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Human Vaccines & Immunotherapeutics Feb 2021Outer membrane vesicles (OMV) are exosomes naturally released from the surface of Gram-negative bacteria. Since the '80s, OMVs have been proposed as powerful vaccine... (Review)
Review
Outer membrane vesicles (OMV) are exosomes naturally released from the surface of Gram-negative bacteria. Since the '80s, OMVs have been proposed as powerful vaccine platforms due to their intrinsic self-adjuvanticity and ability to present multiple antigens in natural conformation. However, the presence of several pathogen-associated molecular patterns (PAMPs), especially lipid A, has raised concerns about potential systemic reactogenicity in humans. Recently, chemical and genetic approaches allowed to efficiently modulate the balance between reactogenicity and immunogenicity for the use of OMV in humans. Several assays (monocyte activation test, rabbit pyrogenicity test, limulus amebocyte lysate, human transfectant cells, and toxicology studies) were developed to test, with highly predictive potential, the risk of reactogenicity in humans before moving to clinical use. In this review, we provide a historical perspective on how different assays were and can be used to successfully evaluate systemic reactogenicity during clinical development and after licensure.
Topics: Animals; Antigen Presentation; Bacterial Outer Membrane Proteins; Humans; Lipid A; Monocytes; Rabbits; Vaccines
PubMed: 32687736
DOI: 10.1080/21645515.2020.1780092 -
Developmental and Comparative Immunology Feb 2017Behavioural fever has been reported in different species of mobile ectotherms including the zebrafish, Danio rerio, in response to exogenous pyrogens. In this study we...
Behavioural fever has been reported in different species of mobile ectotherms including the zebrafish, Danio rerio, in response to exogenous pyrogens. In this study we report, to our knowledge for the first time, upon the ontogenic onset of behavioural fever in zebrafish (Danio rerio) larvae. For this, zebrafish larvae (from first feeding to juveniles) were placed in a continuous thermal gradient providing the opportunity to select their preferred temperature. The novel thermal preference aquarium was based upon a continuous vertical column system and allows for non-invasive observation of larvae vertical distribution under isothermal (T at 28 °C) and thermal gradient conditions (T: 28-32 °C). Larval thermal preference was assessed under both conditions with or without an immersion challenge, in order to detect the onset of the behavioural fever response. Our results defined the onset of the dsRNA induced behavioural fever at 18-20 days post fertilization (dpf). Significant differences were observed in dsRNA challenged larvae, which prefer higher temperatures (1-4 °C increase) throughout the experimental period as compared to non-challenged larvae. In parallel we measured the abundance of antiviral transcripts; viperin, gig2, irf7, trim25 and Mxb mRNAs in dsRNA challenged larvae under both thermal regimes: T and T. Significant increases in the abundance of all measured transcripts were recorded under thermal choice conditions signifying that thermo-coupling and the resultant enhancement of the immune response to dsRNA challenge occurs from 18 dpf onwards in the zebrafish. The results are of importance as they identify a key developmental stage where the neuro-immune interface matures in the zebrafish likely providing increased resistance to viral infection.
Topics: Animals; Cells, Cultured; Fever; Gene Expression Regulation; Homeodomain Proteins; Hot Temperature; Immunity, Innate; Interferon Regulatory Factors; Larva; Neuroimmunomodulation; Proteins; Pyrogens; RNA, Double-Stranded; Transcription Factor Brn-3C; Transcription Factors; Zebrafish; Zebrafish Proteins
PubMed: 27670815
DOI: 10.1016/j.dci.2016.09.008 -
Current Opinion in Toxicology Jun 2023Polycyclic aromatic hydrocarbons (PAHs) are a class of organic compounds produced by a variety of petrogenic and pyrogenic sources. PAHs inherently occur in the...
Polycyclic aromatic hydrocarbons (PAHs) are a class of organic compounds produced by a variety of petrogenic and pyrogenic sources. PAHs inherently occur in the environment in complex mixtures. The early life-stage zebrafish model is a valuable tool for high-throughput screening (HTS) for toxicity of complex chemical mixtures due to its rapid development, high fecundity, and superb sensitivity to chemical insult. Zebrafish are amenable to exposure to surrogate mixtures as well as extracts of environmental samples and effect-directed analysis. In addition to its utility to HTS, the zebrafish has proven an excellent model for assessing chemical modes of action and identifying molecular initiating and other key events in an Adverse Outcome Pathway framework. Traditional methods of assessing PAH mixture toxicity prioritize carcinogenic potential and lack consideration of non-carcinogenic modes of action, assuming a similar molecular initiating event for all PAHs. Recent work in zebrafish has made it clear that while PAHs belong to the same chemical class, their modes of action can be divergent. Future research should use zebrafish to better classify PAHs by their bioactivity and modes of action to better understand mixture hazards.
