Firework injuries remain high in years after legalisation: its impact on children.

PURPOSE: We evaluated the impact of Senate Bill 489 passed in May 2017, allowing the sale and use of fireworks in Iowa 1 June to 8 July and 10 December to 3 January, on hospital presentations for firework injuries in the state. To identify the public health implications of this law, we conducted a detailed subanalysis of hospital presentations to the two level I trauma centres. METHODS: Hospital presentations for firework injuries from 1 June 2014 to 31 July 2019 were identified using the Iowa Hospital Admission database and registries and medical records of Iowa's two level 1 trauma centres. Trauma centres' data were reviewed to obtain demographics, injury information and hospital course. Prefirework and postfirework legalisation state data were compared using negative binomial regression analysis. Trauma centre data detailing injuries were compared using χ2 and Mann-Whitney U tests as appropriate. RESULTS: Emergency department (ED) visits and hospital admissions for firework injuries increased in Iowa post-legalisation (B-estimate=0.598±0.073, p<0.001 and B-estimate=0.612±0.322, p=0.058, respectively). ED visits increased postlegalisation in July (73.6% vs 64.5%; p=0.008), reflecting an increase in paediatric admissions (81.8% vs 62.5%; p=0.006). Trauma centres' data showed similar trends. The most common injury site across both study periods was the hands (48.5%), followed by the eyes (34.3%) and face (28.3%). Amputations increased from 0 prelegalisation to 16.2% postlegalisation. CONCLUSION: Firework legalisation led to an increase in the number of admissions and more severe injuries.

High flow nasal cannula outside the ICU provides optimal care and maximizes hospital resources for patients with multiple rib fractures.

BACKGROUND: High flow nasal cannula (HFNC) use reduces work of breathing and improves oxygenation for patients with hypoxemic respiratory failure. Limited prior work has explored protocolized use of HFNC for trauma patients outside the Intensive Care Unit (ICU). The purpose of this study is to describe and evaluate use of HFNC for patients with rib fractures when therapy was standard of care on all floors of the hospital. METHODS: In 2018, the study hospital expanded use of HFNC (AIRVO; Fisher Paykel, Auckland, NZ) to all floors of the hospital, making it available in the ICU, Emergency Department (ED), and on general inpatient floors. The study group included adult patients with three or more rib fractures who received HFNC at any location in the hospital (Phase 2: January 2018-December 2019). The study group was compared to a historical control group when HFNC was available only in the ICU (Phase 1: March 2013-July 2015). Patients were excluded from the study if they received invasive mechanical ventilation prior to HFNC. Primary outcomes were mechanical ventilation rates, ICU days, length of hospitalization, and mortality. RESULTS: During the study period, 63 patients received HFNC, with 35% of patients (n = 22) receiving the duration of therapy outside the ICU. When compared to the control group (N = 63), there were no significant differences in total hospital days (9 vs. 9, p=.64), mechanical ventilation (19% vs. 13%, p=.47), or mortality (3% vs. 5%, p = 1.00). Twenty-seven percent of patients (n = 17) in the study group avoided the ICU during hospitalization. CONCLUSIONS: Findings suggest that HFNC therapy can be safely initiated and managed on all hospital floors for patients with multiple rib fractures. Making the therapy available outside the ICU may reduce healthcare resource use without adversely affecting patient outcomes.

Comparison between Two Molecular Techniques: Nested and Real-Time Polymerase Chain Reaction Targeting 100-kDa Hc Protein for Detection of Histoplasma capsulatum in Environmental Samples.

Histoplasmosis, one of the most frequent endemic mycoses in the Americas, is caused by the inhalation of airborne conidia of Histoplasma capsulatum. Better understanding of the distribution of this fungus in the environment is important for the development of appropriate public health measures to prevent human infections. Previously, we used Hc100 nested polymerase chain reaction (PCR) to identify H. capsulatum DNA in 10% of environmental samples in Colombia. Here, we validate a 100-kDa real-time PCR assay for the detection of this fungus in the environment. Using this method, we identified H. capsulatum DNA in 80% of samples of raw organic materials, such as chicken manure, soil from caves, and bird and bat guano, as well as in 62% of samples of organic fertilizer that underwent the composting process. We demonstrated that 100-KDa real-time PCR is a useful tool for environmental surveillance that can be used to identify the potential reservoirs of H. capsulatum and to prevent outbreaks, especially in people with the higher risk of exposure, such as spelunkers, farmers, poultry manure collectors, and anyone who handle organic fertilizers or bat and bird excreta.

