Accidental ingestion of sodium molybdate at the workplace followed by short-term biomonitoring

Introduction:Most of the molybdenum (Mo) is used in metallurgical applications, the tetrathiomolybdate form is an experimental chelating agent for Wilson’s disease. Human data of acute Mo exposure are lacking and, no report of no-observed-adverse-effect level (NOAEL) has been described until now.Case study:We report a case of acute occupational exposure to molybdenum, with the related plasma and urine molybdenum concentrations, caused by an accidental ingestion of a sip of an anti-corrosion liquid for metal containing sodium molybdate. Our purpose was to evaluate potential systemic toxicity of molybdenum and to evaluate the dose-response/dose-effect relationship. We estimated the amount of ingested molybdenum to make a mg/kg relationship and performed repeated urine and plasma molybdenum determinations. The patient was hospitalized for three days to monitor possible development of acute symptoms/biochemical alterations.Discussion:We estimated the amount of the sip around 50 ml, with an estimation of a total of 5 gr of sodium molybdate that, for the patient bodyweight of 80 kg, would mean 62,5 mg/kg of ingested Mo. Blood and urine samples collected 2 hours after ingestion showed 50 mcg/L (reference range: 0.43 – 1.8 mcg/L) and 630 mcg/L (refence range: up to 116 mcg/L) of Mo respectively, confirming acute exposure. The patients remained asymptomatic confirming that an estimated oral dose of Mo of 62.5 mg/kg was not associated with adverse effects.Conclusions:Our value, being extrapolated by a single case, will require further confirmations from other studies to allow a full evaluation of a NOAEL. Nevertheless, it does not preclude its use in evaluating the probable absence of adverse effect in the context of acute Mo exposure.     

Reactive vaccination as control strategy for an outbreak of invasive meningococcal disease caused by Neisseria meningitidis C:P1.5-1,10-8:F3-6:ST-11(cc11), Bergamo province,Italy, December 2019 to January 2020

In Italy, serogroup C meningococci of the clonal complex cc11 (MenC/cc11) have caused several outbreaks of invasive meningococcal disease (IMD) during the past 20 years. Between December 2019 and January 2020, an outbreak of six cases of IMD infected with MenC/cc11 was identified in a limited area in the northern part of Italy. All cases presented a severe clinical picture, and two of them were fatal. This report is focused on the microbiological and molecular analysis of meningococcal isolates with the aim to reconstruct the chain of transmission. It further presents the vaccination strategy adopted to control the outbreak. The phylogenetic evaluation demonstrated the close genetic proximity between the strain involved in this outbreak and a strain responsible for a larger epidemic that had occurred in 2015 and 2016 in the Tuscany Region. The rapid identification and characterisation of IMD cases and an extensive vaccination campaign contributed to the successful control of this outbreak caused by a hyperinvasive meningococcal strain.     

Zootechnical wastewater reuse: constructed wetland as a challenge for protozoan parasite removal

Samples of soil, well water, and wastewater from a zootechnical farm, water after phytodepuration and maize plants (Zea mays) grown on soils irrigated with these different kinds of water were analysed for indicator bacteria and the protozoa Giardia and Cryptosporidium. Protozoa and bacterial indicators, except coliforms, were not recovered from well water samples. In the effluent from the zootechnical farm, high parasitological concentrations were observed, whilst water after the phytodepuration process showed a concentration reduction of two orders of magnitude. The high numbers of Giardia and Cryptosporidium in the zootechnical effluent could represent a potential risk for the spread of the pathogens. Nevertheless the environmental spread is minimized when data on soils and plants are observed. From the study, it emerges that this water treatment system could represent an alternative option to other conventional wastewater treatments and an economic and environmental advantage.     

Dual IGF1R/IR inhibitors in combination with GD2-CAR T-cells display a potent anti-tumor activity in diffuse midline glioma H3K27M-mutant

BackgroundDiffuse midline gliomas (DMG) H3K27M-mutant, including diffuse intrinsic pontine glioma (DIPG), are pediatric brain tumors associated with grim prognosis. Although GD2-CAR T-cells demonstrated significant anti-tumor activity against DMG H3K27M-mutant in vivo, a multimodal approach may be needed to more effectively treat patients. We investigated GD2 expression in DMG/DIPG and other pediatric high-grade gliomas (pHGG) and sought to identify chemical compounds that would enhance GD2-CAR T-cell anti-tumor efficacy.MethodsImmunohistochemistry in tumor tissue samples and immunofluorescence in primary patient-derived cell lines were performed to study GD2 expression. We developed a high-throughput cell-based assay to screen 42 kinase inhibitors in combination with GD2-CAR T-cells. Cell viability, western blots, flow-cytometry, real time PCR experiments, DIPG 3D culture models, and orthotopic xenograft model were applied to investigate the effect of selected compounds on DIPG cell death and CAR T-cell function.ResultsGD2 was heterogeneously, but widely, expressed in the tissue tested, while its expression was homogeneous and restricted to DMG/DIPG H3K27M-mutant cell lines. We identified dual IGF1R/IR antagonists, BMS-754807 and linsitinib, able to inhibit tumor cell viability at concentrations that do not affect CAR T-cells. Linsitinib, but not BMS-754807, decreases activation/exhaustion of GD2-CAR T-cells and increases their central memory profile. The enhanced anti-tumor activity of linsitinib/GD2-CAR T-cell combination was confirmed in DIPG models in vitro, ex vivo, and in vivo.ConclusionOur study supports the development of IGF1R/IR inhibitors to be used in combination with GD2-CAR T-cells for treating patients affected by DMG/DIPG and, potentially, by pHGG.     

Absence of Allergic Reactions to Egg White Lysozyme Additive in Grana Padano Cheese

Objective: The negative effects on cheese quality of milk contaminated by spores of Clostridium butyricum and Cl.tyrobutyricum is prevented by the use of egg white lysozyme as additive. Since the presence of lysozyme in cheese could be possibly risky in allergic subjects, we aimed at investigating its absorption as well as serum IgE antibody titers after ingestion of Grana Padano cheese, an Italian DPO, long-ripened hard cheese, in white egg allergic subjects.

Methods: Cheese lysozyme was measured by HPLC. Ten healthy volunteers and 20 patients with hen egg hypersensitivity, RAST positive (binding≥3%) to lysozyme and/or ovomucoid and ovalbumin received 15, 30 and 60 g of cheese at distance of at least 2 weeks each. Serum lysozyme was measured by ELISA and specific IgE binding to lysozyme by the radioallergosorbent test (RAST).

Results: The concentration of lysozyme in cheese was 155 ± 5 mg/kg. The area-under-the-curve of serum lysozyme after 15 g of cheese was 244.5 ± 14.0 in controls and 330.2 ± 9.9 in patients (p < 0.01). Similar results were obtained with 30 and 60 g of cheese. Only 3 patients (15%) showed positive IgE antibody responses to cheese (overall RAST mean 4.45 ± 1.25 % vs. 4.24 ± 1.02 % baseline, p = ns).

Conclusions: The amount of lysozyme absorbed with cheese was globally very low, although it was significantly lower in healthy controls than in allergic patients, where it induced an increase of IgE RAST score in 15% of subjects, without any clinical reaction. Therefore, the use of lysozyme as additive in Grana Padano cheese, does not appear to be harmful in egg allergic subjects.