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Poultry Science Nov 2023To determine whether the antipyretic effect of the mixture of Radix isatidis, Forsythiae, and Gypsum (RIFG) on lipopolysaccharide (LPS) induced fever broilers and its...
To determine whether the antipyretic effect of the mixture of Radix isatidis, Forsythiae, and Gypsum (RIFG) on lipopolysaccharide (LPS) induced fever broilers and its related mechanisms. A total of 315 24-day-old yellow-plumed broilers were randomly divided into 7 groups, except for the control group, other groups were injected with LPS. Two hours later, RIFG were given drinking water to relieve fever, and it was evaluated by the expression of genes and proteins of the maximum body temperature rise (∆T), body temperature response index (TRI), serum and hypothalamic pyrogenic heat factor. RIFG could reduce the body temperature of broilers with fever (P < 0.01). It inhibited the expressions of IL-6 and PGE2 (P < 0.01), down-regulated mRNA expression levels of TNF-ɑ and COX-2 (P < 0.01), and promoted the generation of antipyretic factor AVP mRNA (P < 0.01). In addition, the expression level of TLR4 and NF-κB p65 protein can be down-regulated, and LPS + RM group has the best down-regulated effect. RIFG had a good antipyretic effect on reducing LPS-induced fever of broilers by inhibiting the activation of TLR4/NF-κB signaling pathway and thermogenic factors.
PubMed: 37769495
DOI: 10.1016/j.psj.2023.103032 -
Heliyon Oct 2023Leptospirosis is a perplexing mystification for many clinicians. Clinically often underdiagnosed due to lack of a rapid, sensitive, and specific diagnostic test....
PURPOSE
Leptospirosis is a perplexing mystification for many clinicians. Clinically often underdiagnosed due to lack of a rapid, sensitive, and specific diagnostic test. Currently available diagnostic tests have their own limitations; therefore, monitoring biomarkers that contribute an essential role in pathogenesis is crucial. Herein, a pilot study was conducted to detect the presence of sphingomyelinase in urine of leptospirosis patients.
METHODS
Blood and urine samples were collected from 140 patients having febrile illness. Samples were analyzed through culturing, dark-field microscopy, detecting anti-leptospiral antibodies by MAT, IgM ELISA, Leptocheck-WB and screening for sphingomyelinase using a sphingomyelinase assay kit.
RESULTS
Out of 140 febrile illness patients, 22.14 % were tested leptospirosis, 33.57 % were dengue, 25 % scrub typhus, 18.57 % malaria and 0.71 % co-infection (dengue-leptospirosis). MAT seropositivity of 19.28 % (27/140) was confirmed with the highest agglutinant determined against serovar Icterohaemorrhagiae RGA followed by Autumnalis, Australis, and Pyrogens. IgM ELISA and Leptocheck-WB positivity was 16.42 % and 13.57 % respectively. Whereas culture and dark-field microscopy showed a sensitivity of 4.28 % and 2.1 %, respectively. Out of 31 confirmed cases of leptospirosis, sphingomyelinase was detected in the urine of 25 (80.64 %) patients, MAT positivity was seen in 87.09 % and culture positivity was seen in 12.90 % of cases.
CONCLUSION
Detection of sphingomyelinase in the urine of a leptospirosis patient and its absence in other febrile illnesses like dengue, malaria and scrub typhus establish evidence of secretion of sphingomyelinase in urine during leptospiral infection. Hence, sphingomyelinase could be used as a potential diagnostic biomarker to detect leptospirosis in a non-invasive way.
PubMed: 37916114
DOI: 10.1016/j.heliyon.2023.e21138 -
Biologicals : Journal of the... Nov 2023The rabbit pyrogen test (RPT) was the benchmark for pyrogenicity testing, but scientific advancements have provided innovative and humane methods, such as the in vitro...
The rabbit pyrogen test (RPT) was the benchmark for pyrogenicity testing, but scientific advancements have provided innovative and humane methods, such as the in vitro monocyte-activation test (MAT). However, transitioning from the RPT to the MAT has been challenging. The European Directorate for the Quality of Medicines & HealthCare, the Council of Europe, and the European Partnership for Alternative Approaches to Animal Testing jointly hosted an international conference entitled "The future of pyrogenicity testing: phasing out the rabbit pyrogen test". The conference aimed to show how the European Pharmacopoeia intends to remove the RPT from its texts by 2026, facilitate the use of MAT, and identify gaps in the suppression of RPT. The events contributed to a better understanding of the barriers to RPT replacement and acceptance of in vitro alternatives. Participants comprised stakeholders from Asia, Europe, and North America, including vaccine developers, contract laboratories, and regulators. Participants shared their replacement strategies and experiences with MAT implementation. They emphasised the need for continued cooperation between stakeholders and stressed the importance of international harmonisation of regulatory requirements to help accelerate MAT acceptance outside Europe. Despite the challenges, the willingness to eliminate the unnecessary use of RPT was common across all participants.
