Skin hydration analysis by experiment and computer simulations and its implications for diapered skin.

BACKGROUND: Experimental work on skin hydration is technologically challenging, and mostly limited to observations where environmental conditions are constant. In some cases, like diapered baby skin, such work is practically unfeasible, yet it is important to understand potential effects of diapering on skin condition. To overcome this challenge, in part, we developed a computer simulation model of reversible transient skin hydration effects. METHODS: Skin hydration model by Li et al. (Chem Eng Sci, 138, 2015, 164) was further developed to simulate transient exposure conditions where relative humidity (RH), wind velocity, air, and skin temperature can be any function of time. Computer simulations of evaporative water loss (EWL) decay after different occlusion times were compared with experimental data to calibrate the model. Next, we used the model to investigate EWL and SC thickness in different diapering scenarios. RESULTS: Key results from the experimental work were: (1) For occlusions by RH=100% and free water longer than 30 minutes the absorbed amount of water is almost the same; (2) Longer occlusion times result in higher water absorption by the SC. The EWL decay and skin water content predictions were in agreement with experimental data. Simulations also revealed that skin under occlusion hydrates mainly because the outflux is blocked, not because it absorbs water from the environment. Further, simulations demonstrated that hydration level is sensitive to time, RH and/or free water on skin. In simulated diapering scenarios, skin maintained hydration content very close to the baseline conditions without a diaper for the entire duration of a 24 hours period. CONCLUSION: Different diapers/diaper technologies are known to have different profiles in terms of their ability to provide wetness protection, which can result in consumer-noticeable differences in wetness. Simulation results based on published literature using data from a number of different diapers suggest that diapered skin hydrates within ranges considered reversible.

Electrostatic frequency reduction: A negative stiffness mechanism for measuring dissipation in a mechanical oscillator at low frequency.

Broadband seismometers and gravitational wave detectors make use of mechanical resonators with a high quality factor to reduce Brownian noise. At low frequency, Brownian noise is ultimately dominated by internal friction in the suspension, which has a 1/f noise compared with the white noise arising from viscous dissipation. Internal friction is typically modeled as a frequency-dependent loss and can be challenging to measure reliably through experiment. In this work, we present the physics and experimental implementation of electrostatic frequency reduction (EFR) in a mechanical oscillator-a method to measure dissipation as a function of frequency. By applying a high voltage to two parallel capacitor plates, with the center plate being a suspended mass, an electrostatic force is created that acts as a negative stiffness mechanism to reduce the system's resonance frequency. Through EFR, the loss angle can be measured as a function of frequency by measuring amplitude decay response curves for a range of applied voltages. We present experimental measurements of the loss angle for three metal helical extension springs in the nominal frequency range 0.7-2.9 Hz at 0.2 Hz intervals, demonstrating the possibility for fine adjustment of the resonance frequency for loss angle measurements. A quality factor proportional to the resonance frequency squared was measured, an indication that internal friction and other non-viscous dissipation elements, such as electrostatic damping, were the prominent loss mechanisms in our experiments. Finally, we consider the implications of Brownian noise arising from internal friction on a low 1/f noise seismometer.

Differences in forearm strength, endurance, and hemodynamic kinetics between male boulderers and lead rock climbers.

This study examined differences in the oxygenation kinetics and strength and endurance characteristics of boulderers and lead sport climbers. Using near infrared spectroscopy, 13-boulderers, 10-lead climbers, and 10-controls completed assessments of oxidative capacity index and muscle oxygen consumption (m⩒O2) in the flexor digitorum profundus (FDP), and extensor digitorum communis (EDC). Additionally, forearm strength (maximal volitional contraction MVC), endurance (force-time integral FTI at 40% MVC), and forearm volume (FAV and ΔFAV) was assessed. MVC was significantly greater in boulderers compared to lead climbers (mean difference = 9.6, 95% CI 5.2-14 kg). FDP and EDC oxidative capacity indexes were significantly greater (p = .041 and .013, respectively) in lead climbers and boulderers compared to controls (mean difference = -1.166, 95% CI (-3.264 to 0.931 s) and mean difference = -1.120, 95% CI (-3.316 to 1.075 s), respectively) with no differences between climbing disciplines. Climbers had a significantly greater FTI compared to controls (mean difference = 2205, 95% CI= 1114-3296 and mean difference = 1716, 95% CI = 553-2880, respectively) but not between disciplines. There were no significant group differences in ΔFAV or m⩒O2. The greater MVC in boulderers may be due to neural adaptation and not hypertrophy. A greater oxidative capacity index in both climbing groups suggests that irrespective of climbing discipline, trainers, coaches, and practitioners should consider forearm specific aerobic training to aid performance.