Hemorrhage Control Training: Preparing Adolescents to Act at Home, at School, or in Public.

OBJECTIVES: Uncontrolled bleeding is the leading cause of preventable death after a traumatic event, and early intervention to control bleeding improves opportunities for survival. It is imperative to prepare for local and national disasters by increasing public knowledge on how to control bleeding, and this preparation should extend to both adults and children. The purpose of this study is to describe a training effort to teach basic hemorrhage control techniques to early adolescent children. METHODS: The trauma and emergency departments at a combined level I adult and level II pediatric trauma center piloted a training initiative with early adolescents (grades 6-8) focused on 2 skills: packing a wound and holding direct pressure, and applying a Combat Application Tourniquet. Students were evaluated on each skill and completed presurveys and postsurveys indicating their likelihood to use the skills. RESULTS: Of the 194 adolescents who participated in the trainings, 97% of the students could successfully pack a wound and hold pressure, and 97% of the students could apply a tourniquet. Before the training, 71% of the adolescents indicated that they would take action to assist a bleeding victim; this increased to 96% after the training. CONCLUSIONS: Results demonstrate that basic hemorrhage control skills can be effectively taught to adolescents as young as 6th grade (ages 11-12 years) in a small setting with age-appropriate content and hands-on opportunities to practice the skills and such training increases students' perceived willingness to take action to assist a bleeding victim.

Trauma Response for Elderly Anticoagulated Patients: An Initiative to Reduce Trauma Resource Utilization in the Emergency Department.

BACKGROUND: Trauma centers are challenged to have appropriate criteria to identify injured patients needing a trauma activation; one population that is difficult to triage is injured elderly patients taking anticoagulation or antiplatelet (ACAP) medications with suspected head injury. OBJECTIVE: The study purpose was to evaluate a hospital initiative to improve the trauma triage response for this population. METHODS: A retrospective study at a Level I trauma center evaluated revised trauma response criteria. In Phase 1 (June 2017 to April 2018; n = 91), a limited activation occurred in the trauma bay for injured patients 55 years and older, taking ACAP medications with evidence of head injury. In Phase 2 (June 2018 to April 2019; n = 142), patients taking ACAP medications with evidence of head injury received a rapid emergency department (ED) response. Primary outcomes were timeliness of ED interventions and hospital admission rates. Differences between phases were assessed with Kruskal-Wallis tests. RESULTS: An ED rapid response significantly reduced trauma team involvement (100%-13%, p < .001). Compared with Phase 1, patients in Phase 2 were more frequently discharged from the ED (48% vs. 68%, p = .003), and ED disposition decision was made more quickly (147 vs. 120 min, p = .01). In Phase 2, time to ED disposition decision was longer for patients who required hospital admission (108 vs. 179 min, p < .001); however, there were no significant differences between phases in reversal intervention (6% vs. 11%, p = .39) or timeliness of reversal intervention (49 vs. 118 min, p = .51). CONCLUSION: The ED rapid response delivered safe, timely evaluation to injured elderly patients without overutilizing trauma team activations.

Platelet Reactivity Testing for Aspirin Patients Who Sustain Traumatic Intracranial Hemorrhage.

BACKGROUND: Patients who take aspirin and sustain traumatic intracranial hemorrhage (tICH) are often transfused platelets in an effort to prevent bleeding progression. The efficacy of platelet transfusion is questionable, however, and some medical societies recommend that platelet reactivity testing (PRT) should guide transfusion decisions. The study hypothesis was that utilization of PRT to guide platelet transfusion for tICH patients suspected of taking aspirin would safely identify patients who did not require platelet transfusion. METHODS: This was a retrospective study of patients with blunt tICH who received PRT for known or suspected aspirin use between June 2014 and December 2017 at a level I trauma center. Chart abstraction was conducted to determine home aspirin status, and PRT values were used to classify patients as therapeutic or nontherapeutic on aspirin. Differences were assessed with Kruskal-Wallis and chi-square tests. RESULTS: 157 patients met study inclusion criteria, and 118 (75%) patients had documented prior aspirin use. PRT results were available approximately 1.7 h (IQR: 0.9, 3.2) after arrival. Upon initial PRT, 70% of patients were considered inhibited and 88% of those patients had aspirin documented as a home medication. Conversely, 18% of patients with home aspirin use had normal platelet reactivity. Clinically significant worsening of the tICH did not significantly differ when comparing those who received platelet transfusion with those who did not (8% versus 7%, P = 0.87). CONCLUSIONS: Platelet reactivity testing can detect platelet inhibition related to aspirin and should guide transfusion decisions for head injured patients in the initial hours after trauma.

