Impacto de la COVID-19 en el área de Odontología

Introducción: La COVID-19 es una enfermedad provocada por el virus SARS-CoV-2, que se transmite por medio de la vía respiratoria por lo cual, los odontólogos enfrentan un gran riesgo al trabajar directamente en la cavidad oral. Objetivo: Sistematizar los referentes teóricos sobre el impacto de la COVID-19 en el área de la Odontología. Método: En la Universidad Regional Autónoma de los Andes, entre los meses de septiembre a diciembre de 2022 se realizó una revisión sistemática sobre el tema. De 36 artículos revisados se escogió, según criterios, un total de 23 artículos, disponibles en PUBMED y SciELO que abordan la problemática de COVID-19 en el área odontológica, de varios autores, en idioma inglés y español. Resultados: Se abordaron los temas, tales como: enfermedades bucodentales generadas a causa de COVID-19, Cambios en el área odontológica a causa de la pandemia por COVID-19 y medidas de bioseguridad empleadas para atender al paciente en el consultorio odontológico. Consideraciones finales: La COVID-19 ha tenido gran repercusión en Odontología, lo que afecta la salud bucal y general del paciente, a su vez, conduce al uso de estrictas medidas de bioseguridad dentro y fuera del consultorio odontológico, por lo que resulta ineludible que los odontólogos se empoderen de los referentes teóricos en torno al tema para contribuir a la detección de lesiones que puedan constituir signos primarios que apuntan a la presencia de SARS-CoV-2, adoptar conductas responsables y evitar su propagación.

Introduction: COVID-19 is a disease caused by SARS-CoV-2 virus and transmitted through respiratory track. So, dentists face a great risk working directly in the oral cavity. Objective: Systematization of the theoretical references concerning the impact of COVID-19 in dental areas. Method: A systematic review on the subject was carried out at the Universidad Regional Autónoma de los Andes, from September to December 2022. Of a total of 36 articles reviewed, 23 were selected according to criteria, available in PUBMED and SciELO, published in English and Spanish by different authors, and associated to the COVID-19 transmission in dentistry. Results: the following topics were addressed: oral diseases caused by COVID-19, changes in dental areas due to the COVID-19 pandemic, and biosecurity measures used in the dental service for ensure patient safety receiving treatment. Final considerations: COVID-19 has had great repercussions in dentistry, which affects the oral and general health of patients and, in turn, leads to the use of strict biosecurity measures inside and outside the dental office, so, it is essential for dentists to become empowered of the theoretical references related to the subject and also be focused on detecting lesions that may constitute primary signs of a possible presence of SARS-CoV-2, in adopt responsible behaviors and to avoid any spread of disease.

Introdução: O COVID-19 é uma doença causada pelo vírus SARS-CoV-2, que é transmitido pelo trato respiratório, portanto, os dentistas enfrentam um grande risco ao trabalhar diretamente na cavidade oral. Objetivo: Sistematizar os referenciais teóricos sobre o impacto da COVID-19 na área da Odontologia. Método: Na Universidade Regional Autônoma dos Andes, entre os meses de setembro e dezembro de 2022, foi realizada uma revisão sistemática sobre o tema. Dos 36 artigos revisados, um total de 23 artigos, disponíveis no PUBMED e SciELO, que abordam a problemática da COVID-19 na área odontológica, de diversos autores, em inglês e espanhol, foram escolhidos segundo critérios. Resultados: Foram abordados temas como: doenças bucais causadas pelo COVID-19, Alterações na área odontológica devido à pandemia do COVID-19 e medidas de biossegurança utilizadas no atendimento ao paciente no consultório odontológico. Considerações finais: O COVID-19 tem causado grande impacto na Odontologia, o que afeta a saúde bucal e geral do paciente, por sua vez, leva ao uso de medidas estritas de biossegurança dentro e fora do consultório odontológico, por isso é inevitável que os dentistas sejam capacitados por referenciais teóricos sobre o assunto para contribuir na detecção de lesões que possam constituir sinais primários que apontem para a presença do SARS-CoV-2, adotem condutas responsáveis e evitem sua disseminação.

