Cell apoptosis of taste buds in circumvallate papillae in diabetic rats.

Diabetes mellitus may result in taste disturbance. The present study has revealed that cell apoptosis of taste buds in circumvallate papillae may contribute to the taste disturbance in a rat model of type2 diabetes. Type2 diabetes was induced in Wistar rats by feeding them with a high-fat diet (30% fat), and a single intraperitoneal injection of streptozotocin (30 mg/kg). The increased cell apoptosis of taste buds in circumvallate papilla sections was detected by TUNEL staining in diabetic rats, and the ultrastructure was further examined by transmission electronic microscopy. Immunohistochemical and Western blot analyses revealed the downregulation of Bcl-2, upregulation of Bax, and increased activation of caspase-9 and -3, in diabetic rats, indicating that the apoptosis of taste bud cells may be mediated via the intrinsic mitochondrial pathway in diabetics.

Carbonic anhydrase I, II, and VI, blood plasma, erythrocyte and saliva zinc and copper increase after repetitive transcranial magnetic stimulation.

INTRODUCTION: Repetitive transcranial magnetic stimulation (rTMS) has been used to treat symptoms from many disorders; biochemical changes occurred with this treatment. Preliminary studies with rTMS in patients with taste and smell dysfunction improved sensory function and increased salivary carbonic anhydrase (CA) VI and erythrocyte CA I, II. To obtain more information about these changes after rTMS, we measured changes in several CA enzymes, proteins, and trace metals in their blood plasma, erythrocytes, and saliva. METHODS: Ninety-three patients with taste and smell dysfunction were studied before and after rTMS in an open clinical trial. Before and after rTMS, we measured erythrocyte CA I, II and salivary CA VI, zinc and copper in parotid saliva, blood plasma, and erythrocytes, and appearance of novel salivary proteins by using mass spectrometry. RESULTS: After rTMS, CA I, II and CA VI activity and zinc and copper in saliva, plasma, and erythrocytes increased with significant sensory benefit. Novel salivary proteins were induced at an m/z value of 21.5K with a repetitive pattern at intervals of 5K m/z. CONCLUSIONS: rTMS induced biochemical changes in specific enzymatic activities, trace metal concentrations, and induction of novel salivary proteins, with sensory improvement in patients with taste and smell dysfunction. Because patients with several neurologic disorders exhibit taste and smell dysfunction, including Parkinson disease, Alzheimer disease, and multiple sclerosis, and because rTMS improved their clinical symptoms, the biochemical changes we observed may be relevant not only in our patients with taste and smell dysfunction but also in patients with neurologic disorders with these sensory abnormalities.

Measurements of several metallic elements and matrix metalloproteinases (MMPs) in saliva from patients with taste disorder.

We have measured and compared several metallic elements and matrix metalloproteinases (MMPs) in saliva from patients with taste disorder and healthy subjects. Stimulated whole saliva was collected from 20 patients and 35 healthy subjects. Inductively coupled plasma mass spectrometry (ICP-MS) was used for the determination of metallic elements in saliva. Amounts of MMP-1, MMP-3, MMP-9 and IL-1alpha, IL-6 in saliva were measured using an enzyme-linked immunosorbent assay systems. Zinc in the serum was determined by flame atomic absorption spectrometry. Our results provide evidence that levels of zinc, manganese and the amount of MMP-3 in saliva are significantly decreased in the patients with taste disorder compared to the healthy subjects; Zn (p.p.b.): healthy subjects 79.8 +/- 42.6, patients 47.22 +/- 17.1, (P < 0.001), Mn (p.p.b.): healthy subjects 4.48 +/- 2.46, patients 2.78 +/- 1.23, (P < 0.004), MMP-3 (ng/ml), healthy subjects 0.820 +/- 0.417, patients 0.594 +/- 0.179 (P < 0.01). In contrast, copper is significantly increased in the patients; Cu (p.p.b.): healthy subjects 34.5 +/- 13.5, patients 45.9 +/- 20.8 (P < 0.049). These differences may be closely related with this disease. ICP-MS is an easy and accurate instrument for measurements of salivary metallic elements and may be useful in establishing a diagnosis of taste disorder.

Decreased parotid saliva gustin/carbonic anhydrase VI secretion: an enzyme disorder manifested by gustatory and olfactory dysfunction.

BACKGROUND: Taste and smell dysfunction has been reported to occur in patients with a variety of clinical problems. We wanted to investigate a specific group of patients in whom taste and smell dysfunction occurred putatively related to a specific biochemical abnormality in a salivary growth factor [gustin/carbonic anhydrase (CA) VI] considered responsible for maintenance of taste bud function. METHODS: Eighteen patients developed loss and/or distortion of taste and smell after an acute influenza-type illness. They were evaluated clinically, by psychophysical tests of taste and smell function, by measurement of parotid salivary gustin/CAVI by a radioimmunoassay and by measurement of serum, urine, and salivary zinc. Biopsies of circumvallate papillae were obtained in 6 patients and examined by transmission electron microscopy. Similar studies were performed in 55 asymptomatic volunteers with biopsies of circumvallate papillae performed in 4. RESULTS: Taste and smell acuity were impaired in patients compared with healthy volunteers and parotid gustin/CAVI, salivary, and serum zinc concentrations were lower in patients than in healthy volunteers. Taste buds in circumvallate papillae of patients exhibited severe vacuolization, cellular degeneration, and absence of dense extracellular material. CONCLUSIONS: These results describe a clinical disorder formulated as a syndrome of hyposmia (decreased smell acuity), hypogeusia (decreased taste acuity), dysosmia (distorted smell function), dysgeusia (distorted taste function), and decreased secretion of parotid saliva gustin/CAVI with associated pathological changes in taste bud anatomy. Because gustin/CAVI is found in humans only in parotid saliva and has been associated with taste bud growth and development these results suggest that inhibition of synthesis of gustin/CAVI is associated with development of taste bud abnormalities and thereby loss of taste function.

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.

[The activity of superoxide dismutase in patients with taste and smell dysfunction].

It was revealed that Zinc deficiency might cause taste and smell dysfunction. Superoxide dismutase (SOD), which scavenges superoxide, is a type of zinc enzyme. It was also demonstrated that the overproduction of superoxide damages normal tissue. We therefore measured the activity of SOD in serum and saliva of patients with taste or smell dysfunction by the cytochrome C reduction method using a xanthine-xanthine oxidase system. As a result, in the patients with taste dysfunction, the activities of SOD in both serum and saliva were normal, but mean level of serum Zinc was near to the lower normal limit. On the other hand, in the patients with smell dysfunction caused by chronic sinusitis or common cold, the activity of SOD in serum was significantly lower than that of healthy volunteers, and that in saliva was normal. These results suggest that Zinc enzymes, except serum and salivary SOD, are involved in the sense of taste, and that further investigation is necessary to clarify the relation between serum SOD deficiency and olfactory dysfunction.