Implementation of High-Flow Nasal Cannula Therapy Outside the Intensive Care Setting.

BACKGROUND: High-flow nasal cannula (HFNC) is an option for respiratory support in patients with acute hypoxic respiratory failure. To improve patient outcomes, reduce ICU-associated costs, and ease ICU bed availability, a multi-phased, comprehensive strategy was implemented to make HFNC available outside the ICU under the supervision of pulmonology or trauma providers in cooperation with a dedicated respiratory therapy team. The purpose of this study was to describe the education and implementation process for initiating HFNC therapy outside the ICU and to convey key patient demographics and outcomes from the implementation period. METHODS: HFNC therapy was implemented at a tertiary hospital in the Midwest, with systematic roll-out to all in-patient floors over a 9-month period. Utilization of the therapy and patient outcomes were tracked to ensure safety and efficacy of the effort. RESULTS: During the implementation period, 346 unique subjects met study inclusion criteria. Median (interquartile range) hospital length of stay was 8 d (4-12), and median duration of HFNC therapy was 44 h (18-90). Two thirds of subjects (n = 238) received the entire course of HFNC therapy outside the ICU, and more than half of subjects (n = 184) avoided the ICU for their entire hospitalization. Moreover, 6% of subjects in the study group escalated from HFNC to noninvasive ventilation, and 5% of subjects escalated from HFNC to mechanical ventilation. CONCLUSIONS: A comprehensive implementation process and a robust therapy protocol were integral to initiating and managing HFNC in all hospital locations. Study findings indicate that patients with acute hypoxic respiratory failure can safely receive HFNC therapy outside the ICU with appropriate patient selection and staff education.

Molecular epidemiology of Colombian Histoplasma capsulatum isolates obtained from human and chicken manure samples.

The thermally dimorphic fungus Histoplasma capsulatum is the causative agent of histoplasmosis, one of the most prevalent endemic mycosis in the Americas. In tropical regions, agro-ecosystems require organic matter replacement, therefore, the use of organic fertilizers has increased disregarding the fact that certain number of such fertilizers might be contaminated with the fungus, and with their handling resulting in human cases and even outbreaks of histoplasmosis. Additionally, in Colombia, chicken manure is the most common raw material used in the production of organic fertilizers. In this work, we reported the isolation of this fungus from chicken manure, and genetically compared with 42 clinical isolates. The genetically compared environmental isolates grouped together with the clinical ones. Our result suggests that chicken manure may be one of H. capsulatum infection sources. Also, the phylogenetic analyses done with other H. capsulatum isolates indicate that the Colombian isolates are widely distributed in the relational tree thus reveling towards the great genetic diversity among the H. capsulatum Colombian isolates.

Who Hurts More? A Multicenter Prospective Study of In-Hospital Opioid Use in Pediatric Trauma Patients in the Midwest.

BACKGROUND: Despite increased national attention on misuse of prescription and nonprescription opioids for adolescents and children, little is known about opioid use in a pediatric population during hospitalization for injury. The purpose of this investigation is to describe opioid administration and magnitude of opioid exposure in the first 48 hours of hospitalization in a pediatric trauma population. STUDY DESIGN: This is a secondary analysis of data collected for a randomized, prospective intervention study at 4 Midwestern children's trauma centers. Participants included children ages 10 to 17 years old, admitted to the hospital for unintentional injury. Descriptive statistics and multivariable modeling were used to characterize demographic factors and measure prevalence and magnitude of opioid use within the first 48 hours of hospitalization. RESULTS: Among 299 participants, 82% received at least 1 opioid administration. Children had increased odds of receiving an opioid (odds ratio [OR] 4.25; 95% CI 2.16 to 8.35) for every log increase of Injury Severity Scores (ISS), yet the majority of children with minor injury (61%) also received an opioid. Children with fractures and older children had higher odds of receiving an opioid. Amount of opioid, expressed as morphine milligrams equivalent (MME), significantly increased with child age, ISS, and fracture. CONCLUSIONS: Most pediatric trauma patients received an opioid in the first 48 hours of hospitalization, although prevalence and exposure varied by age, injury, and acuity. Aggressive pain management can be appropriate for injured pediatric patients; however, study results indicate areas for improvement, specifically for children with minor injuries and those receiving excessive opioid amounts.