Pulmonary fate and consequences of transferrin-functionalized gold nanoparticles.

Surface functionalization of nanoparticles (NPs) may alter their biological interactions such as uptake by alveolar macrophages (AMs). Pulmonary delivery of gold NPs (Au NPs) has theranostic potential due to their optoelectronic properties, minimal alveoli to blood translocation, and possibility of specific cell targeting. Here, we examined whether coating Au NPs with transferrin alters their protein corona, uptake by macrophages, and pulmonary translocation. Methods: Rats were intratracheally instilled with transferrin-coated Au NPs (Tf-Au NPs) or polyethylene glycol-coated Au NPs (PEG-Au NPs). AMs were collected and processed for quantitation of Au cell uptake using ICP-MS and electron microscopy. Au retention in the lungs and other organs was also determined. The uptake of fluorescently labeled Tf-Au NPs and PEG-Au NPs by monocyte-derived human macrophages was also evaluated in vitro. Results: We showed that Tf-Au NPs were endocytosed by AMs and were retained in the lungs to a greater extent than PEG-Au NPs. Both Au NPs acquired similar protein coronas after incubation in rat broncho-alveolar lavage fluid (BALf). The translocation of Au from both NPs to other organs was less than 0.5% of the instilled dose. Transferrin coating enhanced the uptake of Au NPs by primary monocyte-derived human macrophages. Conclusions: We report that coating of NP surface with transferrin can target them to rat AMs and human monocyte-derived macrophages. NP functionalization with transferrin may enhance NP-based therapeutic strategies for lung diseases.

Effects of Ingested Nanomaterials on Tissue Distribution of Co-ingested Zinc and Iron in Normal and Zinc-Deficient Mice.

Cellulose nanofibers (CNF) reduced serum triglyceride levels in rats when co-administered with heavy cream by gavage. Do CNF and other nanomaterials (NMs) alter the tissue distribution and retention of co-administered metal ions? We evaluated whether 5 different NMs affected tissue distribution of co-ingested 65Zn++ and 59Fe+++ in zinc-replete versus zinc-deficient mice. Male C57BL/6J mice were fed either zinc-replete or zinc-deficient diets for 3 weeks, followed by gavage with NM suspensions in water containing both 65ZnCl2 and 59FeCl3. Urine and feces were measured for 48 h post-gavage. Mice were euthanized and samples of 22 tissues were collected and analyzed for 65Zn and 59Fe in a gamma counter. Our data show that zinc deficiency alters the tissue distribution of 65Zn but not of 59Fe, indicating that zinc and iron homeostasis are regulated by distinct mechanisms. Among the tested NMs, soluble starch-coated chitosan nanoparticles, cellulose nanocrystals, and TiO2 reduced Zn and Fe tissue retention in zinc-deficient but not in zinc-replete animals.

Tissue Specific Fate of Nanomaterials by Advanced Analytical Imaging Techniques - A Review.

A variety of imaging and analytical methods have been developed to study nanoparticles in cells. Each has its benefits, limitations, and varying degrees of expense and difficulties in implementation. High-resolution analytical scanning transmission electron microscopy (HRSTEM) has the unique ability to image local cellular environments adjacent to a nanoparticle at near atomic resolution and apply analytical tools to these environments such as energy dispersive spectroscopy and electron energy loss spectroscopy. These tools can be used to analyze particle location, translocation and potential reformation, ion dispersion, and in vivo synthesis of second-generation nanoparticles. Such analyses can provide in depth understanding of tissue-particle interactions and effects that are caused by the environmental "invader" nanoparticles. Analytical imaging can also distinguish phases that form due to the transformation of "invader" nanoparticles in contrast to those that are triggered by a response mechanism, including the commonly observed iron biomineralization in the form of ferritin nanoparticles. The analyses can distinguish ion species, crystal phases, and valence of parent nanoparticles and reformed or in vivo synthesized phases throughout the tissue. This article will briefly review the plethora of methods that have been developed over the last 20 years with an emphasis on the state-of-the-art techniques used to image and analyze nanoparticles in cells and highlight the sample preparation necessary for biological thin section observation in a HRSTEM. Specific applications that provide visual and chemical mapping of the local cellular environments surrounding parent nanoparticles and second-generation phases are demonstrated, which will help to identify novel nanoparticle-produced adverse effects and their associated mechanisms.

