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The responsiveness of human eccrine sweat glands to choline and carbachol. Application to the study of peripheral cholinergic functioning in Alzheimer-type dementia.

The responsiveness of human eccrine sweat glands to intradermally injected choline and carbachol was studied in vivo using a plastic paint impression method. Both drugs exerted consistent dose-related effects, choline being significantly less potent than carbachol. The responses to both drugs attained a maximum level approximately 3 min after the injection, but the responses to choline had a less pronounced peak and declined more slowly than the response to carbachol. The response to choline, but not the response to carbachol, was antagonised by hemicholinium-3. Young males showed greater responsiveness to both drugs than young females, this being reflected in higher maxima of the dose-response curves obtained for the males. Smaller responses to both drugs were observed in old females than in young females, this being reflected in lower maxima of the dose-response curves obtained for the elderly group. A group of elderly female patients with clinical diagnoses of Alzheimer-type dementia showed smaller responses to both drugs than the group of non-demented elderly females. The results show that choline can stimulate eccrine sweat glands, possibly by an indirect mechanism involving active uptake and metabolic conversion to acetylcholine. The reduced responsiveness seen in the patients suffering from Alzheimer-type dementia could reflect either a loss of function of cholinergic sympathetic neurones or impaired functioning of the sweat glands themselves.

Adult↗

The effect of diurnal variation on the regional differences in sweating and skin blood flow during exercise.

The aim of the present study was to examine changes in the control of heat-dissipation responses to exercise associated with the diurnal variation in core temperature from the viewpoint of the regional response patterns. We studied seven men during exercise on a cycle ergometer at 100 W for 40 min at 25 degrees C at 0630 (morning) 1630 (evening) hours on 2 separate days. Oesophageal temperature (T(oes)), local skin temperature, local sweating rate (msw) on the forehead, back, forearm and thigh, and skin blood flow by laser Doppler flowmeter (LDF) on the back and forearm were measured continuously. The T(oes) at rest was significantly higher in the evening than in the morning, the difference averaging approximately 0.4 degrees C (P < 0.05). The T(oes) thresholds for each site in msw and that for back in LDF were significantly different between the two times of day (P < 0.05). The change in T(oes) thresholds for sweating and vasodilatation for morning and evening were similar to T(oes) at rest. Although msw on the forehead was significantly higher in the morning than in the evening, msw on the back was significantly higher in the evening than in the morning (P < 0.05). Total local sweating rate (msw,tot) for each site during exercise was significantly higher on the forehead than on the forearm in the morning, and on the back than on the forearm in the evening, respectively (P < 0.05). The results would suggest that the diurnal variation of heat-dissipation responses to exercise is influenced not only by a central controlling mechanism but also by changes in the regional differences.

Adult↗

Twenty-four hour ambulatory monitoring of tremor, sweating, skin temperature and locomotor activity in the alcohol withdrawal syndrome.

An ambulatory monitor has been used to determine the characteristic patterns of tremor, sweating, skin temperature and locomotor activity in subjects undergoing alcohol withdrawal. Twenty-four hour records were obtained from six male subjects who had been consuming an average of 345 g of alcohol per day prior to cessation and from a group of age-matched controls. Consistent with earlier research and clinical observation, tremor, sweating and locomotor activity were elevated in withdrawal subjects. Sweating was greatest in the period from approximately 00.00 h to 06.00 h, as was skin temperature. Tremor and activity levels decreased during this period, but were considerably higher in withdrawal subjects. The data suggest that 24-h monitoring of alcohol withdrawal using objective methods provides a more sensitive assessment technique than the standard clinical approaches. The technique may be of value in other dysautonomic states.

Adult↗

Unilateral loss of facial flushing and sweating with contralateral anhidrosis: harlequin syndrome or Adie's syndrome?

A 45-year-old woman presented with a 10 year history of asymmetrical facial flushing and sweating after exertion or in hot weather. During these episodes the right side of her face remained dry and white, while the left side normally flushed. Sweating was impaired on the left side in the limbs and trunk. She also had areflexia in the lower limbs and slow pupillary reactions to light and darkness, as seen in Adie's syndrome. The topography of the sweating disorder suggested that the lesion involved the sympathetic pathways at the level of spinal cord. The relationship with the harlequin syndrome and related disorders is discussed.