Not all head injured patients on antiplatelet drugs need platelets: Integrating platelet reactivity testing into platelet transfusion guidelines.

INTRODUCTION: Antiplatelet medication use continues to rise in an aging population, and these agents can have a deleterious effect for patients with traumatic intracranial hemorrhage (tICH). The purpose of the current investigation is to assess the safety and efficacy of using platelet reactivity testing (PRT) to direct platelet transfusion for tICH patients. PATIENTS AND METHODS: A Level I trauma center adopted a targeted platelet transfusion guideline using PRT to determine whether platelets were inhibited by an antiplatelet medication (aspirin or P2Y12 inhibitors). Non-inhibited patients were monitored without platelet transfusion, regardless of severity of the head injury. The guideline was analyzed retrospectively to evaluate patient outcomes during the study period (June 2014-December 2016). All patients sustained blunt tICH and received a PRT for known or suspected antiplatelet medication use. Differences were assessed with Kruskal-Wallis and Fisher's Exact tests. RESULTS: 166 patients met study inclusion criteria. PRT results indicated that 48 patients (29%) were not inhibited by an antiplatelet medication, and 92% of those patients (n = 44) were spared platelet transfusion. Seven percent (n = 11) of all patients had a clinically significant progression of the head bleed, but this did not differ by inhibition or transfusion status. Implementation of this guideline reduced platelet transfusions by an estimated 30-50% and associated healthcare costs by 42%. CONCLUSIONS: A targeted platelet transfusion guideline using PRT reduced platelet usage for patients with tICH. If appropriately tested, results suggest that not all tICH patients taking or suspected of taking antiplatelet drugs need platelet transfusion. Platelet reactivity testing can significantly reduce healthcare costs and resource usage.

The Acute Upper Gastrointestinal Bleed.

Upper gastrointestinal bleeding (UGIB), defined as intraluminal hemorrhage proximal to the ligament of Treitz, can range from mild and asymptomatic to massive life-threatening hemorrhage. For the purposes of this article, the authors define an acute UGIB to be one that results in new acute symptoms and is, therefore, potentially life-threatening. UGIB requires a systematic approach to evaluation and treatment, similar to the management of a trauma patient. Surgeon involvement in UGIBs remains integral despite the rare need for operative management. Endoscopy is the primary tool for diagnosis and treatment.

Head CT before Transfer Does Not Decrease Time to Craniotomy for TBI Patients.

Rural trauma education emphasizes that radiologic imaging should be discouraged if it delays transfer to definitive care. With increased capacity for image sharing, however, radiography obtained at referring hospitals (RH) could help providers at trauma centers (TC) prepare for patients with traumatic brain injury. We evaluated whether a head CT prior to transfer accelerated time to neurosurgical intervention at the TC. The study was conducted at a combined adult Level I and pediatric Level II TC with a catchment area that includes rural hospitals within a 150 mile radius. The trauma registry was used to identify patients with traumatic brain injury who went to surgery for a neurosurgical procedure immediately after arrival at the TC. All patients were transferred in from a RH. Differences between groups were assessed using analysis of variance and chi-square. Fifty-six patients met study criteria during the study period (2010-2015). The majority (86%) of patients received head CT imaging at the RH, including a significant percentage of patients (18%) who presented with GCS ≤8. There was no statistically significant decrease in time to surgery when patients received imaging at the RH. CT imaging was associated with a delay in transfer that exceeded 90 minutes. Findings demonstrate that imaging at the RH delayed transfer to definitive care and did not improve time to neurosurgical intervention at the TC. Transfer to the TC should not be obstructed by imaging, especially for patients with severe TBI.

Detection of Histoplasma capsulatum in Organic Fertilizers by Hc100 Nested Polymerase Chain Reaction and Its Correlation with the Physicochemical and Microbiological Characteristics of the Samples.

