Efectividad y seguridad de los nuevos anticuerpos monoclonales en la profilaxis de la migraña / Effectiveness and safety of new monoclonal antibodies in migraine prophylaxis

Objetivos: Analizar la efectividad y seguridad en vida real de los nuevos anticuerpos monoclonales subcutáneos para la profilaxis de la migraña. Métodos: Estudio observacional retrospectivo llevado a cabo desde enero de 2020 hasta abril de 2021 con pacientes diagnosticados de migraña crónica o episódica. Las variables de interés se analizaron por el personal facultativo farmacéutico en una base de datos anonimizada. Esta base se completa como práctica clínica habitual durante la entrevista clínica en la consulta de pacientes externos. Resultados: Se analizaron 53 pacientes. Se observó una reducción del número de crisis respecto al valor basal a los 3, a los 6 y a los 12 meses de tratamiento, así como de otros fármacos para el tratamiento de la migraña. La mayoría de reacciones adversas descritas fueron de tipo leve, obligando a la suspensión del tratamiento de solo uno de los pacientes. Se describió un aumento de la tensión arterial en varios pacientes, así como una incidencia de estreñimiento superior a los ensayos pivotales. Conclusiones: Este estudio muestra una disminución del número de crisis de migraña y del uso de otros fármacos antimigrañosos tras el uso de anticuerpos monoclonales. Los tratamientos se pueden considerar seguros, observándose una baja incidencia de reacciones adversas graves. La mayoría de pacientes fueron tratados con erenumab. Se dispone de menos datos a medida que avanza del tiempo de estudio, por lo que resulta necesario recopilar más información para conocer el perfil de efectividad y seguridad de estos fármacos a largo plazo.(AU)

Objectives: To analyse the effectiveness and safety in real life of new subcutaneous monoclonal antibodies for the prophylaxis of migraine. Methods: Retrospective observational study conducted from January 2020 to April 2021 with patients diagnosed with chronic or episodic migraine. The variables of interest were collected by the pharmacist in an anonymised database during the clinical interview in the outpatient clinic. This databased is completed as standard clinical practice during the clinical interview in the outpatient clinic. Results: 53 patients were analysed. A reduction in the number of attacks from baseline was observed at 3, 6 and 12 months of treatment, as well as for other migraine treatment drugs. Most of the adverse reactions described were mild, leading to discontinuation of treatment in only one patient. An increase in blood pressure was reported in several patients, as well as a higher incidence of constipation than in pivotal trials. Conclusions: This study shows a decrease in the number of migraine attacks and in the use of other anti-migraine drugs after the use of monoclonal antibodies. The treatments can be considered safe, with a low incidence of serious adverse reactions. Most patients were treated with erenumab. Less information is available as the study time progresses, so more information needs to be collected to understand the long-term effectiveness and safety profile of these drugs.(AU)

Isavuconazole-tacrolimus drug-drug interactions in HSCT patients.

OBJECTIVES: Because tacrolimus has a narrow therapeutic window and exhibits both intraindividual and interindividual variability, we attempted to establish the percentage of calcineurin inhibitor (CNI) dose reduction to prevent toxicity and ensure stem cell engraftment when using this immunosuppressant with the antifungal isavuconazole (ISA). By calculating the tacrolimus concentration/dose (C/D) ratio, we expected to demonstrate the magnitude of change in the C/D ratio from baseline after ISA administration. METHODS: We evaluated the interaction between ISA, a new triazole antifungal used in prophylaxis for invasive fungal infections, and the CNI class of immunosuppressive drugs, specifically tacrolimus, in 11 blood samples from HSCT recipients. RESULTS: The mean tacrolimus C/D ratio increased 1.44-fold from baseline 48 h after ISA administration (P = 0.001). CONCLUSIONS: Although further investigation is needed, the results of this study suggest that a reduction of 18% in tacrolimus may be recommended.

