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Efficacy of exogenous oral zinc in treatment of patients with carbonic anhydrase VI deficiency.

BACKGROUND: We previously described a disorder in 18 patients with decreased parotid saliva gustin/carbonic anhydrase (CA) VI secretion associated with loss of taste (hypogeusia) and smell (hyposmia) and distorted taste (dysgeusia) and smell (dysosmia). Because gustin/CAVI is a zinc-dependent enzyme we instituted a study of treatment with exogenous zinc to attempt to stimulate synthesis/secretion of gustin/CAVI and thereby attempt to correct the symptoms of this disorder. METHODS: Fourteen of the 18 patients with this disorder completed the study. They were treated with 100 mg of exogenous zinc daily for 4 to 6 months, in an open clinical trial. Both before and after treatment, measurements were obtained of parotid saliva gustin/CAVI, parotid saliva, serum and urine zinc, taste and smell function, and, in some patients, examination of circumvallate taste buds by electron microscopy. RESULTS: Treatment success was predicated upon significant increases in parotid saliva gustin/CAVI. This occurred in 10 of the 14 patients who were labeled responders; they also exhibited improvement in taste and smell acuity, a diminution in dysgeusia and dysosmia and increased zinc concentrations in parotid saliva, serum, and urine. Taste bud morphology returned to normal in each responder in whom it was measured. No increase in gustin/CAVI occurred in 4 patients who were labeled nonresponders; they exhibited no improvement in taste or smell acuity and no increases in parotid saliva zinc. However, serum and urine zinc increased to levels similar to those measured in the 10 responders. Two of 4 nonresponders reported diminution in dysgeusia and dysosmia. Taste bud morphology did not change from the abnormal state in the 1 nonresponder in whom it was measured. CONCLUSIONS: Zinc treatment is effective in patients in whom this trace metal increases synthesis/secretion of gustin/CAVI and ineffective in those in whom it does not. Increased gustin/CAVI in this disorder is probably associated with zinc stimulation of the gene responsible for the synthesis/secretion of gustin/CAVI. Among nonresponders, zinc was ineffective for several possible reasons, including resistance to zinc and possible sialylation of gustin/CAVI, which may render it functionally ineffective. Results suggest the hypothesis that gustin/CAVI is a trophic factor that promotes growth and development of taste buds through its action on taste bud stem cells.

Administration, Oral↗

Influence of epilepsy and temporal lobe resection on olfactory function.

Olfactory auras accompany some cases of epilepsy. Several aspects of olfactory function, including sensitivity, also may be altered. We reviewed the literature on these topics, as well as studies evaluating the influences of temporal lobe resection and other seizure management procedures on olfactory function. We concluded that: (a) despite several studies, the prevalence of olfactory auras in epilepsy is unknown, with estimates ranging from < 1% to > 30%; (b) epilepsy appears to cause a generalized decrease in olfactory functioning, although increased sensitivity may occur in some epileptic patients at some time in the preictal period; (c) other sensory modalities are also affected by the epileptic process which, in some cases, involve limbic-related temporal lobe structures; (d) many of the olfactory deficits previously attributed to temporal lobe resection actually exist preoperatively; (e) a taste/flavor confusion exists in the reporting of taste auras; (f) unpleasant auras are associated with hyperresponsiveness of neurons, which may explain why most epilepsy-related olfactory auras are described as "bad"; and (g) interesting parallels exist between the effects of the neuroendocrine system on seizure activity and olfactory function.

Epilepsy↗

Chemical senses.

In the last decade, studies using approaches from molecular biology have substantially advanced our understanding of the early events in olfaction and taste. The many odorants that we can recognize may well interact with many distinct receptor proteins. Of the four taste qualities that we recognize, studies on salty and sour suggest that these tastes involve ion channels in the membrane of receptor cells while sweets and bitters bind to receptor proteins. Some volatiles (pheromones) play special roles in reproductive behavior via the vomeronasal organ (VNO) and the accessory olfactory system. Initial belief that humans lack a VNO has been questioned recently, thus raising the fascinating possibility of human pheromones. The roles that taste and smell play in the world of the newborn are very different. Acceptance of sweet and rejection of bitter appear to be hard-wired while the affect associated with odors depends much more on experience. Genetic variation may produce total losses (Kallman's syndrome produces anosmia and familial dysautonomia produces ageusia) or losses specific to certain stimuli. The best known of the specific anosmias is that for androstenone, which has no smell to some, a urinous smell to others, and a smell like sandalwood to still others. Analogous to the specific anosmias, some individuals are unable to taste PROP while others, supertasters, perceive PROP to be exceedingly bitter. Clinical studies reveal pathologies responsible for total or partial losses. The olfactory system, dependent on one cranial nerve, is more vulnerable than taste, and total anosmia is a relatively common clinical problem. Three cranial nerves carry taste and two of those nerves inhibit one another such that damage to one disinhibits the other and preserves over-all taste function. Total ageusia is very rare. Throughout these studies we see that taste and olfaction have different properties and often different functions (e.g. odor and reproduction). Yet taste and smell can also be integrated to determine what does or does not enter the body. In Adrian's words, "we are dealing with the sense organs which signal the quality of the air we breathe and that of the food and drink we propose to swallow."

