The metalloproteome is defined as the set of proteins that have metal-binding capacity by being metalloproteins or having metal-binding sites. A different metalloproteome may exist for each metal. Mass spectrometric characterization of metalloproteomes provides valuable information relating to cellular disposition of metals physiologically and in metal-associated diseases. We examined the Cu and Zn metalloproteomes in three human hepatoma lines: Hep G2 and Mz-Hep-1, which retain many functional characteristics of normal human hepatocytes, and SKHep-1, which is poorly differentiated. Additionally we studied a single specimen of normal human liver and Hep Metals play a pivotal role in cellular metabolism. They function as the catalytic centers in many biochemical reactions and serve as structural elements for a large number of regulatory proteins (1, 2). Characterization of metal-binding proteins is important for understanding the structure and biological functions of such proteins in metal-associated diseases. In the past few years, a variety of mass spectrometric techniques has been used to probe the metal-protein interactions in metal-containing proteins. These studies have been successfully applied to determining metal binding stoichiometry (3-9), metal-binding sites (10, 11), and metal-dependent structure/conformation changes (12,13). A number of metalbinding proteins, such as cytochrome c oxidase (14), albumin (3, 7), metallothionein (12,15,16), prion protein (PrP) (8,9,11,13,17), matrilysin (4, 5), and non-heme iron-containing metalloproteins (6), have been individually well characterized by either overall mass measurements on the intact metal-protein complexes or peptide sequencing on the protein digest with tandem mass spectrometry.Rapid developments in proteomic technology and bioinformatics have permitted identification of proteomes of cell lines and tissue by using mass spectrometry instrumentation (for review, see . The specific advances include the use of two-dimensional gel electrophoresis (2DE),
The present case series describes four patients with asthma, airway hyperresponsiveness and neutrophilic bronchitis who harboured abnormal cystic fibrosis transmembrance conductance regulator (CFTR) gene mutations. It serves both to alert clinicians to consider CFTR-related disease in both young and elderly patients with persistent neutrophilic bronchitis, and to highlight the potential utility of future genetic testing for CFTR abnormalities in patients with asthma and recurrent bronchitis or pansinusitis, and the role of nebulized hypertonic saline as a therapeutic option in these patients.
Study Objectives: The effects of serotonergic agents on respiration neuromodulation may vary according to differences in the serotonin system, such as those linked to depression. This study investigated how sleep-related respiratory disturbances relate to depression and the use of medications commonly prescribed for depression. Methods: Retrospective polysomnography was collated for all 363 individuals who met selection criteria out of 2,528 consecutive individuals referred to a specialized sleep clinic (Ottawa, Canada) between 2006 and 2016. The apnea-hypopnea index (AHI), oxygen saturation nadir, and oxygen desaturation index during REM and NREM sleep were analyzed using mixed analyses of covariance comparing 3 main groups: (1) medicated individuals with depressive disorders (antidepressant group; subdivided into the selective serotonin reuptake inhibitor and norepinephrine-dopamine reuptake inhibitor subgroups), (2) non-medicated individuals with depressive disorders (non-medicated group), and (3) mentally healthy control patients (control group). Results: Individuals with depressive disorders (on antidepressants or not) had significantly higher AHIs compared to control patients (both P ≤ .007). The antidepressant group had a lower NREM sleep oxygen saturation nadir and a higher NREM sleep oxygen desaturation index than the control and non-medicated groups (all P ≤.009). Within individuals with depressive disorders, independent of depression severity, the selective serotonin reuptake inhibitor group had a lower oxygen saturation nadir and a higher oxygen desaturation index during NREM sleep than the norepinephrine-dopamine reuptake inhibitor (both P ≤ .045) and non-medicated groups (both P < .001) and a higher NREM sleep AHI than the non-medicated group (P = .014). Conclusions: These findings suggest that the use of selective serotonin reuptake inhibitors may be associated with impaired breathing and worse nocturnal oxygen saturation in individuals with depressive disorders and sleep complaints, but this needs to be confirmed by prospective studies.
The ability to assess the inflammatory status of a patient's airway using a noninvasive method is the ideal situation for clinicians. Owing in part to the relationship between the levels of exhaled nitric oxide to inflammation and the ease of the technique, the measurement of the fraction of exhaled nitric oxide (F(E)NO) has achieved considerable attention, particularly with respect to asthma. A multitude of studies have shown that when measured in exhaled air, this unique molecule has the potential to have both diagnostic and therapeutic roles in the clinical setting for many pulmonary diseases. The incorporation of F(E)NO into asthma management and treatment algorithms may help shed further insight on the current control and future risk of patients. Research is ongoing to determine the biology and the benefits of the use of F(E)NO in respiratory conditions in addition to asthma. This review will briefly outline the pathophysiology of nitric oxide, the measurement of F(E)NO and the potential clinical uses of F(E)NO in asthma and a number of other respiratory diseases. Despite its promise, until further research is conducted, the use of F(E)NO cannot be recommended for routine clinical management of respiratory diseases at present, but should be considered as an adjuvant to help guide therapy in certain patients with asthma and in those with eosinophilic bronchitis.
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