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In Costa Rica, a land tax valuation model provided by the Technical Standardization Body (ONT) of the Ministry of Finance is used. This model considers homogeneous areas that include properties with similar characteristics and review factors that have not been recently updated. The objective of this article is to determine the effect of the distance to the train station and mobile coverage on the value of land in Oreamuno, Costa Rica, as a proposal to be included in the mass valuation model of the ONT. A multiple regression econometric model was used to establish the functional relationship between the value of the property and its characteristics, through the Ordinary Least Squares (OLS) method, using 10 variables applied to 200 references initially. The results allow demonstrating that other variables such as “Distance to the train station” and “Mobile coverage” are representative for determining the value of properties, in addition to those commonly used by the ONT model. The research allows concluding that the land valuation models should be updated periodically and should include variables related to improvements in technology and access roads, since these increase the market value of properties and improve the social development of localities in study.

Black broom (Sarothamnus scoparius) is a bush that grows abundantly in the region of Extremadura. The potential use of this lignocellulosic material as raw material for the preparation of activated carbon by physical activation is investigated. The activated carbons are characterised by means of chemical analysis, N2 adsorption at 77 K, mercury porosimetry and helium and mercury densities. It has been observed that the activation in CO2 atmosphere leads to better textural properties than those obtained when air was used as activating agent. The effects of the activation procedure on the textural properties of the samples are favoured with the increase in the activation temperature.La retama negra (Sarothamnus scoparius) es un arbusto que crece en forma abundante en la región extremeña. En el presente estudio se investiga su posible utilización como material de partida en la preparación de carbón activado. Ésta se lleva a cabo por el método de activación física. Los carbones son caracterizados mediante análisis químico, adsorción de N2 a 77 K, porosimetría de mercurio y medida de densidades por desplazamiento de helio y de mercurio. Se ha constatado que activando en CO2 se preparan carbones activados que poseen unas mejores propiedades texturales que los obtenidos utilizando aire. Los efectos de la activación sobre las propiedades texturales de los carbones se favorecen con la subida de la temperatura de activación.

El pasado 27 de octubre falleció Clemencia, su muerte prematura para lo que hubiésemos deseado; reiteró nuevamente cómo cada ser humano tiene su propio camino, ya corto, ya extenso y durante el debe construir su historia y su legado para la sociedad. Obtuvo su título de licenciada en enfermería en 1969 en la Pontificia Universidad Javeriana y desde entonces trasegó con el ejercicio de la enfermería; práctica que fue asumida por Clemencia con responsabilidad, compromiso, entereza, calidad y visión futurista.

La conmemoración de los 75 años de creación del primer programa de enfermería vinculado con la Universidad Nacional de Colombia se convierte en momento ideal para la reflexión en torno a su discurrir histórico, a los compromisos actuales y al futuro deseable para nuestra facultad. Dado que en esta ponencia es imposible presentar de manera profunda y detallada todas las etapas de desarrollo; se desarrollará un resumen muy general de algunos apartes de la historia; situación que le imprime a esta primera parte del trabajo un carácter de generalización y por ello se apreciará la ausencia de algunos elementos que en cada momento han sido significativos. En la segunda parte del trabajo se presentará, también de manera general, el plan de desarrollo que se encuentra en proceso de construcción en la facultad, el que se ha de constituir en el documento orientador de nuestro trabajo para los próximos años.

Hoy en día la enfermería tiene el reto de seguir construyéndose en el ámbito profesional y disciplinar, dejando atrás el sello tradicional de lo femenino para continuar su proceso de desarrollo y cambio en términos de su propia esencia; el cuidado de la salud y de la vida del ser humano.

Son múltiples los factores que se han vinculado con el desarrollo de la profesión de enfermería, tanto en su desempeño como en la formación académica, en cada momento histórico en particular. La estructura económico- política, las organizaciones de poder, los conflictos nacionales e internacionales, los papeles del género femenino y de clase social, los avances científicos, tecnológicos y técnicos, el sistema educativo y sanitario, las diferentes categorías socio-profesionales y las propias metas de desarrollo de la profesión han sido determinantes en la evolución que hasta el momento actual ha logrado nuestra profesión.

