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PubMed2006

Generation of multiple stable dermcidin-derived antimicrobial peptides in sweat of different body sites.

Antimicrobial peptides (AMPs) are effector molecules of innate immunity. Dermcidin (DCD), a recently discovered AMP with broad-spectrum activity, is produced constitutively by the eccrine sweat glands and secreted into sweat. In this study, we investigated the proteolytic processing, site-specific expression, and stability of DCD peptides in eccrine sweat. Using surface-enhanced laser desorption ionization time-of-flight mass spectrometry (SELDI-TOF-MS) and reversed-phase high-pressure liquid chromatography analysis, we identified in eccrine sweat 14 proteolytically processed DCD peptides. Semiquantitative SELDI-TOF-MS analysis indicated that processing of DCD-1L is individually different, but generates a few dominant peptides. At body sites with a high probability for contact with pathogenic microorganisms, a high amount of antimicrobial active DCD peptides was detected in sweat. Furthermore, we show that the secretion rate of DCD is constant during a period of prolonged sweating and that DCD peptides are stable in sweat over several hours. Other known AMPs like the human cathelicidin LL-37 and alpha- or beta-defensins were not detected in significant quantity in eccrine sweat. Owing to the durable and abundant presence, DCD-derived peptides contribute to the first line of defense by building a constant barrier that overlies the epithelial skin.

Adult↗
PubMed2001

[From gene to disease; from defective chloride ion transport to cystic fibrosis].

Cystic fibrosis is an autosomal recessive disorder affecting the lungs, pancreas, intestines, sweat ducts and liver, due to an abnormal salt transport across the apical border of epithelial cells. Mutations in the CF underlying gene, the cystic fibrosis transmembrane conductance regulator (CFTR) gene, result in most cell types in an misprocessing so that little of the protein reaches the membranes. In case of clinical suspicion and/or doubtful sweat test results, mutation analysis can support the diagnosis of CF. Also carrier detection is offered.

Adult↗
PubMed1993

Disappearance of seasonal variation of sweating responses in exercising man: effect of pre-heating in cold season.

The present study was designed to investigate the seasonal variation in thermal responses during moderate exercise. In winter, exercise was done after pre-heating for 30 min at an ambient temperature of 30 degrees C. Adult healthy men repeated the exercise at 40% of maximal oxygen uptake by a bicycle ergometer in a climatic chamber of an ambient temperature of 30 degrees C (relative humidity, 45%) in winter, spring, summer, and fall. In summer, the sweat rate increased immediately after the exercise started, whereas in winter it took in several minutes. The average sweat rate during exercise was significantly different (p < 0.01) in winter and compared to the other seasons. Significantly (p < 0.01) negative correlations were found between sweat rate and the rate of change of the mean skin temperature in each season. The regression equation was significantly (p < 0.01) different between winter and summer. After the pre-heating in winter, the sweating responses during exercise were similar to the responses in the summer. Thus, by thermal stimuli, the heat dissipation, especially skin evaporation due to sweating, may be stimulated in the cold season. It is suggested that sweating may be facilitated by not only the heat dissipation capacity of the hypothalamic mechanism with the thermal information via skin thermoreceptors but also by a change of peripheral sweat gland activity. Furthermore, the fall in skin temperature during the initial exercise may not be due to increased evaporative cooling, but to the vasoconstriction probably caused by non-thermal factors.

Acclimatization↗
PubMed2001

Comparison of laboratory studies with predictions of the required sweat rate index (ISO 7933) for climates with moderate to high thermal radiation.

