Taste and Smell Clinic

Biochemical changes after repetitive transcranial magnetic stimulation (rTMS)

There have been no reports of biochemical changes associated with the use of rTMS except preliminary studies in our clinical program (1).

We have measured changes in several physiological parameters after use of rTMS. We have done this in an attempt to evaluate if biochemical changes after rTMS were associated with the inhibition of phantageusia (taste distortions in the absence of any oral stimulus) which we have been monitoring. Indeed, we have found that rTMS has been useful in inhibiting phantageusia in 80% of patients with these distortions (2,3).

Although rTMS has been used by many physicians to treat depression, tinnitus and several neurological disorders and we found it useful in treating sensory distortions, only in our studies have any biochemical changes after rTMS been demonstrated (2).

In order to verify and expand our prior studies in a larger group of patients, we measured carbonic anhydrase in red blood cells (CA I,II) and in saliva (CA VI) in 70 patients with phantageusia before and after rTMS. After rTMS, CA I,II in red blood cells and CA VI in saliva increased significantly from the untreated state consistent with inhibition of their phantageusia.

These results verify our prior studies demonstrating biochemical changes after rTMS. These results demonstrate that CA VI, a specific salivary growth factor necessary for normal taste and smell function, increases after rTMS consistent with its efficacy in improving taste function (4).

1. Henkin RI, Potolicchio SJ, Levy LM, Moharram R, Velicu I, Martin BM. Carbonic anhydrase I, II and VI, blood plasma, erythrocyte and saliva zinc and copper increase after repetitive transcranial magnetic stimulation. Am J Med Sci. 2010;339:249-257.

2. Henkin RI, Potolicchio SJ, Levy LM. Improvement in smell and taste dysfunction after repetitive transcranial magnetic stimulation. Am J Otolaryngol. 2011;32:38-46.

3. Henkin RI. Commentary on “Transcranial magnetic stimulation: a treatment for smell and taste dysfunction” [editorial]. Am J Otolaryngol. 2011;32:178-180.

4. Henkin RI. Human taste and smell disorders. In: Adelman G, Smith BH (eds). Encyclopedia of Neuroscience. 2nd Ed. Amsterdam: Elsevier; 1999

Where are the physicians who treat taste and smell dysfunction?

Most patients who have taste and smell dysfunctions cannot find a physician who can help them. Why not?

First, they may go to their local medical doctor. He/she may not have encountered this problem before and does not know what to do. He/she may be sympathetic and may refer the patient to an otolaryngologist.

The referral to an otolaryngologist may result in the same situation – lack of knowledge of the problems which may cause these symptoms but interest in the issue. He/she may examine the patient including a nasal endoscopy. When this procedure results in a normal examination, the physician may also be sympathetic but without a clue as to how to proceed. He/she may have read about this problem but the anatomy and physiology of the systems as stated in present day text books are out-of-date and do not contain current anatomical descriptions of the olfactory system or current physiological explanation of how these dysfunctions can occur. While sympathetic he/she may be at a loss of what to do to either evaluate or treat these problems. They may treat these symptoms with antibiotics, antihistamines or systemic carbohydrate active steroids which may seem like logical therapies but are usually ineffective or even injurious.

What field of medicine can deal with these patients? Can general physicians deal with these complex problems? Can otolaryngologists who are trained as surgeons and who deal with lesions in the head and oral region deal with these patients? Can allergists who are trained to diagnose issues that often involve the ear and the nose deal with these patients? What physician group has knowledge of current anatomical and physiological concepts to deal with these problems? Consider if there were no ophthalmologists – how would visual problems be evaluated and treated? Consider if there were no otologists – how would hearing problems be evaluated? For the many patients who have problems of taste and smell dysfunction - where are the physicians to take care of them? Which field of medicine should deal with these patients? Indeed, is there such a field?

It seems evident that a concentrated effect to educate physicians about these problems is needed and needed immediately. There are literally millions of patients with these problems but little medical help for them exists in their evaluation or treatment. What are patients to do?

There are several physician groups who may have an interest in dealing with these problems. The most logical groups are the otolaryngologists or the allergists who often come across these patients in their practice but have no tools to treat them.

We, at The Taste and Smell Clinic in Washington, DC, have attempted one solution. We have established an organization, Cyrano Therapeutics, whose mission will be to bring both diagnosis and treatment tools to physicians who have seen patients with taste and smell dysfunction but do not understand how to evaluate or treat them. We will keep you updated as this program makes progress.

