Inhalation of Bacterial Cellulose Nanofibrils Triggers an Inflammatory Response and Changes Lung Tissue Morphology of Mice

Silva-Carvalho, Ricardo,Silva, Joao P.,Ferreirinha, Pedro,Leitao, Alexandre F.,Andrade, Fabia K.,da Costa, Rui M. Gil,Cristelo, Cecilia,Rosa, Morsyleide F.,Vilanova, Manuel,Gama, F. Miguel Korean Society of ToxicologyKorea Environmental Mu 2019 Toxicological Research Vol.35 No.1

In view of the growing industrial use of Bacterial cellulose (BC), and taking into account that it might become airborne and be inhaled after industrial processing, assessing its potential pulmonary toxic effects assumes high relevance. In this work, the murine model was used to assess the effects of exposure to respirable BC nanofibrils (nBC), obtained by disintegration of BC produced by Komagataeibacter hansenii. Murine bone marrow-derived macrophages ($BMM{\Phi}$) were treated with different doses of nBC (0.02 and 0.2 mg/mL, respectively 1 and $10{\mu}g$ of fibrils) in absence or presence of 0.2% Carboxymethyl Cellulose (nBCMC). Furthermore, mice were instilled intratracheally with nBC or nBCMC at different concentrations and at different time-points and analyzed up to 6 months after treatments. Microcrystaline $Avicel-plus^{(R)}$ CM 2159, a plant-derived cellulose, was used for comparison. Markers of cellular damage (lactate dehydrogenase release and total protein) and oxidative stress (hydrogen peroxidase, reduced glutathione, lipid peroxidation and glutathione peroxidase activity) as well presence of inflammatory cells were evaluated in brochoalveolar lavage (BAL) fluids. Histological analysis of lungs, heart and liver tissues was also performed. BAL analysis showed that exposure to nBCMC or CMC did not induce major alterations in the assessed markers of cell damage, oxidative stress or inflammatory cell numbers in BAL fluid over time, even following cumulative treatments. $Avicel-plus^{(R)}$ CM 2159 significantly increased LDH release, detected 3 months after 4 weekly administrations. However, histological results revealed a chronic inflammatory response and tissue alterations, being hypertrophy of pulmonary arteries (observed 3 months after nBCMC treatment) of particular concern. These histological alterations remained after 6 months in animals treated with nBC, possibly due to foreign body reaction and the organism's inability to remove the fibers. Overall, despite being a safe and biocompatible biomaterial, BC-derived nanofibrils inhalation may lead to lung pathology and pose significant health risks.

Inhalation of Bacterial Cellulose Nanofibrils Triggers an Inflammatory Response and Changes Lung Tissue Morphology of Mice

Ricardo Silva-Carvalho,Joao P. Silva,Pedro Ferreirinha,Alexandre F. Leitao,Fabia K. Andrade,Rui M. Gil da Costa,Cecilia Cristelo,Morsyleide F. Rosa,Manuel Vilanova,F. Miguel Gama 한국독성학회 2019 Toxicological Research Vol.35 No.1