La reseña de la carrera se presenta en dos momentos históricos. El primero, desde su vinculaci6n a la Universidad como programa anexo a la Facultad de Medicina y el segundo, a partir de la Facultad de Enfermería, hasta la fecha.

Abstract Background Elucidating the activation pattern of molecular pathways across a given tumour type is a key challenge necessary for understanding the heterogeneity in clinical response and for developing novel more effective therapies. Gene expression signatures of molecular pathway activation derived from perturbation experiments in model systems as well as structural models of molecular interactions ("model signatures") constitute an important resource for estimating corresponding activation levels in tumours. However, relatively few strategies for estimating pathway activity from such model signatures exist and only few studies have used activation patterns of pathways to refine molecular classifications of cancer. Methods Here we propose a novel network-based method for estimating pathway activation in tumours from model signatures. We find that although the pathway networks inferred from cancer expression data are highly consistent with the prior information contained in the model signatures, that they also exhibit a highly modular structure and that estimation of pathway activity is dependent on this modular structure. We apply our methodology to a panel of 438 estrogen receptor negative (ER-) and 785 estrogen receptor positive (ER+) breast cancers to infer activation patterns of important cancer related molecular pathways. Results We show that in ER negative basal and HER2+ breast cancer, gene expression modules reflecting T-cell helper-1 (Th1) and T-cell helper-2 (Th2) mediated immune responses play antagonistic roles as major risk factors for distant metastasis. Using Boolean interaction Cox-regression models to identify non-linear pathway combinations associated with clinical outcome, we show that simultaneous high activation of Th1 and low activation of a TGF-beta pathway module defines a subtype of particularly good prognosis and that this classification provides a better prognostic model than those based on the individual pathways. In ER+ breast cancer, we find that simultaneous high MYC and RAS activity confers significantly worse prognosis than either high MYC or high RAS activity alone. We further validate these novel prognostic classifications in independent sets of 173 ER- and 567 ER+ breast cancers. Conclusion We have proposed a novel method for pathway activity estimation in tumours and have shown that pathway modules antagonize or synergize to delineate novel prognostic subtypes. Specifically, our results suggest that simultaneous modulation of T-helper differentiation and TGF-beta pathways may improve clinical outcome of hormone insensitive breast cancers over treatments that target only one of these pathways.

Objective: Lipoprotein (a) [Lp(a)] is a causal, genetically-inherited risk amplifier for atherosclerotic cardiovascular disease (ASCVD). Practice guidelines increasingly recommend broad Lp(a) screening among various populations to optimize preventive care. Corresponding changes in testing rates and population-level detection of elevated Lp(a) in recent years has not been well described., Methods: Using Veterans Affairs electronic health record data, we performed a retrospective cohort study evaluating temporal trends in Lp(a) testing and detection of elevated Lp(a) levels (defined as greater than 50 mg/dL) from January 1, 2014 to December 31, 2023 among United States Veterans without prior Lp(a) testing. Testing rates were stratified based on demographic and clinical factors to investigate possible drivers for and disparities in testing: age, sex, race and ethnicity, history of ASCVD, and neighborhood social vulnerability., Results: Lp(a) testing increased nationally from 1 test per 10,000 eligible Veterans (558 tests) in 2014 to 9 tests per 10,000 (4,440 tests) in 2023, while the proportion of elevated Lp(a) levels remained stable. Factors associated with higher likelihood of Lp(a) testing over time were a history of ASCVD, Asian race, and residing in neighborhoods with less social vulnerability., Conclusion: Despite a 9-fold increase in Lp(a) testing among US Veterans over the last decade, the overall testing rate remains extremely low. The steady proportion of Veterans with elevated Lp(a) over time supports the clinical utility of testing expansion. Efforts to increase testing, especially among Veterans living in neighborhoods with high social vulnerability, will be important to reduce emerging disparities as novel therapeutics to target Lp(a) become available., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Alexander Sandhu, Fatima Rodriguez, Novartis employees Anthony Lozama and Jonathan Ward reports financial support was provided by Novartis Pharmaceuticals Corporation. This work was supported by 10.13039/100004336Novartis Pharmaceutical Corporation. Mr. Ward and Doctor Lozama are employees of Novartis Pharmaceutical Corporation. Dr. Sandhu is supported by 10.13039/100000050NHLBI and AHA. He also receives research funding from Reprieve Cardiovascular and has done consulting for Lexicon Pharmaceuticals. Dr. Rodriguez reports equity from Carta Healthcare and HealthPals, and consulting fees from HealthPals, Novartis, NovoNordisk, Esperion Therapeutics, Movano Health, Kento Health, Inclusive Health, Edwards, Arrowhead Pharmaceuticals, and HeartFlow outside the submitted work. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier B.V.)