For International Standard ISO 7933 (Hot environments-analytical determination and interpretation of thermal stress using calculation of required sweat rate. International Organization for Standardization, Geneva, 1989) it has been questioned whether the heat stress index "required sweat rate" is applicable in environments where mean radiant temperature (t(r)) exceeds dry air temperature (t(a)). Based on a re-analysis of 556 climatic chamber experiments on 16 subjects the observed sweat rates were compared with required sweat rates predicted according to the ISO standard. Under climatic conditions with t(r) > t(a) the predictions overestimate the observed sweat rates on average by 86% in clothed subjects and by 25% in nude subjects. In climates with t(r) = t(a) the predictions highly agreed with the observed sweat rates in nude subjects and were slightly overestimated (13%) in clothed subjects. The misjudgement of the present ISO standard is obviously caused by an inappropriate calculation of radiative heat exchange. Corrections are proposed to improve the validity concerning climates with t(r) > t(a).

Adult↗
PubMed1985

A study of sweat sodium and chloride; criteria for the diagnosis of cystic fibrosis.

Retrospective analysis of sodium and chloride results from sweat tests carried out in Bristol and Sheffield has shown that misdiagnosis of cystic fibrosis (false negatives and false positives) is considerably less if sodium and chloride are both measured. In patients with cystic fibrosis the chloride concentration is usually higher than the sodium, whereas in normal subjects the reverse usually occurs. This observation is particularly useful when borderline results (50-70 mmol/L) are obtained.

Adolescent↗
PubMed1993

Neonatal screening for cystic fibrosis: addition of molecular diagnostics to increase specificity.

Newborn screening for cystic fibrosis (CF) has been carried out on approximately 106,000 neonates in western Pennsylvania since 1987 using the immunoreactive trypsinogen (IRT) assay on dried filter paper blood specimens (DBS). Molecular analysis utilizing a duplicate DBS from the same sample was implemented in November 1989 for newborns having elevated IRT levels. DNA is amplified directly from the DBS and the amplified products are tested for the delta F508 deletion and several common exon 11 mutations. Substituting dUTP for dTTP in the PCR reaction and an initial treatment with uracil N-glycosylase (UNG) virtually eliminates PCR carryover contamination. The number of confirmed cases of CF is 20, giving an estimated incidence of 1:5287 in the western Pennsylvania population. Eight of the CF patients are homozygous and 12 are compound heterozygotes for the delta F508 deletion and a second mutation. Two of the compound heterozygotes carry the G551D mutation and one has the R553X mutation. Twenty-one additional neonates that are heterozygous for the delta F508 mutation are normal carriers for CF. In approximately 55% of the cases, molecular analysis of the CF gene confirmed the diagnosis of CF prior to sweat testing. The incorporation of molecular analysis into our CF screening program increases the specificity of the screening strategy and has the potential to decrease the false positive and sweat test referral rate, reduce parental anxiety, and bring CF infants to the attention of physicians more rapidly.

Cystic Fibrosis↗
PubMed1969

Sweat in schizophrenic patients: identification of the odorous substance.

The substance causing the peculiar odor in sweat of schizophrenic patients has been isolated and identified as trans-3-methyl-2-hexenoic acid by gas chromatography, mass spectrometry, and nuclear magnetic resonance spectroscopy. The natural and the synthetic compounds were cleaves across the double bond to give 2-pentanone and oxalic acid, thereby confirming the structure.

Caproates↗
PubMed1991

Inherited factors in diffuse bronchiectasis in the adult: a prospective study.

