Tissue distribution and acute toxicity of silver after single intravenous administration in mice: nano-specific and size-dependent effects

Background: Silver nanoparticles (AgNPs) are an important class of nanomaterials used as antimicrobial agents for a wide range of medical and industrial applications. However toxicity of AgNPs and impact of their physicochemical characteristics in in vivo models still need to be comprehensively characterized. The aim of this study was to investigate the effect of size and coating on tissue distribution and toxicity of AgNPs after intravenous administration in mice, and compare the results with those obtained after silver acetate administration. Methods: Male CD-1(ICR) mice were intravenously injected with AgNPs of different sizes (10 nm, 40 nm, 100 nm), citrate-or polyvinylpyrrolidone-coated, at a single dose of 10 mg/kg bw. An equivalent dose of silver ions was administered as silver acetate. Mice were euthanized 24 h after the treatment, and silver quantification by ICP-MS and histopathology were performed on spleen, liver, lungs, kidneys, brain, and blood. Results: For all particle sizes, regardless of their coating, the highest silver concentrations were found in the spleen and liver, followed by lung, kidney, and brain. Silver concentrations were significantly higher in the spleen, lung, kidney, brain, and blood of mice treated with 10 nm AgNPs than those treated with larger particles. Relevant toxic effects (midzonal hepatocellular necrosis, gall bladder hemorrhage) were found in mice treated with 10 nm AgNPs, while in mice treated with 40 nm and 100 nm AgNPs lesions were milder or negligible, respectively. In mice treated with silver acetate, silver concentrations were significantly lower in the spleen and lung, and higher in the kidney than in mice treated with 10 nm AgNPs, and a different target organ of toxicity was identified (kidney). Conclusions: Administration of the smallest (10 nm) nanoparticles resulted in enhanced silver tissue distribution and overt hepatobiliary toxicity compared to larger ones (40 and 100 nm), while coating had no relevant impact. Distinct patterns of tissue distribution and toxicity were observed after silver acetate administration. It is concluded that if AgNPs become systemically available, they behave differently from ionic silver, exerting distinct and size-dependent effects, strictly related to the nanoparticulate form

Behavioral, neuromorphological, and neurobiochemical effects induced by omega-3 fatty acids following basal forebrain cholinergic depletion in aged mice

Background: In recent years, mechanistic, epidemiologic, and interventional studies have indicated beneficial effects of omega-3 polyunsaturated fatty acids (n-3 PUFA) against brain aging and age-related cognitive decline, with the most consistent effects against Alzheimer’s disease (AD) confined especially in the early or prodromal stages of the pathology. In the present study, we investigated the action of n-3 PUFA supplementation on behavioral performances and hippocampal neurogenesis, volume, and astrogliosis in aged mice subjected to a selective depletion of basal forebrain cholinergic neurons. Such a lesion represents a valuable model to mimic one of the most reliable hallmarks of early AD neuropathology. Methods: Aged mice first underwent mu-p75-saporin immunotoxin intraventricular lesions to obtain a massive cholinergic depletion and then were orally supplemented with n-3 PUFA or olive oil (as isocaloric control) for 8 weeks. Four weeks after the beginning of the dietary supplementation, anxiety levels as well as mnesic, social, and depressive-like behaviors were evaluated. Subsequently, hippocampal morphological and biochemical analyses and n-3 PUFA brain quantification were carried out. Results: The n-3 PUFA treatment regulated the anxiety alterations and reverted the novelty recognition memory impairment induced by the cholinergic depletion in aged mice. Moreover, n-3 PUFA preserved hippocampal volume, enhanced neurogenesis in the dentate gyrus, and reduced astrogliosis in the hippocampus. Brain levels of n-3 PUFA were positively related to mnesic abilities. Conclusions: The demonstration that n-3 PUFA are able to counteract behavioral deficits and hippocampal neurodegeneration in cholinergically depleted aged mice promotes their use as a low-cost, safe nutraceutical tool to improve life quality at old age, even in the presence of first stages of AD

The Cardiovascular Disease (CVD) Risk Continuum from Prenatal Life to Adulthood: A Literature Review

The risk of developing cardiovascular diseases (CVDs) arises from the interaction of prenatal factors; epigenetic regulation; neonatal factors; and factors that affect childhood and adolescence, such as early adiposity rebound (AR) and social and environmental influences. Thus, CVD risk varies between the group of low-risk metabolically healthy normal-weight subjects (MHNW); the intermediate-risk group, which includes metabolically healthy obese (MHO) and metabolically unhealthy normal-weight subjects (MUHNW); and the high-risk group of metabolically unhealthy obese (MUHO) subjects. In this continuum, several risk factors come into play and contribute to endothelial damage, vascular and myocardial remodeling, and atherosclerotic processes. These pathologies can occur both in prenatal life and in early childhood and contribute to significantly increasing CVD risk in young adults over time. Early intervention in the pediatric MUHO population to reduce the CVD risk during adulthood remains a challenge. In this review, we focus on CVD risk factors arising at different stages of life by performing a search of the recent literature. It is urgent to focus on preventive or early therapeutic strategies to stop this disturbing negative metabolic trend, which manifests as a continuum from prenatal life to adulthood.SCOPUS: re.jinfo:eu-repo/semantics/publishe

