β-Adrenergic sweat secretion rate determined by evaporimetry is an accurate and reliable technique to assess different levels of CFTR function and to identify patients with CF.

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Key points• Using a small glass capillary, an Ussing chamber was designed and used to measure electrical properties across very small pieces (<1 mm 2 ) of freshly dissected epithelia.• The system was applied to small airways of the lung to show that fluids on the airway surfaces are constantly being simultaneously secreted and absorbed. • A new model proposes that the accordion-like structure of folds and pleats in the epithelial lining of the airways serves to secrete fluid within the pleats and to absorb fluid along the folds so that fluid levels on the airway surfaces are maintained automatically and airways do not flood or become too dry.• These results help us understand the first line of lung defence against infections from bacteria and viruses and may be used to treat or prevent lung disease.Abstract Native small airways must remain wet enough to be pliable and support ciliary clearance, but dry enough to remain patent for gas flow. The airway epithelial lining must both absorb and secrete ions to maintain a critical level of fluid on its surface. Despite frequent involvement in lung diseases, the minuscule size has limited studies of peripheral airways. To meet this challenge, we used a capillary to construct an Ussing chamber (area <1 mm 2 ) to measure electrolyte transport across small native airways (∼1 mm ø) from pig lung. Transepithelial potentials (V t ) were recorded in open circuit conditions while applying constant current pulses across the luminal surface of dissected airways to calculate transepithelial electrical conductance (G t ) and equivalent short circuit current (I eq sc ) in the presence and absence of selected Na + and Cl − transport inhibitors (amiloride, GlyH-101, Niflumic acid) and agonists (Forskolin + IBMX, UTP). Considered together the responses suggest an organ composed of both secreting and absorbing epithelia that constitutively and concurrently transport fluids into and out of the airway, i.e. in opposite directions. Since the epithelial lining of small airways is arranged in long, accordion-like rows of pleats and folds that run axially down the lumen, we surmise that cells within the pleats are mainly secretory while the cells of the folds are principally absorptive. This structural arrangement could provide local fluid transport from within the pleats toward the luminal folds that may autonomously regulate the local surface fluid volume for homeostasis while permitting acute responses to maintain clearance.

Genetic diversity among ten varieties of spring wheat used as parents in a diallel cross was assessed through multivariate analysis (D(2)-statistics) and then related to heterosis and SCA effects of their hybrids. The parents fell into three groups. Group I contained the varieties, 'Nobre', 'Girua' and 'Carazinho'; group II contained 'Sonalika', 'Lyallpur' and 'Pitic 62' and group III contained 'Indus 66', 'Balaka', 'Sonora 64rs and 'MSl'. The varieties of group I were good general combiners, while the varieties of group III were poor combiners. Significant heterotic and SCA effects for yield and yield components were observed in the hybrids of the parents belonging to different groups but not in the same group. Genetic divergence between the parents had a positive relationship with heterosis and SCA effects of the hybrids.

To investigate the pattern changes in the index of sweat ion concentration at skin surface with increasing sweat during passive heat stress in humans, we measured conductivity of the perfused water with sweat as the index of sweat ion concentration and sweat rate, continuously at the chest skin surface. Eight healthy subjects (22.4 +/-1.0 years) were passively heated by lower-leg immersion in a hot water bath of 42 degrees C for 50 min in an ambient temperature of 28 degrees C and relative humidity of 50%. The internal temperature (Tor) thresholds of sweat rate and index of sweat ion concentration were almost similar. Concomitant onset for the index of sweat ion concentration and sweat rate occurred but two types of linear regression lines were identified in the relationship between the index of sweat ion concentration and sweat rate at a boundary sweat rate value of 0.30 +/- 0.08 mg cm(-2) min(-1). The slope of the regression line at low levels of sweat (slope 0.02 +/- 0.01 V mg(-1) cm(-2) min(-1)) was significantly gradual compared with that at moderate levels of sweat (slope 0.30 +/- 0.08 V mg(-1) cm(-2) min(-1)) (P<0.05). These results suggest that at low levels of sweat the index of sweat ion concentration responds gradually with respect to sweat rate, which may be due to the ion reabsorption capacity of the sweat duct, and then the index of sweat ion concentration increased steeply with sweat rate.

