RSV through the COVID-19 pandemic: Burden, shifting epidemiology, and implications for the future.

Respiratory syncytial virus (RSV) represents a major global healthcare burden, particularly in those under 5 years of age. There is no available vaccine, with treatment limited to supportive care or palivizumab for high-risk children. Additionally, although a causal relationship has not been established, RSV has been associated with the development of asthma or wheezing in some children. The COVID-19 pandemic and the introduction of nonpharmaceutical interventions (NPIs) have caused substantial changes to RSV seasonality and epidemiology. Many countries have experienced an absence of RSV during the time of a typical season, followed by an out-of-season surge upon relaxation of NPI use. These dynamics have disrupted traditional RSV disease patterns and assumptions, but also provide a unique opportunity to learn more about the transmission of RSV and other respiratory viruses, as well as inform future approaches to RSV preventive strategies. Here, we review the RSV burden and epidemiology through the COVID-19 pandemic and discuss how new data may affect future decisions regarding RSV prevention.

Exposición ambiental a plomo y biomarcadores de estrés oxidativo en niños sanos de La Plata, Argentina / Environmental exposure to lead and oxidative stress biomarkers among healthy children in La Plata, Argentina

Introducción. La exposición ambiental a plomo (Pb) aún constituye un problema de salud pública, particularmente para los niños. El estrés oxidativo podría representar un mecanismo primario asociado a su toxicidad. El objetivo del presente estudio fue determinar los niveles de Pb en sangre (Pb-S) en niños de 1 a 6 años de La Plata y alrededores con exposición ambiental, y su relación con biomarcadores de estrés oxidativo. Población y métodos. Estudio analítico de corte transversal. Se evaluaron niños clínicamente sanos de 1 a 6 años. Se determinaron los niveles de Pb-S, las actividades de enzimas antioxidantes y el grado de peroxidación lipídica. Se utilizó el paquete estadístico R versión 3.5.1. Resultados. Participaron 131 niños, mediana de edad 2,33 años. La media geométrica de los niveles de Pb-S fue 1,90 µg/dL; el 32 % presentó plombemias cuantificables y el 3 %, niveles ≥5 µg/dL (referencia internacional). Al comparar los biomarcadores de estrés oxidativo según los niveles de Pb-S, solo se observó diferencia significativa entre las medianas de las sustancias reactivas al ácido tiobarbitúrico (TBARS): 12,0 versus 10,0 nmol MDA/mL plasma; p = 0,02. Asimismo, la correlación entre las plombemias y las TBARS fue positiva (r = 0,24; p = 0,012). Conclusiones. La mayoría de los niños mostraron niveles de Pb-S menores a los límites recomendados por agencias internacionales, que si bien, no producen alteraciones en la actividad de enzimas antioxidantes, sí inducen peroxidación lipídica. Estos resultados reflejan la utilidad de este biomarcador como una herramienta diagnóstica temprana para evaluar los efectos subtóxicos del Pb.

Introduction. Environmental exposure to lead is still a major public health problem, especially in children. Oxidative stress may be a primary mechanism associated with toxicity. Theobjective of this study was to measure blood lead levels (BLLs) in children aged 1 to 6 years expos to lead in La Plata and suburban areas and their relation to oxidative stress biomarkers. Population and methods. Cross-sectional,analytical study. Clinically healthy children aged1 to 6 years were analyzed. BLLs, antioxidant enzyme activity, and extent of lipid peroxidation were measured. The statistical softwarepackage R, version 3.5.1, was used. Results. A total of 131 children participated; their median age was 2.33 years. The geometric mean of BLLs was 1.90 µg/dL; 32% showed a measurable BLL and 3%, BLLs ≥ 5 µg/dL (international reference). The comparison ofoxidative stress biomarkers based on BLshowed a significant difference in median thiobarbituric acid reactive substances (TBARS):12.0 versus 10.0 nmol MDA/mL of plasma;p = 0.02. In addition, the correlation between BLLs and TBARS was positive (r = 0.24; p = 0.012 Conclusions. Most children had a BLL below the limit recommended by international agencies; although such BLLs do not affantioxidant enzyme activity, they can induce lipid peroxidation. These results demonstrate theusefulness of this biomarker as an early diagnosistool to assess subtoxic lead effects.