Background: Large-scale data on incidental premature ventricular contraction (PVC) prevalence and morphologies have been lacking, leaving many providers without guidance on further cardiac testing for patients with incidental PVCs on ECG. Athletes offer an intriguing cohort to understand the clinical significance, prevalence, and common morphologies of incidental PVCs because they often undergo ECG screening during preparticipation exams., Methods: Digital ECGs were obtained from 10 728 screened athletes aged 14 to 35 years during mass screenings in schools and professional sports teams between 2014 and 2021. A retrospective analysis of ECGs with PVCs was performed using the simultaneous display of frontal (limb) and horizontal (precordial) plane leads. PVCs were coded for morphology and categorized as benign or nonbenign using recommended criteria., Results: Twenty-six athletes (0.24%) were found to have at least 1 PVC. Among these, 50% were female, 65% were White, 8% were Asian, 4% were Hispanic, and 23% were Black. Nineteen of the 26 (73%) ECGs had PVCs with a left bundle branch block pattern compared with 7 (27%) with a right bundle branch block pattern. Twenty-four ECGs (96%) had PVCs with benign patterns, including 18 with right ventricular outflow tract, 5 with left anterior fascicle, and 2 with left posterior fascicle morphology., Conclusions: There is a low prevalence of PVCs on routine ECG screening of young athletes, and most PVCs are of benign morphology in this population. This study highlights the value of using digital ECG recorders with simultaneous lead display to guide decision-making about further cardiac testing and referrals in young athletes with PVCs. Using our results and review of the literature, we propose methods and algorithms of PVC evaluation on screening ECGs to help guide many providers with risk stratification and decision-making about further cardiac testing and electrophysiology referrals in young athletes with PVCs., Competing Interests: Dr Perez is a consultant for Apple, Inc, Boston Scientific, Janssen, Bristol Myers Squibb, and Thryv, Inc, and has an ownership interest in QALY, Inc. Dr Wheeler had prior consulting income from BioTelemetry. Dr Hadley is employed by Cardiac Insight. Dr Froelicher was contracted by Cardiac Insight to develop patch interpretation software. The other authors report no conflicts.

