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Studies on auditory thresholds in normal man and in patients with adrenal cortical insufficiency: the role of adrenal cortical steroids.

Auditory thresholds for sinusoidal tones were determined in eight patients with adrenal cortical insufficiency (four with Addison's disease and four with panhypopituitarism) and compared to those in normal volunteers. In adrenal cortical insufficiency (ACI) the auditory detection sensitivity is significantly more acute than that of normal subjects over most of the frequency range, but especially in the region of greatest hearing sensitivity of normal subjects, 1,000 to 2,000 cycles per second (cps). Treatment of the patients with deoxycorticosterone acetate decreased serum potassium concentration and produced gains in body weight but did not alter auditory detection thresholds. Treatment with prednisolone or with maintenance doses of carbohydrateactive steroids returned the auditory detection threshold to normal in every patient tested.The mechanism by which carbohydrate-active steroids affect the sensitivity of the nervous system to sound is not known. However, since the senses of taste, smell, and hearing are all affected in similar fashion by their removal and replacement, there appears to be a generalized increase in sensitivity to all sensory stimuli in patients with ACI not receiving steroids. These hormones may play a significant role in maintaining the level of responsiveness of the sensory system to incoming stimuli.

Addison Disease↗

Removal of geosmin and 2-methylisoborneol by biological filtration.

The quality of drinking water is sometimes diminished by the presence of certain compounds that can impart particular tastes or odours. One of the most common and problematic types of taste and odour is the earthy/musty odour produced by geosmin (trans-1, 10-dimethyl-trans-9-decalol) and MIB (2-methylisoborneol). Taste and odour treatment processes including powdered activated carbon, and oxidation using chlorine, chloramines, potassium permanganate, and sometimes even ozone are largely ineffective for reducing these compounds to below their odour threshold concentration levels. Ozonation followed by biological filtration, however, has the potential to provide effective treatment. Ozone provides partial removal of geosmin and MIB but also creates other compounds more amenable to biodegradation and potentially undesirable biological instability. Subsequent biofiltration can remove residual geosmin and MIB in addition to removing these other biodegradable compounds. Bench scale experiments were conducted using two parallel filter columns containing fresh and exhausted granular activated carbon (GAC) media and sand. Source water consisted of dechlorinated tap water to which geosmin and MIB were added, as well as, a cocktail of easily biodegradable organic matter (i.e. typical ozonation by-products) in order to simulate water that had been subjected to ozonation prior to filtration. Using fresh GAC, total removals of geosmin ranged from 76 to 100% and total MIB removals ranged from 47% to 100%. The exhausted GAC initially removed less geosmin and MIB but removals increased over time. Overall the results of these experiments are encouraging for the use of biofiltration following ozonation as a means of geosmin and MIB removal. These results provide important information with respect to the role biofilters play during their startup phase in the reduction of these particular compounds. In addition, the results demonstrate the potential biofilters have in responding to transient geosmin and MIB episodes.

Biodegradation, Environmental↗

Design and application of a GC-SNIff/MS system for solving taste and odour episodes in drinking water.

This paper describes the implementation of a GC-Sniff/MS system that allows the simultaneous determination of the odorous properties of compounds eluting from a GC column and their identification by MS. The technique was first tested with standard compounds then applied to real cases of taste and odour episodes. This approach allowed the identification of geosmin at low levels and suggested the possible implication of methylnaphthalene in the development of chemical odours. It provided the first clue of the presence of a halophenol with a very low odour threshold involved in a chlorophenolic odour episode. The chemical was finally identified as 2,6-dibromophenol. The method was also applied to the characterization of a complex mixture of additives leaching from a flexible rubber pipe. In the latter case, Time-of-Flight MS was also used to confirm the identity of the additives.

Automation↗

Chorda tympani responses to gustatory stimuli in developing rats.