Histoplasma capsulatum is the causative agent of histoplasmosis and this fungus inhabits soils rich in phosphorus and nitrogen that are enriched with bird and bat manure. The replacement of organic matter in agroecosystems is necessary in the tropics, and the use of organic fertilizers has increased. Cases and outbreaks due to the presence of the fungus in these components have been reported. The Instituto Colombiano Agropecuario resolution 150 of 2003 contains the parameters set by the Colombian Technical Standard (NTC 5167) on the physicochemical and microbiological features of fertilizers, but it does not regulate the search for H. capsulatum. The aim of this study was to demonstrate H. capsulatum presence in organic fertilizers by nested polymerase chain reaction (PCR). A total of 239 samples were collected: 201 (84.1%) corresponded to organic fertilizers, 30 (12.5%) to bird excrement, and 8 (3.4%) to cave soils. The Hc100 nested PCR had a detection limit of 0.1 pg/µL and a specificity of 100%. A total of 25 (10.5%) samples were positive and validated by sequencing. Seven of the positive samples represented locations where H. capsulatum was previously detected, suggesting the persistence of the fungus. No significant correlations were detected between the physicochemical and microbiological parameters with the presence of H. capsulatum by nested PCR, indicating the fungus existence in organic fertilizers that complied with the NTC 5167. The Hc100 nested PCR targeting H. capsulatum standardized in this work will improve the evaluation of organic fertilizers and ensure the prevention of outbreaks and cases due to manufacturing, marketing, and use of fertilizers contaminated with H. capsulatum.

Efficient Hemorrhage Control Skills Training for Healthcare Employees.

BACKGROUND: Several national initiatives are aimed at training citizens to assist bleeding victims. The purpose of this study was to evaluate an effort to quickly and efficiently teach basic bleeding control techniques to a clinical and nonclinical workforce. STUDY DESIGN: The research study was conducted at 4 hospitals in a mid-sized metropolitan area. In spring 2017, the trauma department at a Level I trauma center set an ambitious goal to provide hands-on training to 1,000 employees during the course of 6 weeks. Trainings occurred in small groups and lasted approximately 6 to 10 minutes, during which time participants were taught and practiced 2 skills: packing a wound and holding direct pressure, and applying a stretch-wrap-and-tuck tourniquet. Participants completed pre- and post-surveys indicating their likelihood to use these skills. RESULTS: More than 1,000 individuals were trained, and there were survey data for 870 participants. More than 40% of participants worked in nonclinical roles and 29% had no first aid or medical training. After completing skills training, 98% of participants indicated that they would be likely to take action to assist a bleeding victim and that they could correctly apply direct pressure or a tourniquet to control severe bleeding. CONCLUSIONS: Results demonstrate that basic hemorrhage control skills can be taught to clinical and nonclinical people in brief, hands-on training. Efforts like this can be deployed across large workplace environments to prepare the maximum number of employees to take action to assist bleeding victims.

Asymptomatic cervical spine fractures: Current guidelines can fail older patients.

BACKGROUND: Older adults represent a growing proportion of trauma patients treated in the United States, and cervical spine (c-spine) fracture is an injury that is increasingly common in this population. Neck pain is a major component of current clinical clearance guidelines, but some older adults with c-spine fractures report no neck pain after injury. The objective of this study was to investigate the frequency at which c-spine fractures were unassociated with neck pain in an aging population. METHODS: A retrospective review was performed for patients 55 years or older with a c-spine fracture during a 4-year study period. All patients had a Glasgow Coma Scale score of 15 and were considered asymptomatic if they did not complain of neck pain on initial presentation, denied tenderness to palpation of the c-spine on examination, and were without neurologic deficit. Differences between groups were assessed with Kruskal-Wallis and χ tests. RESULTS: Of 173 patients with c-spine fractures, 36 (21%) were asymptomatic and reported no neck pain on presentation or on examination. The group without neck pain had higher median injury severity scores (15 vs 10; p < 0.001), were more likely to have another injured body region (69% vs 42%; p = 0.004), and had longer hospitalization (7 vs 5 days; p = 0.008) than patients with neck pain. Twenty-two percent of the symptomatic group and 19% of the asymptomatic group required halo, fusion, or other surgical intervention. DISCUSSION: Study results indicate that one fifth of patients with a c-spine fracture reported no pain on initial presentation and denied tenderness to palpation on examination. The presence or absence of pain may be an unreliable indicator of c-spine fracture in an aging population. When used in conjunction with existing clearance guidelines, denial of pain may lead to missed injury. We recommend liberal c-spine imaging for older trauma patients with significant mechanism of trauma. LEVEL OF EVIDENCE: Therapeutic study, level III.

