Age-related increase in resistance to acute Trypanosoma cruzi infection in rats is associated with an appropriate antibody response

Inoculation at weaning with Trypanosoma cruzi in inbred 'l' rats resulted in a self-resolving acute infection characterized by marked parasitaemias, whereas challenge to adult rats revealed a mild disease with extremely low parasitaemias. To explore the mechanisms underlying such age-associated differences in disease outcome, we analysed the in vitro replication of T. cruzi, nitric oxide and tumour necrosis factor-α (TNF-α) production in peritoneal macrophages (PMs), the serum concentrations of the specific immunoglobulins (Igs) IgM and IgG, antibodies exhibiting lytic activity against bloodstream forms of T. cruzi and circulating levels of nitrate, TNF-α and interferon-γ (IFN-γ). Macrophages from young rats were as effective as their adult counterparts for restraining intracellular parasite replication. When stimulated with IFN-γ, culture supernatants from young PMs contained higher amounts of nitrite and TNF-α. Serum samples from 4 and 7 days post infection revealed easily detectable amounts of nitrate, with values being further augmented by day 7 post infection and significantly higher in the young group. TNF-α levels were only detected in the young group by day 7 post infection. Both groups had increased amounts of IFN-γ in their sera, although in adult rats, this trend was followed by a significant drop at day 7, with young rats showing values still higher by the same time point evaluation. In contrast, young rats presented significantly lower levels of IgM and IgG antibodies during the first week of infection. Increased resistance in adult rats seems to be the result of a more appropriate antibody production.Fil: Pascutti, María Fernanda. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Inmunología Clinica y Experimental de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología Clinica y Experimental de Rosario; ArgentinaFil: Bottasso, Oscar Adelmo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Inmunología Clinica y Experimental de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología Clinica y Experimental de Rosario; ArgentinaFil: Hourquescos, M. C.. Universidad Nacional de Rosario; ArgentinaFil: Wietzerbin, Jeanne. Institute Curie; FranciaFil: Revelli, Silvia Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Inmunología Clinica y Experimental de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología Clinica y Experimental de Rosario; Argentin

TNF-α Is Involved in the Abnormal Thymocyte Migration during Experimental Trypanosoma cruzi Infection and Favors the Export of Immature Cells

Previous studies revealed a significant production of inflammatory cytokines together with severe thymic atrophy and thymocyte migratory disturbances during experimental Chagas disease. Migratory activity of thymocytes and mature T cells seem to be finely tuned by cytokines, chemokines and extracellular matrix (ECM) components. Systemic TNF-α is enhanced during infection and appears to be crucial in the response against the parasite. However, it also seems to be involved in disease pathology, since it is implicated in the arrival of T cells to effector sites, including the myocardium. Herein, we analyzed the role of TNF-α in the migratory activity of thymocytes in Trypanosoma cruzi (T. cruzi) acutely-infected mice. We found increased expression and deposition of TNF-α in the thymus of infected animals compared to controls, accompanied by increased co-localization of fibronectin, a cell migration-related ECM molecule, whose contents in the thymus of infected mice is also augmented. In-vivo studies showed an enhanced export of thymocytes in T. cruzi-infected mice, as ascertained by intrathymic injection of FITC alone or in combination with TNF-α. The increase of immature CD4+CD8+ T cells in secondary lymphoid organs was even more clear-cut when TNF-α was co-injected with FITC. Ex-vivo transmigration assays also revealed higher number of migrating cells when TNF-α was added onto fibronectin lattices, with higher input of all thymocyte subsets, including immature CD4+CD8+. Infected animals also exhibit enhanced levels of expression of both mRNA TNF-α receptors in the CD4+CD8+ subpopulation. Our findings suggest that in T. cruzi acute infection, when TNF-α is complexed with fibronectin, it favours the altered migration of thymocytes, promoting the release of mature and immature T cells to different compartments of the immune system. Conceptually, this work reinforces the notion that thymocyte migration is a multivectorial biological event in health and disease, and that TNF-α is a further player in the process

Deficient control of Trypanosoma cruzi infection in C57BL/6 mice is related to a delayed specific IgG response and increased macrophage production of pro-inflammatory cytokines

