Tenebrio molitor as a Simple and Cheap Preclinical Pharmacokinetic and Toxicity Model

The progression of drugs into clinical phases requires proper toxicity assessment in animals and the correct identification of possible metabolites. Accordingly, different animal models are used to preliminarily evaluate toxicity and biotransformations. Rodents are the most common models used to preliminarily evaluate the safety of drugs; however, their use is subject to ethical consideration and elevated costs, and strictly regulated by national legislations. Herein, we developed a novel, cheap and convenient toxicity model using Tenebrio molitor coleoptera (TMC). A panel of 15 drugs-including antivirals and antibacterials-with different therapeutic applications was administered to TMC and the LD50 was determined. The values are comparable with those already determined in mice and rats. In addition, a TMC model was used to determine the presence of the main metabolites and in vivo pharmacokinetics (PK), and results were compared with those available from in vitro assays and the literature. Taken together, our results demonstrate that TMC can be used as a novel and convenient preliminary toxicity model to preliminarily evaluate the safety of experimental compounds and the formation of main metabolites, and to reduce the costs and number of rodents, according to 3R principles

Effects of ω-3 PUFA-enriched diet on growth parameters in a syngenic murine model of breast adenocarcinoma: a possible role for estrogen receptor alpha

Background: Breast cancer (BC) is the most common tumour among women and 75% of BC are estrogen receptor (ER)dependent. In particular, ERα promotes tumour growth, while ERβ has an anti-proliferative effect [1]. Epidemiological data have linked ω-3 polyunsaturated fatty acid (PUFA) consumption to lower incidence of BC and several experimental studies showed the anti-proliferative effects of ω-3 fish oil in different tumour models [2,3]. Chia seed oil is rich in α-linolenic acid (ALA 18:3 ω-3), while corn oil is rich in linoleic acid (LA 18:2 ω-6), precursors of eicosapentaenoic acid (EPA) and arachidonic acid (AA), respectively. Based on substrate availability, these FAs give rise to different eicosanoid signatures with opposite effects in cancer [4]. ω-3 PUFAs generate both anti-inflammatory prostanoids and reactive oxygen species (ROS), which in turn could affect NF-κB. Indeed, NF-κB belongs to a family of transcription factors with a key role in inflammation and oxidative stress, but its role in tumour development is still controversial [5]. The aim of the study was to determine possible processes that are activated by dietary lipids regulating BC growth and metastasis.Fil: Vara Messler, Marianela. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Instituto de Biología Celular; Argentina.Fil: Vara Messler, Marianela. Universidad de Padova. Departamento de Ciencias Farmacéuticas y Farmacológicas; Italia.Fil: Pasqualini, María Eugenia. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Instituto de Biología Celular; Argentina.Fil: Comba, Andrea. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Instituto de Biología Celular. Cátedra de Biología, Histología y Embriología; Argentina.Fil:Comba, Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ciencias de la Salud; Argentina.Fil: Toniolo, Alicia. Universidad de Padova. Departamento de Ciencias Farmacéuticas y Farmacológicas; Italia.Fil: Trenti, Annalisa. Universidad de Padova. Departamento de Ciencias Farmacéuticas y Farmacológicas; Italia.Fil: Quiroga, Patricia. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Instituto de Biología Celular; Argentina.Fil: Valentich, Mirta Ana. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Instituto de Biología Celular; Argentina.Fil: Valentich, Mirta Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ciencias de la Salud; Argentina.Fil: Bolego, Chiara. Universidad de Padova. Departamento de Ciencias Farmacéuticas y Farmacológicas; Italia.Otras Ciencias de la Salu

The p50 NF-\u3baB subunit is a prognostic regulator of colorectal cancer-associated inflammation

In most tumors, tumor associated macrophages (TAMs) express an M2-skewed phenotype and are therefore associated with unfavorable prognosis. However, the impact of TAMs in colorectal cancer (CRC) development and outcome is still controversial. We first demonstrate, by parallel studies in colitis-associated cancer (CAC) and in genetically driven ApcMin mouse models, that p50 NF-\u3baB is essential for CRC development by restraining M1-dependent antitumor response. In absence of p50 mice developed fewer and smaller CRC lesions which express enhanced levels of M1/Th1 cytokines/chemokines including IL-12 and CXCL10, whose administration restrained CAC development in vivo. Moreover colons from p50-/- tumor bearers showed a reduced number of TAMs, as opposed to increased NK, NKT, CD8+ T cells and apoptotic cancer cells. Consistently, in CRC patients, high burden of p50+ TAMs was associated with decreased M1/Th1 inflammation and worse outcome indicating p50 as a new candidate for prognostic and target therapeutic intervention

The CCL3 Family of Chemokines and Innate Immunity Cooperate In Vivo in the Eradication of an Established Lymphoma Xenograft by Rituximab

The therapeutic mAb rituximab induced the expression of the CCL3 and CCL4 chemokines in the human lymphoma line BJAB following binding to the CD20 Ag. Induction of CCL3/4 in vitro was specific, was observed in several cell lines and freshly isolated lymphoma samples and also took place at the protein level in vitro and in vivo. To investigate the role of these beta-chemokines in the mechanism of action of rituximab, we synthesized a N-terminally truncated CCL3 molecule CCL3(11\u201370), which had antagonist activity on chemotaxis mediated by either CCL3 or BJAB supernatant. We also set up an established s.c. BJAB tumor model in athymic mice. Rituximab, given weekly after tumors had reached 250 mm2, led to complete disappearance of the lymphoma within 2\u20133 wk. Treatment of mice with cobra venom factor showed that complement was required for rituximab therapeutic activity. Treatment of BJAB tumor bearing mice every 2 days with the CCL3(11\u201370) antagonist, starting 1 wk before rituximab treatment, had no effect on tumor growth by itself, but completely inhibited the therapeutic activity of the Ab. To determine whether CCL3 acts through recruitment/activation of immune cells, we specifically depleted NK cells, polymorphonuclear cells, and macrophages using mAbs, clodronate treatment, or Rag2\u2013/\u2013c\u2013/\u2013 mice. The data demonstrated that these different cell populations are involved in BJAB tumor eradication. We propose that rituximab rapidly activates complement and induces beta-chemokines in vivo, which in turn activate the innate immunity network required for efficient eradication of the bulky BJAB tumor