We investigated the effects of short-term endurance training and detraining on sweating and cutaneous vasodilatation during exercise in young women, taking into account changes in maximal oxygen uptake (V O 2 max ) and the phase of the menstrual cycle. Eleven untrained women participated in endurance training; cycle exercise at ∼60%V O 2 max for 60 min day

Since the discovery of Cl(-) impermeability in cystic fibrosis (CF) and the cloning of the responsible channel, CF pathology has been widely attributed to a defect in epithelial Cl(-) transport. However, loss of bicarbonate (HCO3(-)) transport also plays a major, possibly more critical role in CF pathogenesis. Even though HCO3(-) transport is severely affected in the native pancreas, liver, and intestines in CF, we know very little about HCO3(-) secretion in small airways, the principle site of morbidity in CF. We used a novel, mini-Ussing chamber system to investigate the properties of HCO3(-) transport in native porcine small airways (∼ 1 mm φ). We assayed HCO3(-) transport across small airway epithelia as reflected by the transepithelial voltage, conductance, and equivalent short-circuit current with bilateral 25-mM HCO3(-) plus 125-mM NaGlu Ringer's solution in the presence of luminal amiloride (10 μM). Under these conditions, because no major transportable anions other than HCO3(-) were present, we took the equivalent short-circuit current to be a direct measure of active HCO3(-) secretion. Applying selective agonists and inhibitors, we show constitutive HCO3(-) secretion in small airways, which can be stimulated significantly by β-adrenergic- (cAMP) and purinergic (Ca(2+)) -mediated agonists, independently. These results indicate that two separate components for HCO3(-) secretion, likely via CFTR- and calcium-activated chloride channel-dependent processes, are physiologically regulated for likely roles in mucus clearance and antimicrobial innate defenses of small airways.

With the advent of numerous candidate drugs for therapy in cystic fibrosis (CF), there is an urgent need for easily interpretable assays for testing their therapeutic value. Defects in the cystic fibrosis transmembrane conductance regulator (CFTR) abolished β-adrenergic but not cholinergic sweating in CF. Therefore, the β-adrenergic response of the sweat gland may serve both as an in vivo diagnostic tool for CF and as a quantitative assay for testing the efficacy of new drugs designed to restore CFTR function in CF. Hence, with the objective of defining optimal conditions for stimulating β-adrenergic sweating, we have investigated the components and pharmacology of sweat secretion using cell cultures and intact sweat glands. We studied the electrical responses and ionic mechanisms involved in β-adrenergic and cholinergic sweating. We also tested the efficacy of different β-adrenergic agonists. Our results indicated that in normal subjects the cholinergic secretory response is mediated by activation of Ca 2+ -dependent Cl − conductance as well as K + conductances. In contrast, the β-adrenergic secretory response is mediated exclusively by activation of a cAMP-dependent CFTR Cl − conductance without a concurrent activation of a K + conductance. Thus, the electrochemical driving forces generated by β-adrenergic agonists are significantly smaller compared with those generated by cholinergic agonists, which in turn reflects in smaller β-adrenergic secretory responses compared with cholinergic secretory responses. Furthermore, the β-adrenergic agonists, isoproprenaline and salbutamol, induced sweat secretion only when applied in combination with an adenylyl cyclase activator (forskolin) or a phosphodiesterase inhibitor (3-isobutyl-1-methylxanthine, aminophylline or theophylline). We surmise that to obtain consistent β-adrenergic sweat responses, levels of intracellular cAMP above that achievable with a β-adrenergic agonist alone are essential. β-Adrenergic secretion can be stimulated in vivo by concurrent iontophoresis of these drugs in normal, but not in CF, subjects.