Follow-up study of olfactory deficits, cognitive functions, and volume loss of medial temporal lobe structures in patients with mild cognitive impairment.

BACKGROUND: At 3 years after diagnosis, the risk of Alzheimer disease (AD) for patients with mild cognitive impairment (MCI) is estimated to be 18% to 30%. To improve treatment of patients at high dementia risk there is a need for a better prediction of the risk for transition from MCI to AD. Olfactory deficits are a hypothetical predictor of conversion form MCI to AD. Furthermore, several studies point at volumetric reduction of medial temporal lobe structures as predictors of conversion form MCI to AD. The primary aim of this study was to evaluate whether investigations of odor deficits in MCI combined with neuropsychological tests and MRI examinations can improve prediction of the development of dementia. METHODS: Changes in olfactory functions, cognitive functions, and volume of medial temporal lobe structures (hippocampus, parahippocampal gyrus, and amygdala) were evaluated in a 24-month follow-up study in 49 MCI patients and 33 controls. RESULTS: In the MCI group, a prediction of strong cognitive functions deterioration based on poor performance in Olfactory Identification tests shows sensitivity of 57% and specificity of 88%. The test based on cognitive functions only shows a sensitivity of 44%, and 89%, respectively. Combined tests having a criteria of poor olfactory identification performance AND poor results of neuropsychological tests showed a sensitivity of 100% and specificity of 84%. Furthermore, correlation was found between the results of Olfactory Identification tests at baseline and deterioration of cognitive functions at follow up. Odor identification threshold did not appear to be a dementia predictor. A correlation of progress of cognitive function deterioration, odor identification deterioration, and decrease of volume of the hippocampus was also observed. CONCLUSIONS: Prediction of MCI to dementia conversion can be improved by supplementing the neuropsychological tests with odor identification tests. A follow up study of hippocampus volume reduction, OI performance and cognitive functions deterioration will further increase prediction accuracy.

Increased ethanol intake and preference in cyclin D2 knockout mice.

Inhibitory effects of passive ethanol exposure on brain neurogenesis have been extensively documented in animal models. In contrast, a role of brain neurogenesis in ethanol self-administration has not been addressed, as yet. The aim of this study was to assess intake of, and preference for, ethanol solutions [2-16% (v/v)] in a mouse model of adult neurogenesis deficiency based on permanent knockout (KO) of cyclin D2 (Ccnd2). Wild type (WT) and Ccnd2 KO mice did not differ in 2% and 4% ethanol intake. The KO group consumed significantly more ethanol in g/kg when offered with 8% or 16% ethanol as compared with the WT controls. The WT and KO mice did not differ in 2% ethanol preference, but the KO group showed a significantly higher preference for 4-16% ethanol. Animal and human studies have suggested that the low level of response to the sedative/hypnotic effects of alcohol is genetically associated with enhanced alcohol consumption. However, in this study, there were no between-genotype differences in ethanol-induced loss of righting reflex. Previous reports have also suggested that high ethanol intake is genetically associated with the avidity for sweets and better acceptance of bitter solutions. However, the KO and WT mice consumed similar amounts of saccharin solutions and the KOs consumed less quinine (i.e. bitter) solutions as compared with the WTs. In conclusion, these results may indicate that Ccnd2 and, possibly, brain neurogenesis are involved in central regulation of ethanol intake in mice.

Gamma-aminobutyric acid concentrations in benign parotid tumours and unstimulated parotid saliva.

OBJECTIVE: Apart from its role as an inhibitory neurotransmitter, γ-aminobutyric acid is also thought to regulate various stages of cell proliferation and differentiation in the brain and periphery. The present study aimed to assess the levels of γ-aminobutyric acid and its biochemical precursor glutamic acid (glutamate) in benign parotid tumours and in unstimulated parotid saliva. METHOD: Unstimulated parotid saliva was collected bilaterally, using the swab method, in 20 patients with unilateral pleomorphic adenoma or Warthin's tumour. Samples of tumour and adjacent salivary tissue were collected during tumour resection. RESULTS: Concentrations of γ-aminobutyric acid and glutamate, but not aspartate, were significantly higher in the tumour tissue than in the non-tumour tissue. There was no significant difference in salivary concentrations of γ-aminobutyric acid, glutamate or aspartate, comparing the involved and non-involved side. CONCLUSION: The present results provide preliminary evidence that γ-aminobutyric acid may be involved in the growth of benign parotid tumours.