For more information, see www.CyranoTherapeutics.com.

Sensory Disorder | Loss of Taste & Smell | Smell and Taste Disorders Taste & Smell are often taken for granted until we lose them. Don't ignore these important Sensory disorders. Loss of Smell and Taste have a significant impact on our life, leading to decreased appetite & poor nutrition. We developed an intranasal spray that is intended 
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Please see our latest article: "Smell and taste dysfunction are markers of early and persistent pathology following traumatic brain injury (TBI)" by RI Henkin and M Abdelmeguid. Published in the Journal of Neuroscience and Cognitive Studies, 2018;2:1007. [Open Access Article, see link below]http://www.remedypublications.com/journal-of-neuroscience-and-cognitive-studies/articles/pdfs_folder/jncs-v2-id1007.pdf

www.remedypublications.com

Agnostic pathology defines the evaluation of hyposmia

While there are multiple pathologies which cause hyposmia (smell loss) many of these pathologies appear to have similar pathological mechanisms by which hyposmia is initiated.

There are multiple pathological events which cause hyposmia. Among these are post-viral-like infections (about 30%), allergic rhinitis with both infectious and immunological components (about 25%), head injury associated with the post concussion syndrome (about 15%), idiopathic or unrecognized causes (about 12%) and a variety of other causes (post general anesthesia, post cerebral vascular accident, post chemotherapy for malignancy treatment, post therapeutic radiation, drug related and many other causes).

While these diverse etiologies appear to be quite different, we have found that the biochemical/metabolic mechanisms underlying these diverse pathologies are similar.

These similarities relate to a potential defect at the olfactory receptor itself. These receptors are quite unique in that they do not possess blood vessels or lymphatics, they do not exhibit mitosis or cellular turnover yet they appear to metabolize at a rapid rate, with most receptors turning over on a daily basis. This may be understandable since these receptors are open to the external environment and are under constant potential trauma from external environmental events and local traumatic changes. These phenomena underlie the mechanism of rapid turnover of the receptors of this special epithelium upon which our well-being is dependent. We avoid noxious odors and are attracted to beneficial substances but then traumatic events can and do occur.

Thus, how does the system work in relationship to this rapid turnover? How do we repair these injuries? What are the similarities in the pathology underlying olfactory receptor function and how does this repair mechanism operate?

In order to maintain this critical system there are stem cells which are immortal and which are under the influence of growth/transcription factors secreted into nasal mucus by protein secreting glands in the nose. These growth factors stimulate these stem cells to generate the entire panoply of olfactory receptor cells by which normal olfaction occurs. If any pathology interferes with these secretions smell loss occurs. To our surprise when we analyzed nasal mucus from patients who had these various pathologies, we discovered that they all had similar deficiencies in secretion of these growth/transcription factors necessary to maintain the generation and perpetuation of these receptors. Indeed, following treatment which generated these growth/transcription factors, olfactory function improved so that the action of these multiple pathologies which caused hyposmia was corrected and smell function was restored.

Food is a language by which we communicate with ourselves and with others

People who develop taste and smell dysfunction lose the ability to use the language of food which is basic to life and well-being. They can no longer communicate in their social interactions as they did before dysfunction onset.

To say “Hello” in Chinese one says “have you eaten yet”. This is the basic introduction to the language of food in life. Without the ability to taste and smell food or with the presence of taste or smell distortions, not only do we lose the ability to speak and appreciate this language, we also lose the ability to communicate with others on a basic level of communication.

Food is the common denominator of this language. Its syntax is the gathering around a meal and interacting around both the food and the people involved. Taste and smell dysfunction inhibit people from sharing this language and interactions. Patients avoid eating with others since others understand and speak this language whereas patients have lost the ability to speak or understand this language. They would rather avoid seeing others eat or drink or having to pretend to understand what is “being discussed”. Patients would rather avoid having to participate in a situation where others are speaking this “foreign” language which they can no longer understand. Patients would rather avoid situations in which food is the common denominator of the social situation. This makes patients outcasts, feel isolated from society such that they exhibit discomfort, distress, depression and eventual weight loss and anorexia.

This loss, although not well known or understood by patients or others around them, is of fundamental importance to live a normal life. Sharing a meal is a fundamental way to communicate and share who we are with friends and loved ones. The others are speaking a foreign language which the patient does not understand. The patient feels isolated, alone and if distortions are present, even offended. It is not just a simple loss or distortion of taste or smell but a fundamental loss of ability to speak to one another since food is such a fundamental language of life.