Clinical practice guidelines on leptospirosis in children 2019

Executive Summary@#Leptospirosis is a disease prevalent mostly in tropical and subtropical countries. Its potential to be a concerning problem emerges with the onset of the rainy season, as flooding and heavy rainfall facilitate disease epidemics. Among those at risk of contracting the disease are field workers, veterinarians, sewer workers, military personnel and those who swim or wade in contaminated waters. In the absence of an existing evidence-based guideline for the pediatric age group, this first edition hopes to standardize approach to diagnosis, antibiotic management, and prevention of leptospirosis. The intended users are primary care physicians, family medicine physicians, pediatricians, and other healthcare workers involved in the management of leptospirosis in children. Ten priority questions were identified by a group of experts composed of an oversight committee, a guideline writing panel, and a technical review committee. The GRADE methodology was used to determine the quality of evidence of each recommendation. The draft recommendations (summarized below) were finalized after these were presented to and voted on by a panel of stakeholders.

Bezlotoxumab en la profilaxis de la infección recurrente por Clostridium difficile. Resultados en una serie de 4 casos / Bezlotoxumab in the prophylaxis of recurrent Clostridium difficile infection. Results in a series of 4 patients

Bezlotoxumab es un fármaco usado en la prevención de recurrencias de infección por Clostridium difficile, actuando mediante su unión a la toxina B de la bacteria, produciendo su inactivación. Este tipo de infección es muy frecuente en pacientes inmunodeprimidos, los cuales suelen presentar varias recurrencias que, junto con su enfermedad de base, pueden poner en compromiso la salud e incluso la vida del paciente. El objetivo de este trabajo es evaluar la efectividad de bezlotoxumab en la prevención de recaídas de infección por Clostridium difficile en una serie de cuatro pacientes. Para ello, se recopiló la información clínica necesaria y se anonimizó la base de datos antes de su análisis. Tras el análisis de nuestra serie de datos, obtuvimos resultados positivos ya que tres de los cuatro pacientes no sufrieron episodios de recurrencias en los cuatro meses posteriores a la administración de bezlotoxumab y ninguno presentó efectos adversos o intolerancias. Un paciente falleció un mes después de la administración de bezlotoxumab debido a la situación de inmunosupresión causada por su enfermedad de base y la infección no curada de Clostridium difficile. (AU)

Bezlotoxumab is a drug used in the treatment of recurrences of Clostridium difficile infection, acting by binding to the toxin B of the bacterium, producing its inactivation. This type of infection is very common in immunocompromised patients, who usually present several recurrences that, together with their underlying disease, can compromise the health and even the patient’s life. The aim of this study is to evaluate the effectiveness of bezlotoxumab in the prevention of four patients admitted for relapses of Clostridium difficile infection after the previous therapeutic failure of other drugs such as vancomycin, metronidazole or fidaxomycin. To do this, the necessary clinical information was collected and the database was anonymized before analysis. After analyzing our data series, we obtained positive results as three of the four patients did not suffer relapse episodes in the four months after bezlotoxumab administration and none had adverse effects or intolerances. One patient died one month after administration of bezlotozumab due to immunosuppression caused by his underlying disease and uncured Clostridium difficile infection. (AU)

Setting up regional diagnostic reference levels for pediatric interventional cardiology in Latin America and the Caribbean countries: preliminary results and identified challenges.

The goal of the present study was to propose a set of preliminary regional diagnostic reference levels (DRLs) for pediatric interventional cardiology (IC) procedures in Latin America and the Caribbean countries, classified by age and weight groups. The study was conducted in the framework of the Optimization of Protection in Pediatric Interventional Radiology in Latin America and the Caribbean program coordinated by the World Health Organization and the Pan American Health Organization in cooperation with the International Atomic Energy Agency. The first step of the program was focused on pediatric IC. Dose data from diagnostic and therapeutic procedures were collected between December 2020 and December 2021. Regional DRLs were set as the third quartile of patient dose data (kerma area product) collected in 18 hospitals from 10 countries in an initial sample of 968 procedures. DRLs were set for four age bands and five weight ranges. The values obtained for the four age bands (<1 yr, 1 to <5 yr, 5 to <10 yr and 10 to <16 yr) were 2.9, 6.1, 8.8 and 14.4 Gy cm2for diagnostic procedures, and 4.0, 5.0, 10.0 and 38.1 Gy cm2for therapeutic procedures, respectively. The values obtained for the five weight bands (<5 kg, 5 to <15 kg, 15 to <30 kg, 30 to <50 kg and 50 to <80 kg) were 3.0, 4.5, 8.1, 9.2 and 26.8 Gy cm2for diagnostic procedures and 3.7, 4,3, 7.3, 16.1 and 53.4 Gy cm2for therapeutic procedures, respectively. While initial data were collected manually as patient dose management systems (DMSs) were not available in most of the hospitals involved in the program, a centralized automatic DMS for the collection and management of patient dose indicators has now been introduced and is envisaged to increase the sample size. The possibility of alerting on high dose values and introducing corrective actions will help in optimization.