Post-tonsillectomy dysgeusia with weight loss: possible involvement of soft palate.

OBJECTIVE: To demonstrate the importance of detailed, multidisciplinary examination of patients with post-tonsillectomy taste distortions, and to show that post-tonsillectomy dysgeusia may originate in the caudal part of the soft palate. CASE REPORT: We describe a 29-year-old man who suffered from severe post-tonsillectomy dysgeusia and phantogeusia with secondary weight loss and depression-like symptomatology. The patient had normal electrogustometric thresholds and sensitivity to touch on the posterior tongue. In contrast, elevated taste threshold and reduced sensitivity to touch was found on the caudal part of the soft palate (the palatoglossal arches). More marked elevation of electrogustometric threshold and insensitivity to touch on the right palatoglossal arch correlated with post-operative haemorrhage from the right tonsillar fossa. Psychiatric examination excluded major depression, eating disorders and drug abuse. CONCLUSIONS: Dysgeusia constitutes a rare but significant complication of tonsillectomy. Damage to the lingual branch of the glossopharyngeal nerve innervating the posterior tongue is thought to be a major cause of this complication. However, damage to the tonsillar branches of the glossopharyngeal nerve and the soft palate should also be considered as a cause of post-tonsillectomy dysgeusia. Further studies are needed to assess whether post-operative haemorrhage could indicate heightened risk of dysgeusia.

Taste responses in patients with Parkinson's disease.

OBJECTIVE: Preclinical studies indicate that dopaminergic transmission in the basal ganglia may be involved in processing of both pleasant and unpleasant stimuli. Given this, the aim of the present study was to assess taste responses to sweet, bitter, sour, and salty substances in patients with Parkinson's disease (PD). METHODS: Rated intensity and pleasantness of filter paper discs soaked in sucrose (10-60%), quinine (0.025-0.5%), citric acid (0.25-4.0%), or sodium chloride (1.25-20%) solutions was evaluated in 30 patients with PD and in 33 healthy controls. Paper discs soaked in deionised water served as control stimuli. In addition, reactivity to 100 ml samples of chocolate and vanilla milk was assessed in both groups. Taste detection thresholds were assessed by means of electrogustometry. Sociodemographic and neuropsychiatric data, including cigarette smoking, alcohol consumption, tea and coffee drinking, depressive symptoms, and cognitive functioning were collected. RESULTS: In general, perceived intensity, pleasantness, and identification of the sucrose, quinine, citric acid, or sodium chloride samples did not differ between the PD patients and controls. Intensity ratings of the filter papers soaked in 0.025% quinine were significantly higher in the PD patients compared with the control group. No inter-group differences were found in taste responses to chocolate and vanilla milk. Electrogustometric thresholds were significantly (p = 0.001) more sensitive in the PD patients. CONCLUSIONS: PD is not associated with any major alterations in responses to pleasant or unpleasant taste stimuli. Patients with PD may present enhanced taste acuity in terms of electrogustometric threshold.

Taste responses in alcohol-dependent men.

The aim of the present study was to compare taste responses to sweet, bitter, sour and salty solutions in male alcoholics and control subjects. The groups did not differ in terms of rated intensity or pleasantness of sucrose (1-30%), quinine (0.001-0.005%), citric acid (0.02-0.1%) and sodium chloride (0.18-0.9%) solutions. The proportion of sweet-likers was also similar in both groups.

Effects of a novel uncompetitive NMDA receptor antagonist, MRZ 2/579 on ethanol self-administration and ethanol withdrawal seizures in the rat.