The act of eating and all activities around it, the social interactions of “breaking bread”, sharing meals and speaking to one another over and about food, offers a fundamental sense of well-being and human support. If this were absent an entire concept of well-being has been eliminated from our life, not simply just a loss or distortion of a sensory presence of taste and smell.

For more information, please review the following:

• Henkin RI, Levy LM, Fordyce A. Taste and smell function in chronic disease: A review of clinical and biochemical evaluation of taste and smell dysfunction in over 5000 patients at The Taste and Smell Clinic in Washington, DC. Am J Otolaryngol. 2013;34:477-489.

Women Smell Better Than Men

Gender differences in smell function have been a topic of interest for many years. Some studies suggested that women had better smell acuity then did men whereas others could not determine this.

We studied 312 patients with smell loss (hyposmia) consisting of 178 women and 134 men to evaluate their hyposmia in response to treatment with oral theophylline. Prior to treatment there were no differences in smell function associated with the acuity loss as measured by olfactometry (precise psychophysical measurements of smell function).

As treatment with oral theophylline proceeded with increasing doses of the drug both men and women improved their smell function. However, smell function in women was relatively more sensitive than in men as the drug dose increased. On 200mg theophylline, although both men and women increased their olfactory acuity slightly, acuity was more sensitive in women than in men. On 400mg theophylline, with both men and women showing improved olfactory acuity, acuity was again more sensitive in women than in men but this was not statistically significant. On 600mg theophylline, with both men and women again showing improvement in their olfactory function, women now demonstrated increased sensitivity in their olfactory function than did men which was now statistically significantly different.

The mechanism by which this occurred is not yet clear. Theophylline levels in women were consistently higher than in men suggesting that they absorbed the drug better than did men and this may have allowed them to perceive odor better then did men. Based upon these increased blood levels of theophylline it is possible that women had a different metabolic clearance rate of theophylline than did men which allowed them to metabolize theophylline more efficiently then did men which led to their increased sensitivity for all odors.

How does viral illness cause smell and taste loss?

The most common cause of smell and taste loss is following a viral-type illness. How does this occur?

During the acute phase of a viral cold a patient may experience nasal congestion and blockage caused by nasal obstruction, membrane edema and excess nasal secretions. This congestion may cause temporary loss of smell and taste but with recovery from the cold, over time, these nasal symptoms disappear, ease of nasal breathing is resumed and smell and taste function commonly reappear as they did prior to the onset of the viral cold.

However, in about an estimated 1% of patients who experience a viral-type cold, with the recovery from the acute nasal symptoms they recognize that they have a persistent loss of smell and taste. How does this occur? Since viral colds occur in as many as 30 million patients yearly in the U.S., the loss can occur in as many as 3 million people yearly.

In an effort to understand this problem we initially attempted to culture virus in the nasal airways of patients who had recovered from their cold but had a loss of smell and taste. We were unsuccessful despite careful attempts to do so. If there were no virus present, how did this loss occur?

This question has caused much confusion for several years. What we began to hypothesize was that after recovery, which eliminated the acute systemic viral attack, there was a residual and persistent viral process affecting the protein secreting glands in the nose and mouth which caused smell and taste loss. Although the dynamics of this viral process are still unknown its mechanism of action is critical to our understanding of how smell and taste loss occur after a viral illness.

We hypothesize that a viral replication process is present in the protein secreting glands in the nose and the mouth which is sustained by a dynamic process involving continuous rounds of de novo virus infection and replication, as in (1). We hypothesize that with the initial systemic viral infection the viral RNA enters into specific protein secreting glands in the nose and mouth, replicating their genomes. These are commonly single stranded RNAs which may generate viral factories which can direct the products of proteins and construction of new viral particles which can continue to infect these glands. While the systemic viral infection is eliminated this local process can continue to generate viral RNA which is toxic to the protein secretions generated by these protein secreting glands. This toxicity can inhibit secretion of some of the endogenously secreted proteins [so-called growth factors (2)] produced by these glands. These endogenous proteins consist of multiple chemical moieties (3) including cAMP, cGMP and sonic hedgehog (4-7). Stem cells, which maintain the receptors of both olfactory epithelial cells for smell and taste bud receptor cells for taste, require continual stimulation by these secreted proteins for these receptors to function. Since these receptors turnover as rapidly as every 24 hours, inhibition of these secretions inhibits receptor growth causing loss of smell and taste (8).