Water disrupts stratum corneum lipid lamellae: damage is similar to surfactants.

Using electron microscopy, we investigated the effect of (i) a dilute surfactant and of water alone on the ultrastructure of stratum corneum lipids in pig skin exposed in vitro at 46 degrees C, and (ii) of water alone on human skin exposed in vivo at ambient temperature. For pig skin, the surfactant sodium dodecyl sulfate disrupts stratum corneum intercellular lamellar bilayers, leading to bilayer delamination and "roll-up" in a water milieu after 1 h, extensive bilayer disruption after 6 h, and nearly complete dissociation of corneocytes after 24 h. Corneodesmosomes show progressive degradation with exposure time. Water alone also disrupts the stratum corneum, but with a slower onset. Alterations in intercellular lamellar bilayers, but not intercellular lamellar bilayer roll-up, are detected after 2 h. Intercellular lamellar bilayer roll-up occurs after 6 h. Extensive dissociation of corneocytes occurs after 24 h of water exposure. Unlike sodium dodecyl sulfate, water exposure results in the formation of amorphous intercellular lipid. Corneodesmosome degradation parallels intercellular lamellar bilayer disruption; calcium appears to offer some protection. Similar disruption of intercellular lamellar bilayers occurs in human skin in vivo at ambient temperature. Our studies show that water can directly disrupt the barrier lipids and are consistent with surfactant-induced intercellular lamellar bilayer disruption being due at least in part to the deleterious action of water. Intercellular lamellar bilayer disruption by water would be expected to enhance permeability and susceptibility to irritants; accordingly, increased attention should be given to the potential dangers of prolonged water contact. For common in vitro procedures, such as skin permeation studies or isolation of stratum corneum sheets, exposure to water should also be minimized.

The metabolism of dihomo-gamma-linolenic acid in man.

Orally administered dihomo-gamma-linolenic acid (DHLA) is well absorbed in man; it appears in blood after ca. 4 hr first as triglyceride ester and later as phospholipid. After sustained-dosing, DHLA penetrated membrane pools and all phospholipid components but, depending on the dosage, reached a metabolic equilibrium in 4-16 days. Intact platelets do not accumulate arachidonate following DHLA administration, and species differences occur in the capacity of animals to metabolize DHLA to arachidonic acid (AA). The rat appears to be unusual in having a very active hepatic delta5-desaturase enzyme system. Potentially antithrombotic changes in platelet function which followed the administration of DHLA to man were accompanied by a significant increase in the capacity of platelets to synthesize PGE1. Concomitant increases in PGE2 synthesis do not apparently result from an increased production of AA and suggest that DHLA, or a DHLA metabolite, interferes with the metabolism of AA. Effects on thromboxane and prostacyclin synthesis are being studied.

Can leaflets assist parents in preparing children for hospital?

This article outlines the findings and implications of a small study designed to investigate the perceived usefulness of an information leaflet entitled 'Preparing your child for hospital: a parents' guide'. The study was carried out in an ear, nose and throat unit where children are admitted for elective surgery. A leaflet was developed and field tested before being mailed to a group of parents. An analysis of the data collected demonstrated considerable parental satisfaction with the information contained in the leaflet. The authors believe that similar leaflets should be routinely distributed to families with children awaiting hospital admission.

The role of tetrahydrofolate dehydrogenase in the hepatic supply of tetrahydrobiopterin in rats.

The reduction of 7,8-dihydrobiopterin to 5,6,7,8-tetrahydrobiopterin by rat liver tetrahydrofolate dehydrogenase (5,6,7,8-tetrahydrofolate-NADP+ oxidoreductase, EC 1.5.1.3) is competitively inhibited by trimethoprim lactate (apparent Ki 0.285 muM). An apparent Michaelis constant of 43 muM for dihydrobiopterin was obtained, which is 430 times higher than the reported Km for dihydrofolate with this enzyme. The reduction of dihydrobiopterin is thus more susceptible to inhibition by trimethoprim lactate than is the reduction of dihydrofolate. However, intraperitoneal administration of trimethoprim had no significant effect on the hepatic supply of tetrahydrobiopterin in rats.

The stereochemistry of hexahydroprenol, ubiquinone and ergosterol biosynthesis in the mycelium of Aspergillus fumigatus Fresenius.