Entorno inflamatorio diferencial en pacientes con osteoporosis y diabetes mellitus tipo 2 / Differential inflammatory environment in patients with osteoporosis and type 2 diabetes mellitus

Objetivo: La diabetes mellitus tipo 2 (DM2) y la osteoporosis son enfermedades asociadas con un entorno pro-inflamatorio, cuya prevención mediante nuevas estrategias terapéuticas podría evitar su desarrollo. Sin embargo, existe un escaso número de estudios que evalúen el perfil inflamatorio de la osteoporosis en pacientes con DM2.El objetivo de este estudio se centró en evaluar la respuesta inflamatoria inmunitaria mediante concentraciones séricas de nueve citocinas, dos de ellas de carácter anti-inflamatorio (IL-10, IL-5) y seis pro-inflamatorias (IL-2, IL-6, IL-12 (p70), IL-17A, TNFα e IFNɣ) en 163 individuos con DM2 y 47 controles. Una subpoblación, formada por 43 pacientes DM2 sin osteoporosis, y 33 con osteoporosis, fue analizada en más profundidad a nivel de parámetros óseos. Además, hemos evaluado las hormonas calciotropas, los marcadores de remodelado óseo, densidad mineral ósea y fracturas vertebrales en la población, y hemos analizado la relación de las citocinas ensayadas con la DM2, la osteoporosis y las fracturas vertebrales prevalentes.Los pacientes con DM2 tenían concentraciones séricas significativamente más altas de IL-10 en comparación con el grupo control (0,5±1 vs. 0,14±0,3 pg/ml; p=0,016) y los niveles de IL-12 p70 se mostraron más bajos en pacientes con DM2 respecto a los controles (2,9±1,6 vs. 3,9±3,1 pg/ml; p=0,027).En el grupo de pacientes con DM2 y osteoporosis, los niveles de la citocina IL-6 resultaron elevados respecto al grupo de DM2 sin osteoporosis (10,9±14,6 vs. 4,5±7,0; p=0,017). También se observó una asociación de IL-5, siendo sus niveles más bajos en el grupo DM2 con osteoporosis (1,7±0,2 vs. 3,8±0,6; p=0,032). Además, la IL-5 mostró una correlación directa con los niveles del biomarcador de formación ósea fosfatasa alcalina ósea (r=0,277, p=0,004) en la subpoblación de pacientes con DM2. El resto de citocinas no mostraron diferencias significativas. (AU)

Ischaemic stroke and SARS-CoV-2 infection: A causal or incidental association? / Ictus isquémico e infección por SARS-CoV-2, ¿asociación casual o causal?

