Asthma is a complex syndrome characterized by variable obstruction to airflow, bronchial hyperresponsiveness, and inflammation. The initiation and propagation of airway inflammation arises from many factors, including mediators generated by resident airway cells and recruited leukocytes (1). Leukotrienes are biologically active fatty acids derived from the oxidative metabolism of arachidonic acid, an integral component of the cell membrane (2). A role for leukotrienes in the pathogenesis of asthma has been suggested by their biologic activities, which produce effects that mimic those of clinical asthma, and by the effects of either inhibition of leukotriene production (5-lipoxygenase inhibitors) or antagonism of leukotriene binding to cellular receptors (leukotriene D 4-receptor antagonists). The recent U.S. Food and Drug Administration (FDA) approval of a leukotriene-receptor antagonist, zafirlukast (Accolate), and a leukotriene synthesis inhibitor, zileuton (Zyflo), provides the first mediator-specific therapy for asthma. This review will consider the biochemistry of the leukotrienes, their biologic role in asthma, and the therapeutic potential of drugs that alter the production or action of leukotrienes, as well as provide guidelines for the use of leukotriene modifiers in patients with asthma. MECHANISMS OF MODIFICATION OF LEUKOTRIENE ACTION Two approaches have been developed to decrease the action of leukotrienes. One is to block leukotriene synthesis by en

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Leukotrienes can be generated from a wide variety of cells including mast cells and eosinophils. The biological properties of these products include bronchial smooth muscle contraction, stimulation of mucous production, enhancement of vascular permeability, and recruitment of eosinophils. These properties can contribute significantly to the pathobiology of asthma. Recently, zafirlukast and montelukast, and zileuton, leukotriene D4 receptor antagonists and 5-lipoxygenase inhibitors, respectively, have been developed and are available for treating asthma. Studies have found these compounds modify bronchospasm with exercise, the pulmonary reaction to aspirin in sensitive subjects, and the airway response to inhaled antigen. Furthermore, in patients with chronic asthma, leukotriene modifiers improve airflow obstruction, decrease the need for rescue medication, and diminish symptoms. Moreover, these drugs can prevent asthma exacerbations. However, there is little evidence that these medications have potent anti-inflammatory activity. Nonetheless, leukotriene modifiers represent new, and effective, therapeutics in the treatment of asthma; at present, the positioning of these products in relationship to inhaled corticosteroids, for example, in the treatment of asthma has not been fully defined but will emerge with further study and use in the clinic setting.

The majority of individuals infected with SARS-CoV-2 have mild-to-moderate COVID-19 disease. Convalescence from mild-to-moderate (MtoM) COVID-19 disease may be supported by integrative medicine strategies. Integrative Medicine (IM) is defined as healing-oriented medicine that takes account of the whole person, including all aspects of lifestyle. Integrative medicine strategies that may support recovery from MtoM COVID-19 are proposed given their clinically studied effects in related conditions. Adoption of an anti-inflammatory diet, supplementation with vitamin D, glutathione, melatonin, Cordyceps, Astragalus and garlic have potential utility. Osteopathic manipulation, Qigong, breathing exercises and aerobic exercise may support pulmonary recovery. Stress reduction, environmental optimization, creative expression and aromatherapy can provide healing support and minimize enduring trauma. These modalities would benefit from clinical trials in people recovering from COVID-19 infection.

We have determined the sequence of cDNA for the human histidyl-tRNA synthetase (HRS) in a hepatoma cell line and confirmed it in fetal myoblast and fibroblast cell lines. The newly determined sequence differs in 48 places, including insertions and deletions, from a previously published sequence. By sequence specific probing and by direct sequencing, we have established that only the newly determined sequence is present in genomic DNA and we have sequenced 500 hundred bases upstream of the translation start site. The predicted amino acid sequence now clearly demonstrates all three motifs recognized in class 2 aminoacyl-tRNA synthetases. Alignment of E. coli, yeast, and when available, mammalian predicted amino acid sequences for three of the four members of the class 2a subgroup (his, pro, ser, and thr) shows strong preservation of amino acid specific signature regions proximal to motif 2 and proximal to motif 3. These probably represent the active site binding regions for the proximal acceptor stem and for the amino acid. The first two exons of human HRS contain a 32 amino acid helical motif, first described in human QRS, a class 1 synthetase, which is found also in a yeast RNA polymerase, a rabbit termination factor, and both bovine and human WRS, suggesting that it may be an RNA binding motif.

BackgroundIntegrative medicine (IM) is a patient-centered, healing-oriented clinical paradigm that explicitly includes all appropriate therapeutic approaches whether they originate in conventional or complementary medicine (CM). While there is some evidence for the clinical and cost-effectiveness of IM practice models, the existing evidence base for IM depends largely on studies of individual CM therapies. This may in part be due to the methodological challenges inherent in evaluating a complex intervention (i.e., many interacting components applied flexibly and with tailoring) such as IM.Methods/DesignThis study will use a combination of observational quantitative and qualitative methods to rigorously measure the health and healthcare utilization outcomes of the University of Arizona Integrative Health Center (UAIHC), an IM adult primary care clinic in Phoenix, Arizona. There are four groups of study participants. The primary group consists of clinic patients for whom clinical and cost outcomes will be tracked indicating the impact of the UAIHC clinic (n = 500). In addition to comparing outcomes pre/post clinic enrollment, where possible, these outcomes will be compared to those of two matched control groups, and for some self-report measures, to regional and national data. The second and third study groups consist of clinic patients (n = 180) and clinic personnel (n = 15-20) from whom fidelity data (i.e., data indicating the extent to which the IM practice model was implemented as planned) will be collected. These data will be analyzed to determine the exact nature of the intervention as implemented and to provide covariates to the outcomes analyses as the clinic evolves. The fourth group is made up of patients (n = 8) whose path through the clinic will be studied in detail using qualitative (periodic semi-structured interviews) methods. These data will be used to develop hypotheses regarding how the clinic works.DiscussionThe US health care system needs new models of care that are more patient-centered and empower patients to make positive lifestyle changes. These models have the potential to reduce the burden of chronic disease, lower the cost of healthcare, and offer a sustainable financial paradigm for our nation. This protocol has been designed to test whether the UAIHC can achieve this potential.Trial registrationClinical Trials.gov NCT01785485.

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Synopsis Asthma and chronic obstructive pulmonary disease are two common chronic respiratory disorders in primary care that cause considerable morbidity and mortality. This article reviews disease pathophysiology and outlines an integrative, multi-dimensional approach to evaluation and management of these conditions, including pharmacotreatment, nutrition, supplements, self-care strategies, mind-body therapies, and other integrative modalities.