cAMP and cGMP in Human Parotid Saliva: Relationships to Taste and Smell Dysfunction, Gender, and Age

Henkin, Robert I.; Velicu, Irina; Papathanassiu, Adonia E.

doi:10.1097/maj.0b013e3180de4d97

Cited by 36 publications

(30 citation statements)

References 97 publications

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“…We demonstrated that saliva levels of both moieties were lower than normal in patients with taste and smell dysfunction. 13 These results corroborated a role for these moieties in taste and smell function since these lower than normal levels were associated with taste and smell pathology 14 ; treatment with phosphodiesterase (PDE) inhibitors, which biochemically enhanced levels of these moieties, improved taste and smell function among these patient. 15,16 We also demonstrated in preliminary studies that both moieties were present in human nasal mucus.…”

mentioning

confidence: 54%

“…1, 2) were similar to patterns previously observed in saliva. 13 For cAMP (expressed per ml nasal mucus) there was an U shaped, parabolic function with age increasing up to age 50, then decreasing until age >70 yr (Fig.1); at age >70 yr cAMP increased dramatically to levels higher than among all younger patients (Fig. 1).…”

Section: Nasal Mucus Camp and Cgmp With Respect To Agementioning

confidence: 95%

“…This result differs from findings in saliva in which cGMP was lower than cAMP in both normal subjects and in patients with taste and smell dysfunction. 13 Mean levels of both cAMP and cGMP were significantly higher in women than in men (Table 1). There were no differences in total protein or in age between men and women (Table 1).…”

Section: Nasal Mucus Camp and Cgmp In Normal Subjectsmentioning

confidence: 95%

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cAMP and cGMP in nasal mucus: relationships to taste and smell dysfunction, gender and age

Henkin

Velicu²

2008

CIM

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Clin Invest Med 2008; 31 (2): E71-E77. AbstractPurpose: To evaluate the presence and concentration of cAMP and cGMP in human nasal mucus in normal volunteers, to relate these findings to age and gender, and to compare normal levels with those in patients with taste and smell dysfunction. Methods: Nasal mucus was collected over one to four days in 66 normal subjects and 203 patients with smell loss (hyposmia). Samples were centrifuged at 20,000 rpm, the supernatant removed and analyzed for cAMP and cGMP by using a 96 plate technique with a specific spectrophotometric colorimetric ELISA assay. Results: Both cAMP and cGMP were present in human nasal mucus with both cAMP and cGMP significantly higher in normal women than in normal men [men vs. women; cAMP, 0.23±0.002 vs. 0.34±0.05 (P<0.05); cGMP, 0.28±0.03 vs. 0.63±0.12 (P<0.01)].Both cAMP and cGMP changed with age; both moieties increased in a U shaped, parabolic pattern reaching a peak at age 41-50 with cAMP diminishing thereafter and then increasing to its highest level over age 70. Both cAMP and cGMP were lower in patients with taste and smell dysfunction than in normal subjects [normals vs. patients; cAMP, 0.31±0.05 vs. 0.15±0.02 (P<0.01); cGMP, 0.56±0.07 vs. 0.025±0.02 (P<0.001)] suggesting a relationship to olfactory pathology. Conclusions: This is the first definitive study to demonstrate the presence of these cyclic nucleotides in nasal mucus and the first to reveal decreased levels in patients with impaired taste and smell function. Since olfactory receptor

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confidence: 54%

Section: Nasal Mucus Camp and Cgmp With Respect To Agementioning

confidence: 95%

Section: Nasal Mucus Camp and Cgmp In Normal Subjectsmentioning

confidence: 95%

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cAMP and cGMP in nasal mucus: relationships to taste and smell dysfunction, gender and age

Henkin

Velicu²

2008

CIM

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“…33 Effective treatment to increase secretion of these growth factors is therefore necessary to improve hypogeusia and hyposmia 5,12,13 and return taste and smell function to normal as demonstrated by several previous studies. 5,12,13 To understand more about these processes, a comprehensive study of many patients with loss of smell and taste determined that levels of the salivary 34,35 and nasal mucus 36,37 growth factors cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) were lower than in healthy subjects and were responsible for the onset of hyposmia and hypogeusia in many of these patients. 38,39 Indeed, as hyposmia increased in severity, levels of these salivary 35 and nasal mucus 37 growth factors decreased in a consistent manner.…”