The developmental change in rat taste sensitivity during the period from the 2nd to the 12th postnatal week was studied by recording the responses of the chorda tympani nerve to lingual stimulation by NaCl, LiCl, KCl, NH4Cl, HCl, quinine hydrochloride (Q-HCl), and sucrose. The threshold for all stimulants except sucrose was lower in the 3-week-old rats than in the 12-week-old ones. The order of the magnitudes of the normalized neural responses to the 0.1 M monochloride salts of the gustatory nerves was NH4Cl greater than NaCl = LiCl greater than KCl in the 3-week-old rats, and NaCl = LiCl greater than NH4Cl greater than KCl in the 12-week-old rats. The magnitude of the normalized responses to NH4Cl, HCl, and Q-HCl at nearly all concentrations was greater at 3 weeks than at 12 weeks, while the magnitude of the responses to NaCl and LiCl at high concentrations was lesser at 3 weeks than at 12 weeks. Changes in the gustatory sensitivity to various taste stimuli during development can be classified into the following two types: (1) sensitivity-decreasing type--the magnitude of the response to NH4Cl, Q-HCl, and HCl was greatest during the first few weeks and decreased thereafter, and (2) sensitivity-increasing type--the magnitude of the response to NaCl, LiCl, and sucrose showed an increase accompanying the growth of rats from around the 2nd week after birth.

Age Factors↗

Columnar organization of mechanoreceptive neurons in the cortical taste area in the rat.

Mechanoreceptive neurons with or without taste responsiveness were recorded in the cortical taste area (CTA) of rats every 50 or 100 micro m along an electrode track made as perpendicular to the surface as possible. Three groups of mechanoreceptive neurons were recognized based on the adequate stimulus, i.e., low-threshold mechanoreceptive ( n=16), nociceptive-specific ( n=48), and wide-dynamic range neurons ( n=392). Except for nine neurons, almost all had receptive fields (RFs) in the oral cavity ( n=447). They were categorized into three RF types: those with RFs only in the oral cavity (OC type; n=23), those with RFs both in the oral cavity and on the lip (OL type; n=44) and those with RFs in the oral cavity and on the external surface of the body (WB type; n=380), e.g., tail. Neurons with inhibitory RFs were often located in the infragranular layers. Several neurons with the same receptive features were sequentially recorded along the track, suggesting the presence of columnar organization. The diameter of the possible functional column was the largest (mean 113.85 micro m) for WB type neurons, but smaller in the other two types (mean 85 micro m for the OC type and 62.5 micro m for the OL type). Neurons were segregated according to the adequate stimulus within the column for WB type neurons. Taste-responsive mechanoreceptive neurons ( n=33) were recorded at 15 tracks, and two taste neurons were sequentially recorded in five cases, in three of which two successive neurons sharing the best stimulus were recorded. Taste neurons are possibly arranged in a column with a very small diameter within the large column of mechanoreceptive neurons.

Animals↗

A highly sensitive taste receptor cell for pyrrolizidine alkaloids in the lateral galeal sensillum of a polyphagous caterpillar, Estigmene acraea.

Adult males of Estigmene acraea use pyrrolizidine alkaloids to produce pheromones and all stages probably use pyrrolizidine alkaloids for defense. The alkaloids are obtained from plants by the caterpillars. We demonstrate that a contact chemoreceptor neuron in the lateral galeal sensillum exhibits a dose-dependent response to seneciphylline N-oxide, a widely occurring pyrrolizidine alkaloid, down to concentrations of 10(-9) x mol l(-1), and even at 10(-12) x mol l(-1) the response is greater than to salt alone. At concentrations of 10(-6) mol x l(-1) and above the instantaneous firing rate is very high, and at 10(-4) mol x l(-1) initially exceeds 500 spikes s(-1). The firing rate declines in the 200 ms following stimulus onset but then is sustained with an instantaneous firing rate in excess of 100 spikes s(-1) for at least the next 800 ms. At lower concentrations a delay occurs before firing is initiated, and then the pattern of firing is irregular. The cell is equally sensitive to some but not all of several other pyrrolizidine alkaloids tested as free bases and their N-oxides. It also responds to ouabain, which may also serve as a defensive compound, and to asparagine and fructose but with much higher thresholds than to the pyrrolizidine alkaloids.

Action Potentials↗

The threshold of regulation and its application to indirect food additive contaminants in recycled plastics.

