Cystic fibrosis, vasoactive intestinal polypeptide, and active cutaneous vasodilation.

The transmitter substance for the active cutaneous vasodilation that accompanies sweating during hyperthermia in humans is unknown. H?kfelt et al. (Nature Lond. 284: 515-521, 180) hypothesized that it is vasoactive intestinal polypeptide (VIP) that is cotransmitted with acetylcholine. Heinz-Erian et al. (Science Wash. DC 229: 1407-1408, 1985) reported that VIP innervation is sparse in the skin of persons with cystic fibrosis (CF). A corresponding attenuation of active vasodilation in these subjects would be evidence that VIP is involved in this effector mechanism of human thermor-regulation. Immunocytochemical analysis of skin biopsies from four men with CF confirmed that VIP innervation was sparse. We also analyzed immunoreactivity for calcitonin gene-related peptide (CGRP; normal), substance P (normal), and neuropeptide Y (low). VIP-immunoreactive Merkel cells were abnormal. Despite sparse VIP-immunoreactive innervation, our CF subjects' cutaneous vascular responses to hyperthermia were normal. Because VIP was not completely absent, this evidence is insufficient to rule out VIP as the vasodilator transmitter. However, the CGRP and substance P innervation we observed could mean that release of one or both of these peptides was the mechanism of the fully developed active cutaneous vasodilation.     

Gross Cystic Disease Fluid Protein 15 in Stratum Corneum Is a Potential Marker of Decreased Eccrine Sweating for Atopic Dermatitis

It is well known that eccrine sweating is attenuated in patients with atopic dermatitis (AD). We have reported by using proteome analysis that gross cystic disease fluid protein 15 (GCDFP15), a substance secreted from eccrine sweat glands, is decreased in tape-stripped stratum corneum (SC) samples from AD patients. The aim of this study was to evaluate GCDFP15 production by eccrine glands with SC samples and to assess sweating in AD. SC samples were obtained from 51 healthy control (HC) and 51 AD individuals. Sweat samples were from 18 HC and 12 AD subjects. GCDFP15 was quantified by ELISA. By immunohistochemistry, the expression of GCDFP15 in eccrine glands was examined in normal and AD skin specimens. To identify GCDFP15-producing cells, double immunofluorescence staining for GCDFP15 and S100 protein was performed in frozen sections. To address the mechanism underlying the decreased eccrine sweating in AD patients, we examined the expression of cholinergic receptor M3 (CHRM3), a receptor for acetylcholine-induced sweating, in eccrine sweat glands. The amounts of GCDFP15 in the SC extracts were significantly lower in AD than HC (P < 0.0001). The sweat samples from AD patients also had lower levels of GCDFP15 concentration (P < 0.05). Immunohistochemistry showed positive GCDFP15 staining in the eccrine gland secretory cells and the ductal and acrosyringial lumen in normal skin, but AD lacked clear staining. Immunofluorescence staining revealed that GCDFP15 was co-expressed with S100 protein, suggesting that the clear cell of eccrine glands produces GCDFP15. Finally, we found that the expression of CHRM3 was depressed in AD, suggesting contribution to the low sweating. The SC of AD patients contains a low amount of GCDFP15 due to both low sweating and low GCDFP15 concentration in the sweat. GCDFP15 in SC is a potential marker for dysregulated sweating in AD.     

