Is secondary chemical exposure of hospital personnel of clinical importance?

INTRODUCTION: There is increasing concern among hospital personnel about potential secondary exposure when treating chemically contaminated patients. OBJECTIVE: To assess which circumstances and chemicals require the use of Level C Personal Protective Equipment (chemical splash suit and air-purifying respirator), to prevent secondary contamination of hospital personnel treating a chemically contaminated patient. METHODS: The US National Library of Medicine PubMed database was searched for the years 1985 to 2020 utilizing combinations of relevant search terms. This yielded 557 papers which were reviewed by title and abstract. After excluding papers on biological or radiological agents, or those not related to hospital personnel, 38 papers on chemicals remained. After a full-text review, 13 papers without an in-depth discussion on the risk for secondary contamination were omitted, leaving 25 papers for review. The references of these papers were searched and this yielded another seven additional citations, bringing the total to 32 papers. INCIDENCE OF SECONDARY TOXICITY: Secondary toxicity in hospital personnel is rare: a large-scale inventory of 120,000 chemical incidents identified only nine cases, an occurrence of 0.0075%. SKIN CONTACT AS A SECONDARY EXPOSURE ROUTE: Skin exposure is rare under normal hygienic working conditions, reflected by the very small number of cases reported in the literature: two cases with corrosive effects due to unprotected contact and one case of presumed skin absorption. INHALATION AS A SECONDARY EXPOSURE ROUTE: Most case reports described secondary toxicity as a result of inhalation. The chemicals involved were irritating solid particles (capsaicin spray/CS), toxic gases formed in the stomach of patients (arsine/hydrazoic acid/phosphine) and vapours from volatile liquids (solvents). FEATURES OF SECONDARY TOXICITY: Reported symptoms after secondary inhalation were generally mild and reversible (mostly irritation of eyes and respiratory tract, nausea, headache, dizziness/light-headedness) and did not require treatment. In many cases, special circumstances increased exposure: treatment/decontamination of multiple patients, regurgitation of the chemical agent from the stomach, or inadequate room ventilation. USE OF MORE THAN STANDARD PERSONAL PROTECTIVE EQUIPMENT: Normal hygienic precautions prevent direct skin contact from exposure to common chemical agents. When solid particle contamination is extensive, a mask and eye protection should be applied. Splash proof outer clothing (splash suit) and eye protection is preferred if (partial) wet decontamination is performed on single patients. Adequate ventilation, careful removal of clothing in case of solid particles contamination and adequate disposal of gastric content reduces exposure. Hospital staff can be rotated if symptoms occur, which can be odour-mediated. The use of more elaborate personal protective equipment with an air-purifying respirator (Level C) is only necessary in exceptional cases of contamination with highly toxic volatile chemicals (e.g., sarin). It should also be considered when decontaminating a large number of patients. CONCLUSIONS: The risk of secondary contamination and subsequent toxicity in hospital personnel decontaminating or treating chemically contaminated patients is small. Normal hygienic precautions (gloves and water-resistant gown) will adequately protect hospital staff when treating the majority of chemically contaminated patients. More extensive protection is only necessary infrequently and there is no reason to delay critical care, even if more elaborate protection is not immediately available

Self-Assembly of Supramolecular Triblock Copolymer Complexes

Four different poly(tert-butoxystyrene)-b-polystyrene-b-poly(4-vinylpyridine) (PtBOS-b-PS-b-P4VP) linear triblock copolymers, with the P4VP weight fraction varying from 0.08 to 0.39, were synthesized via sequential anionic polymerization. The values of the unknown interaction parameters between styrene and tert-butoxystyrene and between tert-butoxystyrene and 4-vinylpyridine were determined from random copolymer blend miscibility studies and found to satisfy 0.031<χS,tBOS<0.034 and 0.39<χ4VP,tBOS<0.43, the latter being slightly larger than the known 0.30<χS,4VP≤0.35 value range. All triblock copolymers synthesized adopted a P4VP/PS core/shell cylindrical self-assembled morphology. From these four triblock copolymers supramolecular complexes were prepared by hydrogen bonding a stoichiometric amount of pentadecylphenol (PDP) to the P4VP blocks. Three of these complexes formed a triple lamellar ordered state with additional short length scale ordering inside the P4VP(PDP) layers. The self-assembled state of the supramolecular complex based on the triblock copolymer with the largest fraction of P4VP consisted of alternating layers of PtBOS and P4VP(PDP) layers with PS cylinders inside the latter layers. The difference in morphology between the triblock copolymers and the supramolecular complexes is due to two effects: (i) a change in effective composition and, (ii) a reduction in interfacial tension between the PS and P4VP containing domains. The small angle X-ray scattering patterns of the supramolecules systems are very temperature sensitive. A striking feature is the disappearance of the first order scattering peak of the triple lamellar state in certain temperature intervals, while the higher order peaks (including the third order) remain. This is argued to be due to the thermal sensitivity of the hydrogen bonding and thus directly related to the very nature of these systems.