Recycled plastics have been used in food-contact applications since 1990 in various countries around the world. To date, there have been no reported issues concerning health or off-taste resulting from the use of recycled plastics in food-contact applications. This is due to the fact that the criteria that have been established regarding safety and processing are based on extremely high standards that render the finished recycled material equivalent in virtually all aspects to virgin polymers. The basis for this conclusion is detailed in this document.

Conservation of Natural Resources↗

Electrophysiological responses of three chemosensory systems in the carp to pesticides.

Responses of three chemical senses, olfaction, taste, and pit organ sense, to three pesticides were studied electrophysiologically in carp, Cyprinus carpio. Only olfaction was responsive to the three pesticides at behavioral avoidance levels, which were determined in a previous study. The olfactory thresholds for benthiocarb, isoprothiolane, and fenitrothion were 1.7 x 10(-1) micrograms/l (4 log units lower concentration than 48-h LC50), 6.7 x 10(-3) micrograms/l (6 log units lower than 48-h LC50), and 4.9 x 10(2) micrograms/l (1 log unit lower than 48-h LC50), respectively. There were two distinctive features in the olfactory response to pesticides. One is that these pesticides barely indicated the concentration dependency that is usually recognized in the olfactory response to a typical stimulant such as L-alanine or NaCl. Another is that these pesticides indicated a power spectrum with an overall increase in frequency ranges of less than 10.0 Hz, unlike L-alanine or NaCl, which show a marked peak ranging from 8.0 to 12.0 Hz. These findings suggest that there is a specific mechanism in the chemoreception for these pesticides.

Animals↗

[Occupational impairment of the olfactory sense of chromate producing workers (author's transl)].

Using T & T Olfactometer which had been developed and standardized for clinical use in Japan recently, measurements of olfactory thresholds of odor detection and of odor recognition were carried out on 33 subjects (26 males and 7 females), who had worked in a chromate producing factory. The subjects had left the factory before 7 years or more. Five kinds of test odors were used; beta-phenyl ethyl alcohol, methyl cyclopentenolone, iso-valeric acid, gamma-undecalactone, and scatol. The degree of olfaction loss was expressed with the number of powers of 10 in series of multiple concentrations by 10 of each test odor with reference to the concentration of the detection threshold of young normal people. Seventeen of 33 subjects (51.4%) had a perforation of the nasal septum. Middle and high grade decrease of odor recognition faculty were found in 18 (54.5%) including 2 anosmia, one of whom complained also of the disorder of taste. Any specific pattern of olfactogram characterizing them were not found, namely, chromates impair olfactory sense for all kinds of odors, which means the impairment of olfactory epithelium itself. The degree of olfaction loss was related to the duration of employment in the chromate producing factory. The existence of septal perforation had no direct relation to the degree of olfaction loss.

Adult↗

Previous experience of withdrawal from chronic diazepam ameliorates the aversiveness of precipitated withdrawal and reduces withdrawal-induced c-fos expression in nucleus accumbens.

Flumazenil (20 mg/kg, i.p.)-precipitated withdrawal from chronic treatment with diazepam (DZP, 15 mg/kg, s.c. in sesame oil for 21 days) resulted in a decreased seizure threshold to the convulsant, pentylenetetrazole (PTZ), infused into the tail vein; withdrawal from 21-day chronic diazepam treatment, interspersed with two periods of drug withdrawal, resulted in a greater decrease in convulsant threshold. A separate experiment showed that consumption of a sucrose solution immediately prior to precipitated withdrawal resulted in a decreased subsequent consumption of the sucrose solution; no such evidence of a conditioned taste aversion (CTA) was seen in mice given prior experience of withdrawal. Thus, prior experience of withdrawal enhanced the effects of a subsequent precipitated withdrawal in increasing seizure sensitivity, but weakened the ability of this withdrawal to serve as an aversive unconditioned stimulus (US). The weakening of the aversive properties of precipitated withdrawal may reflect habituation to the withdrawal stimulus, and was accompanied by a loss of the ability of withdrawal to induce c-fos expression in the shell of the nucleus accumbens, an area sensitive to both novel, and stressful, as well as rewarding stimuli.