Effects of ingested nanocellulose on intestinal microbiota and homeostasis in Wistar Han rats.

Micron scale cellulose materials are "generally regarded as safe" (GRAS) as binders and thickeners in food products. However, nanocellulose materials, which have unique properties that can improve food quality and safety, have not received US-Food and Drug Administration (FDA) approval as food ingredients. In vitro and in vivo toxicological studies of ingested nanocellulose revealed minimal cytotoxicity, and no subacute in vivo toxicity. However, ingested materials may modulate gut microbial populations, or alter aspects of intestinal function not elucidated by toxicity testing, which could have important health implications. Here, we report the results of studies conducted in a rat gavage model to assess the effects of ingested cellulose nanofibrils (CNF) on the fecal microbiome and metabolome, intestinal epithelial expression of cell junction genes, and ileal cytokine production. Feces, plasma, and ilea were collected from Wistar Han rats before and after five weeks of biweekly gavages with water or cream, with or without 1% CNF. CNF altered microbial diversity, and diminished specific species that produce short chain fatty acids, and that are associated with increased serum insulin and IgA production. CNF had few effects on the fecal metabolome, with significant changes in only ten metabolites of 366 measured. Exposure to CNF also altered expression of epithelial cell junction genes, and increased production of cytokines that modulate proliferation of CD8 T cells. These perturbations likely represent initiation of an adaptive immune response, however, no associated pathology was seen within the duration of the study. Additional studies are needed to better understand the health implications of these changes in long term.

Fate of Barium Sulfate Nanoparticles Deposited in the Lungs of Rats.

We have shown that barium [from BaSO4 nanoparticles (NPs)] was cleared from the lungs faster than other poorly soluble NPs and translocated mostly to bone. We now studied barium biokinetics in rats during Study 1: two-year inhalation exposure to 50 mg/m3 BaSO4 NP aerosols, and Study 2: single intratracheal (IT) instillation of increasing doses of BaSO4 NPs or BaCl2. Study 1 showed that lung barium content measured by inductively coupled plasma mass spectrometry increased during 360 days of BaSO4 NP aerosol exposures. An equilibrium was established from that time until 2 years. Barium concentrations in BaSO4-exposed animals were in the order (lungs > lymph nodes > hard bone > bone marrow > liver). In Study 2, there was an increase in lung barium post-IT instillation of BaSO4 NPs while barium from BaCl2 was mostly cleared by day 28. Transmission electron microscopy showed intact BaSO4 NPs in alveolar macrophages and type II epithelial cells, and in tracheobronchial lymph nodes. Using stimulated Raman scattering microscopy, specific BaSO4 Raman spectra were detected in BaSO4 NP-instilled lungs and not in other organs. Thus, we posit that barium from BaSO4 NPs translocates from the lungs mainly after dissolution. Barium ions are then incorporated mostly into the bone and other organs.

Toxicological effects of ingested nanocellulose in in vitro intestinal epithelium and in vivo rat models.