Monitoring of indoor bioaerosol for the detection of SARS-CoV-2 in different hospital settings

BackgroundSpore Trap is an environmental detection technology, already used in the field of allergology to monitor the presence and composition of potentially inspirable airborne micronic bioparticulate. This device is potentially suitable for environmental monitoring of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in hospital, as well as in other high-risk closed environments. The aim of the present study is to investigate the accuracy of the Spore Trap system in detecting SARS-CoV-2 in indoor bioaerosol of hospital rooms.MethodsThe Spore Trap was placed in hospital rooms hosting patients with documented SARS-CoV-2 infection (n = 36) or, as a negative control, in rooms where patients with documented negativity to a Real-Time Polymerase Chain Reaction molecular test for SARS-CoV-2 were admitted (n = 10). The monitoring of the bioaerosol was carried on for 24 h. Collected samples were analyzed by real-time polymerase chain reaction.ResultsThe estimated sensitivity of the Spore Trap device for detecting SARS-CoV-2 in an indoor environment is 69.4% (95% C.I. 54.3-84.4%), with a specificity of 100%.ConclusionThe Spore Trap technology is effective in detecting airborne SARS-CoV-2 virus with excellent specificity and high sensitivity, when compared to previous reports. The SARS-CoV-2 pandemic scenario has suggested that indoor air quality control will be a priority in future public health management and will certainly need to include an environmental bio-investigation protocol

Computed micro-tomographic evaluation of glide pathwith nickel-titanium rotary pathFile in maxillary firstmolars curved canals

Introduction: X-ray computed micro-tomography scanning allows high-resolution 3-dimensional imaging of small objects. In this study, micro-CT scanning was used to compare the ability of manual and mechanical glide path to maintain the original root canal anatomy. Methods: Eight extracted upper first permanent molars were scanned at the TOMOLAB station at ELETTRA Synchrotron Light Laboratory in Trieste, Italy, with a microfocus cone-beam geometry system. A total of 2,400 projections on 360 degrees have been acquired at 100 kV and 80 mu A, with a focal spot size of 8 mu m. Buccal root canals of each specimen (n = 16) were randomly assigned to Path File (P) or stainless-steel K-file (K) to perform glide path at the full working length. Specimens were then microscanned at the apical level (A) and at the point of the maximum curvature level (C) for post-treatment analyses. Curvatures of root canals were classified as moderate (<= 35 degrees) or severe (>= 40 degrees). The ratio of diameter ratios (RDRs) and the ratio of cross-sectional areas (RAs) were assessed. For each level of analysis (A and C), 2 balanced 2-way factorial analyses of variance (P < .05) were performed to evaluate the significance of the instrument factor and of canal curvature factor as well as the interactions of the factors both with RDRs and RAs. Results: Specimens in the K group had a mean curvature of 35.4 degrees +/- 11.5 degrees; those in the P group had a curvature of 38 degrees +/- 9.9 degrees. The instrument factor (P and K) was extremely significant (P < .001) for both the RDR and RA parameters, regardless of the point of analysis. Conclusions: Micro-CT scanning confirmed that NiTi rotary Path File instruments preserve the original canal anatomy and cause less canal aberrations. (J Endod 2012;38:389-393

Procedure for short-lived particle detection in the OPERA experiment and its application to charm decays

The OPERA experiment, designed to perform the first observation of $\nu_\mu \rightarrow \nu_\tau$ oscillations in appearance mode through the detection of the $\tau$ leptons produced in $\nu_\tau$ charged current interactions, has collected data from 2008 to 2012. In the present paper, the procedure developed to detect $\tau$ particle decays, occurring over distances of the order of 1 mm from the neutrino interaction point, is described in detail. The results of its application to the search for charmed hadrons are then presented as a validation of the methods for $\nu_\tau$ appearance detection

Crossing the River di Caryl Phillips: proposta di analisi e traduzione di un romanzo musicale

L'elaborato si propone di analizzare Crossing the River di Caryl Phillips in qualità di romazo musicale,ossia di un romanzo nel quale si tenta un'imitazione iconica di un medium altro rispetto a quello letterario, in questo caso della musica. La tesi si apre con un'approfondita introduzione sull'autore e la sua poetica e si focalizza in particolare sul problema della forma dei suoi romanzi per poi procedere alla ricerca, all'interno del mondo dei Word and Music Studies, di una cassetta degli attrezzi adeguata che ci consenta di proporre un'analisi efficace della sperimentazione formale riscontrabile in un romanzo come Crossing the River. Viene inoltre proposta la traduzione di due delle sezioni che compongono il romanzo

Study of a hard X-rayConcentrator via crystal diffraction

The results of a Monte Carlo study of a hard X-ray concentrator for space astronomy are presented. This report is a part of a systematic study devoted to investigate the possibility of utilizing the Bragg diffraction technique to concentrate hard X-rays. In the Monte Carlo study a concentrator made of confocal mirrors with paraboloidal shape is considered. The mirror material is graphite (002) with mosaic structure. The main photon interactions of hard X-rays with the concentrator are simulated. Effective area and optical properties of a particular configuration of concentrator with shape that could be easily accommodate on the Space Station or aboard a free-flyer are given. Expected performances are discussed