1. The mycelium of Aspergillus fumigatus has been shown to incorporate mevalonate into squalene, ubiquinone, ergosterol and hexahydroprenol. 2. The (3)H/(14)C ratio in ubiquinone, biosynthesized from [2-(14)C-(4R)-4-(3)H(1)]mevalonate, is the same as in the squalene; essentially no (3)H was incorporated from [2-(14)C-(4S)-4-(3)H(1)]mevalonate, indicating the biosynthesis of biogenetically trans-isoprene units. 3. The (3)H/(14)C ratio for ergosterol (from ;4R-mevalonate') was 3:5, showing that the proton at C-24 is not lost during alkylation of the side chain; it probably migrates to C-25. 4. As (3)H from both mevalonates was incorporated into the hexahydroprenols the biosynthesis of both cis- and trans-isoprene units must occur. 5. The saturated omega- and psi-isoprene units are shown to be biogenetically trans, as are two of the unsaturated residues. 6. The saturated alpha- and unsaturated beta-isoprene residues are both biogenetically cis. 7. An inexplicable loss of approximately half of the olefinic protons from the cis-portion of hexahydroprenol occurs; possible reasons for this loss are discussed. 8. Increase in chain length of the hexahydroprenols is by a cis addition. 9. A biosynthesis of hexahydroprenols by addition of cis-isoprene units to all-trans-geranylgeranyl pyrophosphate, or a dihydro or tetrahydro derivative thereof, is suggested.

The characterization and distribution of hexahydropolyprenyl esters in cultures of Aspergillus fumigatus Fresenius.

The total mycelial lipid of Aspergillus fumigatus was analysed and over half of its hexahydropolyprenol was shown to be esterified with fatty acids. Comparison of the fatty acid content of the prenyl esters with the sterol ester and the total lipid indicated a marked predominance of saturated fatty acids in the polyprenyl esters. The predominant acids esterified to the prenols were palmitic acid, linoleic acid, oleic acid, lignoceric acid, stearic acid and palmitoleic acid. Most of the unesterified polyprenol was found in the mitochondrial fraction, but the esterified prenol was equally distributed throughout the cell fractions. This distribution was unlike that found for ergosteryl ester in the same tissue.

Prostaglandin-E2-9-ketoreductase in rabbit kidney.

The 100,000 xg supernatant of rabbit kidney contains a prostaglandin-E2-9-ketoreductase which has an obligatory requirement for NADPH. This enzyme is localised in the renal cortex and is able to quantitatively convert PGE2 to PGF2alpha. A broad pH profile was evident with an optimum at pH 7 with 5. Kinetic studies indicated a Km of 3 with 2 x 10-4M PGE2. The isoelectric point was at pH 5 with 65 and the molecular weight, as estimated by gel filtration, was 21,800. These values differ from those obtained with enzyme from monkey brain tissue and suggest a tissue specificity of PGE2-9-ketoreductase. By combining isoelectric focussing techniques with sephadex filtration considerable purification of the renal enzyme was achieved.

Mechanism of action of bacitracin: complexation with metal ion and C 55 -isoprenyl pyrophosphate.

The inhibition by bacitracin of the enzymatic dephosphorylation of C(55)-isoprenyl pyrophosphate is abolished by the addition of chelating agents. If, however, the chelating agent is added after a preincubation of bacitracin with a divalent cation and the lipid substrate, then its addition has little effect, indicating that bacitracin, metal ion, and C(55)-isoprenyl pyrophosphate form a complex. Various divalent cations can participate in complex formation, but monovalent cations are ineffective. A direct demonstration of the formation of a complex between the C(55)-isoprenyl pyrophosphate and bacitracin in the presence of metal ions was obtained. Molecular models that show one possible conformation for a complex between bacitracin and the C(55)-isoprenyl pyrophosphate, in which the metal ion acts as a bridge between the two compounds, are presented.

The effect of L-ascorbate on catecholamine biosynthesis.

l-Ascorbate stimulates the enzymic hydroxylation of phenylalanine in vitro by recycling tetrahydrobiopterin, which reduces O(2) utilized in the reaction. It is suggested that ascorbate might have a similar function in vivo; this would explain the apparent regulation of tyrosine hydroxylase and tryptophan hydroxylase activities by this vitamin.

Inhibition of sterol biosynthesis by bacitracin.

Bacitracin is an inhibitor of the biosynthesis of squalene and sterols from mevalonic acid, C(5)-isopentenyl pyrophosphate, or C(15)-farnesyl pyrophosphate catalyzed by preparations from rat liver. The antibiotic is active at extremely low ratios of antibiotic to substrate. The mechanism of inhibition appears to be the formation of a complex between bacitracin, divalent cation, and C(15)-farnesyl pyrophosphate and other isoprenyl pyrophosphates. It is similar to the formation of the complex with C(55)-isopropenyl pyrophosphate in microbial systems. The toxicity of bacitracin for animal cells could be due in part to the formation of these complexes.

Inhibition of renal PGE2-9-ketoreductase by diuretics.