Cellulose is widely used as a thickener and filler in foods and drugs. It has been designated "generally regarded as safe" (GRAS). Nanocellulose (NC) has many additional potential applications designed to improve food quality and safety, but has not yet been designated as GRAS. Here we present results of toxicological studies of ingested NC in physiologically relevant in vitro and in vivo systems. In vitro studies employed a gastrointestinal tract simulator to digest two widely-used forms of NC, nanocellulose fibrils (CNF) and cellulose nanocrystals (CNC), at 0.75 and 1.5% w/w, in a fasting diet as well as in a standardized food model based on the average American diet. A triculture model of small intestinal epithelium was used to assess effects of a 24-hour incubation with the digested products (digesta) on cell layer integrity, cytotoxicity and oxidative stress. Other than a 10% increase over controls in reactive oxygen species (ROS) production with 1.5% w/w CNC, no significant changes in cytotoxicity, ROS or monolayer integrity were observed. In vivo toxicity was evaluated in rats gavaged twice weekly for five weeks with 1% w/w suspensions of CNF in either water or cream. Blood, serum, lung, liver, kidney, and small intestine were collected for analysis. No significant differences in hematology, serum markers or histology were observed between controls and rats given CNF suspensions. These findings suggest that ingested NC has little acute toxicity, and is likely non-hazardous when ingested in small quantities. Additional chronic feeding studies are required to assess long term effects, and potential detrimental effects on the gut microbiome and absorbance of essential micronutrients. These studies are underway, and their outcome will be reported in the near future.

Repeated pulmonary exposures to zinc ions enhance inflammatory responses to subsequent metal exposures.

AIM OF STUDY: Metal contaminants contribute to adverse human health effects via acute and chronic exposures. Acute metal exposures followed by prolonged secondary metal exposures may elicit exaggerated inflammatory responses in certain individuals. The aim of this study is to determine whether repeated pulmonary exposures to zinc chloride (ZnCl2) alter subsequent responses to zinc or cerium exposures. MATERIALS AND METHODS: Rats were intratracheally (IT) instilled with physiologic saline (n = 24) or 0.05 mg/kg ZnCl2 (n = 16) twice weekly for 4 weeks. Four days after last dosing, the saline group was divided into three subgroups, each IT-instilled with either saline, ZnCl2 or CeCl3 (both at 0.1 mg/kg). The ZnCl2 pre-instilled rats were divided into two subgroups, each instilled with 0.1 mg/kg ZnCl2 or CeCl3. Biomarkers of lung injury/inflammation were assessed in bronchoalveolar lavage (BAL) fluid collected 24 hours later. Oxidative stress was evaluated as total and reduced glutathione in BAL. RESULTS: Increases in inflammatory cells, LDH, albumin, leptin, MCP-1, IP-10, fractalkine, TNFα and RANTES were observed in rats instilled with multiple PBS and then with 0.1 mg/kg ZnCl2 and CeCl3. However, rats pre-exposed repeatedly to 0.05 mg/kg ZnCl2 and then challenged with 0.1 mg/kg ZnCl2 or CeCl3 showed even more eosinophils, lymphocytes, and increased concentrations of hemoglobin and MIP-1α. Significant reduction in GSH/GSSG ratios in BAL in response to all ZnCl2 or CeCl3 exposures indicated oxidative stress. CONCLUSION: Previous exposure to zinc ions increases responsiveness to subsequent exposures to zinc and cerium ions. These findings suggest enhanced sensitization possibly due to a reduction in antioxidant defenses.

Reducing Intestinal Digestion and Absorption of Fat Using a Nature-Derived Biopolymer: Interference of Triglyceride Hydrolysis by Nanocellulose.