Core threshold temperatures for sweating

To detect shifts in the threshold core temperature (Tc) for sweating caused by particular nonthermal stresses, it is necessary to stabilize or standardize all other environmental and physiological variables which cause such shifts. It is, however, difficult to cause progressive changes in Tc without also causing changes in skin temperature (Tsk). This study compares the technique of body warming by immersion in water at 40 degrees C, and subsequent body cooling in water at 28 degrees C, to determine the core threshold for sweating, with one by which Tc was raised by cycling exercise in air at 20 degrees C, and then lowered by immersion in water at 28 degrees C. The first of these procedures involved considerable shifts in Tsk upon immersion in water at 40 degrees C, and again upon transfer to water at 28 degrees C; the second procedure caused only small changes in Tsk. The onset of sweating at a lower esophageal temperature (Tes) during immersion in water at 40 degrees C (36.9 +/- 0.1 degrees C) than during exercise (37.4 +/- 0.3 degree C) is attributed to the high Tsk since Tes was then unchanged. Likewise, the rapid decline in the sweat rate during immersion at 28 degrees C had the same time course to extinction after the pretreatments. This related more to the Tsk, which was common, than to the levels or rates of change of Tes, which both differed between techniques. Tes fell most rapidly, and thus sweating was extinguished at a lower Tes, following 40 degrees C immersion than following exercise.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hot Flashes and Fatigue Relieved by Metformin

ObjectiveTo describe 3 patients with long-standing hot flashes, excessive sweating, and fatigue whose symptoms were ameliorated with metformin.MethodsIn this case series, we report the findings of laboratory evaluations, including assessments for thyroid, gonadal, adrenal, and pancreatic disorders, in 3 patients referred for endocrine evaluation. A 75-g oral glucose tolerance test with measurement of fasting and postprandial glucose and insulin concentrations was conducted. A trial of metformin, 500 mg twice daily, was initiated in all patients.ResultsEvaluation of factors that are associated with hot flashes and increased sweating did not establish the cause of the patients’ symptoms. The 3 patients had normal glucose tolerance test results and hyperinsulinemia. Metformin therapy markedly relieved the symptoms in all patients.ConclusionsHyperinsulinemia without hypoglycemia may produce a sympathoexcitatory response that manifests as hot flashes and increased sweating. Metformin may have sympathoinhibitory actions that alleviate these symptoms. (Endocr Pract. 2009;15:30-34)     

昆虫神经毒素的研究:各种神经毒剂引起毒素的产生

用五类(七种)神经毒性的杀虫药剂,对美洲(虫非)蠊测定了它们能否引起血淋巴中毒素的产生。DDT、溴氰菊酯及六六六均能引起血淋巴中毒素的产生,而E605、西维因、巴丹及杀虫脒均无此效果。纸层析及薄层层析,用标准样品(酪氨酸、酪胺、苯乙胺、L-亮氨酸及异戊胺)作比较,测定了这一产生的血淋巴中的毒素乃是酪胺,或主要是酪胺。增效试验,证明了杀虫脒与DDT或溴氰菊酯合用时,能增加酪胺的产量。讨论了这一毒素产生的条件,以及这一毒素有可能不是单一成分,而是几种单胺及氨基酸的复合物,但酪胺为其主要成分。     

Sweating in the Japanese macaque (Macaca fuscata)

The sweating rates on the palms and chests of three adult male Japanese macaques were measured by the CaCl₂ method at temperatures of 20–40°C. Rectal and skin temperatures on the palms and chests were also measured by means of copper-constantan thermocouples every minute. As ambient temperature was raised from 20°C to 40°C over a one-hour period, the sweating rates on the palms gradually increased and reached a certain plateau level in 30 to 40 minutes, but the sweating rates on the chests, on the other hand, were very low. A good correlation existed between the skin temperatures and the sweating rates on the palms as well as the skin temperatures and the sweating rates on the chests.     

Lateralizing Sensorimotor Deficits in a Case of Pseudopheochromocytoma

Pseudopheochromocytoma is a poorly understood, rare cause of severe paroxysmal hypertension that mimics the symptomatology of pheochromocytoma in the absence of biochemical evidence of this tumor. Symptoms such as headache, nausea, sweating, and palpitations during hypertensive episodes have been described. In this paper, we describe previously unreported findings of lateralizing sensorimotor deficits in a patient with pseudopheochromocytoma. These changes presented during a hypertensive episode and were concerning for stroke but were not accompanied by acute radiologic abnormalities. The deficits improved over 1.5 weeks as blood pressure stabilized with beta-blockade. We also review relevant literature on the clinical features, pathophysiology, and management of pseudopheochromocytoma.     

