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Anti-cancer Agents in Medicinal... 2017Poly(hydroxyalkanoates) (PHA) have recently attracted increasing attention due to their biodegradability and high biocompatibility, which makes them suitable for the...
BACKGROUND
Poly(hydroxyalkanoates) (PHA) have recently attracted increasing attention due to their biodegradability and high biocompatibility, which makes them suitable for the development of new prolong drug formulations.
OBJECTIVE
A preclinical toxicology study of paclitaxel biopolymer formulation (PBF) (paclitaxel-loaded poly(3- hydroxybutyrate) (PHB) microparticles) was done in order to assess its safety and to forecast side and toxic effects in a clinical study on patients.
METHOD
PHB microparticles loaded with antitumor cytostatic drug PTX were obtained by spray-drying method using Nano Spray Dryer B-90. The comprehensive study of cytotoxicity (on bone marrow stem cells), acute and chronic toxicity, allergenic and pyrogenic properties, histological investigation (in mice, rats and rabbits) of obtained PBF was carried out.
RESULTS
The acute toxicity study showed that PBF is much less toxic in equivalent PTX-content doses than PTX in conventional formulation when administered intraperitoneally to mice and rats. However, the chronic toxicity study showed that at intraperitoneal administration PBF has distinct cumulative properties and toxic effects that prevent PBF from clinical testing in current composition.
CONCLUSION
Thus, the PBF as a prolong drug needs to correct its parameters for further drug formulation development.
Topics: Animals; Antineoplastic Agents, Phytogenic; Biopolymers; Dosage Forms; Dose-Response Relationship, Drug; Drug Carriers; Female; Male; Mice; Microspheres; Paclitaxel; Prohibitins; Rabbits; Rats; Tissue Distribution; Toxicity Tests, Acute; Toxicity Tests, Subchronic
PubMed: 27539319
DOI: 10.2174/1871520616666160817104529 -
Comprehensive Physiology Oct 2014Fever is a cardinal symptom of infectious or inflammatory insults, but it can also arise from noninfectious causes. The fever-inducing agent that has been used most... (Review)
Review
Fever is a cardinal symptom of infectious or inflammatory insults, but it can also arise from noninfectious causes. The fever-inducing agent that has been used most frequently in experimental studies designed to characterize the physiological, immunological and neuroendocrine processes and to identify the neuronal circuits that underlie the manifestation of the febrile response is lipopolysaccharide (LPS). Our knowledge of the mechanisms of fever production and lysis is largely based on this model. Fever is usually initiated in the periphery of the challenged host by the immediate activation of the innate immune system by LPS, specifically of the complement (C) cascade and Toll-like receptors. The first results in the immediate generation of the C component C5a and the subsequent rapid production of prostaglandin E2 (PGE2). The second, occurring after some delay, induces the further production of PGE2 by induction of its synthesizing enzymes and transcription and translation of proinflammatory cytokines. The Kupffer cells (Kc) of the liver seem to be essential for these initial processes. The subsequent transfer of the pyrogenic message from the periphery to the brain is achieved by neuronal and humoral mechanisms. These pathways subserve the genesis of early (neuronal signals) and late (humoral signals) phases of the characteristically biphasic febrile response to LPS. During the course of fever, counterinflammatory factors, "endogenous antipyretics," are elaborated peripherally and centrally to limit fever in strength and duration. The multiple interacting pro- and antipyretic signals and their mechanistic effects that underlie endotoxic fever are the subjects of this review.
Topics: Animals; Cytokines; Disease Models, Animal; Fever; Humans; Lipopolysaccharides; Prostaglandins; Pyrogens; Toll-Like Receptors
PubMed: 25428854
DOI: 10.1002/cphy.c130033 -
Analytical Biochemistry Sep 2018Pyrogens are a class of heterogeneous compounds that cause fever and induce inflammatory responses in the host. Lipopolysaccharides (LPS, also known as endotoxin) is the...