Topics: Animals; Rabbits; Humans; Pyrogens; Monocytes; Meningococcal Vaccines; Laboratories; Europe; Animal Testing Alternatives
PubMed: 37643507
DOI: 10.1016/j.biologicals.2023.101702 -
Environmental Science & Technology May 2024This study investigated the reaction pathway of 2,4-dinitroanisole (DNAN) on the pyrogenic carbonaceous matter (PCM) to assess the scope and mechanism of PCM-facilitated...
This study investigated the reaction pathway of 2,4-dinitroanisole (DNAN) on the pyrogenic carbonaceous matter (PCM) to assess the scope and mechanism of PCM-facilitated surface hydrolysis. DNAN degradation was observed at pH 11.5 and 25 °C with a model PCM, graphite, whereas no significant decay occurred without graphite. Experiments were performed at pH 11.5 due to the lack of DNAN decay at pH below 11.0, which was consistent with previous studies. Graphite exhibited a 1.78-fold enhancement toward DNAN decay at 65 °C and pH 11.5 relative to homogeneous solution by lowering the activation energy for DNAN hydrolysis by 54.3 ± 3.9%. This is supported by our results from the computational modeling using Car-Parrinello simulations by ab initio molecular dynamics/molecular mechanics (AIMD/MM) and DFT free energy simulations, which suggest that PCM effectively lowered the reaction barriers by approximately 8 kcal mol compared to a homogeneous solution. Quaternary ammonium (QA)-modified activated carbon performed the best among several PCMs by reducing DNAN half-life from 185 to 2.5 days at pH 11.5 and 25 °C while maintaining its reactivity over 10 consecutive additions of DNAN. We propose that PCM can affect the thermodynamics and kinetics of hydrolysis reactions by confining the reaction species near PCM surfaces, thus making them less accessible to solvent molecules and creating an environment with a weaker dielectric constant that favors nucleophilic substitution reactions. Nitrite formation during DNAN decay confirmed a denitration pathway, whereas demethylation, the preferred pathway in homogeneous solution, produces 2,4-dinitrophenol (DNP). Denitration catalyzed by PCM is advantageous to demethylation because nitrite is less toxic than DNAN and DNP. These findings provide critical insights for reactive adsorbent design that has broad implications for catalyst design and pollutant abatement.
Topics: Hydrolysis; Anisoles; Molecular Dynamics Simulation; Carbon
PubMed: 38739946
DOI: 10.1021/acs.est.4c01069 -
Chemosphere Sep 2023The Amazon is the largest river by discharge volume and one of the most biodiverse biomes in the world. Lately, there has been a rapid increase of the urban population...
The Amazon is the largest river by discharge volume and one of the most biodiverse biomes in the world. Lately, there has been a rapid increase of the urban population in the region, which has been translated into a growing emission of organic contaminants such as polycyclic aromatic hydrocarbons (PAHs) into surface water bodies. This study provides the most comprehensive evaluation of the PAH contamination levels in surface waters of the Amazon basin. We investigated the occurrence and potential sources of 16 priority PAHs and characterised their risks for freshwater ecosystems. For this, we took 40 water samples from different sites along the Brazilian part of the Amazon River, including three major tributaries, and smaller rivers crossing the main urban areas. The results of this study show that PAHs are widespread contaminants in rivers of the Brazilian Amazon. The sum of the total concentration of the 16 priority PAHs reached values of 134 ng L in the Amazon River, and 163 ng L near densely populated areas. On the other hand, the total PAH concentration was generally lower in the monitored tributaries. In most samples, the contamination pattern was dominated by high molecular weight PAHs, suggesting a major contribution of pyrogenic sources, although petrogenic contamination was also present in some locations near urban areas. We assessed ecological risks posed by PAH mixtures using a hazard index. The results indicated that PAH contamination is not likely to pose direct toxic effects for Amazonian freshwater organisms, however continued monitoring is recommended near densely populated areas.
Topics: Ecosystem; Water Pollutants, Chemical; Rivers; Polycyclic Aromatic Hydrocarbons; Environmental Monitoring; Geologic Sediments; Water; China; Risk Assessment
PubMed: 37353170
DOI: 10.1016/j.chemosphere.2023.139285 -
Environmental Science and Pollution... Dec 2023Pristine pyrogenic carbonaceous material (BRH) obtained from rice husk and modified with FeCl (BRH-FeCl) were prepared and explored as carbocatalysts for the activation...
