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Caffeine demethylation monitoring using a transdermal sweat patch.

Caffeine and two metabolites (paraxanthine and theobromine) were quantitated by high-performance liquid chromatography (HPLC) using extracts from transdermal sweat patches that continuously collected and stored analytes lost through the skin. Following caffeine consumption, remarkably clean chromatograms were obtained with minimal sample preparation. Caffeine and paraxanthine accumulated in the patch at comparable rates, and theobromine accumulated more slowly. A major urinary metabolite, 1-methylxanthine, was notably absent in sweat-patch and plasma extracts, a finding which favors a renal source for this metabolite. A simple, noninvasive approximation of N-demethylation can be made by calculating the paraxanthine/ caffeine and theobromine/caffeine ratios in the patch extract. These ratios were significantly reduced in high-dose (600 mg) versus low-dose (200 mg) subjects, possibly reflecting a decreased clearance of caffeine. Because the sweat patches can be worn for several days, the technique gives a multiday historical record which reflects the fluctuating systemic concentration of caffeine and its hepatic metabolites and thus might be useful to noninvasively monitor compliance by caffeine-restricted patients or to assess drug-metabolizing status.

Caffeine↗

PubMed2001

Sweat testing of MDMA with the Drugwipe analytical device: a controlled study with two volunteers.

Rapid on-site tests for the analysis of drugs of abuse in unconventional specimens (e.g., sweat) have recently been developed. Two healthy volunteers familiar with the effects of methylenedioxymethamphetamine (MDMA) were given 100 mg of the drug as a single oral dose. MDMA and its main metabolite 4-hydroxy-3-methoxymethamphetamine (HMMA) were determined in plasma and urine by gas chromatography-mass spectrometry (GC-MS). MDMA was also investigated in sweat with the Drugwipe (an immunochemical strip test). Subjects' armpits were swabbed for 10 s at 0 time (predose) and at 2, 6, 8, 12, and 24 h after MDMA administration. MDMA consumption could be detected using Drugwipe at 2 h and for as long as 12 h after drug administration. However, in one of the volunteers, a faint color change appeared at 0 time, when plasma and urine tested negative for MDMA and did not disappear even 48 h later. Plasma concentrations of MDMA and HMMA measured by GC-MS peaked at 2-4 h, and values greater than 20 ng/mL for MDMA and of 40 ng/mL for HMMA were still detected at 24 h. Urine tested positive by GC-MS for MDMA and HMMA in the 48-h collection period. These findings preliminarily support sweat testing with Drugwipe for monitoring MDMA use.

Humans↗

PubMed1997

Sclerosing sweat duct carcinoma in the peri-anal skin: a case report.

We report a case of sclerosing sweat duct carcinoma, a rare tumor, occurring in the peri-anal skin, a rare position. The patient, a 41-year-old Japanese woman, was admitted to our hospital with recurrence of sclerosing sweat duct carcinoma in the peri-anal skin, which had been initially resected at a local hospital. She underwent abdomino-perineal resection. No lymph node metastases or distant metastases were found. Although we allowed a 2-cm resection margin around the tumor, microscopy showed that the tumor had extended to within 2 mm of this margin at several sites, indicating that sclerosing sweat duct carcinoma is locally aggressive. An ample resection margin should therefore be taken at initial surgery for this type of tumor. Moreover, surgical excision that is wider and deeper than primary excision is required when this tumor recurs.

Adult↗

PubMed1995

Sebaceous epithelioma with sweat gland differentiation.

We examined a neoplasm of > 10 years' duration on the head of a woman. Light microscopically, the neoplasm was composed of multiple epithelial lobules in the dermis. The islands were mainly made up of basaloid cells and sebaceous cells; the latter cells were focally grouped in the lobules. Neither a palisade arrangement of peripheral cells nor the formation of peritumoral clefts were seen. Ductal spaces were scattered in the lobules and their luminal surfaces showed keratinization. Furthermore, in the peripheral parts of some lobules, there were sweat-gland-like structures. Immunohistochemically, most of the lobules were shown to have stratified squamous epithelium-type keratins, while the sweat-gland-like structures were shown to have simple epithelium-type keratins and stained positive for carcinoembryonic antigen. Ultrastructurally, many cells had lipid formation in their cytoplasm, and some cells formed luminal walls keratinizing without microvilli and keratohyaline granules. Although most of this neoplasm showed sebaceous differentiation, it partially differentiated to secretory cells of sweat gland apparatus.