Engineered nanomaterials are increasingly added to foods to improve quality, safety, or nutrition. Here we report the ability of ingested nanocellulose (NC) materials to reduce digestion and absorption of ingested fat. In the small intestinal phase of an acellular simulated gastrointestinal tract, the hydrolysis of free fatty acids (FFA) from triglycerides (TG) in a high-fat food model was reduced by 48.4% when NC was added at 0.75% w/w to the food, as quantified by pH stat titration, and by 40.1% as assessed by fluorometric FFA assay. Furthermore, translocation of TG and FFA across an in vitro cellular model of the intestinal epithelium was significantly reduced by the presence of 0.75% w/w NC in the food (TG by 52% and FFA by 32%). Finally, in in vivo experiments, the postprandial rise in serum TG 1 h after gavage with the high fat food model was reduced by 36% when 1.0% w/w NC was administered with the food. Scanning electron microscopy and molecular dynamics studies suggest two primary mechanisms for this effect: (1) coalescence of fat droplets on fibrillar NC (CNF) fibers, resulting in a reduction of available surface area for lipase binding and (2) sequestration of bile salts, causing impaired interfacial displacement of proteins at the lipid droplet surface and impaired solubilization of lipid digestion products. Together these findings suggest a potential use for NC, as a food additive or supplement, to reduce absorption of ingested fat and thereby assist in weight loss and the management of obesity.

Dolor postoperatorio: frecuencia y caracterización del manejo / Postoperative pain: frequency and management characterization

Abstract Introduction: Acute postoperative pain is a usual symptom and a surgical challenge. Objective: To determine the frequency of pain in the postoperative period of patients undergoing elective surgery and to characterize pain management at a second-level public hospital. Material and methods: A cross-section study of 175 postop patients was conducted, analyzing variables such as level of pain 24 hours after surgery according to the visual analog scale, type of surgery, use of analgesics, and anesthetic technique. Results: The findings indicate that the frequency of moderate, severe, and excruciating pain is 66.3%. In all cases, the analgesia treatment was prescribed by the treating service, and 2 to 3 nonsteroidal anti-inflammatory drugs were used in 86.4% of the cases, with a minimal use of opioids in 13% of the patients. The anesthetic techniques used included balanced general anesthesia, neuro-axial block, and a mixed technique; the latter improved pain control. Conclusion: The frequency of postoperative pain is similar to the level reported in other trials (30%-70%), pointing to the need to review our current management, with more extensive participation and training of the staff involved in pain control.

Resumen Introducción: El dolor agudo postoperatorio es un síntoma frecuente, el cual representa un reto en el ámbito quirúrgico. Objetivo: determinar la frecuencia de dolor en el paciente postoperado de cirugía electiva y caracterizar el manejo del mismo en un hospital público de segundo nivel de atención. Material y métodos: se realizó un estudio transversal en 175 pacientes postoperados, analizando las variables de grado de dolor a las 24 horas del postoperatorio con la escala visual análoga, tipo de cirugía, uso de analgésicos, técnica anestésica. Resultados: Se encontró que la frecuencia de dolor moderado, severo o insoportable es del 66.3%. El tratamiento analgésico en todos los casos fue prescrito por el servicio tratante y en el 86.4% de los casos se emplearon AINE'S, en número de uno a tres. Con un uso mínimo de opioides en el 13% de los pacientes. Las técnicas anestésicas usadas fueron AGB, BNA y técnica mixta; con mejoría en el grado de dolor con la técnica mixta. Conclusión: Existe una frecuencia de dolor postoperatorio similar a lo reportado en otros estudios (30-70%), reflejando la necesidad de revisión del manejo actual, mayor participación y capacitación del personal involucrado en su manejo.

Nanoparticle Wettability Influences Nanoparticle-Phospholipid Interactions.

We explored the influence of nanoparticle (NP) surface charge and hydrophobicity on NP-biomolecule interactions by measuring the composition of adsorbed phospholipids on four NPs, namely, positively charged CeO2 and ZnO and negatively charged BaSO4 and silica-coated CeO2, after exposure to bronchoalveolar lavage fluid (BALf) obtained from rats, and to a mixture of neutral dipalmitoyl phosphatidylcholine (DPPC) and negatively charged dipalmitoyl phosphatidic acid (DPPA). The resulting NP-lipid interactions were examined by cryogenic transmission electron microscopy (cryo-TEM) and atomic force microscopy (AFM). Our data show that the amount of adsorbed lipids on NPs after incubation in BALf and the DPPC/DPPA mixture was higher in CeO2 than in the other NPs, qualitatively consistent with their relative hydrophobicity. The relative concentrations of specific adsorbed phospholipids on NP surfaces were different from their relative concentrations in the BALf. Sphingomyelin was not detected in the extracted lipids from the NPs despite its >20% concentration in the BALf. AFM showed that the more hydrophobic CeO2 NPs tended to be located inside lipid vesicles, whereas less hydrophobic BaSO4 NPs appeared to be outside. In addition, cryo-TEM analysis showed that CeO2 NPs were associated with the formation of multilamellar lipid bilayers, whereas BaSO4 NPs with unilamellar lipid bilayers. These data suggest that the NP surface hydrophobicity predominantly controls the amounts and types of lipids adsorbed, as well as the nature of their interaction with phospholipids.