1. Wei X, Ghosh SK, Taylor ME, et al. Viral dynamics in human immunodeficiency virus type 1 infection. Nature. 1995;373:117-122.
2. Henkin RI. Growth factors in olfaction. In: Preedy VR, Ed. The Handbook of Growth and Growth Monitoring in Health and Disease. Vol II. New York: Springer-Verlag; 2011, p. 1417-1436.
3. Henkin RI, Martin BM. Nasal seroproteins, their physiology and pathology. Am J Rhinol. 2000;14:A-82.
4. Henkin RI, Velicu I. cAMP and cGMP in nasal mucus: relationships to taste and smell dysfunction, gender and age. Clin Invest Med. 2008;31:E71-E77.
5. Henkin RI, Velicu I. cAMP and cGMP in nasal mucus related to severity of smell loss in patients with smell dysfunction. Clin Invest Med. 2008;31:E78-E84.
6. Henkin RI, Hosein S, Stateman WA, et al. Sonic hedgehog in nasal mucus is a biomarker for smell loss in patients with hyposmia. Cell Mol Med. 2016, 2:2.
7. Henkin RI, Knöppel AB, Abdelmeguid M, et al. Sonic hedgehog is present in parotid saliva and is decreased in patients with taste dysfunction. J Oral Pathol Med. 2017;46:829-833.
8. Henkin RI, Levy LM, Fordyce A. Taste and smell function in chronic disease: A review of clinical and biochemical evaluation of taste and smell dysfunction in over 5000 patients at The Taste and Smell Clinic in Washington, DC. Am J Otolaryngol. 2013;34:477-489.

Biochemical Mechanisms Cause Smell Loss in Patients with Traumatic Brain Injury (TBI)

TBI is a common cause of smell loss. However, the mechanisms which cause smell loss have been described as anatomical – related to “shearing” or “tearing” of the small olfactory nerve fibers from their location on the olfactory plate, the cribriform plate, the bony structure in the skull through which these small fibers pass to make their way to form the olfactory bulb in the brain. It has been considered that a head injury tears these fibers from the cribriform plate so that smell function is lost.

While logical, this concept is wrong. There is no clinical or scientific basis for this type of event although it has been considered to be the major cause for smell loss after TBI. Indeed, physicians have usually told patients who experienced TBI that because of this shearing they would never be able to recover their smell function.

We and others have demonstrated that the olfactory system is usually anatomically intact after TBI. We have demonstrated by use of magnetic resonance imaging (MRI) and computerized tomography (CT) scans taken of the brain after TBI that the olfactory nerves are present, albeit sometimes decreased in diameter. We have also shown the anatomical areas of the brain dedicated to olfaction are usually intact after TBI and without any significant pathology. We have also shown by use of functional MRI of brain that patients following TBI may have a significant loss of smell function but they retain the anatomical brain structures necessary to support olfaction (1).

Thus, if not anatomical, what is the cause of smell loss after TBI? We have determined that the cause of smell loss after TBI is related to biochemical changes – biochemical abnormalities in olfactory function which occur after TBI (2). Others before us have also considered this but have not formalized this concept as the primary cause of smell loss after TBI.

We and others have discovered multiple biochemical changes in olfactory function after TBI. We have defined several of these changes in an attempt to understand the nature of these biochemical abnormalities so that these biochemical abnormalities can be corrected and patients can regain their smell function after TBI. By use of this knowledge we have helped many of these patients to restore their smell function after TBI (2).

1. Levy LM, Henkin RI, Lin CS, Hutter A, Schellinger D. Increased brain activation in response to odors in patients with hyposmia after theophylline treatment demonstrated by fMRI. J Comput Assist Tomogr. 1998;22:760-770.

2. Henkin RI, Levy LM, Fordyce A. Taste and smell function in chronic disease: A review of clinical and biochemical evaluation of taste and smell dysfunction in over 5000 patients at The Taste and Smell Clinic in Washington, DC. Am J Otolaryngol. 2013;34:477-489.

