Jeffrey A Brinker, M.D.
- Professor of Medicine
- Joint Appointment in Radiology and Radiological Science
This may account for the autoimmune side effects of some of these compounds (Halliwell and Gutteridge (1999)) generic 250mg lopinavir free shipping medications similar to gabapentin. Thiyl radicals can also lead to order 250 mg lopinavir fast delivery symptoms bladder cancer singlet oxygen production (Wefers and Sies (1983)) 250 mg lopinavir overnight delivery symptoms for hiv. Both free and protein contained-thiyl radicals are essential in detoxification of more potent pro oxidants (Kalyanaraman (1995)). The carbonyl group (C=O) is one of the most important structures in organic chemistry. To cover the chemistry and biochemistry of all carbonyl compounds found in biological systems is way beyond the scope of this handbook. Short chain (carbon length 2 to 9) aliphatic aldehydes are clear liquids with distinct odors. Aldehydes can be formed in the laboratory by a variety of approaches, including careful oxidation of a primary alcohol, Rosenmund’s synthesis (chemical reduction of an acid chloride), ozonolysis of alkenes, or by heating formic acid o and a carboxylic acid with manganous oxide at 300 C. Cytotoxic aldehydes are also found in automobile exhaust, cigarette smoke, cooking emissions, and drinking water. Aldehydes are fairly reactive and can undergo reduction (to alcohols), oxidation (to acids), or nucleophilic addition with alcohols (forming hemi-acetals and acetals), thiols (forming hemi-thioacetals and thioacetals), hydrogen cyanide (forming cyanohydrin) and hydrogen sulfite (forming hydrogen sulfonic acid salts). Unsaturated aldehydes where the carbon-carbon double bond is located in the 2-position. Acrolein will therefore show the chemical reactions typical for compounds containing a carbonyl and a double bond. A typical example of this is the Schiff base (imine) formation between an aldehyde and a primary amine. Here the -amine group of a lysine residue located on the enzyme reacts with carbonyl substrate. Examples of enzymes that make use of Schiff bases include aldolase, aminotransferases, lysyl oxidase, phosphorylase, rhodopsin, and transaldolases – the production of unwanted Schiff bases however is a major problem for the cell. Patients presenting with carbonyl overload are said to be under “carbonyl stress” (Miyata et al. The presence of aldehydes can be determined by their ability to restore the magenta color to Schiff’s reagent (sulfur dioxide treated rosanaline hydrochloride). Alternatively, as they are reducing agents, their presence is indicated by the production of a silver mirror when treated with Tollen’s reagent (ammoniacal silver nitrate) or a precipitate of red Cu (I) oxide when treated with Fehling’s solution (an alkaline complex of copper tartrate). A number of xenobiotic compounds owe their biological activity to their ability to generate pro-oxidants. However, this ability is also responsible for their undesirable side effects and unwanted toxicity. Readers wanting a more comprehensive review of the toxicology of these compounds are referred to Halliwell and Gutteridge (1999), Kehrer (1993) and Sies and de Groot (1992). The separation of compounds based upon their compound class or drug class is not perfect as some compounds may fall into more than one category. For example, some compounds are antiobiotics possess a quinones structure and are antitumor agents. Quinones (and/or semiquinones) can also form adducts with nucleophiles, especially thiols (Figure 2. These adducts may act as toxins directly or indirectly through the inhibition of key enzymes. To go through all the mechanisms of action for the list of compounds presented in Table 2. Second, it can abstract hydrogen atoms directly from lipids and initiate lipid peroxidation. Such compounds include a diverse group of photosensitizing agents, some of which are used as sensitizing agents in photodynamic therapy. Induction of nitrotyrosine-like immunoreactivity in the lower motor neuron of amyotrophic lateral sclerosis. Improved methods for estimation of hydroxyl free radical levels in vivo based on liquid chromatography with electrochemical detection. Nanomolar quantification and identification of various nitrosothiols by high performance liquid chromatography coupled with flow reactors of metals and Griess reagent. Biological activity of hypochlorous acid: Implications for microbicidal mechanisms of leukocyte myeloperoxidase. Continuous flow determination of nitrite with membrane separation/chemi-luminescence detection. Synthesis of creatol, a hydroxyl radical adduct of creatinine and its increase by puromycin aminonucleoside in isolated rat hepatocytes. Products of creatinine with hydroxyl radical as a useful marker of oxidative stress in vivo. Action of hypochlorous acid on the antioxidant protective enzymes superoxide dismutase, catalase and glutathione peroxidase. Scatchard analysis of methane sulfinic acid production from dimethyl sulfoxide: a method to quantify hydroxyl radical formation in physiologic systems. Determination of kainic acid-induced release of nitric oxide using a novel hemoglobin trapping technique with microdialysis. Singlet oxygen: a primary effector in the ultraviolet A/near-visible light induction of the human heme oxygenase gene. Immunocytochemical evidence for a mitochondrially located nitric oxide synthase in brain and liver. Apparent hydroxyl radical production by peroxynitrite: implications for endothelial injury from nitric oxide and superoxide. Kinetics of superoxide dismutase and iron catalyzed nitration of phenolics by peroxynitrite. Adenosine modulates n-methyl-d-aspartate-stimulated hippocampal nitric oxide production in vivo.
