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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 -
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 -
3D Printing in Medicine Feb 2024Low temperature vaporized hydrogen peroxide sterilization (VH2O2) is used in hospitals today to sterilize reusable medical devices. VH2O2 sterilized 3D printed materials...
BACKGROUND
Low temperature vaporized hydrogen peroxide sterilization (VH2O2) is used in hospitals today to sterilize reusable medical devices. VH2O2 sterilized 3D printed materials were evaluated for sterilization, biocompatibility and material compatibility.
MATERIALS & METHODS
Test articles were printed at Formlabs with BioMed Clear™ and BioMed Amber™, and at Stratasys with MED610™, MED615™ and MED620™. Sterilization, biocompatibility and material compatibility studies with 3D printed materials were conducted after VH2O2 sterilization in V-PRO™ Sterilizers. The overkill method was used to evaluate sterilization in a ½ cycle. Biocompatibility testing evaluated the processed materials as limited contact (< 24-hours) surface or externally communicating devices. Material compatibility after VH2O2 sterilization (material strength and dimensionality) was evaluated via ASTM methods and dimensional analysis.
RESULTS
3D printed devices, within a specific design window, were sterile after VH2O2 ½ cycles. After multiple cycle exposure, the materials were not cytotoxic, not sensitizing, not an irritant, not a systemic toxin, not pyrogenic and were hemo-compatible. Material compatibility via ASTM testing and dimensionality evaluations did not indicate any significant changes to the 3D printed materials after VH2O2 sterilization.
CONCLUSION
Low temperature vaporized hydrogen peroxide sterilization is demonstrated as a suitable method to sterilize 3D printed devices. The results are a subset of the data used in a regulatory submission with the US FDA to support claims for sterilization of 3D printed devices with specified materials, printers, and device design .
PubMed: 38416324
DOI: 10.1186/s41205-024-00206-1 -
Nature Communications Feb 2024Innate immunity provides the first line of defense through multiple mechanisms, including pyrogen production and cell death. While elevated body temperature during...
Innate immunity provides the first line of defense through multiple mechanisms, including pyrogen production and cell death. While elevated body temperature during infection is beneficial to clear pathogens, heat stress (HS) can lead to inflammation and pathology. Links between pathogen exposure, HS, cytokine release, and inflammation have been observed, but fundamental innate immune mechanisms driving pathology during pathogen exposure and HS remain unclear. Here, we use multiple genetic approaches to elucidate innate immune pathways in infection or LPS and HS models. Our results show that bacteria and LPS robustly increase inflammatory cell death during HS that is dependent on caspase-1, caspase-11, caspase-8, and RIPK3 through the PANoptosis pathway. Caspase-7 also contributes to PANoptosis in this context. Furthermore, NINJ1 is an important executioner of this cell death to release inflammatory molecules, independent of other pore-forming executioner proteins, gasdermin D, gasdermin E, and MLKL. In an in vivo HS model, mortality is reduced by deleting NINJ1 and fully rescued by deleting key PANoptosis molecules. Our findings suggest that therapeutic strategies blocking NINJ1 or its upstream regulators to prevent PANoptosis may reduce the release of inflammatory mediators and benefit patients.
Topics: Humans; Lipopolysaccharides; Gasdermins; Cell Death; Inflammation; Caspases; Heat Stress Disorders; Heat-Shock Response; Pyroptosis; Apoptosis; Nerve Growth Factors; Cell Adhesion Molecules, Neuronal
PubMed: 38409108
DOI: 10.1038/s41467-024-45466-x -
Toxicon: X Mar 2024As injectable therapeutics, snake antivenoms must meet specifications for endotoxin content. The amebocyte lysate (LAL) test was used to evaluate the endotoxin content...
As injectable therapeutics, snake antivenoms must meet specifications for endotoxin content. The amebocyte lysate (LAL) test was used to evaluate the endotoxin content in several commercially available antivenoms released for clinical use. It was found that some products have endotoxin concentrations higher than the accepted limit for these contaminants. These results emphasize the need to include endotoxin determination as part of the routine evaluation of antivenoms by manufacturers and regulatory agencies.
PubMed: 38404947
DOI: 10.1016/j.toxcx.2024.100187 -
Toxicology Letters Feb 2024Reproducible aerosol generation in combination with stable aerosol properties are essential prerequisites for compliant performance of acute or repeated inhalation...