Murine invariant natural killer T cells recognize glycolipids derived from extracts of the lichen Stereocaulon ramulosum / Células T asesinas naturales invariantes murinas reconocen glicolipidos derivados de extractos del liquen Stereocaulon ramulosum

Background: Invariant natural killer T cells (iNKT) can be activated by certain types of glycolipids that have the potential to generate adjuvant effects which could be used to develop effective and safe immunotherapies. Many of these glycolipids have been isolated from natural organisms, but there is a great amount of these organisms completely unexplored as a source of these types of compounds. Some of these organisms are lichens which are complex symbiotic organisms that have been showed to contain glycolipids. Objectives: We decide to test if glycolipids isolated from lichens would be able to activate iNKT cells in vitro and in vivo. Methods: We have used extracted glycolipids from 43 different species of lichens from Colombia. We have used iNKT hybridoma cells, C57BL/6 mice, IL-2 ELISA and the B16 melanoma to test for the adjuvant capabilities of glycolipids isolated from lichens. Results: In this study we have found two glycolipids with the capacity to activate iNKT cells in vivo. One of the glycolipids was able to activate iNKT cells in vivo, and was competent to induce protection against the B16 melanoma in the mouse model. Conclusions: We propose a possible chemical structure for a novel glycolipid called ß-GalCer-lich (1) derived from the lichen Stereocaulon ramulosum.

Antecedentes: Las células asesinas naturales T (iNKT) pueden ser activadas por ciertos tipos de glicolípidos que tienen el potencial para generar efectos adyuvantes los cuales pueden ser usados para desarrollar inmunoterapias efectivas. Muchos de estos glicolípidos han sido aislados de organismos naturales, pero hay una gran cantidad de organismos completamente inexplorados como fuente de este tipo de compuestos. Algunos de estos organismos son los líquenes, los cuales son organismos simbiontes complejos para los que se ha mostrado que contienen glicolípidos. Objetivos: Nosotros decidimos probar si los glicolípidos aislados de líquenes podrían ser capaces de activar alas celulas iNKT in vitro e in vivo. Metodos: Nosotros hemos extraído glicolípidos de 43 especies de líquenes de Colombia. Nosotros hemos usado células de un hibridoma de iNKTs, ratones C57BL/6, ELISA para IL-2 y el melanoma B16 para probar la capacidad adyuvante de los glicolipidos aislados de los líquenes. Resultados: En este estudio nosotros hemos encontrado dos glicolípidos con la capacidad de activar iNKTs in vitro. Uno de los glicolípidos fue capaz de activar células iNKT in vivo, y fue competente para inducir protección contra el melanoma B16 en el modelo de ratón. Conclusiones: Nosotros proponemos una posible estructura química para el nuevo glicolípido llamado ß-GalCer-lich (1) derivado del liquen Stereocaulon ramulosum.

Interacciones genotóxicas de mutágenos en mezclas binarias mediante ensayo cometa alcalino en linfocitos humanos / Interaction of mutagens in binary mixtures using the alkaline comet assay in human lymphocytes

Introducción. Los mutágenos contenidos en mezclas complejas presentan interacciones de sinergismo, aditivas o antagónicas. Se han desarrollado enfoques experimentales que permitan dilucidar el responsable de las interacciones en la mezcla. Objetivo. Desarrollar un diseño experimental para comprender los procesos que se llevan a cabo entre los compuestos presentes en las mezclas complejas. Materiales y métodos. Se expusieron linfocitos humanos a mezclas binarias de mutágenos B[a]P, DMBA, Trp-P-1 y MX durante una hora, con activación metabólica y sin ella. La viabilidad se evaluó con azul de tripano y, la genotoxicidad, con cometa alcalino. Resultados. Ningún hidrocarburo tuvo efecto con furanona. Con S9 y sin él, se observó que se presentaban interacciones tóxicas entre hidrocarburos. Se observó sinergismo sin S9 entre B[a]P y Trp-P-1 y, con actividad metabólica, entre DMBA y Trp-P-1. Sin S9 se observó interacción antagónica entre Trp-P-1 y DMBA y, con S9, entre Trp-P-1 y MX y entre MX y DMBA. Se observó un incremento dependiente de la dosis en la longitud de la cola. Hubo daño genotóxico medio y aumento de las células dañadas. Para todas las mezclas se pudo determinar la concentración mínima en la que se observaban efectos adversos y solo para algunas se determinó la concentración máxima en la cual no se observaron efectos adversos. Conclusión. Se hace un aporte para comprender los procesos que ocurren cuando en una mezcla hay presentes, al menos, dos mutágenos y se valida un modelo de análisis que permite dilucidar el compuesto que tiene efecto sobre otro. También, se demostró que según el tipo de compuestos en la mezcla, se tendrá o no un umbral de riesgo.