The other human IgG subclasses (and IgGs of most other species) have this same basic structure but differ particularly in the nature and length of the hinge order 250 mg lopinavir fast delivery medications 73. The structure resembles IgG1 but with a relatively long hinge bearing O linked sugar chains 250mg lopinavir medicine man lyrics. In IgA2 order cheap lopinavir online medications 4 times a day, the hinge is very short and, in the predominant allotype, the light chains are disulfide linked not to the heavy chain but to one another. This representa tion relies greatly on comparison of the amino acid sequences of and heavy chains. The hinge can be divided into a region rich in charge (possibly helical) and one rich in O linked sugars. The structure of the hinge may be much less extended in solution than represented schematically here. It is, however, very sensitive to proteolytic attack so that serum IgD is unstable. Mouse IgD has a structure very different to that of human IgD, in contrast to the general similarity in structures for human and mouse Igs. The Fab arms can likely rotate out of the plane about their two fold axis (see also Figure 3. The structures shown were determined by crystallographic analysis of Fcs in complex with Fc receptors. One heavy chain is shown in red, the other in yellow and the N linked carbohydrate chains that are interposed between the penultimate domains are shown in blue. For IgE, the Fc structure is shown for the C 4 –C 3 domain fragment for comparison;. For IgA1, the N linked sugars are attached at a position quite distinct from that for IgG1 and IgE. There is also some evidence that free IgD may help protect against microbes in the human upper respiratory tract. The structures of the Fc regions of human IgA1 and IgE have been determined and are compared with IgG1 in Figure 3. In all three cases, the penultimate domains are unpaired and Star Staple have carbohydrate chains interposed between them. Fc5 Antibodies and complement Flagellum the clustering together of IgG molecules, typically on the surface of a pathogen such as a bacterium, leads to the binding of the complement C1 molecule via the hexavalent C1q Figure 3. Electron micrograph of an uncomplexed IgM protein shows a “star way of complement and a number of processes that can lead to shaped” conformation (see Figure 3. Electron micrograph of a specific sheep IgM most favorable clustered arrangement of antibodies on an antigen bound to a Salmonella paratyphi flagellum as antigen suggests surface for complement triggering may also be hexameric, that the five F(ab) units and C 2 domains have been 2 thereby matching the symmetry of C1q. The subclasses of IgG dislocated relative to the plane of the Fcs to produce a “staple” trigger with different efficiencies. Complement C1 is activated on IgG2 is only triggered by antigens at high density. It is already “clus (star), implying that the dislocation process plays an important tered” (pentameric) but occurs in an inactive form. It is suggested that movement of multivalent antigen appears to alter the conformation of the the Fabs exposes a C1q binding site on the C 3 domains of IgM. This is supported by observations that an Fc5 molecule, IgM molecule to expose binding sites that allow C1q to bind obtained by papain digestion of IgM, can activate complement and the classical pathway of complement to be triggered. Electron micrographs are Electron microscopy studies suggest the conformational change 6 negatively stained preparations of magnification 2 10, i. For example, the clearance of IgG have been characterized, most with several variant forms. In coated erythrocytes from the blood of chimpanzees was addition, the neonatal Fc receptor FcRn also binds IgG and essentially inhibited by the monovalent Fab fragment of a will be dealt with later. It binds monomeric IgG avidly to the surface of the and the synthesis of a variety of inflammatory mediators cell, thus sensitizing it for subsequent encounter with antigen. This process is Its main roles are probably in facilitating phagocytosis, in responsible for the symptoms of hay fever and of extrinsic antigen presentation, and in mediating extracellular killing of asthma when patients with atopic allergy come into contact target cells coated with IgG antibody, a process referred to as with the allergen. It is present on many different is present on monocytes, macrophages, neutrophils, eosino types of hematopoietic cells (Table 3. In fact, it shares closer homology