Ageusia↗

[Eating behavior in the elderly and its consequences for nutrition].

The nutritional situation of the elderly is characterised on the one hand by changes in nutrient requirements resulting from increased age and on the other hand by altered nutritional needs. Faulty eating habits, malnutrition as well as overeating are not uncommon. Experimental research in spontaneous feeding behavior lead to the conclusion that not only is the modifiability of food intake through environmental stimulation reduced in the elderly, but also the efficiency of internal cues through which the degree of satiety is experienced. Investigation of taste and smell in which a total reduction of sensory capacity was ascertained, point in the same direction: sensory deficits have a cumulative effect on the appetite of the elderly. An increased reliance on habit and rational as well as pseudo-rational eating rules was observed on the part of the elderly. Indications for praxis are derived from these observations which are discussed in the context of a theoretical concept.

Aged↗

Taste in dementing diseases and parkinsonism.

Like with many sensory abilities a reduction of taste and smell occurs during aging. Since there are hints to an additional reduction in dementing diseases, we assessed 52 patients, 26 women and 26 men, who were presented to a memory clinic, using the Sniffin' Sticks, Whole Mouth and Taste Strip Tests. While smoking, alcohol consumption, intake of drugs and sex exerted only minor impact, age and the severity of cognitive impairment were of major importance. There was a moderate but significant correlation between the severity of dementia, taste and smell, even if the age effect was partialled out. Notably, patients with Parkinson syndrome showed worse taste and smell abilities than those without. Here the differences were indeed marked enough to play a possible role in making the diagnosis. This exploratory study confirms a mild reduction of gustatory function in dementing diseases over and beyond that of normal aging which--in addition to a reduction of smell--seems to be especially marked in Parkinson syndromes.

Adult↗

Medication and dietary compliance beliefs in heart failure.

Patients with heart failure are required to comply with a medication regimen and dietary sodium restrictions. The objectives of this study were to determine the most frequently perceived benefits of and barriers to compliance with medication and dietary sodium restrictions and evaluate the relevancy of these scale items for testing in tailored intervention studies. Data were collected as part of two studies that evaluated the psychometric properties of two questionnaires. The most frequently identified benefit of medication compliance was decreasing the chance of being hospitalized, and the most commonly reported barrier was disruption of sleep. Patients were knowledgeable about the benefits of compliance with dietary sodium restrictions, and the poor taste of food on the low sodium diet was the most common barrier. Heart failure patients perceive benefits of and barriers to compliance with therapeutic regimens that are likely to be amenable to tailored interventions designed to enhance compliance.

Adult↗

Disordered gustatory acuity in liver disease.

Disordered gustatory acuity was demonstrated in 22 patients with acute viral hepatitis and in 16 patients with chronic liver disease utilizing subjective responses and objective measurements of detection and recognition thresholds and scaling for NaCl, sucrose, HCl, and urea. In patients with early hepatitis and those with chronic liver disease, the magnitude and the uniformity of the threshold elevations were comparable, implying that disordered gustatory acuity reflects disordered hepatic function per se. Patients with acute hepatitis showed a significant fall in taste thresholds (improvement in acuity) as the hepatitis waned, indicating that the gustatory defect is reversible. This disorder of gustatory acuity may contribute to the anorexia commonly found in patients with liver disease.

Anorexia↗

Functional MRI of congenital hyposmia: brain activation to odors and imagination of odors and tastes.