Introduction. Mutagens contained in complex mixtures can present synergistic interactions, either additive or antagonistic. Therefore, development of experimental approaches is necessary to elucidate which is the responsible agent for the effect in the mixtures. Objective. An experimental design was developed that allowed an understanding of the processes between the compounds of complex mixtures. Materials and methods. Human lymphocytes were exposed to binary mixtures of the mutagens B[a]P, DMBA, Trp-P-1 and MX for 1 hour with or without S9. Viability was assessed with trypan blue dye and the genotoxicity by the comet assay. Results. All of the hydrocarbon showed an effect with furanone. With and without S9, the most toxic interactions were observed between hydrocarbons. Synergistic interaction was observed without S9 between B [a] P and Trp-P-1 and between DMBA and Trp-P-1 with metabolic activity. Without S9 antagonistic interaction was observed only between Trp-P-1+DMBA, and with S9 between Trp-P-1+MX and MX+DMBA. It observed an increase dose dependent in tail length. Half the cultures showed genotoxic damage and increased cell damage. For each mixture, minimum concentrations were determined at which adverse effects are observed; for some only the maximum concentration was determined at which no adverse effects are observed. Conclusion. The processes between mutagens present in a mixture have become better understood, and the results validated an analytical model that determined which component had an effect on another. The results also showed that the type of compounds in the mixture determined whether or not a risk threshold was present.

[Interaction of mutagens in binary mixtures using the alkaline comet assay in human lymphocytes]. / Interacciones genotóxicas de mutágenos en mezclas binarias mediante ensayo cometa alcalino en linfocitos humanos.

INTRODUCTION: Mutagens contained in complex mixtures can present synergistic interactions, either additive or antagonistic. Therefore, development of experimental approaches is necessary to elucidate which is the responsible agent for the effect in the mixtures. OBJECTIVE: An experimental design was developed that allowed an understanding of the processes between the compounds of complex mixtures. MATERIALS AND METHODS: Human lymphocytes were exposed to binary mixtures of the mutagens B[a]P, DMBA, Trp-P-1 and MX for 1 hour with or without S9. Viability was assessed with trypan blue dye and the genotoxicity by the comet assay. RESULTS: All of the hydrocarbon showed an effect with furanone. With and without S9, the most toxic interactions were observed between hydrocarbons. Synergistic interaction was observed without S9 between B [a] P and Trp-P-1 and between DMBA and Trp-P-1 with metabolic activity. Without S9 antagonistic interaction was observed only between Trp-P-1+DMBA, and with S9 between Trp-P-1+MX and MX+DMBA. It observed an increase dose dependent in tail length. Half the cultures showed genotoxic damage and increased cell damage. For each mixture, minimum concentrations were determined at which adverse effects are observed; for some only the maximum concentration was determined at which no adverse effects are observed. CONCLUSION: The processes between mutagens present in a mixture have become better understood, and the results validated an analytical model that determined which component had an effect on another. The results also showed that the type of compounds in the mixture determined whether or not a risk threshold was present.

Human monocyte differentiation stage affects response to arachidonic acid.

AA-induced cell death mechanisms acting on human monocytes and monocyte-derived macrophages (MDM), U937 promonocytes and PMA-differentiated U937 cells were studied. Arachidonic acid induced apoptosis and necrosis in monocytes and U937 cells but only apoptosis in MDM and U937D cells. AA increased both types of death in Mycobacterium tuberculosis-infected cells and increased the percentage of TNFalpha+ cells and reduced IL-10+ cells. Experiments blocking these cytokines indicated that AA-mediated death was TNFalpha- and IL-10-independent. The differences in AA-mediated cell death could be explained by high ROS, calpain and sPLA-2 production and activity in monocytes. Blocking sPLA-2 in monocytes and treatment with antioxidants favored M. tuberculosis control whereas AA enhanced M. tuberculosis growth in MDM. Such evidence suggested that AA-modulated effector mechanisms depend on mononuclear phagocytes' differentiation stage.