Adenocarcinoma, Sebaceous↗

PubMed1998

Syringomatous changes of eccrine sweat ducts associated with prurigo nodularis.

Alteration of the eccrine sweat ducts has been observed in association with an expanding list of conditions. To our knowledge, this phenomenon has not been described in association with prurigo nodularis. We report on a 68-year-old man with a fibrotic nodule on his chin that had been present for 8 months. Microscopic examination showed marked hyperkeratosis overlying the epithelium. There was also hypergranulosis, marked acanthosis, and irregular elongation of the rete ridges. These findings were consistent with prurigo nodularis. In addition, within the reticular dermis, there was marked fibrosis and a proliferation of eccrine sweat ducts. The ducts were enlarged and varied from cystic to rarely solid structures. Rare ducts formed a tadpole-shaped tail, reminiscent of syringoma. The duct lining demonstrated a multilayered epithelium that was three to eight cells thick, yielding a solid component to some of the cysts. Although some of these features were similar to those of a syringoma, the typical small gland proliferation and bilayered lining was not evident. This case (a) demonstrates the association of syringomatous changes of eccrine sweat ducts with yet another condition, prurigo nodularis, and (b) emphasizes the importance of differentiating this benign reactive process from the malignant neoplasms microcystic adnexal carcinoma and squamous cell carcinoma.

Aged↗

PubMed1994

Rate and gender dependence of the sweating, vasoconstriction, and shivering thresholds in humans.

BACKGROUND: The range of core temperatures not triggering thermoregulatory responses ("interthreshold range") remains to be determined in humans. Although the rates at which perioperative core temperatures vary typically range from 0.5 to 2 degrees C/h, the thermoregulatory contribution of different core cooling rates also remains unknown. In addition, sweating in women is triggered at a slightly greater core temperature than in men. However, it is unknown whether the vasoconstriction and shivering thresholds are comparably greater in women, or if women tolerate a larger range of core temperatures without triggering thermoregulatory responses. Accordingly, the authors sought to (1) define the interthreshold range; (2) test the hypothesis that, at a constant skin temperature, the vasoconstriction and shivering thresholds are greater during rapid core cooling than during slowly induced hypothermia; and (3) compare the sweating, vasoconstriction, and shivering thresholds in men and women. METHODS: Eight men and eight women participated. The men participated on 2 separate days; no anesthesia or sedatives were administered. On each day, they were cutaneously warmed until sweating was induced and then were cooled by a central venous infusion of cold fluid. The cooling rates were 0.7 +/- 0.1 degrees C/h on 1 day and 1.7 +/- 0.4 degrees C/h on the other, randomly ordered. Skin temperature was maintained near 36.7 degrees C throughout each trial. The women were studied only once, in the follicular phase of their menstrual cycles, at the greater cooling rate. RESULTS: The interthreshold range was approximately 0.2 degrees C in both men and women, but all thermoregulatory response thresholds were approximately 0.3 degrees C higher in women. All thresholds were virtually identical during slow and fast core cooling. CONCLUSIONS: Our findings confirm the existence of an interthreshold range and document that its magnitude is small. They also demonstrate that the interthreshold range does not differ in men and women, but that women thermoregulate at a significantly higher temperature than do men. Typical clinical rates of core cooling do not alter thermoregulatory responses.

Adult↗

PubMed1984

Electrophoretic patterns of proteins in cystic fibrosis sweat.

The abnormal gene product in cystic fibrosis has not been identified. We report that two-dimensional polyacrylamide gel electrophoresis of 125I-labeled sweat proteins coupled with fluorography and rare earth screen radioautography reveals an absence of an acidic protein of molecular weight 60,000 in sweat collected from 9 patients with cystic fibrosis. The protein spot was present in sweat from heterozygotes and from controls.

Child↗

PubMed1996

Glycoproteins of the carcinoembryonic antigen (CEA) family are expressed in sweat and sebaceous glands of human fetal and adult skin.