PubMed: 37377741
DOI: 10.1016/j.cotox.2023.100392 -
Animals : An Open Access Journal From... Aug 2021Body-temperature elevations are multifactorial in origin and classified as hyperthermia as a rise in temperature due to alterations in the thermoregulation mechanism;... (Review)
Review
Body-temperature elevations are multifactorial in origin and classified as hyperthermia as a rise in temperature due to alterations in the thermoregulation mechanism; the body loses the ability to control or regulate body temperature. In contrast, fever is a controlled state, since the body adjusts its stable temperature range to increase body temperature without losing the thermoregulation capacity. Fever refers to an acute phase response that confers a survival benefit on the body, raising core body temperature during infection or systemic inflammation processes to reduce the survival and proliferation of infectious pathogens by altering temperature, restriction of essential nutrients, and the activation of an immune reaction. However, once the infection resolves, the febrile response must be tightly regulated to avoid excessive tissue damage. During fever, neurological, endocrine, immunological, and metabolic changes occur that cause an increase in the stable temperature range, which allows the core body temperature to be considerably increased to stop the invasion of the offending agent and restrict the damage to the organism. There are different metabolic mechanisms of thermoregulation in the febrile response at the central and peripheral levels and cellular events. In response to cold or heat, the brain triggers thermoregulatory responses to coping with changes in body temperature, including autonomic effectors, such as thermogenesis, vasodilation, sweating, and behavioral mechanisms, that trigger flexible, goal-oriented actions, such as seeking heat or cold, nest building, and postural extension. Infrared thermography (IRT) has proven to be a reliable method for the early detection of pathologies affecting animal health and welfare that represent economic losses for farmers. However, the standardization of protocols for IRT use is still needed. Together with the complete understanding of the physiological and behavioral responses involved in the febrile process, it is possible to have timely solutions to serious problem situations. For this reason, the present review aims to analyze the new findings in pathophysiological mechanisms of the febrile process, the heat-loss mechanisms in an animal with fever, thermoregulation, the adverse effects of fever, and recent scientific findings related to different pathologies in farm animals through the use of IRT.
PubMed: 34438772
DOI: 10.3390/ani11082316 -
BMC Veterinary Research Jun 2022In a collaboration between animal and human health care professionals, we assessed the genetic characteristics shared by non-aureus staphylococci (NAS) infecting humans...
BACKGROUND
In a collaboration between animal and human health care professionals, we assessed the genetic characteristics shared by non-aureus staphylococci (NAS) infecting humans and dairy ewes to investigate their relatedness in a region concentrating half of the total National sheep stock. We examined by PCR 125 ovine and 70 human NAS for biofilm production, pyrogenic toxins, adhesins, autolysins genes, and accessory gene regulator (agr) locus. The microtiter plate assay (MPA) was used for the phenotypic screening of biofilm production. Ovine NAS included S. epidermidis, S. chromogenes, S. haemolyticus, S. simulans, S. caprae, S. warneri, S. saprophyticus, S. intermedius, and S. muscae. Human NAS included S. haemolyticus, S. epidermidis, S. hominis, S. lugdunensis, S. capitis, S. warneri, S. xylosus, S. pasteuri, and S. saprophyticus subsp. bovis.
RESULTS
Phenotypically, 41 (32.8%) ovine and 24 (34.3%) human isolates were characterized as biofilm producers. Of the ovine isolates, 12 were classified as biofilm-producing while the remaining 29 as weak biofilm-producing. All 24 human isolates were considered weak biofilm-producing. Few S. epidermidis isolates harbored the icaA/D genes coding for the polysaccharide intercellular adhesin (PIA), while the bhp, aap, and embp genes coding biofilm accumulation proteins were present in both non-producing and biofilm-producing isolates. Fifty-nine sheep NAS (all S. epidermidis, 1 S. chromogenes, and 1 S. haemolyticus) and 27 human NAS (all S. epidermidis and 1 S. warneri) were positive for the agr locus: agr-3se (57.8%) followed by agr-1se (36.8%) predominated in sheep, while agr-1se (65.4%), followed by agr-2se (34.6%) predominated in humans. Concerning virulence genes, 40, 39.2, 47.2%, 52.8, 80 and 43.2% of the sheep isolates carried atlE, aae, sdrF, sdrG, eno and epbS respectively, against 37.1, 42.8, 32.8, 60, 100 and 100% of human isolates. Enterotoxins and tsst were not detected.