Pheochromocytoma - chromaffin cell tumor

Pheochromocytoma is a rare tumor derived from chromaffin cells, which produces catecholamins. The presence of this tumor is considered a cause of secondary hypertension, arrhythmias, sweating and also, but very rarely, mental disorders. Update diagnostic methods of pheochromocytoma are summarized in this article. Pheochromocytoma also coexists with endocrinological syndroms, e.g. multiple endocrine neoplasia type 2 (MEN 2). Studies confirm genetic background of pheochromocytoma occurrence.     

Impetigo herpetiformis occurring during N-butyl-scopolammonium bromide therapy in pregnancy: case report

Impetigo herpetiformis (IH) is a rare dermatosis arising during the third trimester of pregnancy which is generally considered as a form of pustular psoriasis of unknown aetiology. Clinically it is characterized by erythematous plaques surrounded by sterile pustules associated with fever, diarrhea, sweating and increasing risk of stillbirth for placental insufficiency. We describe a case of developed erythematous plaques surrounded by pustules localised initially to the trunk of a 35-year-old woman at the 34th week of gestation after 5 days of treatment with N-Butyl-Scopolammonium, and which later involved the upper and lower limbs. Skin histology confirmed the diagnosis of generalised pregnancy pustular psoriasis (impetigo herpetiformis). IH is reported to be associated with hypocalcemia, hypoparathyroidism, use of oral contraceptives and bacterial infections. This is the first report suggesting the potential role of drugs other than oral contraceptives in the pathogenetic mechanism of this disease. In this case an adverse cutaneous reaction to BB could be the cause of the development of Koebner isomorphism.     

Clinical and genetic aspects of phaeochromocytoma

Phaeochromocytoma is a tumour of the adrenal medulla, which, although rare, is a major cause of correctable hypertension with a prevalence of 0.1-0.5% in the hypertensive population. Clinical symptoms include attacks of paroxysmal headache, sweating, palpitations, stress and a sense of imminent death. Often associated with the above is an increase in blood pressure. Despite the fact that the underlying genetic mechanisms of phaeochromocytoma have been well investigated, they are still incompletely understood. In approximately 80% of cases the tumour occurs sporadically, but it may occur in association with type 2 multiple endocrine neoplasia, type 1 neurofibromatosis or von Hippel-Lindau disease. Molecular evidence suggests that other genes such as SDHD or SDHB may control its development; the possibility of other putative phaeochromocytoma genes is currently being investigated.     

Neutral endopeptidase and neurogenic inflammation in rats with respiratory infections

Neuropeptides such as substance P are implicated in inflammation mediated by sensory nerves (neurogenic inflammation), but the roles in disease of these peptides and the peptidases that degrade them are not understood. It is well established that inflammation is a prominent feature of several airway diseases, including viral infections, asthma, bronchitis, and cystic fibrosis. These diseases are characterized by cough, airway edema, and abnormal secretory and bronchoconstrictor responses, all of which can be elicited by substance P. The effects of substance P and other peptides that may be involved in inflammation are decreased by endogenous neutral endopeptidase (NEP; also called enkephalinase, EC 3.4.24.11), which is a peptidase that degrades substance P and other peptides. In the present study, we report that rats with histories of infections caused by common respiratory tract pathogens (parainfluenza virus type 1, rat corona-virus, and Mycoplasma pulmonis) not only have greater susceptibility to neurogenic inflammatory responses than do pathogen-free rats but also have a lower activity of NEP in the trachea. This reduction in NEP activity may cause the increased susceptibility to neurogenic inflammation by allowing higher concentrations of substance P to reach tachykinin receptors in the trachea. Thus decreased NEP activity may exacerbate some of the pathological responses in animals with respiratory tract infections.     

