ABSTRACT
Gold nanoparticles (AuNP) adsorb macromolecules to form a protein corona (PC) after systemic delivery, to which the kidney as the primary excretory organ is constantly exposed. The role of the PC on AuNP cell uptake and toxicity was investigated in vitro in human proximal tubule cells (HPTC) using 40 and 80nm branched polyethylenimine (BPEI), lipoic acid (LA) and polyethylene glycol (PEG) coated AuNP with or without (bare) PCs composed of human plasma (HP) or human serum albumin (HSA) for 0.25 to 24h. Time-dependent intracellular uptake, assessed by ICP-MS showed PC modulated cell uptake and cytotoxicity; with bare 40nm BPEI-AuNP showing the greatest responses. All AuNP showed minimal to no cytokine release. At the nontoxic dose, 40nm bare BPEI-AuNP significantly modified gene expression related to immunotoxicity, steatosis, and mitochondrial metabolism; while at the high dose, pathways of DNA damage and repair, apoptosis, fatty acid metabolism and heat shock response were modulated. HP corona BPEI-AuNP response was comparable to control. These studies clearly showed reduced uptake and cytotoxicity, as well as differentiated gene expression of AuNP with PCs, questioning the utility of in vitro studies using bare NP to assess in vivo effects. Significantly, only cationic bare BPEI-AuNP had HPTC uptake or cytotoxicity suggesting the relative safety of PEG and LA-AuNP as nanomedicine constructs.
Subject(s)
Gold , Kidney Tubules, Proximal/cytology , Metal Nanoparticles , Protein Corona/chemistry , Serum Albumin/chemistry , Cells, Cultured , Cytokines/metabolism , Gene Expression/drug effects , Gold/administration & dosage , Gold/chemistry , Gold/toxicity , Humans , Metal Nanoparticles/administration & dosage , Metal Nanoparticles/chemistry , Metal Nanoparticles/toxicity , Plasma/chemistry , Polyethylene Glycols/chemistry , Polyethyleneimine/chemistry , Thioctic Acid/chemistryABSTRACT
We developed an in vitro method to assess pet food ingredients safety. Canine bone marrow-derived mesenchymal stem cells (BMSC) were differentiated into enterocyte-like cells (ELC) to assess toxicity in cells representing similar patterns of exposure in vivo. The toxicological profile of clove leave oil, eugenol, guanosine monophosphate (GMP), GMP + inosine monophosphate, sorbose, ginger root extract, cinnamon bark oil, cinnamaldehyde, thyme oil, thymol and citric acid was assessed in BMSC and ELC. The LC50 for GMP + inosine monophosphate was 59.42 ± 0.90 and 56.7 ± 3.5 mg ml(-1) for BMSC and ELC; 56.84 ± 0.95 and 53.66 ± 1.36 mg ml(-1) for GMP; 0.02 ± 0.001 and 1.25 ± 0.47 mg ml(-1) for citric acid; 0.077 ± 0.002 and 0.037 ± 0.01 mg ml(-1) for cinnamaldehyde; 0.002 ± 0.0001 and 0.002 ± 0.0008 mg ml(-1) for thymol; 0.080 ± 0.003 and 0.059 ± 0.001 mg ml(-1) for thyme oil; 0.111 ± 0.002 and 0.054 ± 0.01 mg ml(-1) for cinnamon bark oil; 0.119 ± 0.0004 and 0.099 ± 0.011 mg ml(-1) for clove leave oil; 0.04 ± 0.001 and 0.028 ± 0.002 mg ml(-1) for eugenol; 2.80 ± 0.11 and 1.75 ± 0.51 mg ml(-1) for ginger root extract; > 200 and 116.78 ± 7.35 mg ml(-1) for sorbose. Lemon grass oil was evaluated at 0.003-0.9 in BMSC and .03-0.9 mg ml(-1) in ELC and its mechanistic effect was investigated. The gene toxicology studies showed regulation of 61% genes in CYP450 pathway, 37% in cholestasis and 33% in immunotoxicity pathways for BMSC. For ELC, 80% for heat shock response, 69% for beta-oxidation and 65% for mitochondrial energy metabolism. In conclusion, these studies provide a baseline against which differential toxicity of dietary feed ingredients can be assessed in vitro for direct effects on canine cells and demonstrate differential toxicity in differentiated cells that represent gastrointestinal epithelial cells.
Subject(s)
Animal Feed/toxicity , Bone Marrow/drug effects , Cytotoxins/toxicity , Enterocytes/drug effects , Mesenchymal Stem Cells/drug effects , Plant Oils/toxicity , Acrolein/analogs & derivatives , Acrolein/toxicity , Animals , Citric Acid/toxicity , Clove Oil/toxicity , Dogs , Eugenol/toxicity , Zingiber officinale/toxicity , Guanosine Monophosphate/toxicity , Inosine Monophosphate/toxicity , Oils, Volatile/toxicity , Pets , Plant Roots/toxicity , Sorbose/toxicity , Thymol/toxicityABSTRACT
We estimate mid-2013/14 season vaccine effectiveness (VE) of the influenza trivalent vaccine in Navarre, Spain. Influenza-like illness cases attended in hospital (n=431) and primary healthcare (n=344) were included. The overall adjusted VE in preventing laboratory-confirmed influenza was 24% (95% CI: -14 to 50). The VE was 40% (95% CI: -12 to 68) against influenza A(H1)pdm09 and 13% (95% CI: -36 to 45) against influenza A(H3). These results suggest a moderate preventive effect against influenza A(H1)pdm09 and low protection against influenza A(H3).
Subject(s)
Disease Outbreaks/prevention & control , Influenza A Virus, H1N1 Subtype/immunology , Influenza Vaccines/immunology , Influenza, Human/prevention & control , Adolescent , Adult , Aged , Aged, 80 and over , Case-Control Studies , Child , Child, Preschool , Female , Hospitalization/statistics & numerical data , Humans , Incidence , Infant , Influenza Vaccines/therapeutic use , Influenza, Human/epidemiology , Influenza, Human/immunology , Influenza, Human/virology , Laboratories , Logistic Models , Male , Middle Aged , Primary Health Care , Seasons , Sentinel Surveillance , Spain/epidemiology , Treatment Outcome , Vaccination/statistics & numerical data , Young AdultABSTRACT
The use of tissue expanders in reconstructive surgery has become well established, but their use has been associated with multiple complications. Salvage of expanded tissue after traumatic extrusion of the prosthesis has not been previously reported. We have outlined the principles involved in the management of such a case, and reviewed previously reported complications of tissue expansion.