Adie Syndrome↗

Does acetylcholine change the electrical resistance of the basal membrane of secretory cells in eccrine sweat glands?

The present experiment was intended to study whether or not acetylcholine decreases the electrical resistance of the basal membrane of secretory cells in stimulating eccrine secretion of fluid and electrolytes. An isolated segment of the secretory coil of the monkey palm eccrine sweat gland was dissected out in vitro and immobilized in the tip of a constriction pipette. Using a bridge-balanced single glass microelectrode, input impedance of the secretory cell was compared before and after local superfusion of acetylcholine in each cell. The mean input impedance was 27 Momega, which did not significantly change after application of acetylcholine. Between 15 and 30 sec after cessation of acetylcholine superfusion, input impedance increased by 42% and then returned to normal within 60 sec. The current-induced voltage deflection due to intraluminally injected current pulse was measured across both the basal membrane (deltaVb) and the epithelial wall (deltaVt) as qualitative measures of the respective membrane resistances. Both deltaVb and deltaVt increased by about 10%, but their ratio remained unchanged after stimulation with acetylcholine. A Ca++ ionophore, A23187, which is as potent a stimulant of eccrine sweat secretion as acetylcholine in vitro, also failed to change the above two parameters. It was concluded that the decrease in the electrical resistance of the basal membrane of the secretory cells could not be detected in the sweat gland after stimulation with acetylcholine or A23187. The possibility was discussed that the action of acetylcholine at the basal membrane is one of enhancing the activity of the nonconductive pathway rather than the conductive pathway in this exocrine gland.

Acetylcholine↗

Amiloride impairs the cholinergic regulation of potassium permeability in the human sweat gland but not in the rat submandibular gland.

Potassium permeability was monitored in human sweat glands and rat submandibular glands. Acetylcholine increased permeability in both tissues and the responses consisted of transient, calcium-independent and sustained, calcium-dependent components. Amiloride, a drug which inhibits Na(+)-H+ countertransport, impaired the regulation of potassium permeability in sweat glands but not in the submandibular gland. It is suggested that the stimulus-permeability coupling process in the sweat gland may be sensitive to the lowering of internal pH.

Acetylcholine↗

Botulinum toxin in the therapy of gustatory sweating.

Three patients suffering from gustatory sweating following trauma to the preauricular region from a bullet wound or parotid gland surgery were treated by intracutaneous injection of botulinum toxin A. Within 2 weeks, gustatory sweating in the area injected completely ceased in all patients with no side-effects. The efficacy of treatment was confirmed by repeated Minor's iodine starch tests. So far, sweating has not recurred during a follow-up period of up to 8 months. Botulinum toxin appears to be a promising new drug for the treatment of this autonomic disorder.

Adult↗

Apical heterotrimeric g-proteins activate CFTR in the native sweat duct.

Other than the fact that the cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channel can be activated by cAMP dependent kinase (PKA), little is known about the signal transduction pathways regulating CFTR. Since G-proteins play a principal role in signal transduction regulating several ion channels [4, 5, 9], we sought to test whether G-proteins control CFTR Cl- conductance (CFTR G(Cl)) in the native sweat duct (SD). We permeabilized the basolateral membrane with alpha-toxin so as to manipulate cytosolic nucleotides. We activated G-proteins and monitored CFTR G(Cl) activity as described earlier [20, 23, 25]. We now show that activating G-proteins with GTP-gamma-S (100 microm) also activates CFTR G(Cl) in the presence of 5 mm ATP alone (without exogenous cAMP). GTP-gamma-S increased CFTR G(Cl) by 44 +/- 20 mS/cm(2) (mean +/- se; n = 7). GDP (10 mm) inhibited G-protein activation of CFTR G(Cl) even in the presence of GTP-gamma-S. The heterotrimeric G-protein activator (AlF(4-) in the cytoplasmic bath activated CFTR G(Cl) (increased by 51.5 +/- 9.4 mS/cm(2) in the presence of 5 mm ATP without cAMP, n = 6), the magnitude of which was similar to that induced by GTP-gamma-S. Employing immunocytochemical-labeling techniques, we localized Galphas, Galphai, Galphaq, and Gbeta at the apical membranes of the sweat duct. Further, we showed that the mutant CFTR G(Cl) in ducts from cystic fibrosis (CF) subjects could be partially activated by G-proteins. The magnitude of mutant CFTR G(Cl) activation by G-proteins was smaller as compared to non-CF ducts but comparable to that induced by cAMP in CF ducts. We conclude that heterotrimeric G-proteins are present in the apical membrane of the native human sweat duct which may help regulate salt absorption by controlling CFTR G(Cl) activity.