Effects of a vinegar-based multi-micronutrient supplement in rats: a multi-pronged assessment of dietary impact.

We determined the effects of continuous access to drinking of water with a vinegar-based multi-micronutrient (VMm) supplement containing rice and fruit vinegars, vitamins, organic acids and sugars during gestation, lactation, and early adulthood in rats. Pregnant rats were provided with reverse-osmosis water or VMm water from the start of pregnancy through the time of weaning. Weaned pups consumed the same drinking water for 3-12 additional weeks. We examined fecal metabolite and microbial profiles, and other physiological parameters. Body weights were less in rats that drank VMm water. Thirty fecal metabolites involved in amino acid and dipeptide metabolism were significantly altered in VMm-supplemented rats. Analysis of microbial 16S rRNA showed enrichment of bacteria in the family S24-7 in VMm-supplemented rats, and one in Ruminococcaceae in controls. Our data show that a VMm-containing beverage can alter growth, and gut metabolism and microbial community. Future work to correlate these parameters is warranted.

Protein corona: implications for nanoparticle interactions with pulmonary cells.

BACKGROUND: We previously showed that cerium oxide (CeO2), barium sulfate (BaSO4) and zinc oxide (ZnO) nanoparticles (NPs) exhibited different lung toxicity and pulmonary clearance in rats. We hypothesize that these NPs acquire coronas with different protein compositions that may influence their clearance from the lungs. METHODS: CeO2, silica-coated CeO2, BaSO4, and ZnO NPs were incubated in rat lung lining fluid in vitro. Then, gel electrophoresis followed by quantitative mass spectrometry was used to characterize the adsorbed proteins stripped from these NPs. We also measured uptake of instilled NPs by alveolar macrophages (AMs) in rat lungs using electron microscopy. Finally, we tested whether coating of gold NPs with albumin would alter their lung clearance in rats. RESULTS: We found that the amounts of nine proteins in the coronas formed on the four NPs varied significantly. The amounts of albumin, transferrin and α-1 antitrypsin were greater in the coronas of BaSO4 and ZnO than that of the two CeO2 NPs. The uptake of BaSO4 in AMs was less than CeO2 and silica-coated CeO2 NPs. No identifiable ZnO NPs were observed in AMs. Gold NPs coated with albumin or citrate instilled into the lungs of rats acquired the similar protein coronas and were cleared from the lungs to the same extent. CONCLUSIONS: We show that different NPs variably adsorb proteins from the lung lining fluid. The amount of albumin in the NP corona varies as does NP uptake by AMs. However, albumin coating does not affect the translocation of gold NPs across the air-blood barrier. A more extensive database of corona composition of a diverse NP library will develop a platform to help predict the effects and biokinetics of inhaled NPs.

Pulmonary distribution of nanoceria: comparison of intratracheal, microspray instillation and dry powder insufflation.