To evaluate the prevalence of inherited respiratory ciliary structure and underlying mucus abnormalities in the diffuse bronchiectasis syndrome, we investigated 53 subjects comprising 38 patients with diffuse bronchiectasis confirmed by high-resolution thoracic computed tomography, ten with chronic bronchitis and no diffuse bronchiectasis and five healthy nonsmoking control subjects. The clinical history was determined by means of a standardized questionnaire. Axonemal abnormalities of respiratory cilia were evaluated on bronchial or nasal mucosa samples by transmission electron microscopy (structure) and stroboscopic observation (function). Cystic fibrosis (CF) and Young's syndrome were detected by means of the sweat test and semen analysis when male infertility was suspected. Among the 38 patients with diffuse bronchiectasis, a primary ciliary dyskinesia (PCD) was detected in five (13%) with a high proportion (range: 55-100%) of cilia showing axonemal ultrastructural abnormalities always involving the dynein arms. The prevalence of this inherited condition was higher in North African (36%) than in European patients (4%) (p less than 0.01). After exclusion of the five patients with PCD, the patients with diffuse bronchiectasis showed axonemal ultrastructural abnormalities similar to those with chronic bronchitis. The diagnosis of underlying mucus disorders was based on two types of criterion, i.e. for CF, sweat chloride levels greater than 80 mmol.l-1, or the combination of diagnostic criteria proposed by Stern et al. Respectively, five (three Young's syndrome and two CF) and seven (one Young's syndrome and six CF) cases of inherited mucus disorders were suspected. Our results showed that PCD was highly prevalent among the adult North African patients with diffuse bronchiectasis but relatively rare in the Europeans.

Adult↗
PubMedDate not supplied

Detecting cocaine use through sweat testing: multilevel modeling of sweat patch length-of-wear data.

Although urine analysis remains the standard for detection of drugs of abuse, sweat patches provide a convenient alternative that avoids some of the problems with drug testing such as violations of privacy in observed urination, possibility of disease transmission, and transport of noxious fluids. This study examined minimum length of wear necessary to detect recent or concurrent cocaine use in a convenience sample of active cocaine users and also differences in analyte concentrations with increasing longer-term wear. Twenty-seven subjects (22 active drug users and 5 comparison subjects who did not use drugs) wore short-term ((1/2)h, 1 h, 1(1/2) h, and 2 h), then long-term patches (1, 3, 7, and 14 day). Short- and long-term patches were identical except for duration of wear. The predominant analyte found was cocaine, followed by benzoylecgonine, then ecgonine methylester. The minimum duration that patches must be worn to detect recent or concurrent cocaine use in this sample is more than 2 h and less than or equal to 1 day. Analyte concentrations increase significantly with increasing lengths of wear. However, increases between the one-week and two-week patches were significant for benzoylecgonine only.

Adult↗
PubMed1995

Neuropeptides in the skin of patients with atopic dermatitis.

There is increasing evidence that neuropeptides may be involved in the pathogenesis of atopic dermatitis (AD). This study examines whether neuropeptide distribution in the skin of patients with AD differs from normal controls. The distribution and density of several neuropeptides were examined in lesional and non-lesional skin of AD patients (n = 5) and in normal controls (n = 4) using indirect immunofluorescence and image analysis. Cholinergic innervation was studied using cholinesterase histochemistry. Staining with the general neuronal marker protein gene product 9 x 5 showed a subepidermal network of nerves with fibres penetrating the epidermis, and nerves around blood vessels, sweat glands and hair follicles. Image analysis of nerves around sweat glands showed a significantly higher nerve density in non-lesional compared with both normal controls and lesional skin (P < 0.05); lesional compared with control skin showed no significant difference. In the epidermis the density of nerves was not significantly greater in non-lesional compared with lesional skin and controls. Calcitonin gene-related peptide immunoreactivity was similar in all subjects except in three of the AD patients, where more nerves appeared to penetrate the epidermis. Substance P immunoreactivity in the papillary dermis was seen in all AD patients but no controls. Vasoactive intestinal polypeptide and neuropeptide Y staining were similar in all groups. Acetylcholinesterase-positive nerves were found around sweat glands in all subjects, the staining being greatest in non-lesional and least in lesional skin. Occasional nerves were seen in the papillary dermis in lesional skin of two out of the four patients. We have demonstrated quantitative differences in nerve growth in clinically normal skin of AD patients, and altered cutaneous neuropeptide expression in these patients which may contribute to the pathogenesis of AD. The cause of atopic dermatitis (AD) has not been fully established but it is believed that there is a complex interaction between genetic susceptibility, precipitating environmental factors and disordered immune responsiveness. There is increasing evidence that neuropeptides may be involved in the pathogenesis of AD. Exacerbations of the disease can be provoked by stress, scratching and sweating which may be the result of neurogenic inflammation. One of the first features of an exacerbation is flushing of the affected skin and pruritus. Several neuropeptides that have been identified in human skin are potent inducers of vasodilation and may induce pruritus. Substance P (SP), calcitonin gene-related peptide (CGRP) and vasoactive intestinal polypeptide (VIP) all cause vasodilation when injected intradermally, and SP and CGRP have been shown to be mediators of the weal and flare reaction. Spantide, a competitive antagonist of SP, has been shown to inhibit immediate and delayed-type hypersensitivity reactions. Part of these responses may be due to release of histamine and indeed elevated concentrations of histamine have been found in vivo in the skin and plasma of patients with AD. In this study the distribution and density of several neuropeptides were examined in lesional and nonlesional skin of AD patients and in normal controls using indirect immunofluorescence and image analysis. Cholinergic innervation was studied using cholinesterase histochemistry. Because many afferent fibres do not express CGRP or SP, the general neuronal marker protein gene product (PGP 9 x 5) was used to assess the overall nerve supply to the skin.