Adenosine Triphosphate↗

Accumulation of FDG in axillary sweat glands in hyperhidrosis: a pitfall in whole-body PET examination.

A diabetic male with severe autonomic neuropathy and recently discovered Hodgkin's disease demonstrated bilateral uptake of [2-18F]-2-fluoro-2-deoxy-d-glucose (FDG) in the axillary sweat glands during profuse sweating caused by hypoglycaemia at positron emission tomography examination. It is not yet clear whether the sweating interfered with the distribution of the radiopharmaceutical. Regardless of the cause or mechanism for the uptake, the finding is clinically relevant. A bilateral symmetrical accumulation of FDG in the axillae of a tumour patient does not necessarily indicate malignant involvement of the lymph nodes.

Adult↗

Radon progeny activity in sweat following radon exposure in a warm and humid environment.

The objective was to evaluate whether activity of radon progenies can be detected in sweat following speleotherapeutic radon exposure (40 kBq/m3) in a warm (38 degrees C) and humid (relative humidity > 70%) environment. A group of 11 male patients with spondyloarthropathy (n = 6) or non-inflammatory rheumatic diseases (n = 5) underwent a 1-h treatment in the gallery of the Gasteiner Heilstollen, and 20 min after leaving the treatment area radon progeny activity was measured in sweat by utilizing a special filter set. The results suggest that radon is discharged with sweat, causing a significant activity of radon and radon progenies on the skin. This finding may be important from a clinical point of view, since specialists experienced in radon therapy have repeatedly emphasized the importance of the degree of radioactivity on the skin for the effectiveness of treatment. It has even been claimed that the skin is the major target for radon therapy, possibly because of the influence on Langerhans' cell function.

Fever↗

Time-of-day effect on nonthermal control of sweating response to maintained static exercise in humans.

To investigate the influence of nonthermal factors in the time-of-day effect on the sweating response to maintained static exercise, eight healthy male subjects performed handgrip exercise at 20%, 35% and 50% maximal voluntary contraction (MVC) for 60 s at 0600 hours (morning) and at 1800 hours (evening). Oesophageal temperature ( T(oes)) before the experiment showed a diurnal rhythm [mean (SEM)] [36.3 (0.1) (morning) compared to 36.8 (0.1) degrees C (evening), P<0.01]. Experiments were conducted with subjects in a state of mild hyperthermia during which the mean skin temperature ( T(sk)) was kept constant at 35.5-36.5 degrees C using a water-perfused suit to activate sudomotor responses. The T(oes) and mean T(sk)remained stable during the pre-exercise, handgrip exercise and recovery periods. The response in sweating rate (DeltaSR) on the chest and forearm to handgrip exercise increased significantly with increasing exercise intensity in both the morning and evening tests ( P<0.05). The DeltaSR on the palm did not change significantly with increasing exercise intensity in the morning test ( P>0.1). During handgrip exercise at 50% MVC only, DeltaSR on the chest, forearm and palm in the evening was significantly higher than in the morning ( P<0.05). On the other hand, mean arterial blood pressure and the rating of perceived exertion during 50% MVC handgrip exercise were not significantly different between the morning and evening ( P>0.1). These results indicate the presence of a time-of-day effect on nonthermal control of the sweating response to isometric handgrip exercise, and that this effect is dependent on exercise intensity.

Adult↗

Modification of internal temperature regulation for cutaneous vasodilation and sweating by bright light exposure at night.