Particles can be delivered to the respiratory tract of animals using various techniques. Inhalation mimics environmental exposure but requires large amounts of aerosolized NPs over a prolonged dosing time, varies in deposited dose among individual animals, and results in nasopharyngeal and fur particle deposition. Although less physiological, intratracheal (IT) instillation allows quick and precise dosing. Insufflation delivers particles in their dry form as an aerosol. We compared the distribution of neutron-activated 141CeO2 nanoparticles (5 mg/kg) in rats after (1) IT instillation, (2) left intrabronchial instillation, (3) microspraying of nanoceria suspension and (4) insufflation of nanoceria dry powder. Blood, tracheobronchial lymph nodes, liver, gastrointestinal tract, feces and urine were collected at 5 min and 24 h post-dosing. Excised lungs from each rat were dried at room temperature while inflated at a constant 30 cm water pressure. Dried lungs were then sliced into 50 pieces. The radioactivity of each lung piece and other organs was measured. The evenness index (EI) of each lung piece was calculated [EI = (µCi/mgpiece)/(µCi/mglung)]. The degree of EI value departure from 1.0 is a measure of deposition heterogeneity. We showed that the pulmonary distribution of nanoceria differs among modes of administration. Dosing by IT or microspraying resulted in similar spatial distribution. Insufflation resulted in significant deposition in the trachea and in more heterogeneous lung distribution. Our left intrabronchial instillation technique yielded a concentrated deposition into the left lung. We conclude that animal dosing techniques and devices result in varying patterns of particle deposition that will impact biokinetic and toxicity studies.

Repeated Mouse Lung Exposures to Stachybotrys chartarum Shift Immune Response from Type 1 to Type 2.

After a single or multiple intratracheal instillations of Stachybotrys chartarum (S. chartarum or black mold) spores in BALB/c mice, we characterized cytokine production, metabolites, and inflammatory patterns by analyzing mouse bronchoalveolar lavage (BAL), lung tissue, and plasma. We found marked differences in BAL cell counts, especially large increases in lymphocytes and eosinophils in multiple-dosed mice. Formation of eosinophil-rich granulomas and airway goblet cell metaplasia were prevalent in the lungs of multiple-dosed mice but not in single- or saline-dosed groups. We detected changes in the cytokine expression profiles in both the BAL and plasma. Multiple pulmonary exposures to S. chartarum induced significant metabolic changes in the lungs but not in the plasma. These changes suggest a shift from type 1 inflammation after an acute exposure to type 2 inflammation after multiple exposures to S. chartarum. Eotaxin, vascular endothelial growth factor (VEGF), MIP-1α, MIP-1ß, TNF-α, and the IL-8 analogs macrophage inflammatory protein-2 (MIP-2) and keratinocyte chemoattractant (KC), had more dramatic changes in multiple- than in single-dosed mice, and parallel the cytokines that characterize humans with histories of mold exposures versus unexposed control subjects. This repeated exposure model allows us to more realistically characterize responses to mold, such as cytokine, metabolic, and cellular changes.

Screening for Chemical Toxicity Using Cryopreserved Precision Cut Lung Slices.

To assess chemical toxicity, current high throughput screening (HTS) assays rely primarily on in vitro measurements using cultured cells. Responses frequently differ from in vivo results due to the lack of physical and humoral interactions provided by the extracellular matrix, cell-cell interactions, and other molecular components of the native organ. To more accurately reproduce organ complexity in HTS, we developed an organotypic assay using the cryopreserved precision cut lung slice (PCLS) from rats and mice. Compared to the never-frozen PCLS, their frozen-thawed counterpart slices showed viability or metabolic activity that is decreased to an extent comparable to that observed in other cryopreserved cells and tissues, but shows no differences in further changes in cell viability, mitochondrial integrity, and glutathione activity in response to the model toxin zinc chloride (ZnCl2). Notably, these measurements were successfully miniaturized so as to establish HTS capacity in a 96-well plate format. Finally, PCLS responses correlated with common markers of lung injury measured in lavage fluid from rats intratracheally instilled with ZnCl2. In summary, we establish that the cryopreserved PCLS is a feasible approach for HTS investigations in predictive toxicology.

Surface modification of zinc oxide nanoparticles with amorphous silica alters their fate in the circulation.