Environmental exposure to lead and oxidative stress biomarkers among healthy children in La Plata, Argentina. / Exposición ambiental a plomo y biomarcadores de estrés oxidativo en niños sanos de La Plata, Argentina.

INTRODUCTION: Environmental exposure to lead is still a major public health problem, especially in children. Oxidative stress may be a primary mechanism associated with toxicity. The objective of this study was to measure blood lead levels (BLLs) in children aged 1 to 6 years exposed to lead in La Plata and suburban areas and their relation to oxidative stress biomarkers. POPULATION AND METHODS: Cross-sectional, analytical study. Clinically healthy children aged 1 to 6 years were analyzed. BLLs, antioxidant enzyme activity, and extent of lipid peroxidation were measured. The statistical software package R, version 3.5.1, was used. RESULTS: A total of 131 children participated; their median age was 2.33 years. The geometric mean of BLLs was 1.90 µg/dL; 32% showed a measurable BLL and 3%, BLLs ≥ 5 µg/dL (international reference). The comparison of oxidative stress biomarkers based on BLLs showed a significant difference in median thiobarbituric acid reactive substances (TBARS): 12.0 versus 10.0 nmol MDA/mL of plasma; p = 0.02. In addition, the correlation between BLLs and TBARS was positive (r = 0.24; p = 0.012). CONCLUSIONS: Most children had a BLL below the limit recommended by international agencies; although such BLLs do not affect antioxidant enzyme activity, they can induce lipid peroxidation. These results demonstrate the usefulness of this biomarker as an early diagnosis tool to assess subtoxic lead effects.

Introducción. La exposición ambiental a plomo (Pb) aún constituye un problema de salud pública, particularmente para los niños. El estrés oxidativo podría representar un mecanismo primario asociado a su toxicidad. El objetivo del presente estudio fue determinar los niveles de Pb en sangre (Pb-S) en niños de 1 a 6 años de La Plata y alrededores con exposición ambiental, y su relación con biomarcadores de estrés oxidativo. Población y métodos. Estudio analítico de corte transversal. Se evaluaron niños clínicamente sanos de 1 a 6 años. Se determinaron los niveles de Pb-S, las actividades de enzimas antioxidantes y el grado de peroxidación lipídica. Se utilizó el paquete estadístico R versión 3.5.1. Resultados. Participaron 131 niños, mediana de edad 2,33 años. La media geométrica de los niveles de Pb-S fue 1,90 µg/dL; el 32 % presentó plombemias cuantificables y el 3 %, niveles ≥5 µg/dL (referencia internacional). Al comparar los biomarcadores de estrés oxidativo según los niveles de Pb-S, solo se observó diferencia significativa entre las medianas de las sustancias reactivas al ácido tiobarbitúrico (TBARS): 12,0 versus 10,0 nmol MDA/mL plasma; p = 0,02. Asimismo, la correlación entre las plombemias y las TBARS fue positiva (r = 0,24; p = 0,012). Conclusiones. La mayoría de los niños mostraron niveles de Pb-S menores a los límites recomendados por agencias internacionales, que si bien, no producen alteraciones en la actividad de enzimas antioxidantes, sí inducen peroxidación lipídica. Estos resultados reflejan la utilidad de este biomarcador como una herramienta diagnóstica temprana para evaluar los efectos subtóxicos del Pb.

Pomalidomide-Based Regimens for Treatment of Relapsed and Relapsed/Refractory Multiple Myeloma: Systematic Review and Meta-analysis of Phase 2 and 3 Clinical Trials.