Smell loss (hyposmia) is a lifelong, chronic sensory disease

Smell loss (hyposmia) occurs in about 7% of the U.S. population. It is comprised of a heterogeneous group of diseases with three major groupings: direct (brain or nerve injury), congenital (genetic factors) or acquired (biochemical causes). Smell loss most commonly occurs with acquired factors with specific biochemical pathology initiating the disorder associated with a variety of clinical conditions, e.g., post-viral infection, chronic allergic rhinitis, head injury, inhalational anesthesia and other conditions. The biochemical mechanisms underlying both acquired and congenital hyposmia relate to inhibition of olfactory epithelial receptor cell function due to altered secretion of specific growth or transcription factors in nasal mucus which are required to initiate olfactory receptor stem cell generation and perpetuation. Some growth/transcription factor secretions are decreased to cause these dysfunctions. They include hormones, vitamins, trace metals and a group of biochemical growth/transcription factors – cAMP, cGMP and sonic hedgehog. Some growth/transcription factor secretions are increased to cause these dysfunctions - these are “death factors” which act to inhibit olfactory receptor function. These include cytokines such as TNFalpha. Treatment with oral or intranasal phosphodiesterase (PDE) inhibitors increase secretion of decreased growth/transcription factors and decrease secretion of “death factors” such that stem cells in the olfactory epithelium are stimulated to initiate receptor growth and development. Treatment with PDE inhibitors are required to provide continual stimulation of these stem cells since they initiate the cellular activity by which these receptors (which do not contain blood vessels, lymphatics or exhibit mitosis but turn over rapidly, commonly on a daily basis) are stimulated. In this sense, hyposmia is a chronic disease process similar to diabetes or arthritis. While the disease can be treated it is a lifelong, chronic disorder.

• Henkin RI, Levy LM, Fordyce A. Taste and smell function in chronic disease: A review of clinical and biochemical evaluation of taste and smell dysfunction in over 5000 patients at The Taste and Smell Clinic in Washington, DC. Am J Otolaryngol. 2013;34:477-489.

Treatment of smell loss (hyposmia) – Agnostic pathology of biomarkers in patients with hyposmia

There are multiple pathologies which biochemically initiate and perpetuate smell loss (hyposmia). These pathologies are non-neoplastic diseases and include viral-type infections, allergic rhinitis, traumatic head injuries, inhalational anesthesia and several other pathologies. We have attempted to evaluate specific biochemical parameters, manifested as biomarkers, which identify the pathology underlying these various causes of hyposmia. While each of these pathologies reflects widely different initiating events to cause hyposmia the biomarkers underlying these events are similar in each pathology. These biomarkers are found in nasal mucus, the biological fluid which maintains olfactory receptors. These biomarkers are decreased nasal mucus concentrations of cAMP, cGMP and sonic hedgehog. The mechanisms for these changes are similar across each of these pathologies since these biomarkers reflect diminished activity of these moieties which act as growth or transcription factors which stimulate stem cells in the olfactory epithelium to initiate growth and perpetuation of olfactory epithelial receptor cells. Similarities in these growth factor abnormalities across these multiple initiating pathological events are the basis for this agnostic determination of the biomarkers which induce hyposmia. Indeed, correction of these biochemical abnormalities with treatment with the phosphodiesterase inhibitor theophylline increases nasal mucus levels of each of these biomarkers in each pathology which thereby improves hyposmia in each pathological entity and establishes the agnostic character of these biomarkers.

• Henkin RI, Levy LM, Fordyce A. Taste and smell function in chronic disease: A review of clinical and biochemical evaluation of taste and smell dysfunction in over 5000 patients at The Taste and Smell Clinic in Washington, DC. Am J Otolaryngol. 2013;34:477-489.

Please review our article "Improved smell function with increased nasal mucus sonic hedgehog in hyposmic patients after treatment with oral theophylline." By: RI Henkin, S Hosein, WA Stateman, AB Knöppel, M Abdelmeguid. Published in: American Journal of Otolaryngology. 2017;38:143-147. doi: 10.1016/j.amjoto.2016.11.010

Life and Death of Taste and Smell Receptors: The Role of Stem Cells

Taste and smell receptors commonly turnover on a daily basis. This turnover may be physiologically necessary since taste receptors are exposed to many substances in food or beverages, hot or cold, spicy, noxious or similar substances which could either alter their function or outright kill them. Similarly, olfactory receptors are exposed to the outside environment which can be quite toxic to these exposed receptors. While there is some protection for taste buds in saliva and nasal mucus for olfactory receptors, the toxic effect of incoming substances put these receptors at risk. How many of us have experienced a burning mouth sensation from hot soup or pizza? How many of us have experienced a noxious response to smoke or a pungent, strong odor? These physical sensations are usually transient but in order to survive taste and smell receptors have adapted a unique pattern of reproducing in order to withstand these toxic events.