INTRODUCTION: Ischaemic stroke has been reported in patients with COVID-19, particularly in more severe cases. However, it is unclear to what extent this is linked to systemic inflammation and hypercoagulability secondary to the infection. METHODS: We describe the cases of 4 patients with ischaemic stroke and COVID-19 who were attended at our hospital. Patients are classified according to the likelihood of a causal relationship between the hypercoagulable state and ischaemic stroke. We also conducted a review of studies addressing the possible mechanisms involved in the aetiopathogenesis of ischaemic stroke in these patients. RESULTS: The association between COVID-19 and stroke was probably causal in 2 patients, who presented cortical infarcts and had no relevant arterial or cardioembolic disease, but did show signs of hypercoagulability and systemic inflammation in laboratory analyses. The other 2 patients were of advanced age and presented cardioembolic ischaemic stroke; the association in these patients was probably incidental. CONCLUSIONS: Systemic inflammation and the potential direct action of the virus may cause endothelial dysfunction, resulting in a hypercoagulable state that could be considered a potential cause of ischaemic stroke. However, stroke involves multiple pathophysiological mechanisms; studies with larger samples are therefore needed to confirm our hypothesis. The management protocol for patients with stroke and COVID-19 should include a complete aetiological study, with the appropriate safety precautions always being observed.

Evaluation of methods for DNA extraction from Clostridium tyrobutyricum spores and its detection by qPCR.

Clostridium tyrobutyricum is the major agent that causes the blowing defect in cheese due to the germination of its dormant spores during the ripening stage. As a result, many of the affected cheeses show cavities and cracks, which cause the product loss in most cases. Nowadays, there is not a fast method capable of detecting milk contaminated with C. tyrobutyricum spores. The aim of this study has been to develop a fast and reliable method based on real time PCR (qPCR) to detect C. tyrobutyricum spores in raw milk. One of the main limitations has been to find a good procedure for the spore disruption to extract the DNA due to its high resistance. For this reason, different disruption methods have been tested, including chemical agents, bead beating, enzymatic and microwave treatment. Furthermore, an enzymatic treatment with subtilisin was applied for milk clarification and recovery of spores. The comparison of the assayed methods has been made using sterile milk spiked with C. tyrobutyricum spores, obtained in solid or liquid medium. The results showed that microwave treatment followed by a standard DNA purification step was found to be the best disruption method. The Ct values obtained for spores were higher than those found for vegetative cells by qPCR, for the same quantity of DNA. This difference could be due to the action of the Small Acid Soluble Proteins (SASP) in the DNA packaging of spores. Moreover, spores obtained in agar plate were found more resistant to disruption than those obtained in liquid medium. Subtilisin and microwave treatments were found to be successful for DNA extraction from C. tyrobutyricum spores in milk and subsequent identification by qPCR. However, the differences observed between the amplification of DNA from spores obtained in different media and from vegetative cells have to be taken into account to optimize a method for C. tyrobutyricum detection.

[HaNDL syndrome in a 12-year-old girl]. / Sindrome HaNDL en una niña de 12 años.

INTRODUCTION: HaNDL (headache and neurological deficits with cerebrospinal fluid lymphocytosis) syndrome is a self-limiting benign condition which, as its name suggests, causes episodes of transient neurological deficits of a motor, sensory, aphasic and, less frequently, visual nature lasting several hours, accompanied or followed by moderate-to-severe headache and lymphocytosis of the cerebrospinal fluid. Its incidence is low in adulthood, and it is extremely uncommon in the paediatric age. Recurrence of episodes usually occurs in the first three months. It has an excellent prognosis. CASE REPORT: A 12-year-old female with intense frontal headache that suddenly begins on the tenth day, with clinical signs and symptoms of dysarthria and right hemiparesis with subsequent aphasia and generalised hypotonia. After ruling out other conditions by means of complementary examinations and the clinical course, the patient was finally diagnosed with HaNDL syndrome, since it fulfilled the clinical criteria of the International Headache Society (IHS). CONCLUSIONS: The patient met the criteria established by the IHS for the diagnosis of HaNDL syndrome. The main historical, epidemiological and clinical data are analysed and the differential diagnosis of HaNDL syndrome in the paediatric age is described.