INTRODUCTION: Pomalidomide (Pom) has demonstrated synergistic antiproliferative activity in combination regimens as a result of its distinct anticancer, antiangiogenic, and immunomodulatory effects. This review aimed to compare outcome measures of different Pom regimens for relapsed/refractory multiple myeloma. METHODS: A comprehensive literature search identified a total of 1374 studies. Thirty-five studies assessing 4623 subjects met the inclusion criteria: phase 2/3 trial, ≥ 2 prior lines of therapy, and clearly documented efficacy outcomes like overall response rate (ORR), overall survival, and progression-free survival. Statistical analyses for meta-analysis was performed by CMA version 3 and Cochrane Q statistics (P < .05 considered significant, I2 index for heterogeneity). A random effects model was used if there was significant heterogeneity (P ≥ .05 over I2 ≥ 50%). RESULTS: Pooled analysis showed ORR 47.1% across all Pom-based (2- and 3-drug) regimens. Stratified analysis for efficacy outcomes (pooled ORR [%] and mean progression-free survival [months]) are reported. With doublet regimen, Pom with low-dose dexamethasone (LoDex) was the most common regimen (35.7%, 6.1 months), and overall survival was 14.37 months. With triplet regimens, pooled ORR was 61.9% (I2 = 87.3%). These included bortezomib + Pom + LoDex (83.5%, 15.7 months), carfilzomib-Pom + LoDex (77.1%, 15.3 months), Pom + LoDex-bendamustine (74.2%), Pom-dexamethasone-daratumumab (64.5%), Pom + LoDex-cyclophosphamide (59.4%, 9.5 months), and Pom + LoDex-doxorubicin (32%). Leading adverse events were myelosuppression, with mean incidences of grade 3 or higher neutropenia, anemia, and thrombocytopenia of 47.6%, 26.5%, and 20.8%, respectively. Mean incidence of grade 3 or higher nonhematologic adverse events were infections 29.1%, pneumonia 13.8%, and fatigue 10%. CONCLUSION: Three-drug Pom regimens yielded double the response rates compared to Pom + LoDex (pooled ORR, 61.9% vs. 35.7%), with bortezomib + Pom + LoDex and carfilzomib-Pom + LoDex demonstrating better outcomes than other regimens.

A dinâmica temporal da atenção na memória de trabalho visual / The temporal dynamics of attention in visual working memory / La dinamica temporale de la atención en la memoria de trabajo visual

A orientação da atenção, por meio de uma dica retroativa endógena, para locais de uma cena memorizada, favorece positivamente o processamento de forma equivalente ao favorecimento associado à dica endógena nas tarefas perceptivas. Na percepção dicas endógenas e exógenas têm dinâmicas temporais diferentes. Nós investigamos a eficácia e a dinâmica temporal da recuperação da informação armazenada na memória de trabalho visual utilizando dicas retroativas endógenas e exógenas. Nossos resultados mostram que as dicas retroativas endógena e exógena proporcionam um ganho equivalente na acurácia (d') e no tempo de resposta, e que este ganho aumenta com a assincronia entre dica e estímulo teste. Nossos dados mostram que o ganho no desempenho está ligado tanto à validade da dica, como ao intervalo dica-estímulo, mas não aos diferentes tipos de dica, pelo menos nos intervalos investigados.

Orienting attention to a memorized scene using an endogenous cue positively favors processing, in a manner similar to endogenous cueing in perceptual tasks. In perception, endogenous and exogenous cues have different temporal dynamics. We investigated the efficacy and temporal dynamics of retrieval of information held in working memory using two types of retro-cue (endogenous and exogenous), presented in different intervals before the probed stimulus. Our results show that both cue types provide an equivalent benefit in accuracy and response time, which increases at longer cue-target-asynchrony. Our data indicate that performance is linked with cue validity and also with cue-target-asynchrony, but it is not linked with cue type, at least at the investigated intervals.