Acetylcholinesterase↗
PubMed2006

Sympathetic sudomotor disturbance in early type 1 diabetes mellitus is linked to lipid peroxidation.

The present study was performed to determine whether increased lipid peroxidation, as assessed from malondialdehyde (MDA) excretion, is associated with deterioration in peripheral nerve function in early type 1 diabetes mellitus. These parameters were measured annually for 3 years in 36 patients who entered the study less than 2 years after the diagnosis of diabetes. Malondialdehyde excretion was 1.51 +/- 0.20 micromol/g creatinine in the controls, and 2.43 +/- 0.21, 2.39 +/- 0.22, and 1.93 +/- 0.21 micromol/g creatinine at the first, second, and third evaluations, respectively (P < .005). The increased MDA was seen only in the female participants. Malondialdehyde excretion was increased in those with high vs low hemoglobin Alc across all years (P < .05). Malondialdehyde excretion correlated negatively with sudomotor function below the waist. The mean sweat production from the 3 evaluations correlated with mean MDA excretion across all years in the proximal leg (r = -0.42, P < .005) and distal leg (r = -0.40, P < .01). Below the waist, sweating correlated with MDA (r = -0.40, P < .01) as did total sweat (r = -0.38, P < .01). The response amplitudes of the peroneal nerves correlated negatively with MDA excretion (for the mean values at the second 2 evaluations, P < .005, r = -0.45). Tests of sensory function correlated inconsistently with MDA excretion. In summary, lipid peroxidation, as assessed from malondialdehyde excretion, is associated with sudomotor dysfunction in early diabetes.

Adolescent↗
PubMed1999

[A case of hereditary sensory autonomic neuropathy type II with late onset].

We reported a 22-year-old man with hereditary sensory autonomic neuropathy (HSAN) type II. His initial neurological symptom at the age of 18 years was hypoesthesia on the feet and legs. In spite of late onset and absence of multilating acropathy, we diagnosed this case as HSAN type II because of an absence of sensory nerve action potentials with normal motor nerve conduction velocities and of a total loss of myelinated fibers with a decrease of unmyelinated fibers in the sural nerve. The sweating induced by iontophoretic pilocarpine stimulation was decreased on the dorsum of the foot. In addition, the morphometric analysis of sudomotor nerves around sweat glands showed a decrease of nerve terminals and unmyelinated axons. Because decrease or loss of sweating is one of the cardinal signs in HSAN type II, the quantitative sweating test and morphometric evaluation of the innervation of sweat glands are important for the proof of the autonomic signs.

Adult↗
PubMed2002

Clinical and laboratory predictors of imported malaria in an outpatient setting: an aid to medical decision making in returning travelers with fever.