TITLE: Sindrome HaNDL en una niña de 12 años.Introduccion. El sindrome HaNDL (headache and neurologic deficits with cerebrospinal fluid lymphocytosis) es una entidad autolimitada y benigna que cursa, como su nombre indica, con aparicion de episodios de deficits neurologicos transitorios de naturaleza motora, sensitiva o afasica, y menos frecuentemente visual, de varias horas de duracion, acompañados o seguidos de cefalea moderada-grave y linfocitosis del liquido cefalorraquideo. Su incidencia es baja en la edad adulta, y casi excepcional en la edad pediatrica. La recurrencia de los episodios suele producirse en los primeros tres meses. El pronostico es excelente. Caso clinico. Mujer de 12 años con cefalea frontal intensa que inicia en el decimo dia, de forma brusca, clinica de disartria y hemiparesia derecha con posterior afasia e hipotonia generalizada. Tras descartarse mediante exploraciones complementarias y evolucion clinica otras entidades, fue finalmente diagnosticada de sindrome HaNDL, ya que cumplia los criterios clinicos de la Sociedad Internacional de Cefaleas (IHS). Conclusiones. La paciente reunio los criterios de la IHS para el diagnostico de sindrome HaNDL. Se analizan los principales datos historicos, epidemiologicos y clinicos, y se expone el diagnostico diferencial del sindrome HaNDL en la edad pediatrica.

Stroke-related mortality in a tertiary care hospital in Andalusia: Analysis and reflections. / Mortalidad asociada al ictus en un hospital andaluz de tercer nivel. Análisis y reflexiones.

OBJECTIVES: Stroke is a very common cause of death, especially in southern Spain. The present study analyses in-hospital mortality associated with stroke in an Andalusian tertiary care hospital. METHODS: We gathered the files of all patients who had died at Hospital Universitario Virgen de las Nieves in Granada in 2013 and whose death certificates indicated stroke as the cause of death. We also gathered stroke patients discharge data and compared them to that of patients with acute coronary syndrome (ACS). RESULTS: A total of 825 patients had a diagnosis of stroke (96 deaths, 11.6%); of these, 562 had ischaemic stroke (44 deaths, 7.8%) and 263 haemorrhagic stroke (52 deaths, 19.7%). Patients with haemorrhagic stroke therefore showed greater mortality rate (OR=2.9). Patients in this group died after a shorter time in hospital (median, 4 vs 7 days; mean, 6 days). However, patients with ischaemic stroke were older and presented with more comorbidities. On the other hand, 617 patients had a diagnosis of ACS (36 deaths, 5.8%). The mortality odds ratio (MOR) was 2.1 (stroke/SCA). Around 23% of the patients who died from stroke were taking anticoagulants. 60% of the deceased patients with ischaemic stroke and 20% of those with haemorrhagic stroke had atrial fibrillation (AF); 35% of the patients with ischaemic stroke and AF were taking anticoagulants. CONCLUSIONS: Stroke is associated with higher admission and in-hospital mortality rates than SCA. Likewise, patients with haemorrhagic stroke showed higher mortality rates than those with ischaemic stroke. Patients with fatal stroke usually had a history of long-term treatment with anticoagulants; 2 thirds of the patients with fatal ischaemic stroke and atrial fibrillation were not receiving anticoagulants. According to our results, optimising prevention in patients with AF may have a positive impact on stroke-related in-hospital mortality.

[Descriptive study of bone and joint infections in children in times of community-acquired methicillin- resistant Staphylococcus aureus (CA-MRSA)]. / Estudio descriptivo de infecciones osteo-articulares en niños en tiempos de Staphylococcus aureus resistente a meticilina de la comunidad (SARM-Co).

BACKGROUND: Bone and joint infections (BJI) are relatively common in children, and community -acquired methicillin resistant Staphylococcus aureus (CA-MRSA) is the leading cause in some countries. AIM: To evaluate epidemiological data, clinical and microbiological features and outcome of BJI. METHODS: A prospective descriptive study was conducted. RESULTS: 40 patients (p) completed the study. Bacterial cultures were positives in 30 p (75%): CA-MRSA was found in 19 p, methicillin-sensitive S. aureus in 6 p, and others in 5 p. Cultures were negatives in 10 p (25%). Median treatment duration was 28 days (r: 21-40 d); Analyzing patients with CA-MRSA positive cultures separately, initial CRP was higher (Md 76 vs 50 mg/L, p < 0.02), normalization occurred later (Md 14 days vs 7days, p < 0.03), and duration of treatment (Md 32 days vs 23, p < 0.004) as well as hospital stay (Md 9 days vs 7, p = 0.12) were longer. Sequelae were present in 3 p and 1 relapsed: All of them with CA-SAMR. CONCLUSION: CA-MRSA was the leading cause of BJI and was associated with higher CRP on admission, later normalization and longer treatment duration. Complications as drainage requirement, and sequelae were common in those p.