Nanoparticle (NP) pharmacokinetics and biological effects are influenced by many factors, especially surface physicochemical properties. We assessed the effects of an amorphous silica coating on the fate of zinc after intravenous (IV) injection of neutron activated uncoated (65)ZnO or silica-coated (65)ZnO NPs in male Wistar Han rats. Groups of IV-injected rats were sequentially euthanized, and 18 tissues were collected and analyzed for (65)Zn radioactivity. The protein coronas on each ZnO NP after incubation in rat plasma were analyzed by SDS-PAGE gel electrophoresis and mass spectrometry of selected gel bands. Plasma clearance for both NPs was biphasic with rapid initial and slower terminal clearance rates. Half-lives of plasma clearance of silica-coated (65)ZnO were shorter (initial - <1 min; terminal - 2.5 min) than uncoated (65)ZnO (initial - 1.9 min; terminal - 38 min). Interestingly, the silica-coated (65)ZnO group had higher (65)Zn associated with red blood cells and higher initial uptake in the liver. The (65)Zn concentrations in all the other tissues were significantly lower in the silica-coated than uncoated groups. We also found that the protein corona formed on silica-coated ZnO NPs had higher amounts of plasma proteins, particularly albumin, transferrin, A1 inhibitor 3, α-2-hs-glycoprotein, apoprotein E and α-1 antitrypsin. Surface modification with amorphous silica alters the protein corona, agglomerate size, and zeta potential of ZnO NPs, which in turn influences ZnO biokinetic behavior in the circulation. This emphasizes the critical role of the protein corona in the biokinetics, toxicology and nanomedical applications of NPs.

Antibiotic prophylaxis for chemotherapy-induced febrile neutropenia in hematologic and solid organ malignancies

BACKGROUND AND OBJECTIVE: Febrile neutropenia (FN) frequently develops among cancer patients receiving chemotherapy and is associated with significant morbidity and mortality. Although the use of empiric antibiotics has been a standard of care for FN according to the last 2010 Infectious Disease Society of America (IDSA) guidelines, the role of prophylactic antibiotics in patients with high risk features in preventing febrile neutropenia remains to be elucidated. This study aims to investigate the role of antibiotic prophylaxis in preventing post-chemotherapy FN among patients with hematologic and solid organ malignancies. METHODS: A literature search of published English language clinical trials was performed using PubMed, MEDLINE, and the Cochrane Collaboration from January 1980 - October 2015. Four hundred thirty two articles were extracted from our literature search and narrowed down through specified inclusion and exclusion criteria. Results were analyzed based on 1) incidence of FN in post chemotherapy cancer patients, 2) mortality rate, and 3) incidence of FN with different antibiotics. Assessment of methodological quality of each study was done using the Jadad scale. Odds ratios and Forest plots were computed and generated respectively using RevMan 5.2 (© 2013 the Cochrane Collaboration). RESULTS: Antibiotic prophylaxis reduced the incidence of FN (OR 0.59[0.37, 0.91]). Overall effect was significant; Z= 2.35 (p= 0.02). Febrile episodes occurred less frequently in those patients who received prophylactic antibiotic treatment (OR 0.43 [0.34, 0.53]) Z = 7.59 (p CONCLUSION: Antibiotic prophylaxis reduces the incidence of FN among cancer patients treated with cytotoxic chemotherapy, decreases febrile episodes in neutropenic patients, and overall, prevented FN by up to 3.51-fold.

Double Laser for Depth Measurement of Thin Films of Ice.

The use of thin films is extensive in both science and industry. We have created an experimental system that allows us to measure the thicknesses of thin films (with typical thicknesses of around 1 µm) in real time without the need for any prior knowledge or parameters. Using the proposed system, we can also measure the refractive index of the thin film material exactly under the same experimental conditions. We have also obtained interesting results with regard to structural changes in the solid substance with changing temperature and have observed the corresponding behavior of mixtures of substances.