Bright light (BL) exposure at night leads to suppressed secretion of melatonin and an attenuated fall in internal temperature at rest from the night to the early morning. However, it is unknown at the present whether typical diurnal variations in reflex responses to thermal challenges are similarly affected by BL exposure at night. We investigated the control of cutaneous vasodilator and sweating responses to hyperthermia in the early morning after artificial BL exposure at night, compare with dim light (DL) exposure. Six subjects stayed awake in a semi-supine position under DL (120 lx) or BL (2800 lx) conditions between 21.00 and 04.30 h. Urine samples were collected at 04.30 h. Beginning at 05.30 h, the lower legs were immersed for 50 min in 42 degrees C water. The subjects remained awake for 21 h until the end of hot water immersion. Urinary 6-sulphatoxymelatonin levels following BL were significantly lower than after DL. Oesophageal temperature (T es) before heating was significantly higher following BL [36.41+/-0.10 (DL) vs. 36.55+/-0.09 (BL) degrees C]. The T es thresholds for the onset of cutaneous vasodilation and sweating were significantly higher with BL than with DL conditions (approximately 0.15 degrees C, respectively). We found that the internal temperature threshold for thermoregulatory control of cutaneous vasodilation and sweating responses to passive heating in the early morning can be modified by the level of light exposure the prior night. Thus both basal internal temperature and the regulation of internal temperature are modified by BL exposure at night.

Adult↗

Functional interaction of CFTR and ENaC in sweat glands.

The cystic fibrosis transmembrane conductance regulator (CFTR) plays a significant role in transepithelial salt absorption as well as secretion by a number of epithelial tissues including sweat glands, airways and intestine. Early studies suggested that in absorption significant cross talk occurs between CFTR Cl(-) channels and epithelial Na(+) channels (ENaC). Studies based primarily on cultured cells of the airways and on ex vivo expression systems suggested that activating CFTR inhibits ENaC channels so that activation of CFTR and deactivation of ENaC seem reciprocal. Lack of CFTR Cl(-) conductance (g(CFTR)) in the plasma membranes was seen to enhance ENaC conductance (g(ENaC)) and Na(+) absorption from the airway surface liquid causing airway pathology in cystic fibrosis (CF). To determine if these events hold true for a purely absorptive epithelium, we investigated the role of CFTR in regulating g(ENaC) in native human sweat gland ducts. After permeabilizing the basilateral membrane of the duct with alpha-toxin, the relative activities of ENaC and CFTR in the apical membrane were characterized by correlating the effect of activating CFTR with ENaC function. We found that in contrast to reciprocal activities, activating g(CFTR) by either cAMP, cGMP or the G-proteins plus 5 mM ATP was accompanied by a concomitant activation, not inhibition, of g(ENaC). The activation of g(ENaC) appeared to be critically dependent on CFTR Cl(-) channel function because removal of Cl(-) from the medium, blockage of CFTR with inhibitor DIDS or the absence of CFTR in the DeltaF508 CF ducts prevented activation of g(ENaC) by cAMP, GMP or G-proteins. Most significantly, g(ENaC) was dramatically reduced, not increased, in CF as compared to non-CF sweat ducts. These results showed that lack of CFTR in the plasma membranes is not characteristically coupled to elevated ENaC activity or to increased Na(+) absorption in CF epithelial cells. Not only are CFTR and ENaC activated together in duct salt absorption, but ENaC activation depends on functioning CFTR. NaCl is poorly absorbed in the CF duct because CFTR activity appears to impose a loss of ENaC activity as well.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

Circadian changes in the sweating-to-vasoconstriction interthreshold range.

Thermoregulatory defenses are characterized by thresholds, the core temperatures triggering each response. Core body temperature is normally maintained within the interthreshold range, temperatures between the sweating and vasoconstriction thresholds that do not trigger autonomic defenses. This range usually spans only some 0.2 degrees C, but it remains unknown whether similar precision is maintained during the circadian core temperature cycle of about 0.8 degrees C. Accordingly, we evaluated the interthreshold range at four times of the day. We studied ten male volunteers, each at 3 a.m., 8 a.m., 3 p.m., and 8 p.m. At least 12 h elapsed between tests, and the order was randomly assigned. At each study time, volunteers were warmed peripherally until sweating was observed. Skin temperature was subsequently kept constant while core temperature was decreased by central-venous infusion of ice-cold fluid until peripheral vasoconstriction was detected. The volunteers were not permitted to sleep during threshold determinations, although sleep was not otherwise controlled. The core temperature triggering an evaporative water loss of 40 g.m-2.h-1 identified the sweating threshold. Similarly, the vasoconstriction threshold was defined by the core temperature triggering the initial decreases in plethysmographic finger tip blood flow. The interthreshold range at 3 a.m. was twice that observed at the other study times (P<0.05). Our data suggest that autonomic control of body temperature is reduced at 3 a.m., even when sleep is denied. This result contradicts the general perception that circadian variation alters the thermoregulatory target temperature, but not precision of body temperature control.