Kinetic and thermodynamic parameters for thermal denaturation of ovine milk lactoferrin determined by its loss of immunoreactivity.

Lactoferrin is a protein with important biological functions that can be obtained from milk and by-products derived from the dairy industry, such as whey. Although bovine lactoferrin has been extensively studied, ovine lactoferrin is not quite as well known. In the present study, the effect of several heat treatments in 3 different media, over a temperature range from 66 to 75°C, has been studied on lactoferrin isolated from sheep milk. Denaturation of lactoferrin was determined by measuring its immunoreactivity with specific polyclonal antibodies. Kinetic and thermodynamic parameters obtained indicate that lactoferrin denatures by heat more rapidly in whey than in phosphate buffer or milk. The value of activation energy found for the denaturation process of lactoferrin when treated in whey is higher (390kJ/mol) than that obtained in milk (194kJ/mol) or phosphate buffer (179kJ/mol). This indicates that a great amount of energy is necessary to start denaturation of ovine lactoferrin, probably due to the interaction of this protein with other whey proteins. The changes in the hydrophobicity of lactoferrin after heat treatments were determined by fluorescence measurement using acrylamide. The decrease in the hydrophobicity constant was very small for the treatments from 66 to 75°C, up to 20min, which indicates that lactoferrin conformation did not experienced a great change. The results obtained in this study permit the prediction of behavior of ovine lactoferrin under several heat treatments and show that high-temperature, short-time pasteurization (72°C, 15 s) does not cause loss of its immunoreactivity and, consequently, would not affect its conformation and biological activity.

[Causes and factors associated with reconciliation errors in medical and surgical services]. / Causas y factores asociados a los errores de conciliación en servicios médicos y quirúrgicos.

OBJECTIVE: The objective of this study was to determine the main causes of errors of medication reconciliation at hospital admission in medical and surgical department and establish factors associated with medication reconciliation errors. MATERIAL AND METHOD: Cross-sectional study. We included all patients admitted to two services and two surgical for a month. To determine the presence of error reconciliation, the pharmacist compared the medication history interview by the order physician. The factors associated with errors were identified by multivariate logistic regression analysis. RESULTS: 221 patients were included, of which 58.4% had at least one error reconciliation. We detected 629 discrepancies, 339 (53.9%) reconciliation errors. The incidence of errors in medical services was 24.3% and in the surgical services 43.0% (p <0.001) in both groups being most prevalent error of omission (46.2% and 50.8%). Regarding factors associated, the equation determines that patients older than 65 years, polymedicated and taking oral antidiabetic are more likely to have an error with a sensibility of 75.2% and a specificity of 68.5%. CONCLUSION: There is a high rate of error reconciliation in medical and surgical patients, which confirms the need to implement a strategy to reduce these errors. Given the difficulty of applying the process to all patients, the strategy must be directed to patients who are at increased risk of error.

Objetivo: Determinar las principales causas de errores de conciliacion de la medicacion al ingreso hospitalario tanto en los servicios medicos, como en los quirurgicos y que factores se asocian a dichos errores de conciliacion. Material y método: Estudio observacional transversal. Se incluyeron todos los pacientes que ingresaron en dos servicios medicos y dos quirurgicos durante un mes. Para determinar la presencia de error de conciliacion se cotejo la historia realizada por el farmaceutico con la del medico prescriptor. Los factores asociados a los errores se identificaron mediante un analisis de regresion logistica multivariante. Resultados: Se incluyeron 221 pacientes, de los cuales el 58.4% presentaron al menos un error de conciliacion. Se detectaron un total de 629 discrepancias, 339 (53.9%) errores de conciliacion. La incidencia de errores en los servicios medicos fue del 24.3% y en los quirurgicos del 43.0% (p.