No evidence-based information exists to guide clinicians for giving presumptive treatment to returning travelers when malaria is strongly suspected on clinical grounds but laboratory confirmation is not immediately available or is negative. A prospective study was conducted in travelers or migrants who sought care for fever to identify clinical and laboratory predictors of Plasmodium parasitemia. A total of 336 questionnaires were collected (97 malaria case patients and 239 controls). Multivariate regression analysis showed inadequate prophylaxis, sweating, no abdominal pain, temperature > or = 38 degrees C, poor general health, enlarged spleen, leucocytes < or = 10 x 10(3)/L, platelets < 150 x 10(3)/L, hemoglobin < 12 g/dL, and eosinophils < or = 5% to be associated with parasitemia. Enlarged spleen had the highest positive likelihood ratio for a diagnosis of malaria (13.6), followed by thrombopenia (11.0). Posttest probabilities for malaria were 85% with enlarged spleen and 82% with thrombopenia. A rapid assessment can thus help to decide whether a presumptive treatment should be given or not, especially when the results of the parasitological examination are not immediately available or are uncertain.

Female↗
PubMed1991

Neonatal screening strategy for cystic fibrosis using immunoreactive trypsinogen and direct gene analysis.

OBJECTIVE: To assess the effectiveness of a two tier neonatal screening strategy for cystic fibrosis, which combines estimation of immunoreactive trypsinogen followed by direct gene analysis in dried blood spot samples collected at age 5 days. DESIGN: Prospective study of two tier screening strategy. The first tier of testing immunoreactive trypsinogen concentration was measured in dried blood spot samples from neonates aged 4-5 days. In the second tier direct gene analysis to detect cystic fibrosis mutations deltaF508 and deltaI506 was performed in those blood spot samples which produced the highest 1% of immunoreactive trypsinogen values. Direct gene analysis was also performed on blood spot samples from infants with suspected or confirmed meconium ileus, regardless of the immunoreactive trypsinogen value. SETTING: The South Australian Neonatal Screening Programme, operating from the department of chemical pathology at Adelaide Children's Hospital. Subjects--All 12,056 neonates born in South Australia between December 1989 and June 1990. No selection criteria were applied. INTERVENTIONS: All infants found to have two recognised cystic fibrosis mutations on direct gene analysis were referred directly for clinical management, and those with one recognised cystic fibrosis mutation were recalled for a sweat test; their families were given genetic counselling. MAIN OUTCOME MEASURES: Direct or exclusion of cystic fibrosis by sweat testing of neonates identified as being at high risk of cystic fibrosis on screening and of those at minimum risk but whose subsequent clinical history raised suspicion about the disease. RESULTS: Of the 12,056 infants screened, 11,907 (98.8%) were reported as "cystic fibrosis not indicated" on the basis of low immunoreactive trypsinogen values. Of the 148 (1.23%) infants with raised immunoreactive trypsinogen values and one (0.008%) with meconium ileus, 132 (1.09%) were reported as cystic fibrosis not indicated, four (0.033%) were identified as having cystic fibrosis, and 13 (0.108%) were recalled for sweat testing after direct gene analysis for the presence of the deltaF508 and deltaI506 cystic fibrosis mutations. No cases of affected infants are known to have been missed to date. CONCLUSION: The strategy of measurement of immunoreactive trypsinogen followed by direct gene analysis is a highly specific neonatal screen for cystic fibrosis, requiring only 2.8 families to be contacted for every case of cystic fibrosis diagnosed.

Cystic Fibrosis↗
PubMed1996

Human Adaptation to Work in Two Different Climates.