membrane distal) and D2 (C terminal, membrane proximal). The left hand side and middle columns show views of the crystal structures of the complexes of the FcRs with their respective Fc ligands. The extracellular domains of the receptors are shown in blue; one heavy chain of each Fc region is shown in red and the other in dark yellow. The middle column shows a view where the D2 domains of each of the receptors are positioned so that their C termini face downwards. Here the Fc regions of IgG and IgE are seen in a horizontal position from the side. The right hand column shows a schematic representation of the receptors and their intact ligands from the same viewpoint as the images in the middle column. The necessity for dislocation of IgG and IgE to allow positioning of the Fab tips away from the receptor bearing cell surface is apparent. This requires positions adopted in the other Fc receptors, essentially inverting the antibody to adopt a “dislocated” conformation in which the 84 / part 1: Fundamentals of immunology Fab arms are rotated out of the plane of the Fc. One consequence Antibodies and the neonatal Fc receptor of this mode of interaction, recognized many years ago, is that An important Fc receptor for IgG is the neonatal receptor, it promotes close approach of the target cell membrane (upwards FcRn. This receptor mediates transport of IgG from mother to on the page) to the effector cell membrane. This mode of binding permits an IgA:FcR stoichiom cells of the young infant to the blood.
Requests all interested stakeholders and organizations to purchase lopinavir 250mg amex medications causing pancreatitis provide support order cheap lopinavir on line medicine woman strain, including expertise and financial and in-kind resources buy genuine lopinavir treatment plan goals and objectives, on a voluntary basis, for the cooperative actions, including by participating in developing and mak ing available relevant information and guidance; 9. Invites the participating organizations of the Inter-Organization Programme for the Sound Management of Chemicals to report on the cooperative actions on endocrine-disrupting chemicals and its achievements and recommenda tions for further possible cooperative actions for the consideration of the Conference at its fourth session. American College of Obstetricians and Gynecolo gists Committee on Health Care for Underserved Women; American Society for Reproductive Medicine Practice Committee; the University of California, San Francisco Program on Reproduc tive Health and the Environment. In Chemical Exposures During Pregnancy: Dealing with Potential, but Unproven, Risks to Child Health: Royal College of Obstetricians and Gynaecologists. Endocrine-Disrupting Chemicals and Public Health Protection: A Statement of Principles from the Endocrine Society. Environmental signaling: what embryos and evolution teach us about endocrine disrupting chemicals. Monocrotophos induced dysfunction on estrous cycle and follicular develop ment in mice. Prenatal and postnatal exposure to bisphenol a induces anxio lytic behaviors and cognitive deficits in mice. The contribution of occupational risks to the global burden of disease: summary and next steps. Preventing disease through healthy environments towards an estimate of the environmental burden of disease. Geneva, Switzerland: United Nations Environment Programme and the World Health Organization. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 2007; 16:1070-1076. Developmental aspects of environmental neurotoxicology: Lessons from lead and poly chlorinated biphenyls. Neurotoxicity of brominated flame retardants: (in)direct effects of parent and hydroxylated polybrominated diphenyl ethers on the (developing) nervous system. Behavioral toxicology of cognition: extrapolation from experimental animal models to humans: behavioral toxicology symposium overview. Pesticides, depression and suicide: a systematic review of the epidemiological evidence. Does perinatal exposure to endocrine disruptors induce autism spectrum and attention deficit hyperactivity disorders. Perturbed nuclear receptor signaling by environmental obesogens as emerging factors in the obesity crisis. Prenatal exposure to the environmental obesogen tributyltin predisposes multipotent stem cells to become adipocytes. Metabolic programming: fetal origins of obesity and metabolic syndrome in the adult. Accumulation and endocrine-disrupting effects of the flame retardant mixture firemaster((R)) 550 in rats: an exploratory assessment. Female reproductive disorders: the roles of endocrine-disrupting compounds and developmental timing. Hypothesis: exposure to endocrine-disrupting chemicals may interfere with timing of puberty. The association of bisphenol-A urinary concentrations with antral follicle counts and other measures of ovarian reserve in women undergoing infertility treatments. Epigenetic mechanisms in the actions of endocrine-disrupting chemicals: gonadal effects and role in female reproduction. Increased incidence of infertility treatment among women working in the plastics industry. Regional differences and temporal trends in male reproductive health disorders: semen quality may be a sensitive marker of environ mental exposures. Testicular dysgenesis syndrome: an increasingly common developmental disorder with environmental aspects. Environ mental exposure to xenoestrogens and oestrogen related cancers: reproductive system, breast, lung, kidney, pancreas, and brain. Hormones and endocrine-disrupting chemicals: Low dose effects and nonmonotonic dose response. No threshold dose for estradiol induced sex reversal of turtle embryos: How little is too much. No threshold dose-response curves for nongenotoxic chemicals: Findings and ap plications for risk assessment. Pesticides usage in cabbage (Brassica oleracea) cultivation in the forest ecozone of Ghana. Pesticide residue evaluation in major staple food items of Ethio pia using the Quechers method: A case study from the Jimma zone. Organochlorine pesticide residues in human and cow’s milk in the towns of Asendabo, Serbo and Jimma in South-Western Ethiopia. Melting glaciers: a major source of persistent organochlorines to subalpine Bow Lake in Banff National Park, Canada. Recent climate change in the Arctic and its impact on contami nant pathways and interpretation of temporal trend data. Endocrine-disrupting chemicals and climate change: A worst-case combination for Arctic marine mammals and seabirds. Degradation of bifenthrin, chlorpyrifos and imidacloprid in soil and bedding materials at termiticidal application rates. Degradation and sorption of selected organophosphate and carbamate insec ticides in urban stream sediments. Chlorpyrifos and neurode velopmental effects: a literature review and expert elicitation on research and policy. Exposures of preschool children to chlorpyrifos and its degradation product 3,5,6-trichloro-2-pyrid inol in their everyday environments.
When the temperature induced unfolding was monitored by the enzyme activity the Tm was also decreased by 39 C generic lopinavir 250mg with mastercard symptoms you may be pregnant, see figure 22C and table 4 purchase lopinavir with paypal 6 mp treatment. Midpoint concentration of denaturation (Cm) for native (N) to buy discount lopinavir 250mg on-line medications i can take while pregnant intermediate (I) states and for I to unfolded states (U). Under physiological conditions (37 C) this mutant is unable to fold into the native conformation. The classical molten globule state has been proved to be aggregation prone (Hammarstrom et al. The intermediate molten globule light is indicated with I* and the molten globule with I. These amino acids are strictly conserved in active -carbonic anhydrases, see figure 25, the only exceptions are found bacterial carbonic anhydrases in Helicobacter pylori (S117 instead of H107 and S127 instead of E117) and Neisseria gonorrhea (N99 instead of H107) (Almstedt et al. Five single mutants (H107Y, H107F, H107A, H107N and E117A) and two double mutants (H107A/E117A and H107N/E117A) were generated with the pseudo wild type as background. The mutations H107A and E117A were made to remove the side chains and thereby the hydrogen bonds between residues H107 and E117. H107F was constructed to remove the ability to form hydrogen bonds while retaining the sterical properties of the tyrosine and H107N was designed with respect to the carbonic anhydrase from N. The double mutants were made to probe the interaction energy between H107 and E117 using a double mutant cycle. The double mutants were already in the molten globule state at 4 C, which makes it impossible to calculate midpoints of denaturation for the first transition. This proved to be possible by use of small molecule stabilization for H107N/E117A, see below. The inhibitor appeared to function as a chemical chaperone and therefore we used the small molecule inhibitor acetazolamide to induce folding of the mutant. The interaction energy between