PURPOSE: Our goal was to use functional MRI (fMRI) to define brain activation in response to odors and imagination ("memory") of odors and tastes in patients who never recognized odors (congenital hyposmia). METHOD: Functional MR brain scans were obtained in nine patients with congenital hyposmia using multislice echo planar imaging (EPI) in response to odors of amyl acetate, menthone, and pyridine and to imagination ("memory") of banana and peppermint odors and to salt and sweet tastes. Functional MR brain scans were compared with those in normal subjects and patients with acquired hyposmia. Activation images were derived using correlation analysis, and ratios of areas of brain activated to total and hemispheric brain areas were calculated. Total and hemispheric activated pixel counts were used to quantitate regional brain activation. RESULTS: Brain activation in response to odors was present in patients with congenital hyposmia. Activation was significantly lower than in normal subjects and patients with acquired hyposmia and did not demonstrate differential vapor pressure-dependent detection responsiveness or odor response lateralization. Regional activation localization was in anterior frontal and temporal cortex similar to that in normal subjects and patients with acquired hyposmia. Activation in response to presented odors was diverse, with a larger group exhibiting little or no activation with localization only in anterior frontal and temporal cortex and a smaller group exhibiting greater activation with localization extending to more complex olfactory integration sites. "Memory" of odors and tastes elicited activation in the same central nervous system (CNS) regions in which activation in response to presented odors occurred, but responses were significantly lower than in normal subjects and patients with acquired hyposmia and did not lateralize. CONCLUSION: Odors induced CNS activation in patients with congenital hyposmia, which distinguishes olfaction from vision and audition since neither light nor acoustic stimuli induce CNS activation. Odor activation localized to anterior frontal and temporal cortex, consistent with the hypothesis that olfactory pathways are hard-wired into the CNS and that further pathways are undeveloped with primary olfactory system CNS connections but lack of secondary connections. However, some patients exhibited greater odor activation with response localization extending to cingulate and opercular cortex, indicating some olfactory signals impinge on and maintain secondary connections consistent with similar functions in vision and audition. Activation localization of taste "memory" to anterior frontal and temporal cortex is consistent with CNS plasticity and cross-modal CNS reorganization as described for vision and audition. Thus, there are differences and similarities between olfaction, vision, and audition, the differences dependent on unique qualities of olfaction, perhaps due to its diffuse, primitive, fundamental role in survival. Response heterogeneity to odors may reflect heterogeneous genetic abnormalities, independent of anatomic or hormonal changes but dependent on molecular abnormalities in growth factor function interfering with growth factor/stem cell interactions. Patients with congenital hyposmia offer an unique model system not previously explored in which congenital smell lack as measured by fMRI is reflective of congenital dysfunction of a major sensory system.

Adult↗

The contribution of latent inhibition to reduced generalization after pre-exposure to the test stimulus.

Two experiments assessed the contribution of latent inhibition to the generalization-reducing effects of pre-exposure to the test stimulus using a taste aversion procedure in rats. In both experiments, lithium chloride induced illness was paired with a flavor compound (AX) of either salt or sugar (A or B) and hydrochloric acid (X). Generalization of the resulting aversion to a test compound (BX), was assessed after varying pre-exposure to BX, X, and B. Experiment 1 showed that generalization to BX was less when BX itself had been exposed than equivalent pre-exposure to either B and X separately or to B and a new compound (CX). Experiment 2 showed that levels of generalization varied directly as a function of the amount of pre-exposure to BX. The findings show that latent inhibition alone cannot account for the generalization-reducing effect of pre-exposure to BX.

Animals↗

Effect of tryptophan depletion on smokers and nonsmokers with and without history of major depression.

BACKGROUND: Serotonergic dysregulation is posited to contribute to comorbidity between nicotine dependence and depression. We tested whether acute tryptophan depletion (ATD) triggers depressive symptoms in euthymic, unmedicated smokers and nonsmokers with and without history of major depressive disorder (MDD). METHODS: Acute tryptophan depletion and taste-matched placebo challenges were administered double-blind in counter-balanced order. Participants were four groups of volunteers hypothesized to be of increasing affective vulnerability as follows: nonsmokers lacking recurrent personal and familial history of MDD (n = 20), smokers lacking recurrent personal and familial history of MDD (n = 21), nonsmokers with history of recurrent personal and familial MDD (n = 16), and smokers with recurrent personal and familial history of MDD (n = 16). Depression, dysphoric mood, and plasma amino acids were measured at baseline and around the time of peak depletion. RESULTS: Depressive symptom response to ATD was heightened significantly by history of MDD (p < .001) and marginally by smoking (p = .09). Smoking seemed to magnify the ATD response of those with a history of MDD (effect size = .63) but had no effect on those without MDD history (effect size = .06). CONCLUSIONS: Depressive symptom response to serotonergic challenge is exaggerated in unmedicated, euthymic adults with recurrent personal and familial vulnerability to MDD, perhaps especially if they also smoke.

Adolescent↗

Effects of viscosity, taste, and bolus volume on swallowing apnea duration of normal adults.

OBJECTIVE: The effects of viscosity, taste, and nectar-thick liquid bolus volume on swallowing apnea duration (SAD) were examined. STUDY DESIGN AND SETTING: Twenty-two adults, comprised of 10 males and 12 females, participated. SAD was assessed via nasal airflow during swallow conditions of viscosity (thin liquid, thick liquid, and puree), taste (water, apple juice, lemon concentrate), and nectar-thick liquid bolus volumes (5, 10, 15, and 20 mL) across three trials. RESULTS: A significant main effect of nectar-thick liquid bolus volume was found (P < 0.05). Viscosity and taste were not significant. CONCLUSIONS: SAD increased with increases in bolus volume; however, neither changes in bolus viscosity nor changes in taste affected SAD. SIGNIFICANCE: These findings indicate that since viscosity was not significant, the normative data previously published (by this PI) with 60 healthy adults stratified by age and gender can be utilized for comparison to disordered swallowing without regard to the bolus viscosity being used. EBM RATING: D.