Rice husk-based pyrogenic carbonaceous material efficiently promoted peroxymonosulfate activation toward the non-radical pathway for the degradation of pharmaceuticals in water.
Pristine pyrogenic carbonaceous material (BRH) obtained from rice husk and modified with FeCl (BRH-FeCl) were prepared and explored as carbocatalysts for the activation of peroxymonosulfate (PMS) to degrade a model pharmaceutical (acetaminophen, ACE) in water. The BRH-FeCl/PMS system removed the pharmaceutical faster than the BRH/PMS. This is explained because in BRH-FeCl, compared to BRH, the modification (iron played a role as a structuring agent mainly) increased the average pore diameter and the presence of functional groups such as -COO, -Si-O, or oxygen vacancies, which allowed to remove the pollutant through an adsorption process and significant carbocatalytic degradation. BRH-FeCl was reusable during four cycles and had a higher efficiency for activating PMS than another inorganic peroxide (peroxydisulfate, PDS). The effects of BRH-FeCl and PMS concentrations were evaluated and optimized through an experimental design, maximizing the ACE degradation. In the optimized system, a non-radical pathway (i.e., the action of singlet oxygen, from the interaction of PMS with defects and/or -COO/-Si-O moieties on the BRH-FeCl) was found. The BRH-FeCl/PMS system generated only one primary degradation product that was more susceptible to biodegradation and less active against living organisms than ACE. Also, the BRH-FeCl/PMS system induced partial removals of chemical oxygen demand and dissolved organic carbon. Furthermore, the carbocatalytic system eliminated ACE in a wide pH range and in simulated urine, having a low-moderate electric energy consumption, indicating the feasibility of the carbocatalytic process to treat water polluted with pharmaceuticals.
Topics: Oryza; Water; Peroxides; Pharmaceutical Preparations
PubMed: 37991611
DOI: 10.1007/s11356-023-30785-1 -
Animals : An Open Access Journal From... Nov 2023Working dogs are at a high risk of canine non-pyrogenic hyperthermia, a life-threatening condition that can occur due to physical exertion or environmental factors that...
Working dogs are at a high risk of canine non-pyrogenic hyperthermia, a life-threatening condition that can occur due to physical exertion or environmental factors that inhibit dogs' ability to cool themselves. Two frequently recommended cooling methods to reduce body temperature are water immersion and the application of isopropyl alcohol to paw pads. This cross-over study compared the relative efficacy of these methods in 12 working-dogs-in-training with post-exertional heat stress. On each study day, dogs had a physical exam and performed a warm-up exercise followed by sequential recalls in which dogs ran approximately 25 m between two designated handlers for 10 min until they showed multiple signs of heat stress or their core temperature reached 105 °F (40.6 °C). Dogs' temperature and heart rate were collected after each recall. Dogs completed three study days, and each day, randomly received one of three interventions: passive cooling (no intervention), partial water immersion, or isopropyl alcohol. Post-intervention dogs rested for 20 min. Partial water immersion and isopropyl alcohol both cooled dogs more than no intervention, and water immersion cooled dogs more efficiently than isopropyl alcohol. Additionally, the application of isopropyl alcohol raised dogs' heart rates more than water immersion or no intervention, suggesting that the process of applying isopropyl alcohol is potentially stressful to dogs. Thus, partial water immersion is preferred to cool dogs post-exertion due to its more efficient cooling and better tolerance of use.
PubMed: 38067024
DOI: 10.3390/ani13233673 -
Frontiers in Toxicology 2023Polycyclic aromatic hydrocarbons (PAHs) are persistent environmental contaminants that present several environmental risks including human health. The 16 priority PAHs...
Polycyclic aromatic hydrocarbons (PAHs) are persistent environmental contaminants that present several environmental risks including human health. The 16 priority PAHs including its 1-methylnaphthalene, and 2-methylnaphthalene were determined in sediment and fish samples () of River Owan, Edo State, Nigeria using gas chromatography (GC) equipped with flame ionization detector (FID) and other standard laboratory protocols. The isomeric ratio was used for source diagnosis, sediment quality guidelines, and risk models of incremental lifetime cancer were used for risk assessment. 1-methylnaphthalene and 2-methylnaphthalene were most predominant in all sediment samples analysed. The ∑LMW PAHs ranged between 0.093-0.250 μg/kg; ∑HMW PAHs were 0.107-0.579 μg/kg. The sediment samples range for ∑PAHs was 0.280-0.810 μg/kg with concentration order of increase: SE5>SE4>SE3>SE6>SE1>SE2>SE7 for the seven sampling locations. The ∑PAHs for was 0.190 μg/kg, which is higher than the value of 0.080 μg/kg, and these values were greatly lesser when compared to the European Commission limit of 12.00 μg/kg. The diagnostic ratio indicates that the sources are more pyrogenic than petrogenic, revealing combustion from grass, wood, and bush burning. Sediment quality assessment showed that the ∑PAHs were lower than the regulatory values of sediment quality guidelines (SQG) assessment suggesting no ecotoxicological effects on the benthic organisms in this area at present. The Incremental Life Cancer Risk results were in the range of 9.15 × 10-1.46 × 10 for children, and 7.78 × 10-1.76 × 10 for adults considering the three routes of exposure. The incremental life cancer risk assessment showed a negligible risk.
