrimidine ligands derived from 6-amino-5-nitrosouracil and violuric acid have been prepared and characterized by elemental analysis, IR and NMR ((1)H and (13)C) methods and, two of them, PdCl(DANUH-1)(CH3CN)]·½H2O and [PdCl(2MeOANUH-1)(CH3CN)] by X-ray single-crystal diffraction (DANU: 6-amino-1,3-dimethyl-5-nitrosouracil; 2MeOANU: 6-amino-2-methoxy-5-nitroso-3H-pyrimidin-4-one). The coordination environment around palladium is nearly square planar in the two compounds with different supramolecular arrangements. Crystallographic and spectral data are consistent with a bidentate coordination mode through N5 and O4 atoms when the ligands act in neutral form and N5 and N6 atoms in the monodeprotonated ones. The cytotoxicity of the complexes against human neuroblastoma (NB69) and human glioma (U373-MG) cell lines has been tested showing a considerable antiproliferative activity. Also, the study of the effects of palladium(II) complexes on the renin-angiotensin system (RAS) regulating proteolytic regulatory enzymes aminopeptidase A (APA), aminopeptidase N (APN) and insulin-regulated aminopeptidase (IRAP) shows a strong dependence on the compound tested and the tumoral cell type, also affecting different catalytic routes; the compounds affect in a different way the activities of enzymes of the RAS system, changing their functional roles as initiators of cell proliferation in tumors as autocrine/paracrine mediators.