Earlier work in Trypanosoma cruzi-infected C57BL/6 and BALB/c mice revealed an acute disease, of lethal outcome in the former group and lesser severity in BALB/c mice. Fatal course was not accompanied by an increased parasite load, but by a substantial imbalance between pro- and anti-inflammatory cytokine serum levels. To better characterise the mechanisms allowing the host to restrain the infection, we have now studied the specific IgG production and in vitro behaviour of peritoneal macrophages (PMs) when exposed to T. cruzi. BALC/c mice displayed higher serum levels of specific immunoglobulins in the first weeks of acute infection. In vitro infected PMs showed no between-group differences in the number of intracellular parasites, although TNFalpha levels were significantly higher in culture supernatants from C57BL/6 mice. Because an LPS-based pretreatment (desensitisation protocol followed by a sublethal LPS dose) reduced disease severity of C57BL/6 mice, we next explored the features of the in vitro infection in PMs from mice subjected to such protocol. PMs from LPS-pretreated mice had a decreased production of TNFalpha and IL-1beta, becoming more permissive to parasite replication. It is concluded that deficient control of T. cruzi infection in C57BL/6 mice may also involve a less satisfactory specific IgG response and increased TNFalpha production by PMs. Improved disease outcome in LPS-pretreated mice may be associated with the reduced inflammatory cytokine production by PMs, but the impaired ability of these cells to control parasite growth suggests that compensatory mechanisms are operating in the in vivo situation.Fil: Perez, Ana Rosa. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología; ArgentinaFil: Tamae Kakazu, M.. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología; ArgentinaFil: Pascutti, María Fernanda. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Roggero, Eduardo Angel. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología; ArgentinaFil: Serra, Esteban Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; ArgentinaFil: Revelli, Silvia Susana. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología; ArgentinaFil: Bottasso, Oscar Adelmo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología; Argentin

The impact of chest CT body composition parameters on clinical outcomes in COVID-19 patients

We assessed the impact of chest CT body composition parameters on outcomes and disease severity at hospital presentation of COVID-19 patients, focusing also on the possible mediation of body composition in the relationship between age and death in these patients. Chest CT scans performed at hospital presentation by consecutive COVID-19 patients (02/27/2020-03/13/2020) were retrospectively reviewed to obtain pectoralis muscle density and total, visceral, and intermuscular adipose tissue areas (TAT, VAT, IMAT) at the level of T7-T8 vertebrae. Primary outcomes were: hospitalization, mechanical ventilation (MV) and/or death, death alone. Secondary outcomes were: C-reactive protein (CRP), oxygen saturation (SO2), CT disease extension at hospital presentation. The mediation of body composition in the effect of age on death was explored. Of the 318 patients included in the study (median age 65.7 years, females 37.7%), 205 (64.5%) were hospitalized, 68 (21.4%) needed MV, and 58 (18.2%) died. Increased muscle density was a protective factor while increased TAT, VAT, and IMAT were risk factors for hospitalization and MV/death. All these parameters except TAT had borderline effects on death alone. All parameters were associated with SO2 and extension of lung parenchymal involvement at CT; VAT was associated with CRP. Approximately 3% of the effect of age on death was mediated by decreased muscle density. In conclusion, low muscle quality and ectopic fat accumulation were associated with COVID-19 outcomes, VAT was associated with baseline inflammation. Low muscle quality partly mediated the effect of age on mortality.We assessed the impact of chest CT body composition parameters on outcomes and disease severity at hospital presentation of COVID-19 patients, focusing also on the possible mediation of body composition in the relationship between age and death in these patients. Chest CT scans performed at hospital presentation by consecutive COVID-19 patients (02/ 27/2020-03/13/2020) were retrospectively reviewed to obtain pectoralis muscle density and total, visceral, and intermuscular adipose tissue areas (TAT, VAT, IMAT) at the level of T7-T8 vertebrae. Primary outcomes were: hospitalization, mechanical ventilation (MV) and/or death, death alone. Secondary outcomes were: C-reactive protein (CRP), oxygen saturation (SO2), CT disease extension at hospital presentation. The mediation of body composition in the effect of age on death was explored. Of the 318 patients included in the study (median age 65.7 years, females 37.7%), 205 (64.5%) were hospitalized, 68 (21.4%) needed MV, and 58 (18.2%) died. Increased muscle density was a protective factor while increased TAT, VAT, and IMAT were risk factors for hospitalization and MV/death. All these parameters except TAT had borderline effects on death alone. All parameters were associated with SO2 and extension of lung parenchymal involvement at CT; VAT was associated with CRP. Approximately 3% of the effect of age on death was mediated by decreased muscle density. In conclusion, low muscle quality and ectopic fat accumulation were associated with COVID-19 outcomes, VAT was associated with baseline inflammation. Low muscle quality partly mediated the effect of age on mortality

Combined Treatment of Heterocyclic Analogues and Benznidazole upon Trypanosoma cruzi In Vivo