Background: Frequent premature ventricular contractions (PVCs) and nonsustained ventricular tachycardia (NSVT) have been associated with cardiovascular disease and mortality. Their prevalence, especially in ambulatory populations, is understudied and limited by few female participants and the use of short-duration (24- to 48-hour) monitoring., Objective: The objective of this study was to report the prevalence of frequent PVCs and NSVT in a community-based population of women likely to undergo electrocardiogram (ECG) screening by sequential patch monitoring., Methods: Participants from the Women's Health Initiative Strong and Healthy (WHISH) trial with no history of atrial fibrillation (AF) but 5-year predicted risk of incident AF ≥5% by CHARGE-AF score were randomly selected to undergo screening with 7-day ECG patch monitors at baseline, 6 months, and 12 months. Recordings were reviewed for PVCs and NSVT (>5 beats); data were analyzed with multivariate regression models., Results: There were 1067 participants who underwent ECG screening at baseline, 866 at 6 months, and 777 at 12 months. Frequent PVCs were found on at least 1 patch from 4.3% of participants, and 1 or more episodes of NSVT were found in 12 (1.1%) women. PVC frequency directly correlated with CHARGE-AF score and NSVT on any patch. Detection of frequent PVCs increased with sequential monitoring., Conclusion: In postmenopausal women at high risk for AF, frequent PVCs were relatively common (4.3%) and correlated with higher CHARGE-AF score. As strategies for AF screening continue to evolve, particularly in those individuals at high risk of AF, the prevalence of incidental ventricular arrhythmias is an important benchmark to guide clinical decision-making., Competing Interests: Disclosures Dr Perez is a consultant for Apple Inc, Boston Scientific, Janssen, Bristol Myers Squibb, and Thryv Inc and has ownership interest in QALY, Inc. Dr Wheeler had prior consulting income from BioTelemetry. Dr Froelicher has stock interest in Cardiac Insight (electrocardiographic patch company employed in this study) and is contracted by Cardiac Insight to develop patch interpretation software. The remaining authors have no disclosures., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Atherosclerotic cardiovascular (CV) disease (ASCVD) prevention encompasses interventions across the lifecourse: from primordial to primary and secondary prevention. Primordial prevention begins in childhood and involves the promotion of ideal CV health (CVH) via optimizing physical activity, body mass index, blood glucose levels, total cholesterol levels, blood pressure, and sleep while minimizing tobacco use. Primary and secondary prevention of ASCVD thereafter centers around mitigating ASCVD risk factors via medical therapy and lifestyle interventions. Disparities in optimal preventive efforts exist among historically marginalized groups in each of these three prongs of ASCVD prevention. Children and adults with a high burden of social determinants of health also face inequity in preventive measures. Inadequate screening, risk factor management and prescription of preventive therapeutics permeate the care of certain groups, especially women, Black, and Hispanic individuals in the United States. Beyond this, individuals belonging to historically marginalized groups also are much more likely to experience other ASCVD risk-enhancing factors, placing them at higher risk for ASCVD over their lifetime. These disparities translate to worse outcomes, with higher rates of ASCVD and CV mortality among these groups. Possible solutions to promoting equity involve community-based youth lifestyle interventions, improved risk-factor screening, and increasing accessibility to healthcare resources and novel preventive diagnostics and therapeutics., Competing Interests: Declaration of competing interest FR reports consulting relationships with Healthpals, Novartis, Amgen, NovoNordisk (CEC), and Movano Health., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Tyrosine kinase inhibitors (TKIs) are widely used in the treatment of hematologic malignancies. Limited studies have shown an association between treatment-limiting arrhythmias and TKI, particularly ibrutinib, a Bruton's tyrosine kinase (BTK) inhibitor. We sought to comprehensively assess the arrhythmia burden in patients receiving ibrutinib vs non-BTK TKI vs non-TKI therapies., Methods: We performed a retrospective analysis of consecutive patients who received long-term cardiac event monitors while on ibrutinib, non-BTK TKIs, or non-TKI therapy for a hematologic malignancy between 2014 and 2022., Results: One hundred ninety-three patients with hematologic malignancies were included (ibrutinib = 72, non-BTK TKI = 46, non-TKI therapy = 75). The average duration of TKI therapy was 32 months in the ibrutinib group vs 64 months in the non-BTK TKI group (p = 0.003). The ibrutinib group had a higher prevalence of atrial fibrillation (n = 32 [44%]) compared to the non-BTK TKI (n = 7 [15%], p = 0.001) and non-TKI (n = 15 [20%], p = 0.002) groups. Similarly, the prevalence of non-sustained ventricular tachycardia was higher in the ibrutinib group (n = 31, 43%) than the non-BTK TKI (n = 8 [17%], p = 0.004) and non-TKI groups (n = 20 [27%], p = 0.04). TKI therapy was held in 25% (n = 18) of patients on ibrutinib vs 4% (n = 2) on non-BTK TKIs (p = 0.005) secondary to arrhythmias., Conclusions: In this large retrospective analysis of patients with hematologic malignancies, patients receiving ibrutinib had a higher prevalence of atrial and ventricular arrhythmias compared to those receiving other TKI, with a higher rate of treatment interruption due to arrhythmias., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Tyrosine kinase inhibitors (TKIs) have been increasingly used as first-line therapy in hematologic and solid-organ malignancies. Multiple TKIs have been linked with the development of cardiovascular complications, especially atrial arrhythmias, but data on ventricular arrhythmias (VAs) is scarce., Methods: Herein we describe five detailed cases of VAs related to TKI use in patients with varied baseline cardiovascular risk factors between 2019 and 2022 at three centers. Individual chart review was conducted retrospectively., Results: Patient ages ranged from 43 to 83 years. Three patients were on Bruton's TKI (2 ibrutinib and 1 zanubrutinib) at the time of VAs; other TKIs involved were afatinib and dasatinib. Three patients had a high burden of non-sustained ventricular tachycardia (NSVT) requiring interventions, whereas two patients had sustained VAs. While all patients in our case series had significant improvement in VA burden after TKI cessation, two patients required new long-term antiarrhythmic drug therapy, and one had an implantable defibrillator cardioverter (ICD) placed due to persistent VAs after cessation of TKI therapy. One patient reinitiated TKI therapy after control of arrhythmia was achieved with antiarrhythmic drug therapy., Conclusions: Given the expanding long-term use of TKIs among a growing population of cancer patients, it is critical to acknowledge the association of TKIs with cardiovascular complications such as VAs, to characterize those at risk, and deploy preventive and therapeutic measures to avoid such complications and interference with oncologic therapy. Further efforts are warranted to develop monitoring protocols and optimal treatment strategies for TKI-induced VAs., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Atrial fibrillation (AF) affects around 6 million Americans. AF management involves pharmacologic therapy and/or interventional procedures to control rate and rhythm, as well as anticoagulation for stroke prevention. Different populations may respond differently to distinct management strategies. This review will describe disparities in rate and rhythm control and their impact on outcomes among women and historically underrepresented racial and/or ethnic groups., Methods: This is a narrative review exploring the topic of sex and racial and/or ethnic disparities in rate and rhythm management of AF. We describe basic terminology, summarize AF epidemiology, discuss diversity in clinical research, and review landmark clinical trials., Results: Despite having higher rates of traditional AF risk factors, Black and Hispanic adults have lower risk of AF than non-Hispanic White (NHW) patients, although those with AF experience more severe symptoms and report lower quality-of-life scores than NHW patients with AF. NHW patients receive antiarrhythmic drugs, cardioversions, and invasive therapies more frequently than Black and Hispanic patients. Women have lower rates of AF than men, but experience more severe symptoms, heart failure, stroke, and death after AF diagnosis. Women and people from diverse racial and ethnic backgrounds are inadequately represented in AF trials; prevalence findings may be a result of underdetection., Conclusion: Race, ethnicity, and gender are social determinants of health that may impact the prevalence, evolution, and management of AF. This impact reflects differences in biology as well as disparities in treatment and representation in clinical trials., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Statins are the cornerstone of treatment of patients with atherosclerotic cardiovascular disease (ASCVD). Despite this, multiple studies have shown that women with ASCVD are less likely to be prescribed statins than men. The objective of this study was to use Natural Language Processing (NLP) to elucidate factors contributing to this disparity., Methods: Our cohort included adult patients with two or more encounters between 2014 and 2021 with an ASCVD diagnosis within a multisite electronic health record (EHR) in Northern California. After reviewing structured EHR prescription data, we used a benchmark deep learning NLP approach, Clinical Bidirectional Encoder Representations from Transformers (BERT), to identify and interpret discussions of statin prescriptions documented in clinical notes. Clinical BERT was evaluated against expert clinician review in 20% test sets., Results: There were 88,913 patients with ASCVD (mean age 67.8±13.1 years) and 35,901 (40.4%) were women. Women with ASCVD were less likely to be prescribed statins compared with men (56.6% vs 67.6%, p <0.001), and, when prescribed, less likely to be prescribed guideline-directed high-intensity dosing (41.4% vs 49.8%, p <0.001). These disparities were more pronounced among younger patients, patients with private insurance, and those for whom English is their preferred language. Among those not prescribed statins, women were less likely than men to have statins mentioned in their clinical notes (16.9% vs 19.1%, p <0.001). Women were less likely than men to have statin use reported in clinical notes despite absence of recorded prescription (32.8% vs 42.6%, p <0.001). Women were slightly more likely than men to have statin intolerance documented in structured data or clinical notes (6.0% vs 5.3%, p =0.003)., Conclusions: Women with ASCVD were less likely to be prescribed guideline-directed statins compared with men. NLP identified additional sex-based statin disparities and reasons for statin non-prescription in clinical notes of patients with ASCVD., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests., (© 2023 The Authors. Published by Elsevier B.V.)