Sublingual sufentanil tablet system Zalviso® for postoperative analgesia after knee replacement in fast track surgery: a pilot observational study

Abstract Background Currently many TKA protocols rely on multimodal analgesic protocols with patient-controlled analgesia systems that administer opioids through a patient controlled IV infusion pump, in addition to concomitant peripheral nerve blocks and local anesthetics. Although effective, PCA IV opioids do not provide optimal results with fast track rehabilitation protocols. Methods The present is a retrospective study comparing the novel sublingual sufentanil PCA system (SSTS) to our standard of care foreseeing continuous femoral nerve block (cFNB) within a multimodal analgesic in a TKA fast-track protocol. The study evaluated 95 patients on SSTS (SSTS group) and 87 on cFNB (cFNB/control group) and collected data on numeric rating scores for pain from day 1–3 after surgery (T1, T2, T3), both at rest (NRS) and during movement (mNRS), patient’s ability to walk, need for supplementary analgesia (rescue dose), occurrence of adverse effects, length of hospital stay, and usability rating for SSTS by both patients and hospital staff. Results NRS at rest was lower in the cFNB than in the SSTS group for all 3 days after surgery, whereas mNRS scores were lower in the SSTS group at all time points measured. Adverse effects were significantly fewer among patients of the SSTS group (6% patients) than those of the cFNB (74% patients) (p <  0.001). Rescue doses were needed by 5% of SSTS patients vs 60% of cFNB. The fewer adverse events and lower pain scores for the SSTS group were associated to a notably better ability to ambulate, with all patients (100%) of the SSTS group being able to stand and walk for 10 m from T1 on; patients in the cFNB group showed a slower recovery with only 40% being able to stand and walk on T1, 70% on T2 and 85% on T3. All patients of the SSTS group had a length of stay of 4 days (day of surgery plus 3 after) as foreseen by the fast track protocol, in comparison only 36% of cFNB. Lastly, patient and nursing staff judged SSTS easy to use. Conclusion Our experience suggests that SSTS is a valuable strategy for routine postoperative analgesia following TKA in the context of a multimodal analgesic approach within the fast-track setting

Determination of total silicon and SiO2 particles using an ICP-MS based analytical platform for toxicokinetic studies of synthetic amorphous silica

Synthetic amorphous silica (SAS), manufactured in pyrogenic or precipitated form, is a nanomaterial with a widespread use as food additive (E 551). Oral exposure to SAS results from its use in food and dietary supplements, pharmaceuticals and toothpaste. Recent evidence suggests that oral exposure to SAS may pose health risks and highlights the need to address the toxic potential of SAS as affected by the physicochemical characteristics of the different forms of SAS. For this aim, investigating SAS toxicokinetics is of crucial importance and an analytical strategy for such an undertaking is presented. The minimization of silicon background in tissues, control of contamination (including silicon release from equipment), high-throughput sample treatment, elimination of spectral interferences affecting inductively coupled plasma mass spectrometry (ICP-MS) silicon detection, and development of analytical quality control tools are the cornerstones of this strategy. A validated method combining sample digestion with silicon determination by reaction cell ICP-MS is presented. Silica particles are converted to soluble silicon by microwave dissolution with mixtures of HNO3, H2O2 and hydrofluoric acid (HF), whereas interference-free ICP-MS detection of total silicon is achieved by ion-molecule chemistry with limits of detection (LoDs) in the range 0.2–0.5 µg Si g−1 for most tissues. Deposition of particulate SiO2 in tissues is assessed by single particle ICP-MS105Nanotechnology in Agriculture and Food IndustryThis work arises from the NANOGENOTOX Joint Action which has received funding from the European Union, in the framework of the Health Programme. The NANOGENOTOX Joint Action was co-funded by the Executive Agency for Health and Consumers (Grant Agreement 2009 21 01). This publication reflects only the authors’ views and the Executive Agency for Health and Consumers (now CHAFEA) is not liable for any use that may be made of the information contained therei

Selenium Bioaccessibility and Speciation in Selenium-Enriched Lettuce: Investigation of the Selenocompounds Liberated after in Vitro Simulated Human Digestion Using Two-Dimensional HPLC-ICP-MS

The evaluation of selenium-enriched vegetables as potential dietary sources of selenium, an essential element for humans, requires an assessment of the plant’s accumulation ability as well as of the bioaccessibility and speciation of the accumulated selenium, which influence its biological effects in humans. Lettuce hydroponically grown at three selenite (SeVI)/selenate (SeIV) amendment levels was characterized accordingly. Selenium accumulation in lettuce leaves was greatest with Se­(VI) amendment, whereas bioaccessibility was 70% on average in both cases. Selenium speciation in gastrointestinal hydrolysates, characterized by anion and cation exchange HPLC-ICP-MS, showed that Se­(IV) was largely biotransformed into organoselenium metabolites, with selenomethionine accounting for 1/3 of the total detected species, whereas Se­(VI) was incorporated as such in the edible portion of the plant, with only a small fraction (∼20%) converted into organic species. Taking into account both nutritional quality and safety, the Se­(IV)-enriched lettuce appeared more favorable as a potential selenium source for human consumption