The metabolism of PGE2 by extracts of renal cortex is species dependent. In the rat PGE2-15-hydroxydehydrogenase initiates metabolism whereas in the rabbit PGE2-9-ketoreductase predominates. In man both mechanisms may operate. Each of the metabolic enzymes, which limits the vasodilator-diuretic actions of PGE2, was inhibited by ethacrynic acid, furosemide and indomethacin. Some inhibition of PGE2-9-ketoreductase was also observed with chlorthalidone, hydralazine and phentolamine but the thiazide diuretics and a number of other cardiovascular-active agents were without significant effect. We conclude that the inhibition of PGE2-9-ketoreductase and PGE2-15-hydroxydehydrogeanse could contribute to the mechanism of action of the non-thiaxide diuretics in man.

Characterization of the hexahydropolyprenols of Aspergillus fumigatus Fresenius.

The isolation and properties of a group of alcohols from the mycelium of Aspergillus fumigatus Fresenius are described. Mass-, nuclear-magnetic-resonance- and infrared-spectrometric studies coupled with evidence from ozonolytic degradation and chromatography show the mixture to contain hexahydroprenols-18, -19, -20, -21, -22, -23 and -24. Each contains a saturated ;hydroxy-terminal' isoprene residue, a saturated omega-terminal isoprene residue and a saturated zeta-isoprene residue (adjacent to the omega-residue). The presence of only two trans-isoprene residues is also a feature of the series of alcohols, but the precise position of these in each molecule is not known.

Isolation of polyisoprenyl alcohols from Streptococcus faecalis.

C(55)-isoprenyl alcohol and its derivatives have been isolated from Streptococcus faecalis and characterized. The relative amounts present as free alcohol, neutral lipid esters, and phosphate ester derivatives were determined. The chain lengths, mass spectra, and cis to trans ratio of double bonds are reported.

Selective inhibition of prostaglandin biosynthesis by gold salts and phenylbutazone.

Gold salts and phenylbutazone selectively inhibit the synthesis of PGF2alpha and PGE2 respectively. Lowered production of one prostaglandin species is accompanied by an increased production of the other. Selective inhibition by these drugs was observed in the presence of adrenaline, reduced glutathione and copper sulphate under conditions when most anti-inflammatory compounds inhibited PGE2 and PGF2alpha syntheses equally. It is postulated that selective inhibitors may have a different mode of action in vivo and beneficial effects may be related to the endogenous ratio of PGE to PGF required for normal function.

The characterization of ficaprenol-10, -11 and 12 from the leaves of Ficus elastica (decorative rubber plant).

Evidence from mass, nuclear-magnetic-resonance and infrared spectrometry and from gas-liquid and thin-layer chromatography is presented in favour of the presence of cis-trans-decaprenol, -undecaprenol and -dodecaprenol in the mixture of polyprenols (2.6mg./g.) isolated from leaf tissue of Ficus elastica. The trivial names ficaprenol-10, -11 and -12 are proposed. Nuclear-magnetic-resonance studies showed that each of these prenols contains three trans internal isoprene residues and a cis ;OH-terminal' isoprene residue. Ficaprenol-11 is the major component of the mixture. Chromatographic evidence suggests the presence also of small amounts of ficaprenol-9 and -13. The precise position of the three trans internal isoprene residues was not determined but it is suggested that these are adjacent to the omega-terminal isoprene residue and that the ficaprenols are formed from all-trans-geranylgeranyl pyrophosphate. It is also suggested that ficaprenol-10, -11, -12 and -13 are probably the same compounds as castaprenol-10, -11, -12 and -13.

Antithrombotic potential of dihomo-gamma-linolenic acid in man.

The effects of orally ingested dihomo-gamma-linolenic acid (DHLA), the natural biosynthetic precursor of prostaglandin E1 (PGE1), were assessed in human volunteers. Single doses of DHLA (0.1--2g) increased the proportion of DHLA relative to arachidonic acid in plasma and platelets and also increased the ex-vivo capacity of platelets to produce PGE1 and PGE2. More pronounced effects were observed during sustained treatment (five days to four weeks) when DHLA also accumulated in red cell membranes. These biochemical changes were accompanied by potentially antithrombotic changes in haemostatic function. The most common effect, which was consistently detected after 0.1-g single doses of DHLA or its methyl ester, was a decrease in plasma heparin-neutralising activity. Inhibition of platelet aggregation induced by adenosine diphosphate was also detected, though this was generally less pronounced. Sustained treatment in one subject also produced definite inhibition of ristocetin-induced platelet aggregation. There was only one possible adverse effect--a transient cough in a subject with a history of asthma. DHLA therefore seems to have considerable potential as an agent for preventing and treating human thromboembolic disease.