Background: Inflammatory cytokines play a role in atrial fibrillation (AF). Interleukin (IL)-1β, which is targeted in the treatment of ischemic heart disease, has not been well-studied in relation to AF., Methods: Postmenopausal women from the Women's Health Initiative were included. Cox proportional hazards regression models were used to evaluate the association between log-transformed baseline cytokine levels and future AF incidence. Models were adjusted for body mass index, age, race, education, hypertension, diabetes, hyperlipidemia, current smoking, and history of coronary heart disease, congestive heart failure, or peripheral artery disease., Results: Of 16,729 women, 3,943 developed AF over an average of 8.5 years. Racial and ethnic groups included White (77.4%), Black/African-American (16.1%), Asian (2.7%), American Indian/Alaska Native (1.0%), and Hispanic (5.5%). Baseline IL-1β log continuous levels were not significantly associated with incident AF (HR 0.86 per 1 log [pg/mL] increase, P= .24), similar to those of other inflammatory cytokines, IL-7, IL-8, IL-10, IGF-1, and TNF-α. There were significant associations between C-reactive protein (CRP) and IL-6 with incident AF., Conclusions: In this large cohort of postmenopausal women, there was no significant association between IL-1β and incident AF, although downstream effectors, CRP and IL-6, were associated with incident AF., Competing Interests: Conflict of interest None reported., (Copyright © 2023 Elsevier Inc. All rights reserved.)

