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Henkin R.I.,Center for Molecular Nutrition and Sensory Disorders
Nutrition | Year: 2014

Objective: Smell loss (hyposmia) inhibits flavor perception and influences food intake. To compensate for flavor loss, some patients with hyposmia appear to increase salt usage. The purpose of this study was to compare self-reported salt usage in patients with hyposmia with that in normal volunteers. Methods: Salt usage was compared in 56 patients with hyposmia but with normal taste function with that in 27 normal volunteers. Salt usage was formulated with respect to 1) a standard quantitative salt intake scale, 2) salt addition related to food intake, 3) intake of foods and beverages with high salt content, and 4) salt intake related to presence or absence of hypertension. Results: Eighteen (32%) of the 56 patients self-reported increased salt usage they were labeled "increased users." The other 38 hyposmic patients (68%) did not report increased salt usage they were labeled "non-changers." Increased users estimated their salt usage rose an average 2.8 times that experienced before their hyposmia onset. They also reported adding salt to their food before tasting it and ate more highly salted foods than did the non-changers. Salt usage was not increased further among increased users with hypertension but was increased further among non-changers with hypertension. Conclusions: Salt usage is increased among some patients with hyposmia presumably to enhance flavor perception to compensate for diminished flavor perception related to loss of smell. © 2014 Elsevier Inc. Source


Henkin R.I.,Center for Molecular Nutrition and Sensory Disorders
Nutrition | Year: 2010

Background: Intranasal insulin has proven useful to control hyperglycemia in diabetics but its mechanism of action has not been well defined. We attempted to understand several aspects of human insulin metabolism by measurement of and interaction of insulin and its associated moieties in nasal mucus, saliva and blood plasma under various physiological and pathological conditions. Methods: Insulin, insulin receptors, insulin-like growth factor 1 (IGF1) and insulin-like growth receptor 3 (IGFR3) were measured in nasal mucus, saliva and blood plasma in normal subjects, in thin and obese subjects and in diabetics under fasting and fed conditions. Results: There are complex relationships among each of these moieties in each biological fluid. Insulin and its associated moieties are present in both nasal mucus and saliva. These moieties in nasal mucus and saliva report on physiological and pathological changes in glucose metabolism as do these moieties in plasma. Indeed, insulin and its associated moieties in nasal mucus may offer specific data on how insulin enters the brain and thereby play essential roles in control of insulin metabolism. Interpretation: These data support the concept that insulin is synthesized not only in parotid glands but also in nasal serous glands. They also support the concept that insulin enters the brain following intranasal administration either 1) by direct entry through the cribriform plate, along the olfactory nerves and into brain parenchyma, 2) by entry through specific receptors in blood-brain barrier and thereby into the brain or 3) some combination of 1) and 2). Conversely, data also show that insulin introduced directly into the brain is secreted out of brain into the peripheral circulation. Data in this study demonstrate for the first time that insulin and its associated moieties are present not only in saliva but also in nasal mucus. How these complex relationships among nasal mucus, saliva and plasma occur are unclear but results demonstrate these relationships play separate yet interrelated roles in physiology and pathology of human insulin metabolism. © 2010 Elsevier Inc. Source


Henkin R.I.,Center for Molecular Nutrition and Sensory Disorders
Nutrition | Year: 2010

Background: After discovery of insulin as a hypoglycemic agent in 1921 various routes of administration to control blood glucose were attempted. These included subcutaneous, oral, rectal, sublingual, buccal, transdermal, vaginal, intramuscular, intrapulmonary and intranasal delivery systems. While each delivery system controlled hyperglycemia the subcutaneous route was given priority until 2006 when the Federal Drug Administration (FDA) approved the first commercially available pulmonary inhaled insulin. Methods: A review of major publications dealing with intrapulmonary administration of insulin was made to understand the physiological basis for its use, its efficacy in controlling hyperglycemia, its side effects and a comparison of its efficacy with other delivery methods. Results: The large surface area of the lung, its good vascularization, capacity for solute exchange and ultra thin membranes of alveolar epithelia are unique features that facilitate pulmonary insulin delivery. Large lung surface area (∼75 m2) and thin alveolar epithelium (∼0.1-0.5 μm) permit rapid drug absorption. First pass metabolism avoids gastrointestinal tract metabolism. Lung drug delivery depends upon a complex of factors including size, shape, density, charge and pH of delivery entity, velocity of entry, quality of aerosol deposition, character of alveoli, binding characteristics of aerosol on the alveolar surface, quality of alveolar capillary bed and its subsequent vascular tree. Many studies were performed to optimize each of these factors using several delivery systems to enhance pulmonary absorption. Availability was about 80% of subcutaneous administration with peak activity within 40-60 min of administration. Intranasal insulin delivery faces a smaller surface area (∼180 cm2) with quite different absorption characteristics in nasal epithelium and its associated vasculature. Absorption depends upon many factors including composition and character of nasal mucus. Absorption of intranasal insulin resulted in a faster absorption time course than with subcutaneous insulin. Interpretation: After many studies the FDA approved Pfizer's product, Exubera, for intrapulmonary insulin delivery. While the system was effective its expense and putative side effects caused the drug company to withdraw the drug from the marketplace. Attempts by other pharmaceutical companies to use intrapulmonary insulin delivery are presently being made as well as some minor attempts to use intranasal delivery systems. © 2010 Elsevier Inc. All rights reserved. Source


Henkin R.I.,Center for Molecular Nutrition and Sensory Disorders
Therapeutic Drug Monitoring | Year: 2012

Background: Theophylline, used in the treatment for various pulmonary pathologies, is usually given orally with drug levels measured primarily in blood serum and occasionally in saliva. Although theophylline treatment is now not commonly used it has been effective to correct smell loss (hyposmia). This is important because 21 million people in the United States exhibit hyposmia and oral theophylline has corrected hyposmia in about 50% of these patients. This result suggests that oral theophylline may result in the drug not only appearing in the serum but also in nasal mucus, thereby playing a role in correcting hyposmia. No prior report of theophylline in nasal mucus has been made and no comparison of levels in nasal mucus, blood serum, or saliva has been previously reported. Purpose: The aim was to determine, after oral theophylline treatment, if it is present in nasal mucus and, if present, to compare the levels with those in serum and saliva. Methods: Oral theophylline was given to 23 hyposmic patients at daily doses of 200, 300, 400, 600, and 800 mg for periods of 2-10 months. During each period, blood serum, saliva, and nasal mucus were collected and theophylline measured in each fluid. Results: Theophylline was found in nasal mucus and in saliva and blood serum at each drug dose in each patient to whom it was given. The mean level of theophylline in nasal mucus was 74% that of serum; mean level in saliva was 67% of serum; mean level in nasal mucus was 111% that in saliva. Conclusions: Theophylline is present in nasal mucus after oral administration. Levels in nasal mucus reflect blood and saliva levels in a consistent manner and offer a simple convenient noninvasive method to monitor theophylline doses of the oral drug. © 2012 Lippincott Williams & Wilkins. Source


Henkin R.I.,Center for Molecular Nutrition and Sensory Disorders | Schultz M.,Foundation Care | Minnick-Poppe L.,St. Louis College of Pharmacy
Archives of Otolaryngology - Head and Neck Surgery | Year: 2012

Objective: 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. ©2012 American Medical Association. All rights reserved. Source

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