Adult↗

Local and systemic administration of corticosteroids in the treatment of olfactory loss.

BACKGROUND: The aim of this study was to evaluate the benefit of patients with olfactory dysfunction from local (group A) or systemic (group B) administration of corticosteroids. METHODS: This unblinded study was conducted at a smell and taste outpatient clinic of an institutional referral center. Patients with olfactory loss after infections of the upper respiratory tract, patients with apparent sinonasal disease, and patients suffering from "idiopathic" smell loss were included. Effects of mometasone nasal spray, administered for 1-3 months, were studied in 37 patients. In addition, effects of oral prednisolone were analyzed in 55 patients who received decreasing doses over 21 days, starting with a dose of 40 mg. Olfactory function before and after treatment was measured. RESULTS: Although odor identification scores tended to increase (p = 0.05), mometasone nasal spray did not significantly improve olfactory function, when looking at the entire group of patients or when analyzing the three diagnostic categories separately. In contrast, after systemic administration of corticosteroids, improvement of olfactory function was seen over all diagnostic categories (p < 0.001). Interestingly, olfactory function also improved in patients diagnosed with olfactory loss after upper respiratory tract infection (p = 0.05) and in patients initially diagnosed with "idiopathic," olfactory dysfunction (p = 0.008). CONCLUSION: In many patients, local application of corticosteroids appears to have little or no positive effect on olfactory dysfunction, especially when considering long-term changes. Duration of disease, the patient's age/sex, or the presence of parosmia does not appear to predict the response to therapy with corticosteroids.

Administration, Intranasal↗

The changes in taste preferences during 4 years period of methadone maintenance treatment.

The aim of the study was the analysis of the changes in the kind and the frequency of particular nutritional products consumption by opiate addicted persons during 4-year lasting methadone programme. There were 30 opiate addicted patients under examination (23 men and 7 women). Food consumption quality was estimated with the use of the Intake Frequency of Food Products Questionnaire. The examinations were performed before methadone administration had started, after 9 months and after 4 years of methadone maintenance treatment. Three categories of consumption frequency were established: rarely, moderately and often. The classification of different products was done with the use of hierarchic cluster analysis. For general illustration of the data the consumed products were compared by the means of hierarchical cluster analysis (this was done with the help of Euclidean distances and the Ward's algorithm). Then the k-means (with k=3) method was used in order to identify groups of products that were similarly often consumed. Each k-means analysis was performed separately for each examination. This was done in order to find out the products that change the cluster from one examination to another. Twenty labile products were identified. The examined products were moving between the adherent categories. This means that the consumption pattern undergoes some changes over the course of methadone therapy. Additionally, the analysis of the diet of this group of people shows improper and unhealthy nutritional behaviours: too big intake of sweets and too low intake of complex carbohydrates, fish and vegetable fats. This was especially visible at the beginning of the therapy, later this unfavourable diet habits changed but not to the desired level.

Adult↗

Combining sensory reinforcement and texture fading procedures to overcome chronic food refusal.

Previous research has demonstrated behavioral programs to be effective in treating children with selective food preferences. However, there are few examples of interventions for the child displaying almost total food refusal. The present program combined sensory reinforcement and texture fading procedures to treat a 4-year-old deaf, visually impaired child who only consumed milk and, occasionally, pureed baby food. Sensory reinforcement consisted of the contingent presentation of light and rocking motion following consummatory responses. Texture fading entailed gradually increasing food composition. Results indicated that treatment was associated with substantial increases in the consumption of solid foods. Effects were maintained following the withdrawal of sensory reinforcement and with meals presented outside of the original treatment settings. Various features of the program are highlighted and discussed.

Anorexia↗

Anorexia in the elderly.

Weight loss and anorexia occur commonly in the elderly. While in many cases the anorexia can be attributed to associated disease processes, it does appear that a true anorexia of aging exists. Animal studies have suggested that older rodents have an excessive satiety effect of cholecystokinin and a decreased opioid feeding drive. Other older persons develop anorexia in association with depression. In these subjects, excess corticotropin-releasing factor may be the neurotransmitter involved in the pathogenesis of the anorexia. In Alzheimer's disease, decreases in norepinephrine and neuropeptide Y may be involved in the anorexia seen in the these patients.

Aged↗