In view of the growing industrial use of Bacterial cellulose (BC), and taking into account that it might become airborne and be inhaled after industrial processing, assessing its potential pulmonary toxic effects assumes high relevance. In this work, the murine model was used to assess the effects of exposure to respirable BC nanofibrils (nBC), obtained by disintegration of BC produced by Komagataeibacter hansenii. Murine bone marrow-derived macrophages (BMMΦ) were treated with different doses of nBC (0.02 and 0.2 mg/mL, respectively 1 and 10 μg of fibrils) in absence or presence of 0.2% Carboxymethyl Cellulose (nBCMC). Furthermore, mice were instilled intratracheally with nBC or nBCMC at different concentrations and at different time-points and analyzed up to 6 months after treatments. Microcrystaline Avicel-plus® CM 2159, a plant-derived cellulose, was used for comparison. Markers of cellular damage (lactate dehydrogenase release and total protein) and oxidative stress (hydrogen peroxidase, reduced glutathione, lipid peroxidation and glutathione peroxidase activity) as well presence of inflammatory cells were evaluated in brochoalveolar lavage (BAL) fluids. Histological analysis of lungs, heart and liver tissues was also performed. BAL analysis showed that exposure to nBCMC or CMC did not induce major alterations in the assessed markers of cell damage, oxidative stress or inflammatory cell numbers in BAL fluid over time, even following cumulative treatments. Avicel-plus® CM 2159 significantly increased LDH release, detected 3 months after 4 weekly administrations. However, histological results revealed a chronic inflammatory response and tissue alterations, being hypertrophy of pulmonary arteries (observed 3 months after nBCMC treatment) of particular concern. These histological alterations remained after 6 months in animals treated with nBC, possibly due to foreign body reaction and the organism’s inability to remove the fibers. Overall, despite being a safe and biocompatible biomaterial, BC-derived nanofibrils inhalation may lead to lung pathology and pose significant health risks.

Quantification of the available acid sites in the hydrocracking of nitrogen-containing feedstocks over USY shaped NiMo-catalysts

Pedro S. F. Mendes,Joao M. Silva,M. Filipa Ribeiro,Christophe Bouchy,Antoine Daudin 한국공업화학회 2019 Journal of Industrial and Engineering Chemistry Vol.71 No.-

The inhibition of Brønsted acid sites by nitrogen-containing molecules was quantified under industriallyrelevant hydrocracking conditions. This was achieved by testing bifunctional catalysts based on HUSYzeolite in cyclohexane hydroconversion. For ammonia partial pressures within 0.2-2.8 kPa, thepercentage of inhibited Brønsted sites was superior to 98% at 623 K. Significant reduction in theammonia content caused rather moderate variations on the number of available sites. Conversely, atemperature raise from 600 to 640 K triplicated the vacant Brønsted sites due to the significantendothermicity of ammonia desorption. The inhibiting effect of ammonia can be therefore easilymodulated by temperature.

A 6-Point TACS Score Predicts In-Hospital Mortality Following Total Anterior Circulation Stroke

Adrian D Wood,Nicholas D Gollop,Joao H Bettencourt-Silva,Allan B Clark,Anthony K Metcalf,Kristian M Bowles,Marcus D Flather,John F Potter,Phyo Kyaw Myinta 대한신경과학회 2016 Journal of Clinical Neurology Vol.12 No.4

Background and Purpose Little is known about the factors associated with in-hospital mortality following total anterior circulation stroke (TACS). We examined the characteristics and comorbidity data for TACS patients in relation to in-hospital mortality with the aim of developing a simple clinical rule for predicting the acute mortality outcome in TACS. Methods A routine data registry of one regional hospital in the UK was analyzed. The sub¬jects were 2,971 stroke patients with TACS (82% ischemic; median age=81 years, interquar¬tile age range=74–86 years) admitted between 1996 and 2012. Uni- and multivariate regres¬sion models were used to estimate in-hospital mortality odds ratios for the study covariates. A 6-point TACS scoring system was developed from regression analyses to predict in-hospi¬tal mortality as the outcome. Results Factors associated with in-hospital mortality of TACS were male sex [adjusted odds ratio (AOR)=1.19], age (AOR=4.96 for ≥85 years vs. <65 years), hemorrhagic subtype (AOR=1.70), nonlateralization (AOR=1.75), prestroke disability (AOR=1.73 for moderate disability vs. no symptoms), and congestive heart failure (CHF) (AOR=1.61). Risk stratifica¬tion using the 6-point TACS Score [T=type (hemorrhage=1 point) and territory (nonlateral¬ization=1 point), A=age (65–84 years=1 point, ≥85 years=2 points), C=CHF (if present=1 point), S=status before stroke (prestroke modified Rankin Scale score of 4 or 5=1 point)] reli-ably predicted a mortality outcome: score=0, 29.4% mortality; score=1, 46.2% mortality [negative predictive value (NPV)=70.6%, positive predictive value (PPV)=46.2%]; score=2, 64.1% mortality (NPV=70.6, PPV=64.1%); score=3, 73.7% mortality (NPV=70.6%, PPV=73.7%); and score=4 or 5, 81.2% mortality (NPV=70.6%, PPV=81.2%). Conclusions We have identified the key determinants of in-hospital mortality following TACS and derived a 6-point TACS Score that can be used to predict the prognosis of particular patients.