It has been repeatedly reported that NMDA receptors may contribute to ethanol-induced discriminative stimulus effects and withdrawal syndrome. However, the role of NMDA receptors in the reinforcing properties of ethanol remains unclear. The aim of the present study was to evaluate effects of the novel low-affinity, uncompetitive NMDA receptor antagonist, 1-amino-1,3,3,5,5-pentamethyl-cyclohexane hydrochloride (MRZ 2/579), on ethanol self-administration and ethanol withdrawal-associated seizures in rats. Both an operant (lever pressing for ethanol) and non-operant two-bottle choice setups were employed to initiate ethanol self-administration. In another procedure, forced treatment with high doses (9--15 g/kg/day) was used to induce physical dependence on ethanol. MRZ 2/579 delivered chronically by osmotic minipumps (9.6 mg/day, s.c.) did not alter either operant or non-operant ethanol drinking behaviour in a maintenance phase of ethanol self-administration. In contrast, repeated daily injections of the drug (5 mg/kg, i.p.) led to a progressive decrease in operant responding for ethanol. MRZ 2/579 (0.5--7.5 mg/kg, i.p.) and another low-affinity NMDA receptor antagonist, memantine (1--10 mg/kg, i.p.) dose-dependently suppressed ethanol withdrawal seizures with efficacies comparable with that of a standard benzodiazepine derivative, diazepam. The results of the present study indicate that: (i) intermittent administration of MRZ 2/579 may lead to a gradual decrease of operant responding for ethanol; and (ii) the group of low-affinity uncompetitive NMDA receptor antagonists may be an interesting alternative to benzodiazepines in the treatment of alcohol withdrawal.

Taste responses in sons of male alcoholics.

The aim of the present study was to compare taste responses (intensity and pleasantness/unpleasantness) to sweet, bitter, sour, and salty solutions in sons of male alcoholics (SOMAs) and control subjects with no family history of alcoholism. In addition, responses to Coca-Cola flavour were evaluated in both groups. Unpleasantness of salty solutions was significantly enhanced and intensity of sour solutions tended to be higher in the SOMAs. There were no other differences between the groups. Thus, contrary to previous suggestions, genetically determined vulnerability to alcohol dependence may not be associated with altered responses to sweet substances. The present findings would rather suggest that increased aversive responses to salt taste may predict future development of alcohol dependence.

Bitter and sweet components of ethanol taste in humans.

This study examined taste descriptions elicited by ethanol and by other tastants in humans. All subjects described 10% ethanol as bitter and approximately 30% of the subjects described it as sweet and/or sour. Highly significant correlations were found between sweetness of some sucrose solutions (0.6-1%) and intensity of the taste of ethanol. In another experiment, quinine (bitter) solutions were rated as similar to 10% ethanol taste and this effect was potentiated by the addition of sucrose. In contrast, citric acid (sour) tended to decrease similarity ratings when added to the quinine solutions. Taken together, these findings suggest that: (1) in humans ethanol tastes both bitter and sweet; and (2) the relationship between sucrose and ethanol intakes previously found in animals and humans may result, at least partially, from similar taste responses elicited by sucrose and ethanol.

An opioid receptor antagonist, naltrexone, does not alter taste and smell responses in humans.

Several studies have shown that an opioid receptor antagonist, naltrexone, decreases palatable food consumption. Naltrexone has also been reported to reduce ethanol intake in alcohol-preferring rodents and human alcoholics. The aim of the present study was to assess the effects of naltrexone on taste and smell responses in healthy male volunteers. Naltrexone did not alter intensity and pleasantness of sucrose, quinine, citric acid, sodium chloride, and ethanol taste. Similarly, ratings of olfactory stimuli (orange extract and ethanol) and Coca-Cola flavor were not influenced by the opioid antagonist. Our findings may indicate that: (i) naltrexone exerts marginal, if any, effects on gustatory and olfactory responses in humans; (ii) the drug does not alter orosensory responses to ethanol.

[Ototoxic mechanism of aminoglycoside antibiotics--role of glutaminergic NMDA receptors]. / Mechanizm ototoksycznego dzialania antybiotyków aminoglikozydowych--rola receptorów glutamatergicznych NMDA.

Recent studies have indicated that glutamatergic NMDA receptors in the cochlea may be involved in ototoxic effects of aminoglycosides in animal subjects. Aminoglycoside antibiotics enhance the function of NMDA receptors by interaction with a polyamine modulatory site. Accordingly, high doses of aminoglycosides may increase calcium entry through the NMDA receptor-associated channel and promote degeneration of hair cells and cochlear nerve fibers. In line with the above, a polyamine site antagonist, ifenprodil as well as a high-affinity channel blocker, dizocilpine (MK-801) attenuates ototoxic effects of aminoglycosides in rats. Notably, ifenprodil as well as low-affinity channel blockers (e.g. memantine and amantadine) may be safely used in humans. Taken together, the above findings seem to open new avenues of research on selective pharmacotherapy of aminoglycosides-induced ototoxicity in humans.