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confidence: 99%

Intranasal Theophylline Treatment of Hyposmia and Hypogeusia

Henkin¹,

Schultz²,

Minnick-Poppe³

2012

Arch Otolaryngol Head Neck Surg

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To determine whether intranasal theophylline methylpropyl paraben can correct hyposmia and hypogeusia. Design:We performed an open-label pilot study in patients with hyposmia and hypogeusia under the following 3 conditions: (1) before treatment, (2) after oral theophylline anhydrous treatment, and (3) after intranasal theophylline treatment. Under each condition, we performed subjective evaluations of taste and smell functions, quantitative measurements of taste (gustometry) and smell (olfactometry), and measurements of serum theophylline level and body weight.Setting: The Taste and Smell Clinic in Washington, DC.Patients: Ten patients with hyposmia and hypogeusia clinically related to the effects of viral illness, allergic rhinitis, traumatic brain injury, congenital hyposmia, and other chronic disease processes were selected.Interventions: Oral theophylline anhydrous, 200 to 800 mg/d for 2 to 12 months, was administered to each patient. This treatment was discontinued for 3 weeks to 4 months when intranasal theophylline methylpropyl paraben, 20 µg/d in each naris, was administered for 4 weeks.Main Outcome Measures: At termination of each condition, taste and smell function was determined subjectively, by means of gustometry and olfactometry, with measurement of serum theophylline levels and body weight.Results: Oral theophylline treatment improved taste and smell acuity in 6 patients after 2 to 12 months of treatment. Intranasal theophylline treatment improved taste and smell acuity in 8 patients after 4 weeks, with improvement greater than after oral administration. No adverse effects accompanied intranasal drug use. Body weight increased with each treatment but was greater after intranasal than after oral administration.Conclusions: Intranasal theophylline treatment is safer and more effective in improving hyposmia and hypogeusia than oral theophylline anhydrous treatment.

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“…Amino acids, proteins, anions, vitamins, hormones and other small molecules have been intensively studied in saliva and found to include important biomarkers for several diseases [91,93,[154][155][156].…”

Section: Discussionmentioning

confidence: 99%

Biochemistry of salivary nucleotide metabolites and their role in the innate immunity of neonates

Shehri¹

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Saliva contains a variety of biochemical components, some of which may be used for the diagnosis of metabolic disorders, as cancer and heart disease markers, and the drug monitoring purposes.Saliva collection is particularly attractive as a non-invasive sampling method for infants and elderly patients. However, the use of saliva to evaluate metabolic status has not been widely studied; in particular, nucleotide metabolites in saliva have received little attention.Nucleotides are divided mainly into purines and pyrimidines, and they play an essential role in many cellular processes involving biosynthesis, energy supply, DNA/RNA synthesis, essential coenzymes, and regulatory mechanisms. Nucleotides are synthesised in mammalian cells by de novo pathways, which are energy-consuming; alternatively they are recycled by energy-saving pathways from nucleosides and bases that act as nucleotide salvage metabolites.This project was initiated by the discovery of a wide variation in salivary concentrations of nucleosides and bases between individuals, raising questions about their biological function. A method was developed and validated for the collection of small volumes of saliva as well as the extraction of purines and pyrimidines from oral swabs. These were then analysed by HPLC with tandem mass spectrometry.A survey of salivary nucleotide metabolites in 77 adults was performed, followed by a study of 60 neonates. Concentrations of the major salivary nucleobases and nucleosides were significantly higher in neonatal compared to adult saliva. The median concentrations (µM) in neonates\adults respectively were: Uracil 7.3\<1.5, Uridine 12\0.4, Hypoxanthine 27\2.1, Xanthine 19\1.7, Adenosine 12\0.1, Inosine 11\0.2, Guanosine 6.8\0.1. These nucleotide metabolites were not simply in equilibrium with plasma, but appeared to be actively secreted into saliva. The high levels of xanthine and hypoxanthine in neonates were particularly interesting, because these are substrates for xanthine oxidase (XO), which occurs with high activity in breast milk.These observations led to a general hypothesis that the role of these nucleotide metabolites in neonatal saliva is concerned with regulation of the oral microbiota of infants. XO is involved in the final stage of degradation of purine nucleotides, and it has been proposed to have a role in the innate immunity of babies arising from its ability to generate antibacterial 'reactive oxygen species'. The hypothesis proposed that high concentrations of nucleotide metabolites in neonatal saliva, together with stimulation of antibacterial breast milk XO activity, may play significant roles in early innate immunity in neonates. As part of the project, it was decided to also screen saliva from a selection of domestic mammals, which were found to have large differences in metabolite concentrations.iii Investigation of the generation of hydrogen peroxide (H 2 O 2 ) by breast milk XO was conducted in three stages: (1) fresh breast milk samples were collected and the endogenous H 2 O 2 concen...

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cAMP and cGMP in Human Parotid Saliva: Relationships to Taste and Smell Dysfunction, Gender, and Age

Cited by 36 publications

References 97 publications

cAMP and cGMP in nasal mucus: relationships to taste and smell dysfunction, gender and age

cAMP and cGMP in nasal mucus: relationships to taste and smell dysfunction, gender and age

Intranasal Theophylline Treatment of Hyposmia and Hypogeusia

Biochemistry of salivary nucleotide metabolites and their role in the innate immunity of neonates

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