There is a growing body of literature focusing on the morphology, management, and outcomes of PVCs in athletes. This review summarizes this literature and establishes recommendations on management, treatment, and indications for specialist referral in this patient population. The sports medicine physician's responses and recommendation should be made in conjunction with the athletes wishes. Medications or ablations are not always necessary in all athletes if they are followed with regular evaluations., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose of Review: Racial, ethnic, and gender disparities in cardiovascular care are well-documented. This review aims to highlight the disparities and impact on a group particularly vulnerable to disparities, women from racial/ethnic minority backgrounds., Recent Findings: Women from racial/ethnic minority backgrounds remain underrepresented in major cardiovascular trials, limiting the generalizability of cardiovascular research to this population. Certain cardiovascular risk factors are more prevalent in women from racial/ethnic minority backgrounds, including traditional risk factors such as hypertension, obesity, and diabetes. Female-specific risk factors including gestational diabetes and preeclampsia as well as non-traditional psychosocial risk factors like depressive and anxiety disorders, increased child care, and familial and home care responsibility have been shown to increase risk for cardiovascular disease events in women more so than in men, and disproportionately affect women from racial/ethnic minority backgrounds. Despite this, minimal interventions to address differential risk have been proposed. Furthermore, disparities in treatment and outcomes that disadvantage minority women persist. The limited improvement in outcomes over time, especially among non-Hispanic Black women, is an area that requires further research and active interventions., Summary: Understanding the lack of representation in cardiovascular trials, differential cardiovascular risk, and disparities in treatment and outcomes among women from racial/ethnic minority backgrounds highlights opportunities for improving cardiovascular care among this particularly vulnerable population., Competing Interests: Conflict of InterestFatima Rodriguez was funded by a career development award from the National Heart, Lung, and Blood Institute (K01 HL 144607) and the American Heart Association/Robert Wood Johnson Harold Amos Medical Faculty Development Program. Sujana Balla declares that she has no conflict of interest. Sofia Elena Gomez declares that she has no conflict of interest., (© Springer Science+Business Media, LLC, part of Springer Nature 2020.)