The processes of acclimation to hot-dry and to warm-humid climates were studied using two approaches: a quantitative analysis of literature data and an experimental study in the laboratory concerning the physiological parameters of heart rate, rectal temperature, sweat loss, and subjective assessment. Analysis o f literature data: Data from 62 experiments with a total of 813 participants were pooled and recalculated. The experiments ranged from 6 to 24 days, air temperatures from 30.4 to 50.0°C, water vapor pressures from 1.5 to 6.5 kPa, and wet bulb globe temperatures (WBGT) from 27.4 to 38.6°C. Laboratory studies: In the laboratory, 8 participants were acclimated during 15 consecutive days to a hot-dry climate and to a warm-humid climate, which were equivalent in terms of the WBGT (33.5 and 33.6°C, respectively). The participants walked four times for 25 min on a treadmill at a speed of 4 km/h. The hot-dry climate caused somewhat greater strain than the warm-humid condition. In the course of acclimation to the hot-dry climate, heart rate and rectal temperature started at higher levels, decreased slightly steeper but remained on a higher level throughout. Nevertheless, the differences between both thermal conditions were small, and both physiologic functions reached the point of acclimation almost at the same time under warm-humid and under hot-dry exposure. Sweat loss, which is not regarded as a valid predictor for acclimation, was considerably higher but increased less in the hot-dry than in the warm-humid climate.

acclimation↗
PubMed1997

Auditory and inspiratory gasp-evoked sympathetic skin response: age effects.

The sympathetic skin response (SSR) has been employed to assess peripheral neuropathy as an index of sympathetic sudomotor activity. A variety of stimuli can be used to elicit the SSR, but their relative ease of use and reliability have not been studied. In addition, the extent to which age affects the SSR remains unresolved. We compared two different stimuli, a sudden loud noise and an inspiratory gasp, whilst recording SSRs from the hand and foot. We also investigated the effects of age on SSR amplitude and latency in 58 healthy volunteers (ages 13-79). SSRs evoked by the auditory stimulus were recorded in all subjects, while gasp-induced SSRs were not elicited in two subjects. We found that SSRs evoked by the auditory stimulus had less inter- and intra-subject latency and waveform variability than the gasp-induced response. The increased latency variability associated with the inspiratory gasp technique was probably due to triggering errors. Our results confirmed that the amplitude of the SSR is extremely variable and appears to be affected by many factors. Auditory-evoked SSR latencies revealed a significant non-linear increase with age, while SSRs evoked by an inspiratory gasp did not demonstrate age dependence. We conclude that an auditory stimulus is superior to an inspiratory gasp in evoking SSRs, both in terms of consistent appearance and reduced latency variability. As the SSR latency increases significantly with age, this effect should be carefully considered when interpreting the response.

Acoustic Stimulation↗
PubMed2002

Cloning and sequencing of the 3'-region of the canine parathyroid hormone-related protein gene and analysis of alternate mRNA splicing in two canine carcinomas.

A canine genomic library in Lambda FIX II vector was screened with a 281-base pair canine PTHrP cDNA to the prepro- and coding regions. Two genomic clones were isolated and mapped to the 3'-end of the PTHrP gene by polymerase chain reaction (PCR) amplification of exons in this region. One clone (3.5 kb) was amplified by PCR, partially sequenced, and compared to the human PTHrP gene. Regions were identified with a high degree of homology to exons 6, 7, and 8 of the human PTHrP gene. A polyadenylation site was present 3' to the exon 8-like region. Reverse transcriptase-polymerase chain reaction (RT-PCR) demonstrated that exon 7 of the PTHrP gene was transcribed in two canine carcinomas (SCC 2/88 cells and CAC-8 tumor line) which produce PTHrP. This confirmed that the 3'-region of the canine PTHrP gene is alternately spliced with splicing of exon 6 to exons 7 or 9. Transcription of exon 8 was not demonstrated by RT-PCR and suggests that the exon 8-like region of the dog PTHrP gene is not utilized. The exon 8-like region contained an early stop codon that was not present in exon 8 of the human PTHrP gene.

Adenocarcinoma↗