Chagas disease caused by Trypanosoma cruzi is an important cause of mortality and morbidity in Latin America but no vaccines or safe chemotherapeutic agents are available. Combined therapy is envisioned as an ideal approach since it may enhance efficacy by acting upon different cellular targets, may reduce toxicity and minimize the risk of drug resistance. Therefore, we investigated the activity of benznidazole (Bz) in combination with the diamidine prodrug DB289 and in combination with the arylimidamide DB766 upon T. cruzi infection in vivo. The oral treatment of T.cruzi-infected mice with DB289 and Benznidazole (Bz) alone reduced the number of circulating parasites compared with untreated mice by about 70% and 90%, respectively. However, the combination of these two compounds decreased the parasitemia by 99% and protected against animal mortality by 100%, but without providing a parasitological cure. When Bz (p.o) was combined with DB766 (via ip route), at least a 99.5% decrease in parasitemia levels was observed. DB766+Bz also provided 100% protection against mice mortality while Bz alone provided about 87% protection. This combined therapy also reduced the tissular lesions induced by T. cruzi infection: Bz alone reduced GPT and CK plasma levels by about 12% and 78% compared to untreated mice group, the combination of Bz with DB766 resulted in a reduction of GPT and CK plasma levels of 56% and 91%. Cure assessment through hemocultive and PCR approaches showed that Bz did not provide a parasitological cure, however, DB766 alone or associated with Bz cured ≥13% of surviving animals

Le rappresentazioni degli italiani regionali: esperienze di formazione alla ricerca linguistica (2a parte)

Questa seconda parte dell’articolo pubblicato in ESP n. 47 riassume i risultati di un progetto di formazione alla ricerca linguistica intrapresa congiuntamente dall’Istituto di Lingua e letteratura italiana dell’università di Berna e dal Dipartimento di Scienze umane e Sociali dell’università della Valle d’Aosta durante l’anno accademico 2019/2020. Accanto alla metodologia ed alle tecniche d’inchiesta elaborate allo scopo di far conoscere agli studenti un’esperienza di ricerca applicata in laboratorio, vengono presentati alcuni dati dello studio condotto parallelamente dai due siti. Il tema degli atteggiamenti e comportamenti di fronte agli italiani regionali è stato esplorato dall’équipe bernese, riferito a variabili come il luogo di residenza, il livello d’istruzione, il sesso e l’uso delle lingue in famiglia, mentre l’équipe aostana si è concentrata principalmente sulla capacità di situare correttamente le varietà di italiano secondo le età (10-19 anni), rispetto anche alla pronuncia dei non italofoni

Le rappresentazioni degli italiani regionali: esperienze di formazione alla ricerca linguistica

Der Beitrag stellt eine interuniversitäre Initiative innerhalb der Ausbildung der Sprachforschung vor, die gemeinsam vom Institut für italienische Sprache und Literatur der Universität Bern und dem Departement für Human- und Sozialwissenschaften der Universität des Aostatals initiiert wurde. Die Aktivität konzentriert sich auf das Thema des Regionalitalienischen bzw. auf die Reaktionen, die es bei Sprechern auslösen kann. Das Thema der Spracheinstellungen eignet sich für Gruppenanalysen, die darauf abzielen, mit unterschiedlichen methodischen Ansätzen zu experimentieren. Die gemeinsame Durchführung von Aktivitäten der beiden Universitäten wird als eine alternative Erfahrung zum Selbststudiums konzipiert, das nach wie vor sowohl in der universitären Didaktik als auch in der Forschung innerhalb der Geisteswissenschaften überwiegt

Chlorate formation in water distribution systems: a modeling study

Chlorine-based disinfection agents are known to favor the production of Disinfection By-Products (DBPs), whose concentrations are restricted by international guidelines to ensure a safe consumption of drinking water. Hence, it is important to understand the behavior of DBPs within Water Distribution Networks (WDNs) to avoid users exposure to concentrations higher than guideline values. The buildup in chlorate concentration resulting from chlorinated disinfectants is here simulated with the EPANET 2.0 software for one benchmark WDN serving about 130,000 inhabitants. Chlorate generation was accounted by means of an empirical model, considering different boundary conditions (physic-chemical features of raw water, disinfectant dose). The gathered results indicate that increases in chlorate concentration within the considered WDN are narrow. Chlorate neo formation in the WDN is however strictly related to the initial amount of chlorate released by the WTP, i.e. to the input value in the WDN. If chlorate concentration in treatment plants is kept below 700 μg/L (i.e. WHO guideline), depending on the mixing conditions in tanks, the simulation results referred to the considered WDN show that the DBP buildup within the network is limited (in any case lower than 5-7% of the threshold value)