A History of Falls is Associated with a Significant Increase in Acute Mortality in Women after Stroke

Emma J. Foster,Raphae S. Barlas,Adrian D Wood,Joao H. Bettencourt-Silva,Allan B Clark,Anthony K Metcalf,Kristian M Bowles,John F Potter,Phyo K. Myint 대한신경과학회 2017 Journal of Clinical Neurology Vol.13 No.4

Background and Purpose The risks of falls and fractures increase after stroke. Little is known about the prognostic significance of previous falls and fractures after stroke. This study examined whether having a history of either event is associated with poststroke mortality. Methods We analyzed stroke register data collected prospectively between 2003 and 2015. Eight sex-specific models were analyzed, to which the following variables were incrementally added to examine their potential confounding effects: age, type of stroke, Oxfordshire Community Stroke Project classification, previous comorbidities, frailty as indicated by the prestroke modified Rankin Scale score, and acute illness parameters. Logistic regression was applied to investigate in-hospital and 30-day mortality, and Cox proportional-hazards models were applied to investigate longer-term outcomes of mortality. Results In total, 10,477 patients with stroke (86.1% ischemic) were included in the analysis. They were aged 77.7±11.9 years (mean±SD), and 52.2% were women. A history of falls was present in 8.6% of the men (n=430) and 20.2% of the women (n=1,105), while 3.8% (n=189) of the men and 12.9% of the women (n=706) had a history of both falls and fractures. Of the outcomes examined, a history of falls alone was associated with increased in-hospital mortality [odds ratio (OR)=1.33, 95% confidence interval (CI)=1.03–1.71] and 30-day mortality (OR=1.34, 95% CI=1.03–1.73) in women in the fully adjusted models. The Cox proportional-hazards models for longer-term outcomes and the history of falls and fractures combined showed no significant results. Conclusions The history of falls is an important factor for acute stroke mortality in women. A previous history of falls may therefore be an important factor to consider in the short-term stroke prognosis, particularly in women.

Intraoperative discomfort associated with the use of a rotary or reciprocating system: a prospective randomized clinical trial

Gomes, Aline Cristine,Soares, Adriana Jesus,Souza, Erick M,Zaia, Alexandre Augusto,Silva, Emmanuel Joao Nogueira Leal The Korean Academy of Conservative Dentistry 2017 Restorative Dentistry & Endodontics Vol.42 No.2

Objectives: The aim of this randomized, controlled, prospective clinical study was to evaluate patients' intraoperative discomfort during root canal preparations in which either multi-file rotary (Mtwo) or single-file reciprocating (Reciproc) systems were used. Materials and Methods: Fifty-five adult patients, aged between 25 and 69 years old, with irreversible pulpitis or pulp necrosis participated in this study. Either the mesiobuccal or the distobuccal canals for maxillary molars and either the mesiobuccal or the mesiolingual canals for mandibular molars were randomly chosen to be instrumented with Mtwo multi-file rotary or Reciproc single-file reciprocating systems. Immediately after each canal instrumentation under anesthesia, patient discomfort was assessed using a 1 - 10 visual analog scale (VAS), ranging from 'least possible discomfort' (1) to 'greatest possible discomfort' (10). The Wilcoxon signed-rank test was used to determine significant differences at p < 0.05. Results: Little intraoperative discomfort was found in all cases. No statistically significant differences in intraoperative discomfort between the 2 systems were found (p = 0.660). Conclusions: Root canal preparation with multi-file rotary or single-file reciprocating systems had similar and minimal effects on patients' intraoperative discomfort.