Early chronic lead exposure reduces exploratory activity in young C57BL/6J mice

Research has suggested that chronic low‐level lead exposure diminishes neurocognitive function in children. Tests that are sensitive to behavioral effects at lowest levels of lead exposure are needed for the development of animal models. In this study we investigated the effects of chronic low‐level lead exposure on exploratory activity (unbaited nose poke task), exploratory ambulation (open field task) and motor coordination (Rotarod task) in pre‐adolescent mice. C57BL/6J pups were exposed to 0 ppm (controls), 30 ppm (low‐dose) or 230 ppm (high‐dose) lead acetate via dams’ drinking water administered from birth to postnatal day 28, to achieve a range of blood lead levels (BLLs) from not detectable to 14.84 µg dl^–1). At postnatal day 28, mice completed behavioral testing and were killed (n = 61). BLLs were determined by inductively coupled plasma mass spectrometry. The effects of lead exposure on behavior were tested using generalized linear mixed model analyses with BLL, sex and the interaction as fixed effects, and litter as the random effect. BLL predicted decreased exploratory activity and no threshold of effect was apparent. As BLL increased, nose pokes decreased. The C57BL/6J mouse is a useful model for examining effects of early chronic low‐level lead exposure on behavior. In the C57BL/6J mouse, the unbaited nose poke task is sensitive to the effects of early chronic low‐level lead exposure. This is the first animal study to show behavioral effects in pre‐adolescent lead‐exposed mice with BLL below 5 µg dl^–1. Copyright © 2014 John Wiley & Sons, Ltd.     

Immunization with plasmids encoding M2 acetylcholine muscarinic receptor epitopes impairs cardiac function in mice and induces autophagy in the myocardium

Abstract

Autoantibodies against the M2 subtype of muscarinic acetylcholine receptors with functional activities have been found in the sera of patients with dilated cardiomyopathy (DCM), and the second extracellular loop has been established as the predominant epitope. However, it has been shown that the third intracellular loop is recognized by Chagas disease patients with severe cardiac dysfunction. In this work, BALB/c mice were immunized with plasmids encoding these two epitopes, and a control group received the empty plasmid (pcDNA3 vector). Serum from these DNA-immunized animals had elevated and persistent titres of antibodies against respective antigens. Heart echocardiography indicated diminished left ventricular wall thickness and reduced ejection fraction for both epitope-immunized groups, and ergospirometry tests showed a significant decrease in the exercise time and oxygen consumption. Transfer of serum from these immunized mice into naïve recipients induced the same alterations in cardiac structure and function. Furthermore, electron microscopy analysis of donor-immunized animals revealed several ultrastructural alterations suggestive of autophagy and mitophagy, suggesting novel roles for these autoantibodies. Overall, greater functional and structural impairment was observed in the donor and recipient epitope groups, implicating the third intracellular loop epitope in the pathological effects for the first-time. Therefore, the corresponding peptides could be useful for autoimmune DCM diagnosis and targeted therapy.     

Ganglioglioma anaplásico: diseminación leptomeníngea cervico-dorso-lumbar. A propósito de un caso

Gangliogliomas are well-differentiated, slow-growing tumors. The majority are grade I of WHO. It appears predominantly in children and young adults. Most are located at the temporal lobe, and as symptomatology more frequent epileptic seizures of difficult pharmacological control. In general, they have a good prognosis after surgical resection. The anaplasic variant, considered to be grade III of the WHO, presents greater clinical and radiological aggressiveness. Leptomeningeal dissemination is exceptional in these types of tumors, but when diagnosed it presents a rapidly progressive and fatal course for the patient.     

Hallazgos iniciales en la radiografía de tórax como predictores de empeoramiento en la infección pulmonar por SARS-CoV-2. Correlación en 265 pacientes

Background and aimsWe aimed to analyze the relationship between the initial chest X-ray findings in patients with severe acute respiratory syndrome due to infection with SARS-CoV-2 and eventual clinical worsening and to compare three systems of quantifying these findings.Material and methodsThis retrospective study reviewed the clinical and radiological evolution of 265 adult patients with COVID-19 attended at our center between March 2020 and April 2020. We recorded data related to patients’ comorbidities, hospital stay, and clinical worsening (admission to the ICU, intubation, and death). We used three scoring systems taking into consideration 6 or 8 lung fields (designated 6 A, 6 B, and 8) to quantify lung involvement in each patient's initial abnormal chest X-ray and to classify its severity as mild, moderate, or severe, and we compared these three systems. We also recorded the presence of alveolar opacities and linear opacities (fundamentally linear atelectasis) in the first chest X-ray with pathologic findings.ResultsIn the χ2 analysis, moderate or severe involvement in the three classification systems correlated with hospital admission (p = 0.009 in 6 A, p = 0.001 in 6 B, and p = 0.001 in 8) and with death (p = 0.02 in 6 A, p = 0.01 in 6 B, and p = 0.006 in 8). In the regression analysis, the most significant associations were 6 B with alveolar involvement (OR 2.3; 95%CI 1.1.–4.7; p = 0.025;) and 8 with alveolar involvement (OR 2.07; 95% CI 1.01.–4.25; p = 0.046). No differences were observed in the ability of the three systems to predict clinical worsening by classifications of involvement in chest X-rays as moderate or severe.ConclusionModerate/severe extension in the three chest X-ray scoring systems evaluating the extent of involvement over 6 or 8 lung fields and the finding of alveolar opacities in the first abnormal X-ray correlated with mortality and the rate of hospitalization in the patients studied. No significant difference was found in the predictive ability of the three classification systems proposed.