Pyrogens are a class of heterogeneous compounds that cause fever and induce inflammatory responses in the host. Lipopolysaccharides (LPS, also known as endotoxin) is the major pyrogen in the category of drug quality control. Accurate and fast quantification of pyrogens is crucial for drug safety. In the present study, we aimed to develop a sensitive and reliable method for rapid detection of pyrogens using luciferase reporter assay. Stable human A549 luciferase reporter cells were constructed under the control of a NF-κB-responsive element or IFN-β promoter. Our results showed that several monoclonal stable cell clones responded to 0.1 EU/ml endotoxin, which was less than human fever threshold at 0.3 EU/ml of endotoxin. Further, compared with original A549 cells, TLR4 expression on the reporter cells were significantly increased after low amount LPS stimulation. In addition, reporter cells also responded to zymosan stimulation. Therefore, these results indicated that the stable luciferase reporter cells respond to endotoxin and non-endotoxin pyrogens and have the potential to further develop into a sensitive and fast pyrogen evaluation method.
Topics: Biological Assay; Clone Cells; Genes, Reporter; Humans; Luciferases; Pyrogens; Tumor Cells, Cultured
PubMed: 30030993
DOI: 10.1016/j.ab.2018.07.016 -
Qatar Medical Journal 2022Intravenous immunoglobulin (IVIG) therapy has been used as antibody replacement therapy in primary immunodeficiency diseases (PID) for more than 50 years. In this study,...
BACKGROUND
Intravenous immunoglobulin (IVIG) therapy has been used as antibody replacement therapy in primary immunodeficiency diseases (PID) for more than 50 years. In this study, we aimed to define IVIG usage and adverse reactions and complications in PID and explain how subcutaneous immunoglobulin (SCIG) replacement therapy is an alternative that improves the patient experience. In addition, the additional nursing responsibilities associated with this service were also identified.
METHODS
Data and service satisfaction surveys for the last 10 years were reviewed from the Allergy and Immunology Division log registry for those on IVIG and SCIG.
RESULTS
IVIG practice: Most patients currently on IVIG in our unit have PID. Adverse reactions occur during the initial 30 to 60 minutes of the infusion and are mild and self-limited. Infusion reactions are more likely to occur in patients receiving IVIG for the first time. Infusion-related complications included pyrogenic reactions, allergic reactions, and vasomotor symptoms. Complications reported in the literature such as the transmission of blood-borne pathogens and other serious complications, including thrombotic events, renal adverse events, and aseptic meningitis were never reported. Pyrogenic reactions occurred at a rate ≥ 100 mL/hr in at least 3 patients, and a slower infusion rate of ≤ 75 mL/hr mitigated this rate-related complication. SCIG program: This program started in Qatar in 2017. Usually, the clinician assesses and evaluates several factors to help select candidates for this therapy, including the perceptions of inconvenience and/or pain of IV infusions, presence of difficult vein access, and other relevant clinical and social factors. Once training in the appropriate techniques has been accomplished (3-6 sessions), it is most often self-administered in the home setting by the patient or a parent for a child. Table 1 summarizes patients on SCIG. Additional nursing responsibilities: The nursing role in subcutaneous IgG administration is primarily that of an educator and to help the patient/family become independent. This can be achieved by the assessment of appropriate patient selection for self-administration. Determining which patients are suitable include adequate patient education with return demonstration of the necessary skill set, monitoring parameters, educating patients about their medication, and providing educational resources and support.
CONCLUSION
SCIG administration can be a convenient alternative for patients with PID receiving long-term IVIG.
PubMed: 35909401
DOI: 10.5339/qmj.2022.fqac.29 -
The Science of the Total Environment May 2019Biochar produced from pyrolysis of biomass is a candidate with great potential for climate change mitigation by carbon sequestration and reduction of greenhouse gases... (Review)
Review
Biochar produced from pyrolysis of biomass is a candidate with great potential for climate change mitigation by carbon sequestration and reduction of greenhouse gases (GHG) emission in soil. Its potential depends considerably on biochar properties. Biochar stability or biochar C recalcitrance is decisive to its carbon storage/sequestration potential in soil. Three groups of methods including: I) biochar C structure or composition analyses, II) biochar oxidation resistance determination, and III) biochar persistence assessment by incubation & modelling, have been developed for evaluation of biochar stability. Amongst, incubation & modelling is the most commonly used one and is the basis of the other two assessment methods. However, the strategies for incubation experiment designing and data modelling significantly influence the biochar stability results. Drastic differences were observed for stability results obtained from different studies partly because of the large flexibility of the incubation & modelling method. Biased biochar stability would be obtained if the method was used improperly. The present review aims to provide comprehensive information on method strategies used for incubation and modelling, followed by discussions on the key issues such as what kind of biochar to use, how the experiment should be designed, how to determine biochar C mineralization, how the mineralization data should be expressed, and what model should be used, for an accurate biochar stability evaluation. In general, incubating biochar at long-term duration, modelling incubation data with double-exponential model, using C isotopic technology for CO evolution determination with C mineralization data express as percentage of total organic carbon mineralized, applying biochar in the field are favorable to biochar stability assessment. Other strategies such as the use of standard (reference) biochar materials may be effective to improve the assessment.