Amygdala↗

Responsiveness of antennal taste hairs of the apterygotan insect, Thermobia domestica (Zygentoma); an electrophysiological investigation.

Antennal taste hairs of Thermobia domestica were investigated by a modified tip recording technique. They are sensitive to aqueous salt solutions but do not show the characteristic features of a water and a salt receptor cell. Sucrose and fructose stimulated approximately half of the tested hairs. As revealed by spike amplitude histograms, in most cases two sense cells responded. Proline stimulated the hairs with a threshold concentration of about 2 mM. Again, in most cases, two sense cells responded. In relation to sucrose the major sensitivities to both fructose and proline were not found in clearly defined receptor cells as in flies, but were realized in different cells of either a higher or smaller spike amplitude. This suggests, that the number of specific binding sites varies among the receptor cells from one taste hair to the other. As in cockroaches, but unlike flies, spike series are mainly generated in the apical dendritic segments. It is suggested that these features of the sense cells in thermobian taste hairs represent a primitive condition in relation to the specification of taste hairs cells in higher insect taxa

Journal Article↗

Further characterization of high mobility group box 1 (HMGB1) as a proinflammatory cytokine: central nervous system effects.

High mobility group box 1 (HMGB1), an abundant, highly conserved cellular protein, is widely known as a nuclear DNA-binding protein. HMGB1 has been recently implicated as a proinflammatory cytokine because of its role as a late mediator of endotoxin lethality and ability to stimulate release of proinflammatory cytokines from monocytes. Production of central cytokines is a critical step in the pathway by which endotoxin and peripheral proinflammatory cytokines, including interleukin-1beta (IL-1) and tumor necrosis factor-alpha (TNF), produce sickness behaviors and fever. Intracerebroventricular (ICV) administration of HMGB1 has been shown to increase TNF expression in mouse brain and induce aphagia and taste aversion. Here we show that ICV injections of HMGB1 induce fever and hypothalamic IL-1 in rats. Furthermore, we show that intrathecal administration of HMGB1 produces mechanical allodynia (lowering of the response threshold to calibrated stimuli). Finally, while endotoxin (lipopolysaccharide, LPS) administration elevates IL-1 and TNF mRNA in various brain regions, HMGB1 mRNA is unchanged. It remains possible that HMGB1 protein is released in brain in response to LPS. Nonetheless, these data suggest that HMGB1 may play a role as an endogenous pyrogen and support the concept that HMGB1 has proinflammatory characteristics within the central nervous system.

Animals↗

Proton currents through amiloride-sensitive Na channels in hamster taste cells. Role in acid transduction.

The activity of taste cells maintained in the intact hamster tongue was monitored in response to acid stimulation by recording action currents from taste receptor cells with an extracellular "macro" patch pipette: a glass pipette was pressed over the taste pore of fungiform papillae and perfused with citric acid, hydrochloric acid, or NaCl. Because this technique restricted stimulus application to the small surface area of the apical membranes of the taste cells, many nonspecific, and potentially detrimental, effects of acid stimulation could be avoided. Acid stimulation reliably elicited fast transient currents (action currents of average amplitude, 9 pA) which were consistently smaller than those elicited by NaCl (29 pA). The frequency of action currents elicited by acid stimuli increased in a dose-dependent manner with decreasing pH from a threshold of about pH 5.0. Acid-elicited responses were independent of K+, Na+, Cl-, or Ca2+ at physiological (salivary) concentrations, and were unaffected by anthracene-9-carboxylic acid, tetraethylammonium bromide, diisothiocyanate-stilbene-2,2'-disulfonic acid, vanadate, or Cd2+. In contrast, amiloride (< or = 30 microM) fully and reversibly suppressed acid-evoked action currents. At submaximal amiloride concentrations, the frequency and amplitude of the action currents were reduced, indicating a reduction of the taste cell apical conductance concomitant with a decrease in cell excitation. Exposure to low pH elicited, in addition to transient currents, an amiloride-sensitive sustained d.c. current. This current is apparently carried by protons instead of Na+ through amiloride-sensitive channels. When citric acid was applied while the taste bud was stimulated by NaCl, the action currents became smaller and the response resembled that produced by acid alone. Because of the strong interdependence of the acid and salt (NaCl) responses when both stimuli are applied simultaneously, and because of the similarity in the concentration dependence of amiloride block, we conclude that amiloride-sensitive Na+ channels on hamster taste receptor cells are permeable to protons and may play a role in acid (sour) taste.