The carcinoembryonic antigen (CEA) family comprises a group of glycoproteins including the classical CEA, nonspecific cross-reacting antigens (NCA), and biliary glycoprotein (BGP). CEA glycoproteins have been identified in many glandular and mucosal tissues. In view of their putative role in cell adhesion, protein sorting, and signal transduction, CEA glycoproteins are thought to be involved in embryogenesis, architectual integrity, and secretory mechanisms of glandular epithelia. Since there are few data available on the expression of CEA-like proteins in human skin, the aim of this study was to immunohistochemically specify and localize the CEA glycoproteins in cutaneous adult and fetal glands using a panel of well-characterized antibodies. The secretory parts of eccrine sweat glands expressed CEA, NCA-90, and BGP, whereas apocrine glands remained unreactive for CEA glycoproteins. The ductal epithelia of both eccrine and apocrine glands contained CEA and NCA-90. Sebaceous glands were stained for BGP only. Electron microscopy of sweat glands showed CEA glycoprotein expression in cytoplasmic organelles and on microvilli lining the ductal surface. In sebaceous glands, BGP were demonstrated in small vesicles and along the cell membranes of differentiating sebocytes. Fetal development of cutaneous glands was associated with early expression of CEA glycoproteins. Additionally, mice transgenic for human CEA were shown to express CEA in sweat glands. The overall distribution of CEA glycoproteins in cutaneous glands was consistent with that in epithelia of other glandular tissues.

Adult↗

PubMed1996

Nitric oxide is generated on the skin surface by reduction of sweat nitrate.

Nitric oxide (NO) is known to be synthesized by mammalian cells from L-arginine by a group of NO synthase enzymes. We now show that NO is generated from human skin and propose a different mechanism of production. Whereas enzymatic NO synthesis is inhibited by monomethyl L-arginine, this arginine analog, when infused into the brachial artery at concentrations sufficient to inhibit endothelial NO synthase activity, has little effect on hand skin NO production. Hand skin NO production is increased by topical acidification of the skin surface and greatly increased by the addition of nitrite solutions. We propose that NO generation from skin derives from sweat nitrite (the concentration of which was found to average 3.4 microM in six subjects) due to chemical reduction consequent to the acidic nature of sweat. Sweat contains nitrate in appreciable amounts, and skin commensal bacteria can synthesize nitrate reductase enzyme. Patients on long-term tetracycline antibiotics showed significantly reduced skin NO synthesis, although topical antiseptic and antibiotics had little effect on NO generation in the short-term. We propose that NO generation from skin is dependent on bacterial nitrate reduction to nitrite and subsequent reduction by acidification. We speculate that this has a physiologic role in the inhibition of infection by pathogenic fungi and other susceptible microorganisms and may affect cutaneous T-cell function, keratinocyte differentiation, and skin blood flow.

Administration, Topical↗

PubMed1992

Changes of expression of intermediate filament proteins during ontogenesis of eccrine sweat glands.

The intermediate filament expression in fetal and adult human eccrine sweat glands was studied by immunoperoxidase microscopy performed on cryostat sections using monoclonal antibodies against various cytokeratins (CK), vimentin, and actin. In palmar skin of 14-week-old fetuses, the early dermal cords showed a primitive CK pattern similar to that of epidermal basal cells. From week 15 on (distal finger skin), inner cells of the proximal (ductal) portion of the glandular anlagen expressed CK 1/10/11 and 19 (markers of adult eccrine ductal luminal cells). In addition, CK 4 was expressed in ductal luminal cells mainly in the fetal period. In the distal portion of the sweat gland anlagen the increased or new expression of the simple-epithelium-type CK 7, 8, 18, and 19 was detected at week 15, indicating the onset of the secretory differentiation pathway. Two subsegments of the prospective secretory portion could be distinguished (elongated part and end bud). Interestingly, in fetuses, most secretory portion cells co-expressed vimentin in addition to CK. From week 22 on, peripheral cells of the secretory portion were stained for CK 17 and smooth-muscle-type actin, suggesting myoepithelial differentiation. In newborn and adult eccrine glands, secretory cells expressed mainly CK 7, 8, 18, and 19, whereas myoepithelial cells were conspicuous by their co-expression of certain CK (including CK 5 and 17), vimentin, and smooth-muscle-type actin and sometimes even glial filament protein (GFP), similar to myoepithelial cells of other glands. These results throw further light onto the complex processes of fetal development of eccrine sweat glands and their cellular diversification. The possible biologic significance of the differential CK expression in the various glandular cell types is discussed.

Adult↗

PubMed2004

Ischaemia in working muscles potentiates the exercise-induced sweating response in man.