PubMed: 38090359
DOI: 10.3389/ftox.2023.1250943 -
EJNMMI Radiopharmacy and Chemistry May 2024Parkinson's disease is a neurodegenerative disorder that is characterized by a degeneration of the dopaminergic system. Dopamine transporter (DAT) positron emission...
BACKGROUND
Parkinson's disease is a neurodegenerative disorder that is characterized by a degeneration of the dopaminergic system. Dopamine transporter (DAT) positron emission tomography (PET) imaging has emerged as a powerful and non-invasive method to quantify dopaminergic function in the living brain. The PET radioligand, [F]FE-PE2I, a cocaine chemical derivative, has shown promising properties for in vivo PET imaging of DAT, including high affinity and selectivity for DAT, excellent brain permeability, and favorable metabolism. The aim of the current study was to scale up the production of [F]FE-PE2I to fulfil the increasing clinical demand for this tracer.
RESULTS
Thus, a fully automated and GMP-compliant production procedure has been developed using a commercially available radiosynthesis module GE TRACERLab FX2 N. [F]FE-PE2I was produced with a radiochemical yield of 39 ± 8% (n = 4, relative [F]F delivered to the module). The synthesis time was 70 min, and the molar activity was 925.3 ± 763 GBq/µmol (250 ± 20 Ci/µmol). The produced [F]FE-PE2I was stable over 6 h at room temperature.
CONCLUSION
The protocol reliably provides a sterile and pyrogen-free GMP-compliant product.
PubMed: 38696063
DOI: 10.1186/s41181-024-00269-9 -
Physiological Research Mar 2024To explore the mechanism whereby cGAS-STING pathway regulates the pyroptosis of cryptorchidism cells, with a view to finding a new strategy for clinically treating...
To explore the mechanism whereby cGAS-STING pathway regulates the pyroptosis of cryptorchidism cells, with a view to finding a new strategy for clinically treating cryptorchidism-induced infertility. Spermatogonial GC-1 cells were heat stimulated to simulate the heat hurt microenvironment of cryptorchidism. The cell viability was assayed by CCK-8, and cellular DNA damage was detected by gamma-H2AX immunofluo-rescence assay. Flow cytometry was employed to assess pyroptosis index, while western blot, ELISA and PCR were used to examine the expressions of pyroptosis-related proteins (Caspase-1, IL-1beta, NLRP3) and cGAS-STING pathway proteins (cGAS, STING). After STING silencing by siRNA, the expressions of pyroptosis-related proteins were determined. Pyroptosis occurred after heat stimulation of cells. Morphological detection found cell swelling and karyopyknosis. According to the gamma-H2AX immunofluorescence (IFA) assay, the endonuclear green fluorescence was significantly enhanced, the gamma-H2AX content markedly increased, and the endonuclear DNA was damaged. Flow cytometry revealed a significant increase in pyroptosis index. Western blot and PCR assays showed that the expressions of intracellular pyrogenic proteins like Caspase-1, NLRP3 and GSDMD were elevated. The increased STING protein and gene expressions in cGAS-STING pathway suggested that the pathway was intracellularly activated. Silencing STING protein in cGAS-STING pathway led to significantly inhibited pyroptosis. These results indicate that cGAS-STING pathway plays an important role in heat stress-induced pyroptosis of spermatogonial cells. After heat stimulation of spermatogonial GC-1 cells, pyroptosis was induced and cGAS-STING pathway was activated. This study can further enrich and improve the molecular mechanism of cryptorchidism.
Topics: Male; Humans; NLR Family, Pyrin Domain-Containing 3 Protein; Pyroptosis; Cryptorchidism; Spermatogonia; Heat Stroke; Nucleotidyltransferases; Chromogranin A; Caspase 1; Signal Transduction; Acetates; Phenols
PubMed: 38466010
DOI: 10.33549/physiolres.935163