CONCLUSIONS
Considerable variation in biofilm formation ability was observed among NAS isolates from ovine and human samples. S. epidermidis was the best biofilm producer with the highest prevalence of adhesin-encoding genes.
Topics: Adhesins, Bacterial; Animals; Biofilms; Enterotoxins; Female; Humans; Sheep; Staphylococcus; Virulence
PubMed: 35655210
DOI: 10.1186/s12917-022-03257-w -
Carbon Balance and Management Mar 2024Black carbon (BC) encompasses a range of carbonaceous materials--including soot, char, and charcoal--derived from the incomplete combustion of fossil fuels and biomass.... (Review)
Review
BACKGROUND
Black carbon (BC) encompasses a range of carbonaceous materials--including soot, char, and charcoal--derived from the incomplete combustion of fossil fuels and biomass. Urban soils can become enriched in BC due to proximity to these combustion sources. We conducted a literature review of BC in urban soils globally and found 26 studies reporting BC and total organic carbon (TOC) content collected to a maximum of 578 cm depth in urban soils across 35 cities and 10 countries. We recorded data on city, climate, and land use/land cover characteristics to examine drivers of BC content and contribution to TOC in soil.
RESULTS
All studies were conducted in the northern hemisphere, with 68% of the data points collected in China and the United States. Surface samples (0-20 cm) accounted for 62% of samples in the dataset. Therefore, we focused our analysis on 0-10 cm and 10-20 cm depths. Urban soil BC content ranged from 0-124 mg/g (median = 3 mg/g) at 0-10 cm and from 0-53 mg/g (median = 2.8 mg/g) at 10-20 cm depth. The median proportional contribution of BC to TOC was 23% and 15% at 0-10 cm and 10-20 cm, respectively. Surface soils sampled in industrial land use and near roads had the highest BC contents and proportions, whereas samples from residential sites had among the lowest. Soil BC content decreased with mean annual soil temperature.
CONCLUSIONS
Our review indicates that BC comprises a major fraction (nearly one quarter) of the TOC in urban surface soils, yet sampling bias towards the surface could hide the potential for BC storage at depth. Land use emerged as an importer driver of soil BC contents and proportions, whereas land cover effects remain uncertain. Warmer and wetter soils were found to have lower soil BC than cooler and drier soils, differences that likely reflect soil BC loss mechanisms. Additional research on urban soil BC at depth and from diverse climates is critical to better understand the role of cities in the global carbon cycle.
PubMed: 38429441
DOI: 10.1186/s13021-024-00255-3 -
Chemosphere Jul 2019The Grenfell Tower fire in central London, started within a flat, engulfed the whole 24 storey building in flames, killed 72 people and spread toxic effluent via the...
The Grenfell Tower fire in central London, started within a flat, engulfed the whole 24 storey building in flames, killed 72 people and spread toxic effluent via the plume and particulate deposits. Soil samples from 6 locations up to 1,2 km from the Tower, together with semi-burnt fire debris and char samples, were collected 1 and 6 months after the fire. Additionally, dust samples and condensates were collected from a flat 160 m away from the Tower after 17 months. Samples were analysed for common potentially toxic components of fire effluents and synthetic vitreous fibres. Samples collected within 140 m of the Tower showed, amongst other toxicants, polychlorinated dibenzo-p-dioxin concentrations 60 times greater than UK urban reference soil levels; benzene levels were 40 times greater; levels of 6 key polycyclic aromatic hydrocarbons (PAHs) were approximately 160 times greater. PAHs levels are approximately 20 times greater than those reported from nearby Hyde Park before the fire. To explain the presence of these pyrogenic contaminants char and partially burnt debris were also collected and analysed. Benzene, PAHs, isocyanates and phosphorus flame retardants were found. Hydrogen cyanide and synthetic vitreous fibres were present in both soil and debris. Particulate and pyrogenic contamination in the immediate vicinity is clearly evident, and may have leached out of fire debris, char and dust. Further analysis of the area around the Tower is necessary to understand potential health risks.