AIM: The purpose was to examine whether graded ischaemia in the working muscles affects the rate of sweating and the control of exercise core temperature. METHODS: Eight subjects performed cycle ergometry exercise in the supine position with (ischaemic exercise) and without (control exercise) restriction of blood flow in the contracting muscles, accomplished by exposure of the legs to a supra-atmospheric pressure of 6.6 kPa. Each subject performed one exhaustive incremental work rate trial and one steady-state exercise trial (at 33% of control peak work rate), in both the control and ischaemia conditions. RESULTS: Ischaemia decreased work performance by 45% so that in this condition the steady-state work rate level corresponded to 63% of ischaemic peak work rate. Ischaemia did not affect the oesophageal temperature equilibrium in the steady-state trials, but potentiated the exercise sweating response. Exercise responses of mean arterial pressure, heart rate and pulmonary ventilation were potentiated by ischaemia. CONCLUSION: During ischaemic exercise sweat secretion was potentiated by non-thermal and/or local thermal stimuli.

Adult↗

PubMed1985

Hyper-responsiveness of eccrine sweat glands to carbachol in anxiety neurosis: comparison of male and female patients.

The responsiveness of eccrine sweat glands to intradermally injected carbachol was studied in six male and six female healthy volunteers and six male and six female patients suffering from anxiety neurosis. Consistently greater responses to carbachol were obtained in the healthy males than in the healthy females. Analysis of the dose-response curves showed that this was reflected in a higher value of Emax in the males. Consistently greater responses to carbachol were obtained in the anxious males than in the healthy males, this being reflected in a higher value of Emax for the anxious subjects. Consistently greater responses to carbachol were obtained in the anxious females than in the healthy females, this being reflected in a higher value of Emax for the anxious subjects. In contrast to the results obtained with the healthy subjects, there was no sex-related difference in responsiveness to carbachol among the anxious patients. It is suggested that the hyper-responsiveness of sweat glands in anxiety states involves the sensitization of normally 'dormant' sweat glands by impulse flow in sudomotor sympathetic fibres. The upper limit to the value of Emax for carbachol, which may be determined by the number of potentially responsive glands, may be similar in the two sexes.

Adult↗

PubMed1980

Pharmacological responsiveness of the myoepithelium of the isolated human axillary apocrine sweat gland.

Human axillary apocrine glands are endowed with well developed myoepithelium, but its pharmacological responsiveness has remained unknown. The present study is part of our efforts in determining the role(s) played by exocrine myoepithelium in the overall secretory processes. Single human apocrine glands were isolated from biopsy skin specimens and were stimulated with various pharmacological agents in vitro. Tubular contraction was recorded photomicrographically and was interpreted as being due to myoepithelial contraction. The tubular contraction was induced by stimulation with phenylephrine (5 X 10(-6)M) or adrenaline (5 X 10(-6)M) but not with isoproterenol (5 X 10(-6)M) or acetylcholine (5 X 10(-6)M). A higher concentration of acetylcholine (10(-4)M) produced a minor degree of contraction. The phenylephrine-induced contraction was blocked by phentolamine (10(-5)M) or by EGTA (5 mM) but not by propranolol (10(-5)M) or by atropine (10(-5)M). It was concluded that the contractile response of the apocrine myoepithelium is selectively controlled by the alpha-adrenergic stimulation. The possibility is discussed that the major function of the apocrine myoepithelium is not just the pumping out of the preformed sweat but is, as in the eccrine sweat gland myoepithelium, the provision of structural support for the apocrine secretory epithelium to withstand the increase, if any, in the luminal hydrostatic pressure during apocrine sweat secretion.

Acetylcholine↗

PubMed1983

Anti-D47: a monoclonal antibody reacting with the secretory cells of human eccrine sweat glands.

Anti-D47 is a monoclonal antibody reacting with a surface antigen of human cortical thymocytes (different from the T6 antigen). It was prepared by immunization of mice with human thymocytes. The known cross-reactivity of monoclonal antibodies prepared against thymic cells with skin components prompted us to test anti-D47 on human skin as well as animal tissues. No labelling was observed on animal tissues. On human skin, anti-D47 was found to react with the secretory portion of eccrine sweat glands (ESG), i.e. with a cytoplasmic antigen of the secretory cells lining the deep portion of ESG glomeruli. No labelling was observed on apocrine sweat glands or on the excretory portion of ESG. Anti-D47 was also tested on histologically proven extramammary (vulvar) Paget's disease and basal cell epitheliomas: no staining of the neoplastic cells was observed. Anti-D47 appears to be an immunological marker of the secretory cells of human ESG and a new tool for the investigation of human sweat gland pathology.