Topics: Biomass; Carbon; Carbon Dioxide; Carbon Sequestration; Charcoal; Climate Change; Environmental Pollutants; Greenhouse Gases; Minerals; Models, Chemical; Soil
PubMed: 30738273
DOI: 10.1016/j.scitotenv.2019.01.298 -
British Journal of Clinical Pharmacology Mar 2016Antivenom is the mainstay of treatment of snakebite envenoming. However, adverse reactions to snake antivenom that is available are common in many parts of the world... (Review)
Review
Antivenom is the mainstay of treatment of snakebite envenoming. However, adverse reactions to snake antivenom that is available are common in many parts of the world where snakebite is prevalent. Both acute (anaphylactic or pyrogenic) and delayed (serum sickness type) reactions occur. Acute reactions are usually mild but severe systemic anaphylaxis may develop, often within an hour or so of exposure to antivenom. Serum sickness after antivenom has a delayed onset between 5 and 14 days after its administration. Ultimately, the prevention reactions will depend mainly on improving the quality of antivenom. Until these overdue improvements take place, doctors will have to depend on pharmacological prophylaxis, where the search for the best prophylactic agent is still on-going, as well as careful observation of patients receiving antivenom in preparation for prompt management of acute as well as delayed reactions when they occur.
Topics: Anaphylaxis; Antivenins; Fever; Humans; Serum Sickness
PubMed: 26256124
DOI: 10.1111/bcp.12739 -
ALTEX 2018Pyrogenicity presents a challenge to clinicians, medical device manufacturers, and regulators. A febrile response may be caused by endotoxin contamination, microbial... (Review)
Review
Pyrogenicity presents a challenge to clinicians, medical device manufacturers, and regulators. A febrile response may be caused by endotoxin contamination, microbial components other than endotoxin, or chemical agents that generate a material-mediated pyrogenic response. While test methods for the assessment of endotoxin contamination and some microbial components other than endotoxin are well-established, material-mediated pyrogens remain elusively undefined. This review presents the findings of literature searches conducted to identify material-mediated pyrogens associated with medical devices. The in vivo rabbit pyrogen test (RPT) is considered to be the “gold standard” for medical device pyrogenicity testing, despite the fact that few medical device-derived material-mediated pyrogens are known. In line with global efforts to reduce the use of research animals, an in vitro monocyte activation test (MAT) has the potential to replace the RPT. The MAT is used to detect substances that activate human monocytes to release cytokines. This review will also describe the potential opportunities and challenges associated with MAT adoption for the detection of material-mediated pyrogens in medical device testing.
Topics: Animal Testing Alternatives; Animals; Biological Assay; Endotoxins; Equipment and Supplies; Humans; In Vitro Techniques; Lipopolysaccharides; Monocytes; Pyrogens
PubMed: 29901209
DOI: 10.14573/altex.1709221 -
Japanese Journal of Infectious Diseases Mar 2020Fever is a systemic inflammatory response of the body to pyrogens. Nuclear factor κB (NF-κB) is a central signaling molecule that causes the excessive secretion of...