The detection of DNA radicals by immuno-spin trapping (IST) is based on the trapping of radicals with 5,5-dimethyl-1-pyrroline N-oxide (DMPO), forming stable nitrone adducts that are then detected using an anti-DMPO serum. DNA radicals are very reactive species, and because they are paramagnetic they have previously been detected only by electron spin resonance (ESR) with or without spin trapping, which is not available in most bioresearch laboratories. IST combines the simplicity, reliability, specificity and sensitivity of spin trapping with heterogeneous immunoassays for the detection of DNA radicals, and complements existing methods for the measurement of oxidatively generated DNA damage. Here we have used IST to demonstrate that DMPO traps Cu(II)-H(2)O(2)-induced DNA radicals in situ and in real time, forming DMPO-DNA nitrone adducts, but preventing both 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG) formation and DNA fragmentation. We also applied IST to detect DNA radicals in rat hepatocytes exposed to Cu(II) and H(2)O(2) under nonlethal conditions.

It is well known that hydrogen peroxide (H2O2)-induced copper-catalyzed fragmentation of proteins follows a site-specific oxidative mechanism mediated by hydroxyl radical-like species (i.e. Cu(I)O, Cu(II)/*OH or Cu(III)) that ends in increased carbonyl formation and protein fragmentation. We have found that the nitrone spin trap DMPO (5,5-dimethyl-1-pyrroline N-oxide) prevented such processes by trapping human serum albumin (HSA)-centered radicals, in situ and in real time, before they reacted with oxygen. When (bi)carbonate (CO2, H2CO3, HCO3- and CO3(-2)) was added to the reaction mixture, it blocked fragmentation mediated by hydroxyl radical-like species but enhanced DMPO-trappable radical sites in HSA. In the past, this effect would have been explained by oxidation of (bi)carbonate to a carbonate radical anion (CO3*) by a bound hydroxyl radical-like species. We now propose that the CO3* radical is formed by the reduction of HOOCO2- (a complex of H2O2 with CO2) by the protein-Cu(I) complex. CO3* diffuses and produces more DMPO-trappable radical sites but does not fragment HSA. We were also able, for the first time, to detect discrete but highly specific H2O2-induced copper-catalyzed CO3*-mediated induction of DMPO-trappable protein radicals in functioning RAW 264.7 macrophages. We conclude that carbon dioxide modulates H2O2-induced copper-catalyzed oxidative damage to proteins by preventing site-specific fragmentation and enhancing DMPO-trappable protein radicals in functioning cells. The pathophysiological significance of our findings is discussed.

We reported previously that the thromboxane A(2) (TxA(2)) mimetic U-46619 stimulates cardiac vagal afferent nerves, eliciting a reflex decrease in heart rate (HR) and arterial blood pressure (ABP). The present experiments were designed to test the hypothesis that TxA(2) evokes these changes via the release of serotonin [5-hydroxytryptamine (5-HT)] and activation of the 5-HT(3) receptor. Injections of the 5-HT(3) antagonist tropisetron (1 mg of 3-tropanyl-indole-3-carboxylate or ICS-205-930) attenuated the decreases in HR and ABP induced by left atrial injections of U-46619 (20 microg). Tropisetron administration also eliminated the U-46619-induced increase in impulse frequency in a majority of cardiac, vagal afferent units tested. Measurement of serum 5-HT levels revealed an elevation in serum 5-HT levels after U-46619 injection in those rabbits that displayed a significant HR change following injection of U-46619. These results indicate that although other factors may also contribute to these reflex responses, the release of 5-HT and stimulation of the 5-HT(3) receptor plays a significant role in coronary reflexes induced by TxA(2).