How does protection from these toxic events occur? One method is that taste and smell receptors turnover rapidly, not uncommonly, on a daily basis. This turnover depends upon the activation of stem cells in each organ by specific growth factors which maintain these systems.

However, if we view receptors themselves, in their normal state, we recognize that some cells of the receptors exhibit a normal, anatomical appearance whereas others appear to be degenerating. Thus, these tissues are experiencing an active growth and degeneration of their cellular receptors on a daily basis.

Anatomical examination of receptors for both taste and smell indicate newly forming cells and dying cells. Dying cells exhibit death by programmed apoptosis, a physiological mechanism by which cells die exhibiting large vacuoles and elements of cellular detritus. This phenomenon is associated with a process called necrosis, by which cells die due to an inflammatory process. There are multiple inflammatory cells, both acute and chronic, in the tissues associated with taste and smell receptors. The cellular components of these receptors die off at a rapid rate exhibiting apoptosis and are rapidly replaced by the persistent secretion of taste bud and olfactory epithelial growth factors which initiate rapid turnover of these organs in order to allow taste and smell perception to occur.

Please review our article: "Sonic hedgehog in nasal mucus is a biomarker for smell loss in patients with hyposmia", by R. Henkin, S. Hosein, W. Stateman, A. Knöppel, in Cellular and Molecular Medicine.
http://cellular-molecular-medicine.imedpub.com/sonic-hedgehog-in-nasal-mucus-is-a-biomarker-for-smell-loss-in-patients-withhyposmia.php?aid=11183

Sonic Hedgehog in Nasal Mucus is a Biomarker for Smell Loss in Patients with Hyposmia | Insight Medical Publishing Sonic Hedgehog in Nasal Mucus is a Biomarker for Smell Loss in Patients with Hyposmia, Robert I Henkin, Suzanna Hosein, William A Stateman and Alexandr

Stem Cells in Taste and Smell Function

Stem cells play a role in development of many tissues including erythrocytes, leukocytes, hair cells and many other tissues. These cells are controlled by activities which initiate growth and development and inhibitors which inhibit growth and development of these tissues. Activators and inhibitors of these tissues differ for each cell type but they all display function in each tissue type. Some of these growth factors act intermittently and some are continually active. In hematological tissues these activators and inhibitors are continually active whereas in the hair follicle these growth factors and inhibitors appear to be more cyclic.

Taste and smell receptors are dependent upon stem cell activation to initiate their growth and development as well as inhibitors which control their growth and development. Our work at The Taste and Smell Clinic in Washington, DC has uncovered the system for activation and inhibition of both taste and smell receptors. These factors are responsible for maintaining taste and smell function in most animal species including humans. In humans these factors are secreted in saliva for taste receptors and in nasal mucus for smell receptors.

There are many of these factors which involve hormones, trace metals, vitamins and other chemical moieties. Among the most recent findings we have discovered that cAMP, cGMP and sonic hedgehog are critical to activate and stimulate taste and smell stem cells to induce growth and development of both taste and smell receptors whereas TNFalpha inhibits growth of these tissues. Previously we identified and isolated gustin or carbonic anhydrase VI as a growth factor in both taste and smell receptor function. Whereas in some tissues growth factors are secreted intermittently, in the taste and smell system, these moieties are secreted on a continuous basis since both taste and smell receptors turn over rapidly, commonly on a 24 hour basis. This rapid turnover makes the taste and smell systems very plastic in their function since their physical exposure to external factors make them amenable to injury. However, these stimulating and inhibiting moieties exhibit an equilibrium, as in many tissues, with activation and inhibition of growth carefully controlled.

Inhibition of these growth factors and activation of these inhibitory factors lead to loss of taste and smell function. Methods to increase secretion of these growth factors or inhibition of these inhibiting factors are responsible for correction of many of the pathological features which inhibit taste and smell function. Age is one component which inhibits secretion of these chemical moieties as well as many other physiological and pathological phenomena.

It has been the function of our work at The Taste and Smell Clinic to identify and characterize these moieties and how they function in order to restore taste and smell function in the many patients who lose these sensory modalities.