H107 and E117 was almost negligible and the destabilizing effects of H107Y and E117A were essentially additive. This independence of stabilization between these two interacting residues is surprising and shows that the direct interaction is not responsible for the destabilization, but rather due to the disturbances in the H-bond network surrounding the active site. We selected 9 inhibitors (see table 6) to get a wide spectrum of poor to very strong binders to address whether the best binders also were superior in preventing misfolding. Inhibitors 2-5 are simple para-amino substituted benzo-sulfonamides and the introduction of one or two halo-substituents in meta position lowers their stabilizing effects. The more complex inhibitors (6-9) showed a more complex correlation pattern between the stabilizing effects and inhibition potency i. In our case the disease mutant is so extremely destabilized only the most potent inhibitors could stabilize the protein so that half of the protein molecules were in the native form at 37 C, but at the high concentration this demanded all activity was lost. We thereafter investigated if the binding of the activators could slow down the kinetics of thermal unfolding. There were no alteration in the decay rate when the activators were present even in a 750 fold molecular excess. The initial finding that scrapie associated infections prions formed amyloid-like structures was shown 25 years ago by Prusiner and Glenner (Prusiner et al. Hence aggregation and amyloidogenesis of PrP is strongly correlated with prion disease and is an intense research field (Aguzzi, 2008). Amyloid fibrillation and oligomer formation of PrP in in vitro studies have so far been performed under conditions where mild to harsh conditions of denaturants of various sorts have been included. Under these gentle conditions we could induce irreversible conversion of native recombinant HuPrP variants into aggregates composed of amyloid fibrils within hours. Formed aggregates were positive using Thioflavin T (ThT) fluorescence and showed Congo red birefringence under polarized light. These methods show that the initial native largely helical native recombinant HuPrP variants had misfolded into the aggregated state of cross -sheet structure of amyloid. Amyloid fibrillation kinetics followed by Thioflavin T the rate of amyloid fibril formation was analyzed using Thioflavin T, ThT fluorescence. A large number of identical samples were subjected to fibrillation conditions in buffer F under intense shaking (350 rpm) at 37 °C (as above) and aliquots were taken at different time points to be assayed for ThT fluorescence. The amyloid fibrillation kinetics followed a trajectory with a lag phase, a growth phase and an equilibrium phase. The longest lag-phase in the spontaneous fibrillation kinetics was obtained for HisHuPrP90-231, hence this variant was selected for seeding experiments. Samples were run using preformed fibrils as seeds at two different concentrations (1% and 5% of the total amount of protein). As expected the lag phase was shortened for the seeded reactions and the final ThT signal was higher, indicating a more efficient conversion into the amyloid fibrillar state, see figure 29. Average fibrillation kinetics curves for HisHuPrP (solid line), 90-231 with 1% seed (dotted line) and with 5% seed (dashed line) Amyloid fibrils are formed after initial aggregation During sampling of the fibrillation reaction we noted that samples were turbid already after a few minutes of fibrillation conditions, long before any ThT fluorescence appeared. To quantify the aggregation rate we subjected identical samples of HisHuPrP90-231 to turbidity measurements. Comparing the trace of turbidity with the onset of ThT fluorescence revealed dramatically different kinetics, figure 30b. At different time points aliquots were withdrawn and analyzed by transmission electron microscopy to assess the morphology of the formed HisHuPrP90-231 aggregates. From the micrographs it was evident that early formed aggregates up to 2 h was composed of heavily clustered material which over time (>2 h) transformed into fibrillar material, figure 30a. Transmission electron 90-231 microscopy images of negatively stained aggregates at different time points taken at 200000 fold magnification, showing the conversion of disordered aggregates towards fibrils over time. Interestingly, lowering the protein concentration to half does not affect the lag phase but increased the rate of fibril growth.