Animals↗

PubMed1987

Cytochemical localization of VIP-stimulated adenylate cyclase activity in human sweat glands.

Vasoactive intestinal polypeptide (VIP)-stimulated adenylate cyclase was demonstrated cytochemically in human sweat glands. Biopsies containing axillary sweat glands were incubated with 5 micron VIP and adenylate cyclase was demonstrated using the cerium-salt technique. Reaction products were localized in the plasma membranes of glandular and myoepithelial cells. Thus, VIP appears to stimulate adenylate cyclase activity without acetylcholine. VIP and acetylcholine in human sweat glands most probably act through a receptor complex, where adenylate cyclase is coupled to that part of the receptor stimulated by VIP.

Adenylyl Cyclases↗

PubMed1990

Immunohistochemical identification of interleukin I alpha and beta in human eccrine sweat-gland apparatus.

Bouin-fixed paraffin sections or acetone-fixed cryostat sections were labelled with the avidin-biotin complex (ABC) or peroxidase-antiperoxidase (PAP) method using three monoclonal antibodies (MAbs) and two polyclonal antisera to human recombinant interleukin I beta (IL-I beta) and three polyclonal antisera to human recombinant interleukin I alpha (IL-I alpha). In the secretory coil both IL-alpha and beta were detected in the clear, but not in the dark cells. Both luminal and basal cells of the coiled and straight ducts expressed IL-I alpha and beta, the IL-I labelling being more intense in the luminal cells. IL-I was not usually detected in the initial portion of the intraepidermal eccrine sweat duct, whereas intense labelling was seen in the upper part including through the stratum corneum. In skin biopsies of the palm, taken after exercise, there was only faint IL-I labelling of the secretory cells, whereas the luminal cells of the dermal ducts showed intense labelling for both IL-I alpha and beta. In the acrosyringium, exercise did not alter the pattern for IL-I alpha and beta, except that in the palm, some of the antibodies to IL-I beta produced a more intense immunolabelling of the acrosyringeal cells. This study identifies a distinct and similar distribution of the two forms of IL-I throughout the eccrine sweat-gland apparatus and indicates that part of the IL-I epidermal pool originates from the sweat.

Exercise↗

PubMed1995

Sweat secretion, stratum corneum hydration, small nerve function and pruritus in patients with advanced chronic renal failure.

Sweat secretion, stratum corneum hydration and small nerve fibre function were measured in 40 patients with advanced chronic renal failure (CRF), using pilocarpine iontophoresis, electrical capacitance and a thermal sensory analyser which measures the thresholds of warm and heat pain sensation. Correlations were sought between these parameters, and the presence and severity of pruritus and skin xerosis were compared with 45 healthy control subjects. The mean sweat secretion and stratum corneum hydration of CRF patients were significantly lower than in controls. Thirteen patients had pathological thresholds to warm sensation on the foot, and eight on the hand. None had pathological thresholds to heat-pain. The presence of pruritus did not correlate with any of the following: xerosis, stratum corneum hydration, sweat secretion or the results of thermal testing.

Aged↗

PubMed1993

Levels of fluconazole in serum, stratum corneum, epidermis-dermis (without stratum corneum) and eccrine sweat.

The distribution in the skin of orally active antifungals and other drugs claimed to be active in the treatment of skin diseases is of major importance, but to date has been studied only rarely. In the present study the distribution of fluconazole in stratum corneum, epidermis-dermis (without stratum corneum), eccrine sweat and serum was studied in human male volunteers after dosages of 50 mg daily for 12 days and 150 mg once weekly for 2 weeks. In the present study high levels of fluconazole were found especially in the stratum corneum. At a dose of 50 mg once daily the concentration of fluconazole after 12 days was 73.0 micrograms/g and 7 days after cessation of treatment the concentration was still 5.8 micrograms/g. At the 150 mg once a week dose the concentration 7 days after the second dose was still 7.1 micrograms/g in stratum corneum indicating that medication once a week may be effective in the treatment of dermatomycoses. High concentrations, all above the serum concentrations, were also seen in sweat and epidermis/dermis. These results indicate that fluconazole is delivered to the stratum corneum, where it is accumulated, through sweat and by direct diffusion through the dermis-epidermis. These pharmacokinetic results indicate that the drug should be very effective in the treatment of dermatomycoses. An extremely high concentration of the drug in the stratum corneum combined with concentrations from 2.93 to 4.62 micrograms/g in the rest of the epidermis and dermis is important in the treatment of these diseases.

Adult↗