Action Potentials↗

The Novolizer: overcoming inherent problems of dry powder inhalers.

For most dry powder inhalers (DPIs) a defined minimal inspiratory flow must be achieved immediately after the start of the inspiration procedure, to avoid insufficient deposition in the lung and excessive drug deposition in the patient's mouth and/or oropharynx. The Novolizer" (VIATRIS GmbH and Co. KG, Frankfurt, Germany) provides a combination of technical features that ensure that every inhalation manoeuvre is performed with adequate inspiratory and sufficient drug particles are delivered to the patient's lung. One of these technical features is an inspiratory flow rate threshold triggering feedback mechanisms to the patient which confirm that an adequate inspiratory flow rate (minimum 35-50 l/min) has been achieved. Correct inhalation manoeuvre is confirmed to the patient by optical, acoustic and taste feedback which is likely to improve patient compliance. The Novolizer also delivers a high-quality aerosol (high fine particle fraction representing the proportion of respirable particles), provides a refillable cartridge system, an accurate dose counter, a low intrinsic resistance, and enables reliable and consistent dose delivery. The Novolizer is at the cutting edge of inhalation technology and represents a major step forward in DPI design.

Anti-Asthmatic Agents↗

A quantitative study of the enhancing effect of nickel ions on the taste response to sodium ions of single fibers of the frog glossopharyngeal nerve: competitive inhibition by calcium ions of the nickel-enhanced response to sodium ions.

Single water fibers of the frog glossopharyngeal nerve respond to relatively high concentrations of NaCl ( > 80 mM). NiCl2 at 1 mM enhanced the Na+ response and reduced the threshold concentration for NaCl to 20 mM. CaCl2 at 0.5-1 mM induced an inhibition of the Ni2+ -enhanced response to Na+ ions. A quantitative explanations for these results is provided by the hypothesis that Ni2+ ions secondarily affect a sodium receptor or channel (designated XNa*) that is responsible for the Na+ response and that Ca2+ ions inhibit the Ni2+ -enhanced response to Na+ ions by competing with Na+ ions for XNa*. Double-reciprocal plots of the experimental data indicate that the affinity of XNa* for both Na+ ions (agonist) and Ca2+ ions (competitive antagonist) in the presence of 1 mM NiCl2 was five times higher than the previously reported values obtained in the absence of NiCl2 (Kitada, 1991). Ni2+ ions at 1 mM enhanced the maximal response to Na+ ions by 190%. It appears that a sodium receptor (or channel) interacts with a Ni2+ -binding element that is affected by Ni2+ ions and, thus, Ni2+ ions can induce both an increase in the affinity of the sodium receptor for the respective cations and an enhancement of the Na+ response.

Animals↗

Contribution of benzenemethanethiol to smoky aroma of certain Vitis vinifera L. wines.

Benzenemethanethiol, a volatile thiol with a strong empyreumatic aroma reminiscent of smoke, has been identified in boxwood (Buxus sempervirens L.) as well as in red and white Vitis vinifera L. wines. The perception threshold in a model hydroalcoholic solution is approximately 0.3 ng/L. All of the wines analyzed for this study contained this compound in concentrations of several dozen nanograms per liter. The Chardonnay wines had 30-40 ng/L. Sensory discrimination between a wine containing 7 ng/L benzenemethanethiol and the same wine with an additional 4 ng/L is very significant; the difference in smell is described as "empyreumatic". This compound can therefore significantly contribute to the aroma of certain wines (Sauvignon Blanc, Semillon, Chardonnay, etc.) containing concentrations as high as 30-100 times higher than their perception threshold.

Benzaldehydes↗