Release of calcitonin gene-related peptide from rat enteric nerves is Ca2+-dependent but is not induced by K+ depolarization

The effect of extracellular calcium on the release of calcitonin gene-related peptide (CGRP) induced by electrical field stimulation from enteric nerves of isolated rat ileum was studied; the effect of high potassium, veratridine and caffeine was also examined. Release of endogenous substance P from enteric nerves was also measured for comparison. Electrical field stimulation (10 Hz, 0.3 ms for 2 min) of the ileum preparation caused a significant (P less than 0.001) increase in the release of CGRP and substance P from enteric nerves. The evoked, but not the basal, release of both CGRP and substance P was inhibited in the presence of tetrodotoxin (TTX). The release of CGRP and substance P induced by electrical stimulation was abolished in Ca2+-free medium containing CDTA and also in normal medium containing the calcium channel blocker cadmium chloride (CdCl2), with no change in the level of the basal release of both peptides. However, potassium depolarization (76 and 110 mM) failed to evoke an increase in the release of endogenous CGRP, although it did cause an increase in the release can be induced by mobilization of calcium from intracellular Ca2+ stores. Veratridine, on the other hand, did not cause an increase in CGRP release, although substance P and VIP release was induced by veratridine from the same preparations. The results of the present study have demonstrated that CGRP release from enteric nerves requires the presence of extracellular calcium but, unlike substance P and most other transmitters reported to show calcium-dependent release, potassium depolarization does not induce CGRP release from enteric nerves of rat ileum.(ABSTRACT TRUNCATED AT 250 WORDS)     

Sweating responses and the muscle metaboreflex under mildly hyperthermic conditions in sprinters and distance runners

To investigate the effects of different training methods on nonthermal sweating during activation of the muscle metaboreflex, we compared sweating responses during postexercise muscle occlusion in endurance runners, sprinters, and untrained men under mild hyperthermia (ambient temperature, 35°C; relative humidity, 50%). Ten endurance runners, nine sprinters, and ten untrained men (maximal oxygen uptakes: 57.5 ± 1.5, 49.3 ± 1.5, and 36.6 ± 1.6 ml·kg(-1)·min(-1), respectively; P < 0.05) performed an isometric handgrip exercise at 40% maximal voluntary contraction for 2 min, and then a pressure of 280 mmHg was applied to the forearm to occlude blood circulation for 2 min. The Δ change in mean arterial blood pressure between the resting level and the occlusion was significantly higher in sprinters than in untrained men (32.2 ± 4.4 vs. 17.3 ± 2.6 mmHg, respectively; P < 0.05); however, no difference was observed between distance runners and untrained men. The Δ mean sweating rate (averaged value of the forehead, chest, forearm, and thigh) during the occlusion was significantly higher in distance runners than in sprinters and untrained men (0.38 ± 0.07, 0.19 ± 0.03, and 0.11 ± 0.04 mg·cm(-2)·min(-1), respectively; P < 0.05) and did not differ between sprinters and untrained men. Our results suggest that the specificity of training modalities influences the sweating response during activation of the muscle metaboreflex. In addition, these results imply that a greater activation of the muscle metaboreflex does not cause a greater sweating response in sprinters.     

Heat regulation during exercise with controlled cooling

During heavy sustained exercise, when sweating is usually needed to dissipate the extra metabolic heat, controlled cooling caused heat loss to match total heat production with little sweating. The total heat produced and metabolic rate were varied independently by having subjects walk uphill and down. Heat loss was measured directly with a suit calorimeter; other measurements included metabolic energy from respiratory gas exchange and body temperatures. Thermoregulatory sweating was minimized by adjusting cooling in the calorimeter suit. Heat loss rose to match total heat, not metabolic rate, and there was a slow rise in rectal temperature. In the absence of major thermoregulatory response rectal temperature correlated most closely with total heat; it also correlated with the relative oxygen cost of exercise. Heat flow or heat content appeared to be the controlled variable and body temperature rise a secondary event resulting from thermal transport lag.     