Reproducible aerosol generation in combination with stable aerosol properties are essential prerequisites for compliant performance of acute or repeated inhalation toxicity tests of particulate materials according to OECD TG 403, 436, 412, or 413. A frequent problem of powder aerosol generation is the formation of coarse agglomerates with low shear resistance, which are beyond the tolerable size range but not detected by the prescribed aerodynamic measurement techniques by cascade impactor as the measurement conditions cause a disintegration into smaller fragments. But such agglomerates are observed during the transport to the inhalation chambers. These effects particularly apply to high mass concentrations and low-density powders, i.e., pyrogenic oxides. This study describes the transport influence in the airflow on the change of powder aerosols and on their respirability. A simplified short tube set-up was developed for the aerosol transport pre-tests, which allows the determination of the optimal aerosol formation conditions for the inhalation tests. The particles were measured with low shear using laser diffraction measurement or optical particle counters. The calculation of the aerodynamic particle sizes prescribed in the guidelines requires knowledge of the effective particle density of the porous aerosol particles. A practicable method for determining these is presented and described. In the outlook, first low concentration measurements show that clear agglomeration effects can also occur at particle concentrations around 20 mg/m³.
PubMed: 38401876
DOI: 10.1016/j.toxlet.2024.02.006 -
Biomedicine & Pharmacotherapy =... Apr 2024Lipopolysaccharide (LPS, endotoxin) is ubiquitous and represents a harmful contaminant of pharmaceutical compounds, recombinant biologicals and drug products. The...
Lipopolysaccharide (LPS, endotoxin) is ubiquitous and represents a harmful contaminant of pharmaceutical compounds, recombinant biologicals and drug products. The pyrogen can induce severe immune responses and pathology in vitro and in vivo. Health authorities require strict control of endotoxin in parenteral drugs. However, for research and pre-clinical compound analysis, endotoxin testing is not a required quality control, which may cause potential drawbacks in the translational pipeline. Endotoxin testing is usually performed by the Limulus amebocyte lysate (LAL) assay, which is hampered by the so-called low endotoxin recovery (LER) effect when certain drug formulations are tested. A comprehensive study including structural, biophysical, and biological analyses was conducted to identify LER root cause for phosphate- and polysorbate-containing parenteral drug products. LPS in water showed extended ribbon-like aggregate structures. In placebo (formulation buffer without drug) and in drug product (drug in formulation buffer), a reaggregation of LPS into a network of interlinked micelles with hidden head group charges, and a strong reduction of the negative surface potential was observed. The non-accessibility of the LPS backbone has a direct impact leading (i) to a loss of activation of the LAL-cascade, (ii) reduced activation of the TLR4/MD-2 receptor system, and (iii) increased survival in a mouse model of endotoxemia. These data provide a structure-based explanation of the LER-underlying mechanisms. A human whole blood assay is shown to resolve LER and detect the pyrogenic activity of endotoxin with high sensitivity. This may open new test options to improve quality control in drug development and drug safety.
Topics: Animals; Mice; Humans; Endotoxins; Lipopolysaccharides; Micelles; Limulus Test; Drug Compounding
PubMed: 38401515
DOI: 10.1016/j.biopha.2024.116286 -
ACS Omega Feb 2024Pyrogenic carbon and magnetite (FeO) were mixed together for the activation of hydrogen peroxide (HO), aiming to enhance the oxidation of refractory pollutants in a...
Pyrogenic carbon and magnetite (FeO) were mixed together for the activation of hydrogen peroxide (HO), aiming to enhance the oxidation of refractory pollutants in a sustainable way. The experimental results indicated that the straw-derived carbon obtained by pyrolysis at 500-800 °C was efficient on coactivation of HO, and the most efficient one was that prepared at 700 °C (C700) featured with abundant defects. Specifically, the reaction rate constant () for removal of an antibiotic ciprofloxacin in the coactivation system (C700/FeO/HO) is 12.5 times that in the magnetite-catalyzed system (FeO/HO). The faster pollutant oxidation is attributed to the sustainable production of OH in the coactivation process, in which the carbon facilitated decomposition of HO and regeneration of Fe(II). Besides the enhanced HO utilization in the coactivation process, the leaching of iron was controlled within the concentration limit in drinking water (0.3 mg·L) set by the World Health Organization.