La orientación de la atención, por medio de una pista retroactiva endógena, para lugares de una escena memorizada, favorece positivamente el procesamiento de forma equivalente al favorecimiento asociado a la pista endógena en las tareas perceptivas. En la percepción pistas endógenas y exógenas tienen dinámicas temporales diferentes. Hemos investigamos la eficacia y la dinámica temporal de la recuperación de la información almacenada en la memoria de trabajo utilizando pistas retroactivas endógenas y exógenas, presentadas a diferentes intervalos antes del estímulo test. Nuestros resultados muestran que las pistas retroactivas endógenas y exógenas proporcionan un beneficio equivalente en exactitude (d') y tiempo de respuesta, y que este beneficio aumenta con la asincronía entre pista y estímulo test. El rendimiento parece estar vinculado tanto a la validez de la pista, como al intervalo de estímulo, pero no a los diferentes tipos de pista, al menos en los intervalos investigados.

Assessing knowledge of symptoms and first-aid care of epilepsy in Grenada, West Indies.

Epilepsy is a chronic neurological disorder that is increasingly prevalent in developing countries. It is critical to provide appropriate support to patients during seizures in order to prevent injuries. False beliefs regarding the etiology or pathogenesis of the epilepsy and inadequate health information may put patients with epilepsy or other seizure disorders at increased risk of injury. Our objective was to assess the level of epilepsy awareness amongst the general population in Grenada and educate the participants regarding proper first-aid measures. A pilot questionnaire containing a total of 25 items surveying the knowledge, attitudes, and first-aid care of epilepsy was presented to 200 adult residents of Grenada as face-to-face interviews. Study participants were recruited over a nine-month period on a voluntary basis at health fairs, in local communities, and on the campus of St. George's University. Our results indicate that 35 out of 198 (17.7%) respondents erroneously believed that medicine should be placed in a person's mouth during a seizure, and 83 out of 200 (41.5%) answered that a person who is convulsing should be held down. Furthermore, 128 out of 195 (65.6%) respondents erroneously believed that seizures occur when there is low brain activity and an additional 35 out of 199 (17.6%) regarded epilepsy as a contagious disorder. Our data suggest that persons with seizures and/or epilepsy may be at increased risk of injury in Grenada due to common misconceptions and false beliefs. It is critical that epilepsy awareness is promoted in developing countries, such as Grenada, where inadequate health information may be common.

Respiratory syncytial virus hospitalization and mortality: Systematic review and meta-analysis.

BACKGROUND: Respiratory syncytial virus (RSV) is a major public health burden worldwide. We aimed to review the current literature on the incidence and mortality of severe RSV in children globally. METHODS: Systematic literature review and meta-analysis of published data from 2000 onwards, reporting on burden of acute respiratory infection (ARI) due to RSV in children. Main outcomes were hospitalization for severe RSV-ARI and death. RESULTS: Five thousand two hundred and seventy-four references were identified. Fifty-five studies were included from 32 countries. The global RSV-ARI hospitalization estimates, reported per 1,000 children per year (95% Credible Interval (CrI), were 4.37 (2.98, 6.42) among children <5 years, 19.19 (15.04, 24.48) among children <1 year, 20.01 (9.65, 41.31) among children <6 months and 63.85 (37.52, 109.70) among premature children <1 year. The RSV-ARI global case-fatality estimates, reported per 1,000 children, (95% Crl) were 6.21 (2.64, 13.73) among children <5 years, 6.60 (1.85, 16.93) for children <1 year, and 1.04 (0.17, 12.06) among preterm children <1 year. CONCLUSIONS: A substantial proportion of RSV-associated morbidity occurs in the first year of life, especially in children born prematurely. These data affirm the importance of RSV disease in the causation of hospitalization and as a significant contributor to pediatric mortality and further demonstrate gestational age as a critical determinant of disease severity. An important limitation of case-fatality ratios is the absence of individual patient characteristics of non-surviving patients. Moreover, case-fatality ratios cannot be translated to population-based mortality. Pediatr Pulmonol. 2017;52:556-569. © 2016 The Authors. Pediatric Pulmonology. Published by Wiley Periodicals, Inc.

