Methoxyflurane is an inhaled analgesic administered via a disposable inhaler which has been used in Australia for over 40 years for the management of pain associated with trauma and for medical ...procedures in children and adults. Now available in 16 countries worldwide, it is licensed in Europe for moderate to severe pain associated with trauma in conscious adults, although additional applications are being made to widen the range of approved indications. Considering these ongoing developments, we reviewed the available evidence on clinical usage and safety of inhaled analgesic methoxyflurane in trauma pain and in medical procedures in both adults and children. Published data on methoxyflurane in trauma and procedural pain show it to be effective, well tolerated, and highly rated by patients, providing rapid onset of analgesia. Methoxyflurane has a well-established safety profile; adverse events are usually brief and self-limiting, and no clinically significant effects on vital signs or consciousness levels have been reported. Nephrotoxicity previously associated with methoxyflurane at high anesthetic doses is not reported with low analgesic doses. Although two large retrospective comparative studies in the prehospital setting showed inhaled analgesic methoxyflurane to be less effective than intravenous morphine and intranasal fentanyl, this should be balanced against the administration, supervision times, and safety profile of these agents. Given the limitations of currently available analgesic agents in the prehospital and emergency department settings, the ease of use and portability of methoxyflurane combined with its rapid onset of effective pain relief and favorable safety profile make it a useful nonopioid option for pain management. Except for the STOP! study, which formed the basis for approval in trauma pain in Europe, and a few smaller randomized controlled trials (RCTs), much of the available data are observational or retrospective, and further RCTs are currently underway to provide more robust data. Keywords: analgesia, clinical safety, Penthrox, procedural pain, review, trauma
Human living skin equivalents (LSEs) offer an alternative to the use of split-thickness autografts for the treatment of hard-to-heal wounds. LSEs consist of 4 active components: a well-differentiated ...stratum corneum derived from epidermal keratinocytes, dermal fibroblasts, and an extracellular collagen matrix. Neonatal foreskins are used as the source of keratinocytes and dermal fibroblasts for the manufacture of LSEs. Following isolation and expansion in vitro, the cells are cultured on a 3-dimensional scaffold to give an upper epidermal layer and supporting dermal layer. The resulting product has the appearance and handling characteristics of human skin. Safety evaluation of LSEs begins with insuring that foreskins are obtained only from healthy infants whose mothers are negative for a panel of adventitious agents. Keratinocyte and fibroblast cell banks are characterized using morphologic, biochemical, and histologic criteria; checked for the absence of contaminating cell types such as melanocytes, macrophages, lymphocytes, and Langerhans cells; subjected to rigorous microbiological testing (with any production materials of biological origin); and evaluated for in vivo tumorigenicity. The consistency of certain key morphologic and functional characteristics are regularly assessed. Because an LSE represents an allogeneic graft, preclinical safety studies include in vitro and in vivo determinations of its potential immunogenicity. Immunocompromised (SCID) mice reconstituted with human leukocytes or engrafted with human fetal hematolymphoid organs have been useful animal models for assessing possible immunologic responses to LSEs. Additional preclinical studies are being conducted to show that LSEs are noncytotoxic and lack allergenic, sensitizing, or irritation potential.
The effect of diet composition on the uptake of particulates across the gastrointestinal epithelium has been examined in fasted male weanling Sprague-Dawley rats by estimating the systemic uptake of ...orally administered 2-microns latex polystyrene microspheres. Using a tissue solubilization assay, particle transfer in animals maintained on a fluid diet was determined. A larger number of particles was transferred from the gut lumen to the internal organs, including the mesenteric lymph node, spleen, bone marrow, liver, kidney, and heart of animals fed solid pelleted diet than those maintained on a fluid-diet 4 hr after oral administration of particles. The increase in particle number in rats fed the solid diet was only statistically significant (P < 0.05) for brain tissue in the analysis for trend. However, the number of particles retained in the proximal region of the gut at the end of this period was greater in animals fed the fluid diet. This work demonstrates that diet composition is important in gastrointestinal transepithelial translocation of microspheres.
Developmental immunotoxicity is new both as an area of scientific study and as a potential source of concern in the protection of the public health. It is a combination of three nascent sciences and ...one older established area of study–immunology, `Development’, toxicological science and the practical application of experimental findings to indicate risks to man and means to control them. This hardworking and very successful meeting, organized by the Immunotoxicology Technical Committee (ITC) of the International Life Sciences Institute (ILSI) Health and Environmental Sciences Institute (HESI) with input from the U.S. Environmental Protection Agency (EPA), provided an appropriate setting in which scientists from industrial, academic and regulatory backgrounds were able to debate how the development of the immune system might be affected by toxicity, and ways in which transient and permanent harmful effects might occur. There was considerable interest in how the basic processes and structures of immunity and development might be affected by model substances, which could afford examples to demonstrate the value of laboratory methods to detect developmental immunotoxicity. There were vigorous discussions about testing strategies, about techniques, about how to `validate’ laboratory methods when there was relatively little consistent information from man to identify suitable positive control substances and cardinal disorders, and about how best to employ the sparse information to support the effective prediction of risk.
Risk assessment and risk communication Dayan, Anthony D.
Journal of toxicology. Cutaneous and ocular toxicology,
20/1/1/, Letnik:
21, Številka:
1-2
Journal Article
The goal of this chapter is to discuss the general principles of risk assessment and risk communication as they relate to the use of excipients in drug products. A vital need of the user of any ...product is to understand its "safety," to know when and under what conditions its employment will not be harmful, and correspondingly when it may carry some risk. Safety, in this sense, is the complement of toxicity, and it represents the best judgment of the circumstances when any hazard of the product will not be realized as a risk.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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