Eicosanoids mediate control of thermoregulatory sweating in the cicada,Tibicen dealbatus (Insecta: Homoptera)

Cicadas prevent body temperature from exceeding tolerable levels by a combination of behavioral responses and sweating. Sweating is activated when body temperature reaches a critical set-point temperature. We investigated control of sweating in the cicada, Tibicen dealbatus, by chemically manipulating biosynthesis of prostaglandins and other eicosanoids. Injecting prostaglandins in amounts equal to those that induce behavioral fever in scorpions and crustaceans resulted in only a small increase in set-point temperature. Blocking prostaglandin biosynthesis with cyclo-oxygenase inhibitors such as aspirin produced significant changes in set-point temperature, confirming that prostaglandins are involved in control of sweating. However, the effect of cyclo-oxygenase inhibitors was not the opposite of the effect of prostaglandins. Instead, the effect of cyclo-oxygenase inhibitors depended strongly on the value of setpoint temperature prior to treatment. Results of biochemical manipulations of other steps in eicosanoid biosynthetic pathways corroborated the results of cyclo-oxygenase inhibition and indicated that eicosanoids other than prostaglandins may be involved in control of body temperature in normothermic T. dealbatus. The effect of cyclo-oxygenase inhibitors on a given set-point temperature depended on the ambient temperature experienced by cicadas during the experiment. Surprisingly, cicadas exposed to ambient temperatures 40°C delayed activation of sweating until body temperature exceeded values normally recorded from T. dealbatus in the field. Control of body temperature in normothermic cicadas is thus complex, involving inputs from body temperature sensors, ambient temperature sensors, and at least two cyclo-oxygenase-dependent regulatory pathways.Abbreviations PUFA polyunsatured fatty acid(s) - T _a ambient temperature - T _b body temperature - T _set set-point of body temperature for activation of sweating     

Proposal of leukotoxin, 9,10-epoxy-12-octadecenoate, as a burn toxin

It is postulated that toxic substances (burn toxin) synthesized in burned skin are transferred into general circulation and cause multiple organ failure. We found a highly cytotoxic substance, leukotoxin, a linoleate epoxide, exists in burned skin. Leukotoxin, as the name indicates, was synthesized by leukocytes from linoleate as a substrate. The aim of this study is to evaluate the possibility of leukotoxin as a burn toxin. We studied plasma leukotoxin level of four patients with extensive burns (over 50% of body surface area) and examined coagulation studies in these patients. We detected considerable amounts of leukotoxin (11.4 nmol/ml-37.0 nmol/ml) in all patients. Leukotoxin was not detected in the control subjects. Pulmonary edema, cardiac failure, and coagulation abnormalities were found in these patients. Exogeneously administered leukotoxin induced similar pathological conditions in experimental animals to those observed in patients with extensive burns. Hence, it is concluded that leukotoxin is a responsible substance as a burn toxin.     

Primate models to study eccrine sweating

The histochemistry and histology of the eccrine sweat gland in the rhesus monkey (Macaca mulatta) are described. The histochemical distribution and localization of enzymes and substrates are very similar to those found in the human; innervation is cholinergic. Active eccrine glands on the general body surface average 136 glands/cm². Above the thermal neutral zone (TNZ), sweating is the major avenue for heat loss and the role of panting in dissipating heat is relatively insignificant. The intrahypothalamic administration of prostaglandin E₁ (PGE₁) suppresses sweating and leads to an increase in core temperature. A linear relation is found between local sweat rates on the general body surface and clamped hypothalamic temperature. Studies also provide direct support for the concept that brain temperature and skin temperature interact additively in the control of sweating in higher primates. The functional characteristics of eccrine sweating in the patas monkey (Erythocebus) are qualitatively similar to those in the rhesus monkey. The patas monkey maintains a relatively constant rectal temperature (37.6–38.4°C) when equilibrated to a wide range of ambient temperaures of 15–40°C. Eccrine sweating is the main effector system for heat dissipation above the TNZ. We emphasize here that evaporative heat loss that is due to sweating is related to both mean skin and mean body temperature and at 40°C is 40% higher than that recorded from the rhesus monkey. These results indicate that the patas monkey, because of its high sweating capacity and other similarities with the human eccrine system, is a most appropriate animal model for comparative studies of eccrine sweat gland function in primates in general.     