Improvements in lung function of a pediatric cystic fibrosis population in a developing country.

OBJECTIVE: To document the change in pulmonary function of a pediatric cystic fibrosis population managed at the Red Cross War Memorial Children's Hospital, Cape Town, South Africa, between January 1999 and December 2006. METHODS: Retrospective review of the medical records and best spirometry results within 3-monthly intervals. RESULTS: A total of 1,139 pulmonary function tests from 79 patients showed a significant improvement over the 8 years studied. When comparing the first quarter of 1999 with the last quarter of 2006, 78 pulmonary function tests were performed on 65 patients with equal patient numbers in both groups and similar in terms of gender, age, age at diagnosis, ethnicity, cystic fibrosis genotype and number of patients colonized with either Staphylococcus aureus or Pseudomonas aeruginosa. In 2006, 15 patients (38.5%) were on azithromycin treatment compared to one (2.6%) patient in 1999 (p = 0.0003). Median (interquartile range) forced expiratory volume in 1 second, forced vital capacity, and average expiratory flow between 25 and 75% of forced vital capacity increased from 61% (51-73), 63% (52-89), and 40% (27-57), predicted in the first quarter of 1999, to 81% (69-100, p = 0.004), 82% (70-98, p = 0.007), and 62% (41-87, p = 0.01), predicted during the last quarter of 2006, respectively. CONCLUSIONS: Pulmonary function tests increased by 20% over 8 years in comparable patient groups. This likely reflects improved care of South African children with cystic fibrosis.

Melhoras na função pulmonar de uma população com fibrose cística em um país em desenvolvimento / Improvements in lung function of a pediatric cystic fibrosis population in a developing country

OBJETIVO: Documentar a alteração em função pulmonar de uma população pediátrica com fibrose cística tratada no Red Cross War Memorial Children's Hospital, Cidade do Cabo, África do Sul, entre janeiro de 1999 e dezembro de 2006. MÉTODOS: Revisão retrospectiva dos prontuários médicos e melhores resultados de espirometria em intervalos de 3 meses. RESULTADOS: Um total de 1.139 testes de função pulmonar de 79 pacientes mostrou melhora significativa ao longo dos 8 anos estudados. Ao comparar o primeiro trimestre de 1999 com o último trimestre de 2006, 78 testes de função pulmonar foram realizados em 65 pacientes com números iguais de pacientes em ambos os grupos e semelhante em termos de gênero, idade, idade ao diagnóstico, etnia, genótipo da fibrose cística e número de pacientes colonizados com Staphylococcus aureus ou Pseudomonas aeruginosa.Em 2006, 15 pacientes (38,5 por cento) estavam em tratamento com azitromicina, comparados com um (2,6 por cento) paciente em 1999 (p = 0,0003). Volume expiratório forçado no primeiro segundo mediano (intervalo interquartil), capacidade vital forçada e fluxo expiratório médio entre 25 e 75 por cento da capacidade vital forçada aumentaram de 61 por cento (51-73), 63 por cento (52-89) e 40 por cento (27-57) previstos no primeiro trimestre de 1999 para 81 por cento (69-100, p = 0,004), 82 por cento (70-98, p = 0,007) e 62 por cento (41-87, p = 0,01) previstos durante o último trimestre de 2006, respectivamente. CONCLUSÕES: Testes de função pulmonar aumentaram em 20 por cento ao longo de 8 anos em grupos comparáveis de pacientes. Isso provavelmente reflete a melhora na prestação de cuidados a crianças sul-africanas com fibrose cística.

