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Therapeutic Innovation & Regulatory... Sep 2015Quality and safety tests are required for regulatory approval of drugs and pharmaceuticals in the country to guarantee minimum safety standards, and most of these tests...
Quality and safety tests are required for regulatory approval of drugs and pharmaceuticals in the country to guarantee minimum safety standards, and most of these tests include animal usage. In the case of biological medicines, these safety and quality tests have to be performed on a batch-to-batch basis and require a large number of animals. Russell and Burch's 1959 principle of the 3 Rs- replacement, reduction, and refinement-is now being increasingly adopted worldwide, and various national and international pharmacopoeias have taken initiatives to safeguard animals. This article details the Indian Pharmacopoeia Commission's initiative to implement the 3 Rs through the Indian Pharmacopoeia. Explored are the deletion of animal tests, such as the abnormal toxicity test at final lot for biologicals; the replacement of in vivo methods by in vitro methods; the reduction in the number of animals used where deletion of the animal test is not possible; and the refinement of tests to cause minimal suffering to the animals. In Indian Pharmacopoeia 2014, pyrogen testing using rabbits has been replaced by the bacterial endotoxin test in the majority of biological monographs-keeping in view international trends and, especially for vaccine monographs, validated in vitro tests such as the bacterial endotoxin test as an alternative to the pyrogen test where justified and authorized. Steps are taken for introducing a single-dilution assay for the potency testing of diphtheria and tetanus vaccine (adsorbed) with the aim of minimizing number of animals used. The justified and authorized use of animals in drug manufacturing, analytic laboratories, and research will not only help in the expedited development/production of drugs but also be useful in protecting and promoting animal health.
PubMed: 30227040
DOI: 10.1177/2168479015572371 -
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 -
Environmental Science & Technology Nov 2023Heating temperature (HT) during forest fires is a critical factor in regulating the quantity and quality of pyrogenic dissolved organic matter (DOM). However, the...
Heating temperature (HT) during forest fires is a critical factor in regulating the quantity and quality of pyrogenic dissolved organic matter (DOM). However, the temperature thresholds at which maximum amounts of DOM are produced (TT) and at which the DOC gain turns into net DOC loss (TT) remain unidentified on a component-specific basis. Here, based on solid-state C nuclear magnetic resonance, absorbance and fluorescence spectroscopies, and Fourier transform ion cyclotron resonance mass spectrometry, we analyzed variations in DOM composition in detritus and soil with HT (150-500 °C) and identified temperature thresholds for components on structural, fluorophoric, and molecular formula levels. TT was similar for detritus and soil and ranged between 225 and 250 °C for bulk dissolved organic carbon (DOC) and most DOM components. TT was consistently lower in detritus than in soil. Moreover, temperature thresholds differed across the DOM components. As the HT increased, net loss was observed initially in molecular formulas tentatively associated with carbohydrates and aliphatics, then proteins, peptides, and polyphenolics, and ultimately condensed aromatics. Notably, at temperatures lower than TT, particularly at TT, burning increased the DOC quantity and thus might increase labile substrates to fuel soil microbial community. These composition-specific variations of DOM with temperature imply nonlinear and multiple temperature-dependent wildfire impacts on soil organic matter properties.
Topics: Dissolved Organic Matter; Wildfires; Temperature; Heating; Soil
PubMed: 37916767
DOI: 10.1021/acs.est.3c05265 -
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 -
Pharmaceutical Development and... Sep 2017In recent years, drug delivery systems such as liposomes and microparticles have been used in clinic for the treatment of different diseases and from a regulatory point...
In recent years, drug delivery systems such as liposomes and microparticles have been used in clinic for the treatment of different diseases and from a regulatory point of view, a parenterally applied drug and drug delivery systems must be sterile and pyrogen free. Radiation sterilization is a method recognized by pharmacopoeias to achieve sterility criteria of parenterals. It has the ability to kill microorganisms in therapeutic products. The ability of, however, irradiation might also affect the performance of drug delivery systems. One of the most critical points is irradiation dose, because certain undesirable chemical and physical changes may accompany with the irradiation, especially with the traditionally applied dose of 25 kGy. Its ionizing property may cause fragmentation of covalent bond. The care must be paid to the applied dose. In this research, the effects of gamma irradiation on different drug delivery systems such as chitosan microparticles, liposomes, niosomes and sphingosomes were investigated. According to the experimental data, it can be concluded that gamma irradiation can be a suitable sterilization technique for liposome, niosome and sphingosome dispersions. When all irradiated drug carrier systems were taken into consideration, chitosan glutamate microparticles were found as the most radioresistant drug delivery system among the others.