Topics: Benzene; Coal; Dioxins; Dust; Environmental Monitoring; Environmental Pollution; Fires; Flame Retardants; Humans; Hydrogen Cyanide; London; Metals; Polycyclic Aromatic Hydrocarbons; Soil; Soil Pollutants
PubMed: 30953902
DOI: 10.1016/j.chemosphere.2019.03.153 -
Frontiers in Bioengineering and... 2024Clinical grade magnetic bead implants have important applications in interfacing with the human body, providing contactless mechanical attachment or wireless...
Clinical grade magnetic bead implants have important applications in interfacing with the human body, providing contactless mechanical attachment or wireless communication through human tissue. We recently developed a new strategy, magnetomicrometry, that uses magnetic bead implants as passive communication devices to wirelessly sense muscle tissue lengths. We manufactured clinical-grade magnetic bead implants and verified their biocompatibility via intramuscular implantation, cytotoxicity, sensitization, and intracutaneous irritation testing. In this work, we test the pyrogenicity of the magnetic bead implants via a lagomorph model, and we test the biocompatibility of the magnetic bead implants via a full chemical characterization and toxicological risk assessment. Further, we test the cleaning, sterilization, and dry time of the devices that are used to deploy these magnetic bead implants. We find that the magnetic bead implants are non-pyrogenic and biocompatible, with the insertion device determined to be safe to clean, sterilize, and dry in a healthcare setting. These results provide confidence for the safe use of these magnetic bead implants in humans.
PubMed: 38444650
DOI: 10.3389/fbioe.2024.1290453 -
Biomolecules May 2020The 8488 lipopolysaccharide (LPS) was isolated, purified and characterized by monosaccharide and fatty acid analysis. The O-polysaccharide and lipid A components of the...
The 8488 lipopolysaccharide (LPS) was isolated, purified and characterized by monosaccharide and fatty acid analysis. The O-polysaccharide and lipid A components of the LPS were separated by mild acid degradation. Lipid A was studied by electrospray ionization mass spectrometry (ESI-MS) and found to consist of hexa-, penta-, tetra- and tri-acylated species. Two-dimensional nuclear magnetic resonance (NMR) spectroscopy revealed the following structure of the O-polysaccharide repeating unit →3)-α-L-Rha(1→6)-α-D-Man(1→3)-α-L-Fuc-(1→3)-β-D-GlcNAc-(1→. The LPS showed a low level of toxicity, was not pyrogenic, and reduced the adhesiveness index of microorganisms to 2.12, which was twofold less than the control. LPS modified by complex compounds of germanium (IV) and tin (IV) were obtained. It was found that six LPS samples modified by Sn compounds and two LPS samples modified by Ge compounds lost their toxic activity when administered to mice in a dose of LD (105 µg/mice or 5 mg/kg). However, none of the modified LPS samples changed their serological activity in an Ouchterlony double immunodiffusion test in agar.
Topics: Animals; Germanium; Lethal Dose 50; Lipid A; Mice; O Antigens; Organometallic Compounds; Pantoea; Tin
PubMed: 32456025
DOI: 10.3390/biom10050804 -
ALTEX 2022Pharmaceutical products intended for parenteral use must be free from pyrogenic (fever-inducing) contamination. Pyrogens comprise endotoxins from Gram-negative bacteria...
Pharmaceutical products intended for parenteral use must be free from pyrogenic (fever-inducing) contamination. Pyrogens comprise endotoxins from Gram-negative bacteria and non-endotoxin pyrogens from Gram-positive bacteria, viruses, and fungi. The longstanding compendial test for pyrogens is the rabbit pyrogen test, but in 2010 the monocyte acti-vation test (MAT) for pyrogenic and pro-inflammatory contaminants was introduced into the European Pharmacopoeia (Ph. Eur.) as a non-animal replacement for the rabbit pyrogen test. The present study describes the first product-specific Good Manufacturing Practice validation of Ph. Eur. MAT, Quantitative Test, Method A for the testing of three therapeutic monoclonal antibodies. The study used the MAT version with cryo-preserved peripheral blood mononuclear cells and interleukin-6 as the readout. Much of the data presented here for one of the antibodies was included in a successful product license application to the European Medicines Agency.
Topics: Animals; Rabbits; Pyrogens; Monocytes; Antibodies, Monoclonal; Leukocytes, Mononuclear; Animal Testing Alternatives; Endotoxins
PubMed: 35502618
DOI: 10.14573/altex.2111301