OBJECTIVE: To document the change in pulmonary function of a pediatric cystic fibrosis population managed at the Red Cross War Memorial Children's Hospital, Cape Town, South Africa, between January 1999 and December 2006. METHODS: Retrospective review of the medical records and best spirometry results within 3-monthly intervals. RESULTS: A total of 1,139 pulmonary function tests from 79 patients showed a significant improvement over the 8 years studied. When comparing the first quarter of 1999 with the last quarter of 2006, 78 pulmonary function tests were performed on 65 patients with equal patient numbers in both groups and similar in terms of gender, age, age at diagnosis, ethnicity, cystic fibrosis genotype and number of patients colonized with either Staphylococcus aureus or Pseudomonas aeruginosa. In 2006, 15 patients (38.5 percent) were on azithromycin treatment compared to one (2.6 percent) patient in 1999 (p = 0.0003). Median (interquartile range) forced expiratory volume in 1 second, forced vital capacity, and average expiratory flow between 25 and 75 percent of forced vital capacity increased from 61 percent (51-73), 63 percent (52-89), and 40 percent (27-57), predicted in the first quarter of 1999, to 81 percent (69-100, p = 0.004), 82 percent (70-98, p = 0.007), and 62 percent (41-87, p = 0.01), predicted during the last quarter of 2006, respectively. CONCLUSIONS: Pulmonary function tests increased by 20 percent over 8 years in comparable patient groups. This likely reflects improved care of South African children with cystic fibrosis.

Multiple pulses improve electroporation efficiency in Agrobacterium tumefaciens

Electroporation entails brief, high intensity pulse to create transient pores in the cell membrane to facilitate the entry of exogenous macromolecules, which may otherwise be excluded. Removal of the external field leads to the resealing of the membrane electropores permitting the survival of the electrically stimulated recipient cells. Using this technique foreign deoxyribonucleic acid (DNA) has been successfully introduced into many cell types both from prokaryotes and eukaryotes. Increase in pulse voltage and length beyond a critical limit has been reported to decrease transformation efficiency, hence in this study we have investigated another strategy i.e. increase in the number of pulses at constant high voltage and pulse duration. Commonly used Agrobacterium strains LBA4404 and EHA101 and binary vector pCAMBIA1301 were used. Transformants were selected on a combination of hygromycin and kanamycin, and confirmed by polymerase chain reaction (PCR) and restriction analysis. Increase in the number of pulses was found to show a significant and linear increase in transformation efficiency.

Prevalence and reversibility of lower airway obstruction in children with sickle cell disease.

OBJECTIVE: To determine the prevalence and reversibility of lower airway obstruction (LAO) in children and adolescents with hemoglobin SS sickle cell disease (HbSS SCD). STUDY DESIGN: Retrospective evaluation of lung function in a cross-section of 35 African American and 28 Hispanic children and adolescents with HbSS SCD. Lung function was evaluated with maximal respiratory flow-volume curves and body plethysmography. Each patient was assigned to 1 of 3 patterns of lung function (normal, obstructive, or restrictive). Airway hyperresponsiveness was assessed by means of a trial with bronchodilator. RESULTS: Normal pattern was detected in 57% of the patients, LAO in 35%, and restrictive lung disease in 8%. Positive response to bronchodilator was documented in 30% of those with normal pattern of lung function, 78% in those with LAO, and 67% of those with restrictive lung disease. The pattern of lung function was not associated with race or with history of vaso-occlusive crises, acute chest syndrome, reactive airways disease/asthma, or long-term transfusion therapy. CONCLUSION: Obstructive lung disease possibly precedes the development of restrictive lung disease, and airway reactivity may be part of the pathogenic mechanism.

Binding of Pseudomonas aeruginosa to respiratory epithelial cells from patients with various mutations in the cystic fibrosis transmembrane regulator.