When we involve people in our projects without their consent we use them as a means to order lopinavir amex medicine park lodging our own ends buy generic lopinavir pills symptoms 0f ovarian cancer. The principle of respect for auton 60 omy is based on the principle of respect for persons discount 250 mg lopinavir overnight delivery treatment quincke edema. Respecting people implies that they should be o ered ethically appropriate and clearly understandable ways to consent (or not) to have their health records included in central databases. Except for purely privacy related concerns, de-identi cation of health data cannot overcome any of the important ethical concerns that many people have about the creation and use of databases and/or tissue banks for research 61 purposes. For example, various studies indicate that people may consider commercial uses to be at odds with their original motiva tion to participate in research even when they explicitly agreed to 62 take part in research. At most, anonymisation might o er protection with regard to privacy, although various studies suggest that even this cannot be guaranteed. This is doubly problematic since genome data have implications for the patient and her family members. Informed consent and biobank research in a Norwegian context’ (2005) 15 Critical Public Health 335–47. Broad consent could be argued to be morally justi ed in the name of ‘We Medicine’: seeking consent for individual studies could slow down research of potential social value. However, the question arises as to how the potential for bene t to the common good of any research project can be assessed. Without an answer to this question, it is di cult to justify the use of broad consent on the grounds of the common good. Further questions arise, such as how public and individual interests can be balanced and who should carry out these balancing exercises. As we will discuss next, notions of altruism and solidarity are some times invoked in arguments supporting broad consent. Caul eld and Kaye have pointed out that there is a danger of con ating the idea that people want to participate in a project ‘altruistically’–in the name of the common good – with the idea that the ethical and legal norm. Interestingly, some research suggests that the public and patients do not see broad consent as accep table. Moreover, one survey of over 1000 participants found that initial support for broad consent diminished once speci c types of controversial research. Other research has shown that the general public is generally positive towards medical research and is usually willing to participate without 68 expecting any personal bene t. However, the willingness to participate decreases if the bene ts to society are unclear or if private pro ts might 69 be derived. Donna Dickenson identi es corporate interests and political neoliberal ism as one of the key drivers of ‘Me Medicine’. Neoliberalism includes making signi cant cuts in public spending while at the same time increasing the involvement of private corporations in areas such as healthcare, education and scienti c research (and outsourcing from the 70 public to the private sector of an increasing number of services). With regard to biomedicine and healthcare, the neoliberal nature of the poli tical agenda is very clear. For health services, the agenda translates into the following strati cation: (a) to keep the voters happy, a basic, low-level service should be paid for by the state; (b) a higher-level service should be available to those who pay, directly or via insurance; 67 Raymond G. Critchley, ‘Bene t sharing and biobanking in Australia’ (2012) 21(5) Public Understanding of Science 534–55. Indeed, as Donna Dickenson observes, ‘at the highest governmental levels, public backing has been solicited to underpin private-sector pro t 71 making from biotechnology’. Moreover, ‘[the] public sector, as the entrepreneurial state, is being asked to sponsor the growth and shoulder 72 the risks for the private sector’. A total of 44 geographical areas (‘foot prints’) are created that need to develop strategic plans to rationalise services. Moreover, ‘Individuals, rather than organisations or public insti tutions, are forced to deal with the healthcare, social and nancial con sequences of ever-increasing and ambiguous data dissemination 73 practices among entities they are not always aware of’. Yet, as we have hinted at in our discussion about broad consent, the neoliberal political agenda is veiled with references to bene ts for all and altruism. It draws on the language of ‘We Medicine’, with the ultimate promise of (and hopes for immediate) ‘Me Medicine’. The form of altruism applied in such discourses was Richard Titmuss’s (1970) ‘gift relation ship’. An altruistic act within a gift relationship is one that is voluntary and that has no expectation of return. Speaking to the Financial Times, Professor Mark Caul eld (Chief Scienti cO cer) has assumed that the partici pants are well aware that few will see pharmaceutical bene ts themselves: ‘[T]hey’ve enrolled on the principle that this is altruistic, and they don’t expect any personal bene t. They’re doing it because they want someone 76 else to have a better chance than they did. What function is this rhetoric about common good, civic duty and altruism serving. It also de ects from the glimmer of hope that there will be a diagnosis or a treatment (the ‘Me Medicine’ aspect). Making up research subjects in genetics research’ (2011) 33(7) Sociology of Health and Illness 1081–95; Lars O. While the two schemes we discuss in this chapter purport to promote the common good, we would submit that fairness requires real bene t sharing and not just rhetoric. However, we should emphasise that there is a di erence between being trusted and meriting trust.
