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      Diagnosing cystic fibrosis by elevated sodium concentration in saliva

      Trace Elements and Electrolytes

      Dustri-Verlgag Dr. Karl Feistle

      saliva, cystic fibrosis, sodium, diagnosis


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          Abstract

          Abstract. Introduction: Cystic fibrosis (CF) is a serious hereditary disease that afflicts the cystic fibrosis transmembrane conductor regulator (CFTR) gene responsible for coding the CFTR anion channel. Therefore, CF can alter the secretion of the exocrine glands, including the salivary glands, which renders the possibility of diagnosing CF by analyzing the ionic composition of saliva, such as sodium ion content. Method: A literature search in the Medline database for the Medical Subject Headings (MeSH) terms “cystic fibrosis”, “saliva”, and “inorganic chemicals” yielded 17 articles. Results: Existing data suggests no apparent difference in the concentration of the sodium ion in the parotid or submandibular gland. The sodium ion concentration in whole saliva did show a raised sodium ion concentration in patients with CF. Discussion: Many of the reviewed studies had scant descriptions of the methodology and were subject to much variation. Some studies used troublesome analytical methods. Some of the articles predate the discovery of the CFTR channel, suggesting that salivary chloride might be more relevant. Conclusion: It seems unlikely that sodium concentration in saliva can be utilized to diagnose CF when saliva is obtained from the parotid or submandibular gland. However, employment of sodium-responsive electrodes has shown some potential as a screening tool for CF.


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          Most cited references 10

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          Selenium, selenoproteins and human health: a review.

           KM Brown,  JR Arthur (2001)
          Selenium is of fundamental importance to human health. It is an essential component of several major metabolic pathways, including thyroid hormone metabolism, antioxidant defence systems, and immune function. The decline in blood selenium concentration in the UK and other European Union countries has therefore several potential public health implications, particularly in relation to the chronic disease prevalence of the Western world such as cancer and cardiovascular disease. Ten years have elapsed since recommended dietary intakes of selenium were introduced on the basis of blood glutathione peroxidase activity. Since then 30 new selenoproteins have been identified, of which 15 have been purified to allow characterisation of their biological function. The long term health implications in relation to declining selenium intakes have not yet been thoroughly examined, yet the implicit importance of selenium to human health is recognised universally. Selenium is incorporated as selenocysteine at the active site of a wide range of selenoproteins. The four glutathione peroxidase enzymes (classical GPx1, gastrointestinal GPx2, plasma GPx3, phospholipid hydroperoxide GPx4)) which represent a major class of functionally important selenoproteins, were the first to be characterised. Thioredoxin reductase (TR) is a recently identified seleno-cysteine containing enzyme which catalyzes the NADPH dependent reduction of thioredoxin and therefore plays a regulatory role in its metabolic activity. Approximately 60% of Se in plasma is incorporated in selenoprotein P which contains 10 Se atoms per molecule as selenocysteine, and may serve as a transport protein for Se. However, selenoprotein-P is also expressed in many tissues which suggests that although it may facilitate whole body Se distribution, this may not be its sole function. A second major class of selenoproteins are the iodothyronine deiodinase enzymes which catalyse the 5'5-mono-deiodination of the prohormone thyroxine (T4) to the active thyroid hormone 3,3'5-triiodothyronine (T3). Sperm capsule selenoprotein is localised in the mid-peice portion of spermatozoa where it stabilises the integrity of the sperm flagella. Se intake effects tissue concentrations of selenoprotein W which is reported to be necessary for muscle metabolism. It is of great concern that the health implications of the decline in Se status in the UK over the past two decades have not been systematically investigated. It is well recognised that dietary selenium is important for a healthy immune response. There is also evidence that Se has a protective effect against some forms of cancer; that it may enhance male fertility; decrease cardiovascular disease mortality, and regulate the inflammatory mediators in asthma. The potential influence of Se on these chronic diseases within the European population are important considerations when assessing Se requirement.
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            The value of the chloride: sodium ratio in differentiating the aetiology of metabolic acidosis.

            Stewart's physicochemical approach to acid-base balance defines the aetiology of a metabolic acidosis by quantifying anions of tissue acids (TA), which consist of unmeasured anions (UMA) and/or lactate. We hypothesised that an increase in TA during metabolic acidosis would lead to a compensatory fall in the plasma chloride (Cl) relative to sodium (Cl:Na ratio) in order to preserve electro-neutrality. Thus, the Cl:Na ratio could be used as a simple alternative to the anion gap in identifying raised TA. Two hundred and eighty two consecutive patients who were admitted to our Paediatric Intensive Care were enrolled in the study. We obtained 540 samples (admission n = 282, 24 h n = 258) for analysis of blood chemistry, lactate and quantification of TA and UMA. Samples were subgrouped into those with metabolic acidosis (standard bicarbonate 3 mEq/l). Metabolic acidosis occurred in 46% of samples, of which 52.3% (120/230) had increased UMA. The dominant component of TA was UMA rather than lactate, and these two components did not always rise in tandem. Our hypothesis of relative hypochloraemia was supported by a lower Cl:Na ratio (P 0.79) excluded TA (PPV 81%, LR 4.5). Base deficit (BD) and lactate performed poorly. In metabolic acidosis due to TA, plasma Cl concentration decreases relative to sodium. The Cl:Na ratio is a simple alternative to the AG for detecting TA in this setting.
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              Brain uptake, retention, and efflux of aluminum and manganese.

              My colleagues and I investigated the sites and mechanisms of aluminum (Al) and manganese (Mn) distribution through the blood-brain barrier (BBB). Microdialysis was used to sample non-protein-bound Al in the extracellular fluid (ECF) of blood (plasma) and brain. Brain ECF Al appearance after intravenous Al citrate injection was too rapid to attribute to diffusion or to transferrin-receptor-mediated endocytosis, suggesting another carrier-mediated process. The brain:blood ECF Al concentration ratio was 0.15 at constant blood and brain ECF Al concentrations, suggesting carrier-mediated brain Al efflux. Pharmacological manipulations suggested the efflux carrier might be a monocarboxylate transporter (MCT). However, the lack of Al (14)C-citrate uptake into rat erythrocytes suggested it is not a good substrate for isoform MCT1 or for the band 3 anion exchanger. Al (14)C-citrate uptake into murine-derived brain endothelial cells appeared to be carrier mediated, Na independent, pH independent, and energy dependent. Uptake was inhibited by substrate/inhibitors of the MCT and organic anion transporter families. Determination of (26)Al in rat brain at various times after intravenous (26)Al suggested a prolonged brain (26)Al half-life. It appears that Al transferrin and Al citrate cross the BBB by different mechanisms, that much of the Al entering brain ECF is rapidly effluxed, probably as Al citrate, but that some Al is retained for quite some time. Brain influx of the Mn(2+) ion and Mn citrate, determined with the in situ brain perfusion technique, was greater than that attributable to diffusion, suggesting carrier-mediated uptake. Mn citrate uptake was approximately 3-fold greater than the Mn(2+) ion, suggesting it is a primary Mn species entering the brain. After Mn(2+) ion, Mn citrate, or Mn transferrin injection into the brain, brain Mn efflux was not more rapid than that predicted from diffusion. The BBB permeation of Al and Mn is mediated by carriers that may help regulate their brain concentrations.
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                Author and article information

                Journal
                Trace Elements and Electrolytes
                TE
                Dustri-Verlgag Dr. Karl Feistle
                0946-2104
                2017
                July 01 2017
                : 34
                : 07
                : 107-110
                Article
                10.5414/TEX01483
                © 2017

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