Fever is a systemic inflammatory response of the body to pyrogens. Nuclear factor κB (NF-κB) is a central signaling molecule that causes the excessive secretion of various pyrogen-induced pro-inflammatory factors. This study explored the feasibility of a novel reporter gene assay (RGA) for pyrogen detection using RAW264.7 cells stably transfected with the NF-κB reporter gene as a pyrogenic marker. The RGA could detect different types of pyrogens, including the lipopolysaccharide of gram-negative bacteria, the lipoteichoic acid of gram-positive bacteria, and the zymosan of fungi, and a good dose-effect relationship was observed in terms of NF-κB activity. The limits of detection of the RGA to those pyrogens were 0.03 EU/ml, 0.001 μg/ml, and 1 μg/ml, respectively. The method had good precision and accuracy and could be applied to many molecules (e.g., nivolumab, rituximab, bevacizumab, etanercept, basiliximab, Haemophilus influenzae type b conjugate vaccine, 23-valent pneumococcal polysaccharide vaccine, group A and group C meningococcal conjugate vaccine, diphtheria, tetanus, pertussis [acellular, component], poliomyelitis [inactivated] vaccine, and imject alum adjuvant). The results of this study suggest that the novel RGA has a wide pyrogen detection spectrum and is sufficiently sensitive, stable, and accurate for various applications.
Topics: Animals; Biological Assay; Fever; Genes, Reporter; Limit of Detection; Mice; NF-kappa B; Pyrogens; RAW 264.7 Cells; Sensitivity and Specificity
PubMed: 31666494
DOI: 10.7883/yoken.JJID.2019.163 -
Temperature (Austin, Tex.) 2015There has been great progress in the 30 y since the reporting in 1984 of the cDNA for interleukin1 (IL1) β in the human and IL1α in the mouse. However, the history of...
There has been great progress in the 30 y since the reporting in 1984 of the cDNA for interleukin1 (IL1) β in the human and IL1α in the mouse. However, the history of IL1 begins in the early 1940s with investigations into the nature of an endogenous fever-producing protein released rabbit peritoneal neutrophils. Most researchers in immunology today are unaware that the field of cytokines, particularly the field of inflammatory cytokines. Toll-like receptors and innate immunity traces back to studies on fever. Researchers in infectious diseases wanted to know about an endogenous protein that caused fever, independent of infection. The endogenous fever-producing protein was called by various names: granulocyte, endogenous or leukocytic pyrogen. It is a fascinating and sometimes controversial story for biology and medicine and for the treatment of inflammatory diseases. Few imagined that this fever-producing protein would play such a major role in nearly every cell and in most diseases. This paper reviews the true background and milestones of interleukin1 from the purification of leukocytic pyrogen to the first cDNA of IL1β and the validation of cytokine biology from ill-defined factors to its present day importance.
PubMed: 27226996
DOI: 10.1080/23328940.2015.1017086 -
Immunology Letters Dec 2018Fever is one of the cardinal symptoms of onset of an infection or inflammation and is the common clinical indicator for medical consultation in mammalian host worldwide.... (Review)
Review
Fever is one of the cardinal symptoms of onset of an infection or inflammation and is the common clinical indicator for medical consultation in mammalian host worldwide. Simply, fever manifested with elevation of body temperature from normal physiological range represents adaptive response of immune system on challenge with an infectious and non-infectious circumstance. Fever usually initiated in the periphery as a result of interaction of immune cells with exogenous or endogenous pyrogens. Peripheral pyrogenic signals gain access to the central nervous system via humoral and neural route. Humoral pathway was initiated with production of pyrogenic cytokines and prostaglandins from immune cells of blood as well as liver, transmitted directly to pre-optic area of hypothalamus through the circumventricular organ of brain. On the other hand an alternative pathway was initiated by the same cytokines indirectly via stimulating the vagal sensory neurons result in pyrogenic fever; so-called neuronal pathway. If the magnitude of pyrogens associated fever is very high, it will lead to severe illness ranging from septic shock to death. So it is necessary to evaluate the presence of pyrogens in implants, medical devices, drugs and biological materials to ensure safety in biomedical applications and therapeutics. Classification, route of administration, mechanism of action and detection of pyrogens and associated products are the major subject of this review.
Topics: Animals; Cyclooxygenase 2; Cytokines; Dinoprostone; Energy Metabolism; Fever; Humans; Hypothalamus; Inflammation Mediators; Lipopolysaccharides; Phagocytosis; Pyrogens
PubMed: 30336182
DOI: 10.1016/j.imlet.2018.10.006