Topics: Chitosan; Drug Delivery Systems; Gamma Rays; Humans; Nanoparticles; Sterilization
PubMed: 27050500
DOI: 10.3109/10837450.2016.1163393 -
Bioresource Technology Dec 2018Biochar produced from biomass pyrolysis is becoming a powerful tool for carbon sequestration and greenhouse gas (GHG) emission reduction. Biochar C recalcitrance or... (Review)
Review
Biochar produced from biomass pyrolysis is becoming a powerful tool for carbon sequestration and greenhouse gas (GHG) emission reduction. Biochar C recalcitrance or biochar stability is the decisive property determining its carbon sequestration potential. The effect of pyrolysis process parameters on biochar stability is becoming a frontier of biochar study. This review discussed comprehensively how and why biomass compositions and physicochemical properties and biomass processing conditions such as pyrolysis temperature and reaction residence time affect the stability of biochar. The review found that relative high temperature (400-700 °C), long reaction residence time, slow heating rate, high pressure, the presence of some minerals and biomass feedstock of high-lignin content with large particle size are preferable to biochar stability. However, challenges exist to mediate the trade-offs between biochar stability and other potential wins. Strategies were then proposed to promote the utilization of biochar as a climate change mitigation tool.
Topics: Biomass; Carbon Sequestration; Charcoal; Climate Change; Humans; Lignin; Pyrolysis
PubMed: 30220436
DOI: 10.1016/j.biortech.2018.09.030 -
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 -
The Journal of the Royal College of... Mar 2018We present a case of a previously healthy 37-year-old male who developed fever, nausea, vomiting, diarrhoea, and hypovolaemia. Within 5.5 h he presented with...
We present a case of a previously healthy 37-year-old male who developed fever, nausea, vomiting, diarrhoea, and hypovolaemia. Within 5.5 h he presented with tachycardia, tachypnoea, became hypotensive and displayed a diffuse erythematous rash. In the following hours he developed persistent hypotension, acute respiratory distress syndrome, liver failure, kidney failure and disseminated intravascular coagulation. A diagnosis of toxic shock syndrome was made, but despite antibiotic therapy, immunoglobulin administration, and supportive measures, the patient died 50 h after presentation. Streptococcus pyogenes was isolated from blood cultures.
Topics: Adult; Anti-Bacterial Agents; Fatal Outcome; Humans; Male; Paronychia; Shock, Septic; Staphylococcal Infections; Staphylococcus epidermidis; Streptococcal Infections; Streptococcus pyogenes
PubMed: 29741523
DOI: 10.4997/JRCPE.2018.107 -
The Science of the Total Environment Oct 2022Biochar plays a key role in soil phosphorus (P) forms and distribution by affecting soil biochemical characteristics with relevant effects on the microbial community. In...
Biochar plays a key role in soil phosphorus (P) forms and distribution by affecting soil biochemical characteristics with relevant effects on the microbial community. In this study, we aimed to study the role of biochar in the variation of microbial community and P forms, and the relationships between soil properties, microbial community, and P forms. Here, we conducted a five-year field experiment NPK minerally fertilized with different application rates of biochar; control (B0, 0 kg ha yr), low rate (B1500, 1500 kg ha yr), medium rate (B3000, 3000 kg ha yr), high rate (B6000, 6000 kg ha yr). Our study showed that the highest increases in bacterial diversity and abundances coincided with increases in P forms typically retained in bacterial cells (β-glucosidase, adenosine monophosphate-AMP, choline phosphate, and glucose-6 phosphate) and occurred at medium application rates. At low application rates, N-fixing and P solubilizing and mineralizing bacteria (Sphingomonas, Haliangium, and Bradyrhizobium) increased. P forms retained in bacterial cells decreased at the highest application rates while the most stable forms such as DNA and inositol hexaphosphate (IHP), steadily increased. Stereoisomers of IHP derived from soil microbes (scyllo-IHP and D-chiro-IHP) accounted for the total IHP increases at high application rates. pH and available P and K and total P were highest at high biochar application rates whereas the proportion of organic P was reduced. The most relevant genus in such soils was Gemmatimonas, a polyphosphate accumulating and pyrogenic material degrading bacterium. Therefore, it appears that applying biochar at higher rates reduced the abundance of plant growth promoting bacteria while enhancing the abundance of P accumulating and pyrogenic degrading types.
Topics: Bacteria; Charcoal; Fertilization; Phosphorus; Soil; Soil Microbiology
PubMed: 35772528
DOI: 10.1016/j.scitotenv.2022.157022 -
Journal of AOAC International Jul 2018Staphylococcus aureus is a Gram-positive bacterium capable of causing a wide array of infections. Generally a commensal organism, S. aureus encodes several virulence... (Review)
Review
Staphylococcus aureus is a Gram-positive bacterium capable of causing a wide array of infections. Generally a commensal organism, S. aureus encodes several virulence mechanisms that contribute to disease progression. This review highlights toxins as a secreted virulence factor by S. aureus, the diseases that manifest as a result, and the methods used to detect them. In particular, the advantages and limitations of current toxin detection methods are discussed.
Topics: Bacterial Toxins; Disease Reservoirs; Humans; Immunoassay; Staphylococcal Food Poisoning; Staphylococcal Infections; Staphylococcus aureus; Toxins, Biological; Virulence Factors
PubMed: 29216934
DOI: 10.5740/jaoacint.17-0366