Adult↗

Sympathetic co-activation of skin blood vessels and sweat glands.

Skin blood vessels and sweat glands are both innervated by sympathetic C fibers. We investigated whether during diverse respiratory maneuvers the vasomotor responses (VRs) and the sympathetic skin responses (SSRs) were frequently or occasionally co-activated. We simultaneously recorded the amplitude of the vasomotor responses and the sympathetic skin responses, the ECG and the respiratory movements in 30 healthy subjects during natural breathing at rest, rhythmic respirations at 6 per minute, sudden deep inspiration and Valsalva maneuver. We found: 1) The SSR habituates with all respiratory maneuvers whereas the VRs do not habituate. 2) There was slight co-activation between the SSRs and VRs during natural default breathing (56 percent). 3) During rhythmic breathing at 6 per minute the VRs and the SSRs were frequently co-activated (97 percent). The SSR appeared at the end of the inspiration coinciding with the end of the decreased blood flow. However the SSR habituated after few rhythmic respirations. 4) During sudden deep inspiration one hundred percent of co-activations were between the initial phase of the VRs and the SSR. The SSR is large in amplitude and longer in duration than during rhythmic breathing. 5) During the Valsalva maneuver there was a strong co-activation (100 percent) particularly during the phases II and III that are characterized by vaso-constriction but also during phase IV. The SSR is the longest of duration in all of the maneuvers. The sympathetic innervation to the sweat glands of the palm of the hand and to the skin blood vessels of the fingertips is differentiated. Under normothermic conditions sudden deep inspiration and Valsalva maneuver induced a large sympathetic simultaneous outflow to the skin blood vessels and sweat glands. The simultaneous recording of skin blood flow and the SSRs provides a more complete assessment of the sympathetic outflow to the skin than either one alone.

Adolescent↗

Sweat testing for cystic fibrosis: characteristics of a combination chloride ion-selective electrode.

Filling solution leakage, reproducibility, stability, interferences and temperature effects have been studied in relation to the use of the Orion 96-17-01 combination chloride ion-selective electrode in sweat testing for cystic fibrosis. While stability and reproducibility is good, certain antiseptic systems and especially Hibitaine (chlorhexidine gluconate) interfere with the electrode and therefore need to be absent during sweat testing. Temperature conditions during calibration and sweat testing need to be controlled in view of the extent of response variations for even modest temperature differences between sensor-skin interface and electrode stem.

Chemistry, Clinical↗

Enzymatic determination of sodium and chloride in sweat.

OBJECTIVE: To develop methods based on enzyme activation for the analysis of sweat sodium and chloride using beta-galactosidase and alpha-amylase, respectively. METHODS: Both were monitored kinetically on the Cobas Fara centrifugal analyzer. The sweat, collected with the Macroduct system, was diluted no more than five-fold for the volumes obtained of 16 to 80 mu L, median 32.5 mu L. The sodium assay utilized a sodium-binding cryptand to maximize linearity. RESULTS: Between-run coefficients of variation (%) at 10, 20, and 50 mmol/L were 3.6, 4.5, and 1.3 for sodium and 7.1, 6.1, and 6.0 for chloride, respectively. The sodium method showed excellent agreement with flame photometry (y = 0.997x + 0.742; r = 0.998), and chloride with a mercuric thiocyanate method (y = 0.995x + 0.485; r = 0.996), giving equivalent discrimination between patients with and without cystic fibrosis. CONCLUSIONS: The methods enable the rapid analysis on the same analyzer of both sodium and chloride in a single dilution of sweat collections of low volume.

Bridged Bicyclo Compounds, Heterocyclic↗

Comparative studies of the effect of thermal stimulation on the permeability of the luminal cell junctions of the sweat gland to lanthanum.

Lanthanum injected intradermally in vivo into the skin of cattle, sheep, goats and ponies penetrated the intercellular spaces of the sweat glands. It was not, however, detected in the glandular lumen either visually or by electron probe microanalysis even at elevated ambient temperatures when the animals were sweating. It is concluded that the luminal intercellular connections between epithelial cells in these glands are tight junctions, which remain so during sweating despite the occurrence of cell death and extrusion into the lumen.

Animals↗