OBJECTIVE: To determine whether there is an association between mutations of the cystic fibrosis transmembrane regulator (CFTR) and the predilection of patients with cystic fibrosis (CF) for Pseudomonas aeruginosa infection. METHOD: We quantified the adherence of P. aeruginosa PA01, labeled with sulfur 35-methionine, to epithelial monolayers derived from nasal scrapings of patients with specific CFTR mutations, and of carriers and normal subjects. RESULTS: Adherence of P. aeruginosa to epithelial cells from patients with CF was significantly greater than to cells from either carriers (t = 2.94; p = 0.009) or normal subjects (t = 3.32; p = 0.004). Adherence to epithelial cells from patients with CF who were homozygous for the delta F508 mutation ranged from 12% to 35% (mean, 23.7%) of the added inoculum, which was significantly greater than the binding to cells from patients with other mutations, which ranged from 3% to 18% (mean, 9.4%; t = 3.71; p = 0.002), from heterozygote carriers (3% to 11%; mean, 7.9%; t = 4.87; p = 0.002), or from normal subjects (2% to 10%: mean, 7.0%; t = 5.21; p = 0.002). CONCLUSION: Adherence to P. aeruginosa can be correlated with homozygosity for the delta 508 mutation; CFTR dysfunction may be one of the factors involved in the pathogenesis of pulmonary infection in CF.

The effects of melatonin in human platelets.

Pineal melatonin has been implicated in the control of several physiological processes, including circadian rhythmicity and the photoperiodic control of seasonal breeding in mammals. However, its role in humans remains largely undefined. Presumably, melatonin acts on the CNS to affect biologic rhythms; additionally, a number of studies indicate the existence of direct effects of melatonin in peripheral organs, like the platelets. This article discusses experimental data indicating that the human platelets are peripheral cells sensitive to melatonin that could be potentially employed in clinic studies. Melatonin inhibits several physiological processes in platelets including the aggregation phenomenon the release of ATP and serotonin (indexes of the platelet secretory mechanism), and the production of thromboxane B2 A generally greater, and dose-dependent, effect of nanomolar melatonin concentrations in the evening as compared to morning melatonin found in vivo. The maximum in melatonin activity on platelet function precedes the peak in melatonin concentration in blood, indicating the existence of a dissociation between circulating levels and sensitivity to platelet the hormone in normal subjects. In binding studies employing 3H-melatonin as ligand, binding sites in human platelet membranes with a Kd within the nanomolar range were detected. The data suggest the feasibility to employ platelets as peripheral "windows" of central melatonin activity in humans.

The effects of melatonin in human platelets

La melatonina pineal ha sido implicada en el control de varios procesos fisiológicos, como la ritmicidad circadiana y la reproducción estacional en mamíferos. Sin embargo la función de la melatonina en el hombre permanece aún indefinida. La melatonina actúa en el SNC para modificar distintos ritmos biológicos; además se han descrito varios efectos periféricos de la hormona pineal entre ellos su actividad plaquetaria. En este trabajo se analizan los datos experimentales que indican que las plaquetas son células sensibles a la melatonina de posible utilidad clínica para elucidar la función de la melatonina y la glándula pineal en el hombre. La melatonina inhibe distintos procesos fisiológicos plaquetarios, como la agregación plaquetaria, la producción de tromboxanos y la liberación de ATP y serotonina, ambos índices de secreción plaquetaria. En general, el efecto de la melatonina es mayor en horas de la tarde y comienzo de la noche, coincidiendo con los datos in vivo que indican un mayor efecto de la melatonina administrada sistématicamente. El máximo en actividad in vitro de la melatonina en plaquetas precede al máximo en niveles circulantes de la hormona, indicando la existencia de disociación entre niveles circulantes y sensibilidad tisular a la hormona. En estudios de unión de radiologando in vitro se detectaron sitios aceptores para la 3H-melatonina en membranas de plaquetas humanas, con Kd de rango nanomolar. Estos resultados sugieren en conjunto que las plaquetas pueden utilizar-se clínicamente como "ventanas" circulantes de los procesos modificados por la melatonina en el SNC