PubMed: 38371804
DOI: 10.1021/acsomega.3c07525 -
Food Science & Nutrition Feb 2024While gut-to-systemic translocation of pyrogenic endotoxin due to a leaky gut elicits systemic inflammation, at the intestine, the endocannabinoid system (eCB) also...
Prebiotics Plus Probiotics May Favorably Impact on Gut Permeability, Endocannabinoid Receptors, and Inflammatory Biomarkers in Patients with Coronary Artery Diseases: A Clinical Trial.
While gut-to-systemic translocation of pyrogenic endotoxin due to a leaky gut elicits systemic inflammation, at the intestine, the endocannabinoid system (eCB) also plays a major role in modulating the impact of gut dysbiosis on the host system. Therefore, we hypothesized that coadministration of prebiotic inulin with probiotics would improve the eCB system, gut microbial composition, and inflammatory parameters associated with coronary artery diseases (CAD). We designed a randomized, double-blind trial with 92 CAD patients. Patients were randomly allocated to receive inulin (15 mg/day), LGG capsules 1.9 × 10 colony-forming unit (CFU) or inulin plus probiotic (synbiotics) supplements, for a duration of 60 days. We assessed gut microbiota composition, expression of cannabinoid receptors (i.e., CB1 and CB2), serum levels of interleukin-6 (IL-6), toll-like receptor 4 (TLR-4), lipopolysaccharides (LPS), total antioxidant capacity (TAC), and malondialdehyde (MDA) before and after the supplementation. Probiotic-inulin cosupplementation significantly decreased IL6, LPS, and TLR-4 and increased serum TAC concentrations compared with the placebo. While CB1 receptor expression had no difference, significant differences were observed for the CB2 receptor expression among the four treatments. CB2 receptor mRNA expression significantly ( < .05) correlated with serum levels of LPS ( = -.10) and F/B ratio ( = -.407, = .047). Our data collectively provide preliminary evidence that gut microbiota determines gut permeability through the LPS-eCB system. We also have found that synbiotics improved the eCB receptors, and inflammatory biomarkers more than either of the two supplementations given alone.
PubMed: 38370067
DOI: 10.1002/fsn3.3835 -
Signal Transduction and Targeted Therapy Feb 2024Pyrogen, often as a contaminant, is a key indicator affecting the safety of almost all parenteral drugs (including biologicals, chemicals, traditional Chinese medicines...
Pyrogen, often as a contaminant, is a key indicator affecting the safety of almost all parenteral drugs (including biologicals, chemicals, traditional Chinese medicines and medical devices). It has become a goal to completely replace the in vivo rabbit pyrogen test by using the in vitro pyrogen test based on the promoted 'reduction, replacement and refinement' principle, which has been highly considered by regulatory agencies from different countries. We used NF-κB, a central signalling molecule mediating inflammatory responses, as a pyrogenic marker and the monocyte line THP-1 transfected with a luciferase reporter gene regulated by NF-κB as an in vitro model to detect pyrogens by measuring the intensity of a fluorescence signal. Here, we show that this test can quantitatively and sensitively detect endotoxin (lipopolysaccharide from different strains) and nonendotoxin (lipoteichoic acid, zymosan, peptidoglycan, lectin and glucan), has good stability in terms of NF-κB activity and cell phenotypes at 39 cell passages and can be applied to detect pyrogens in biologicals (group A & C meningococcal polysaccharide vaccine; basiliximab; rabies vaccine (Vero cells) for human use, freeze-dried; Japanese encephalitis vaccine (Vero cells), inactivated; insulin aspart injection; human albumin; recombinant human erythropoietin injection (CHO Cell)). The within-laboratory reproducibility of the test in three independent laboratories was 85%, 80% and 80% and the interlaboratory reproducibility among laboratories was 83.3%, 95.6% and 86.7%. The sensitivity (true positive rate) and specificity (true negative rate) of the test were 89.9% and 90.9%, respectively. In summary, the test provides a novel alternative for pyrogen detection.
Topics: Animals; Chlorocebus aethiops; Rabbits; Humans; Pyrogens; NF-kappa B; Vero Cells; Reproducibility of Results; Cell Line
PubMed: 38369543
DOI: 10.1038/s41392-024-01744-0