Opposing Roles of Membrane and Soluble Forms of the Receptor for Advanced Glycation End Products in Primary Respiratory Syncytial Virus Infection

Respiratory syncytial virus (RSV), a common respiratory pathogen in infants and the older population, causes pulmonary inflammation and airway occlusion that leads to impairment of lung function. Here, we have established a role for receptor for advanced glycation end products (RAGE) in RSV infection. RAGE-deficient (ager−/−) mice were protected from RSV-induced weight loss and inflammation. This protection correlated with an early increase in type I interferons, later decreases in proinflammatory cytokines, and a reduction in viral load. To assess the contribution of soluble RAGE (sRAGE) to RSV-induced disease, wild-type and ager−/− mice were given doses of sRAGE following RSV infection. Of interest, sRAGE treatment prevented RSV-induced weight loss and neutrophilic inflammation to a degree similar to that observed in ager−/− mice. Our work further elucidates the roles of RAGE in the pathogenesis of respiratory infections and highlights the opposing roles of membrane and sRAGE in modulating the host response to RSV infection

Low-molecular-weight heparin reduces hyperoxia-augmented ventilator-induced lung injury via serine/threonine kinase-protein kinase B

<p>Abstract</p> <p>Background</p> <p>High-tidal-volume mechanical ventilation and hyperoxia used in patients with acute lung injury (ALI) can induce the release of cytokines, including high-mobility group box-1 (HMGB1), oxygen radicals, neutrophil infiltration, and the disruption of epithelial and endothelial barriers. Hyperoxia has been shown to increase ventilator-induced lung injury, but the mechanisms regulating interaction between high tidal volume and hyperoxia are unclear. We hypothesized that subcutaneous injections of enoxaparin would decrease the effects of hyperoxia on high-tidal-volume ventilation-induced HMGB1 production and neutrophil infiltration via the serine/threonine kinase/protein kinase B (Akt) pathway.</p> <p>Methods</p> <p>Male C57BL/6, either wild type or Akt^+/-, aged between 6 and 8 weeks, weighing between 20 and 25 g, were exposed to high-tidal-volume (30 ml/kg) mechanical ventilation with room air or hyperoxia for 2 to 8 hours with or without 4 mg/kg enoxaparin administration. Nonventilated mice served as a control group. Evan blue dye, lung wet-to-dry weight ratio, free radicals, myeloperoxidase, Western blot of Akt, and gene expression of HMGB1 were measured. The expression of HMGB1 was studied by immunohistochemistry.</p> <p>Results</p> <p>High-tidal-volume ventilation using hyperoxia induced microvascular permeability, Akt activation, HMGB1 mRNA expression, neutrophil infiltration, oxygen radicals, HMGB1 production, and positive staining of Akt in bronchial epithelium. Hyperoxia-induced augmentation of ventilator-induced lung injury was attenuated with Akt deficient mice and pharmacological inhibition of Akt activity by enoxaparin.</p> <p>Conclusion</p> <p>These data suggest that enoxaparin attenuates hyperoxia-augmented high-tidal-volume ventilation-induced neutrophil influx and HMGB1 production through inhibition of the Akt pathway. Understanding the protective mechanism of enoxaparin related with the reduction of HMGB1 may help further knowledge of the effects of mechanical forces in the lung and development of possible therapeutic strategies involved in acute lung injury.</p

Attract and deter: a dual role for pyrrolizidine alkaloids in plant–insect interactions

Pyrrolizidine alkaloids (PAs) are the major defense compounds of plants in the Senecio genus. Here I will review the effects of PAs in Senecio on the preference and performance of specialist and generalist insect herbivores. Specialist herbivores have evolved adaptation to PAs in their host plant. They can use the alkaloids as cue to find their host plant and often they sequester PAs for their own defense against predators. Generalists, on the other hand, can be deterred by PAs. PAs can also affect survival of generalist herbivores. Usually generalist insects avoid feeding on young Senecio leaves, which contain a high concentration of alkaloids. Structurally related PAs can differ in their effects on insect herbivores, some are more toxic than others. The differences in effects of PAs on specialist and generalists could lead to opposing selection on PAs, which may maintain the genetic diversity in PA concentration and composition in Senecio species

Cell Death or Survival Promoted by Alternative Isoforms of ErbB4

The report demonstrates that two distinct isoforms of the ErbB4 receptor tyrosine kinase stimulate either proliferation or apoptosis by mechanisms involving differential transcriptional regulation of the PDGFRA gene. These data have implications for developing approaches to target ErbB4 signaling in cancer

Thrombospondin-1 Contributes to Mortality in Murine Sepsis through Effects on Innate Immunity

BACKGROUND:Thrombospondin-1 (TSP-1) is involved in many biological processes, including immune and tissue injury response, but its role in sepsis is unknown. Cell surface expression of TSP-1 on platelets is increased in sepsis and could activate the anti-inflammatory cytokine transforming growth factor beta (TGFβ1) affecting outcome. Because of these observations we sought to determine the importance of TSP-1 in sepsis. METHODOLOGY/PRINCIPAL FINDINGS:We performed studies on TSP-1 null and wild type (WT) C57BL/6J mice to determine the importance of TSP-1 in sepsis. We utilized the cecal ligation puncture (CLP) and intraperitoneal E. coli injection (i.p. E. coli) models of peritoneal sepsis. Additionally, bone-marrow-derived macrophages (BMMs) were used to determine phagocytic activity. TSP-1-/- animals experienced lower mortality than WT mice after CLP. Tissue and peritoneal lavage TGFβ1 levels were unchanged between animals of each genotype. In addition, there is no difference between the levels of major innate cytokines between the two groups of animals. PLF from WT mice contained a greater bacterial load than TSP-1-/- mice after CLP. The survival advantage for TSP-1-/- animals persisted when i.p. E. coli injections were performed. TSP-1-/- BMMs had increased phagocytic capacity compared to WT. CONCLUSIONS:TSP-1 deficiency was protective in two murine models of peritoneal sepsis, independent of TGFβ1 activation. Our studies suggest TSP-1 expression is associated with decreased phagocytosis and possibly bacterial clearance, leading to increased peritoneal inflammation and mortality in WT mice. These data support the contention that TSP-1 should be more fully explored in the human condition