Buy generic lopinavir 250 mg on line. After The Fall â€Žâ€“ Everything.
Randomized clinical trial of high concentration versus titrated oxygen use in pediatric asthma order lopinavir 250mg without prescription symptoms 5dpo. Hasegawa T purchase lopinavir on line medications safe while breastfeeding, Ishihara K cheap lopinavir 250mg otc treatment 3 nail fungus, Takakura S, Fujii H, Nishimura T, Okazaki M, Katakami N, et al. Duration of systemic corticosteroids in the treatment of asthma exacerbation; a randomized study. Prospective, placebo controlled trial of 5 vs 10 days of oral prednisolone in acute adult asthma. A 5 versus 3-day course of oral corticosteroids for children with asthma exacerbations who are not hospitalised: a randomised controlled trial. Evaluation of SaO2 as a predictor of outcome in 280 children presenting with acute asthma. Arterial blood gas analysis or oxygen saturation in the assessment of acute asthma. Chest radiograph in the evaluation of first time wheezing episodes: review of current clinical practice and efficacy. Exhaled air and aerosolized droplet dispersion during application of a jet nebulizer. Addition of intravenous beta(2)-agonists to inhaled beta(2)-agonists for acute asthma. Intramuscular versus oral corticosteroids to reduce relapses following discharge from the emergency department for acute asthma. Early use of inhaled corticosteroids in the emergency department treatment of acute asthma. Need for intravenous hydrocortisone in addition to oral prednisolone in patients admitted to hospital with severe asthma without ventilatory failure. A single dose of intramuscularly administered dexamethasone acetate is as effective as oral prednisone to treat asthma exacerbations in young children. Adverse behavioral effects of treatment for acute exacerbation of asthma in children: a comparison of two doses of oral steroids. Two days of dexamethasone versus 5 days of prednisone in the treatment of acute asthma: a randomized controlled trial. A randomized trial of single dose oral dexamethasone versus multidose prednisolone for acute exacerbations of asthma in children who attend the emergency department. Anticholinergics in the treatment of children and adults with acute asthma: a systematic review with meta-analysis. Combined inhaled anticholinergics and short-acting beta2-agonists for initial treatment of acute asthma in children. Combined inhaled beta-agonist and anticholinergic agents for emergency management in adults with asthma. Inhaled anticholinergics and short-acting beta(2)-agonists versus short acting beta2-agonists alone for children with acute asthma in hospital. Addition of intravenous aminophylline to inhaled beta(2)-agonists in adults with acute asthma. Magnesium sulfate for treating exacerbations of acute asthma in the emergency department. Magnesium sulfate is effective for severe acute asthma treated in the emergency department. Usefulness of inhaled magnesium sulfate in the coadjuvant management of severe asthma crisis in an emergency department. Intravenous or nebulised magnesium sulphate versus standard therapy for severe acute asthma (3Mg trial): a double-blind, randomised controlled trial. Intravenous magnesium sulfate for treating children with acute asthma in the emergency department. The effect of nebulised magnesium sulphate in the management of childhood moderate asthma exacerbations as adjuvant treatment. Heliox-driven beta2-agonists nebulization for children and adults with acute asthma: a systematic review with meta-analysis. Oral montelukast in acute asthma exacerbations: a randomised, double-blind, placebo-controlled trial. Leukotriene receptor antagonists in addition to usual care for acute asthma in adults and children. Efficacy and safety of budesonide/formoterol compared with salbutamol in the treatment of acute asthma. A randomized, placebo-controlled study to evaluate the role of salmeterol in the in-hospital management of asthma. Increased morbidity and mortality related to asthma among asthmatic patients who use major tranquillisers. Non-invasive positive pressure ventilation for treatment of respiratory failure due to severe acute exacerbations of asthma. Is severity assessment after one hour of treatment better for predicting the need for admission in acute asthma. A prospective evaluation of the 1-hour decision point for admission versus discharge in acute asthma. Discharge considerations for adult asthmatic patients treated in emergency departments.