Individual variability in the peripheral and core interthreshold zones

The purpose of the study was to investigate the degree of subject variability in the peripheral and core temperature thresholds of the onset of shivering and sweating. Nine healthy young male subjects participated in three trials. In the first two trials, wearing only shorts, they were exposed to air temperatures of 5 degrees C and 40 degrees C until the onset of shivering and sweating, respectively. In the second experiment, subjects wore a water perfused suit that was perfused with 25 degrees C water at a rate of 600 cc/min. They exercised on an ergometer at 50% of their maximum work rate for 10-15 min. At the onset of sweating, the exercise was terminated, and they remained seated until the onset of shivering, as reflected in oxygen uptake. In the first two trials, rectal temperature (Tre) was stable, despite displacements in skin temperature (Tsk), whereas in the third trial, Tsk (measured at four sites) was almost constant (30-32 degrees C), and the thermoregulatory responses were initiated due to changes in Tre alone. The results of the first two trials established the peripheral interthreshold zone, whereas the results of the third trial established the core interthreshold zone. The results demonstrated individual variability in the peripheral and core interthreshold zones, a proportional correlation between both zones (r=0.87), and a relatively higher contribution of adiposity in both zones as compared with those of other non-thermal factors such as height, weight, body surface area, surface area-to mass ratio, and the maximum work load.     

Local sweating and cutaneous blood flow during exercise in hypobaric environments

The effect of acute hypobaric hypoxia on local sweating and cutaneous blood flow was studied in four men and four women (follicular phase of menstrual cycle), who exercised at 60% of their altitude-specific peak aerobic power for 35 min at barometric pressures (PB) of 770 Torr (sea level), 552 Torr (2,596 m), and 428 Torr (4,575 m) at an ambient temperature of 30 degrees C. We measured esophageal temperature (Tes), mean skin temperature (Tsk, 8 sites), and local sweating (ms) from dew-point sensors attached to the skin at the chest, arm, and thigh. Skin blood flow (SkBF) of the forearm was measured once each minute by venous occlusion plethysmography. There were no gender differences in the sensitivity (slope) or the threshold of either ms/Tes or SkBF/Tes at any altitude. No change in the Tes for sweating onset occurred with altitude. The mean slopes of the ms/Tes relationships for the three regional sites decreased with increasing altitude, although these differences were not significant between the two lower PBS. The slope of SkBF/Tes was reduced in five of the eight subjects at 428 Torr. Enhanced body cooling as a response to the higher evaporative capacity of the environment is suggested as a component of these peripheral changes occurring in hypobaric hypoxia.     

Importance of dynamics of sweating in men during exercise

Influence of dynamics of sweating on rectal temperature increase was tested in 3 groups of men performing cycle exercise with intensity of 65, 90 and 120 W, respectively, in 22 degrees C chamber temperature and 30% of relative air humidity. During exercise at 65 and 90 W the subjects wore suits while exercising with intensity of 120 W they wore only shorts. The dynamics of sweating was described by delay in onset of sweating and time constant of the reaction. Wearing caused significant increase in skin humidity and decreased evaporative rate of sweating. Sweat rate during steady state was related to the metabolic rate in naked (r = 0.89, p less than 0.002) as well as in wearing subjects (r = 0.93, p less than 0.01). Delay in onset of sweating was, in average, 5 min with a time constant of 7 min. Both factors showed a tendency to be shorter with increasing work intensity. Mean increase in rectal temperature was proportional to the intensity of exercise although the individual delta Tre correlated well with the dynamics of sweating in naked (r = 0.83, p less than 0.01) and wearing subjects (r = 0.84, p less than 0.01). Since delta Tre was smaller in subjects with shorter inertia time of sweating in response to beginning of exercise at the same intensity it is concluded that the dynamics of sweating can play an important role in limiting body temperature increase in working men.