Rapid analysis of persistent organic pollutants by solid phase microextraction in serum samples.

A simple and rapid headspace solid-phase microextraction (HS SPME) based method is presented for the determination of Persistent Organic Pollutants (POPs) in human serum by gas chromatography (GC) coupled to mass detector (MS) with electron impact ionization (EI). As an outcome of the assessment of several polymer phases; the one with the best result was the PDMS fiber (100 µm). A multivariate analysis of variance by permutations (PERMANOVA) was performed to establish the optimal extraction conditions as a function of temperature and time variables. The results were 1 mL serum+200 µL H2SO4 9M+1 mL of deionized water at 600 rpm with a temperature of 80°C for 50 min to expose the fiber. The limits of detection (LOD) for POPs pesticides fell within the 0.22-5.41 ng/mL interval, and within 0.07-1.79 ng/mL for PCBs; a linear method was used with correlation coefficients (r) higher than 0.99. Recovery percentages at low concentrations (15 ng/mL) were 67.8-120.2%, and at high concentrations (75 ng/mL) 80.2-119.2%. Evaluated precision as percentage Relative Standard Deviation (RSD%) of repeatability and reproducibility was within a range of 0.5-9% and 0.3-21%, respectively. This analytical method prevents some of the main problems for quantifying POPs in human serum, such as the elimination of the solvents, sample handling, integration of extraction steps, pre-concentration and introduction of samples; consequently, the time and cost of analyzing the sample can be significantly reduced. The method developed was applied to determine exposure to POPs in samples of children living in different polluted sites in Mexico. In children living in indigenous communities results show exposure to DDE (median 29.2 ng/mL range 17.4-52.2 ng/mL) and HCB (median 2.53 ng/mL range 2.50-2.64 ng/mL); whereas in the industrial scenario, exposure to HCB (median 2.81 ng/mL range 2.61-3.4 ng/mL) and PCBs (median Σ-PCBs 22.2 ng/ml range 8.2-74.6 ng/mL) and finally in petrochemical scenario was demonstrated exposure to HCB (median 2.81 ng/mL range 2.61-3.4 ng/mL) and PCBs (Σ-PCBs median 7.9 ng/mL range 5.4-114.5 ng/mL).

Arsenic and fluoride co-exposure affects the expression of apoptotic and inflammatory genes and proteins in mononuclear cells from children.

Humans may be exposed to arsenic (As) and fluoride (F) through water consumption. However, the interaction between these two elements and gene expression in apoptosis or inflammatory processes in children has not been thoroughly investigated. Herein, the expression of cIAP-1, XIAP, TNF-α, ENA-78, survivin, CD25, and CD40 was evaluated by RT-PCR. Additionally, the surface expression of CD25, CD40, and CD40L on peripheral blood mononuclear cells was analyzed by flow cytometry, and TNF-α was measured by Western blotting. This study examined 72 children aged 6-12 years who were chronically exposed to As (154.2µg/L) and F (5.3mg/L) in drinking water and in food cooked with the same water. The urine concentrations of As (6.9-122.4µg/L) were positively correlated with the urine concentrations of F (1.0-8.8mg/L) (r(2)=0.413, p<0.0001). The CD25 gene expression levels and urine concentrations of As and F were negatively correlated, though the CD40 expression levels were negatively correlated only with the As concentration. Age and height influenced the expression of cIAP-1, whereas XIAP expression was correlated only with age. Additionally, there was a lower percentage of CD25- and CD40-positive cells in the group of 6- to 8-year-old children exposed to the highest concentrations of both As and F when compared to the 9- to 12-year-old group (CD25: 0.7±0.8 vs. 1.1±0.9, p<0.0014; CD40: 16.0±7.0 vs. 21.8±5.8, p<0.0003). PHA-stimulated lymphocytes did not show any changes in the induction of CD25, CD69, or CD95. In summary, high concentrations of As and F alter the expression patterns of CD25 and CD40 at both the genetic and protein levels. These changes could decrease immune responses in children exposed to As and F.