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Biomedical subjects

S B Hoath

Publications and source records attributed to S B Hoath.

At least 37 records · Page 2Linked to original sources

Effect of prenatal steroids on skin surface hydrophobicity in the premature rat.

The skin surface of the newborn rat at term is highly hydrophobic. This surface hydrophobicity plays a putative role in the transition from an aqueous to a gaseous environment at birth and is dependent on the presence of an intact periderm. Glucocorticoids given to pregnant dams, during late gestation, will accelerate formation of the stratum corneum and reduce transepidermal water loss in prematurely delivered pups. We tested the related hypotheses that surface hydrophobicity and maturation of the periderm are developmentally accelerated by prenatal exposure to steroids. Thirty pregnant Sprague-Dawley rats received either normal saline or 0.5 mg/kg betamethasone on d 17 of gestation. After cesarean delivery on d 18, 19, and 20, dorsal skin surface hydrophobicity was quantified by direct surface electrical capacitance (SEC) measurement. Initial skin surface hydration at birth was significantly lower in steroid-treated pups than in control pups at gestational ages 19 and 20 d (3060 +/- 1379 versus 4441 +/- 153 pF and 646 +/- 295 versus 1493 +/- 1019 pF, respectively, p < 0.001, mean +/- SD). Likewise, after desorption of amniotic fluid, baseline skin hydration was significantly lower in steroid-treated pups than in control pups at gestational ages 19 and 20 d (1862 +/- 1560 pF versus 4278 +/- 97 pF and 60 +/- 56 pF versus 128 +/- 264 pF, p < 0.001). Scanning and transmission electron microscopy showed morphologic maturation of the periderm after steroid treatment. These results demonstrate accelerated development of both functional and structural correlates of skin surface hydrophobicity in the premature rat after prenatal exposure to steroids.

Animals↗

Surface electrical capacitance as a noninvasive bedside measure of epidermal barrier maturation in the newborn infant.

OBJECTIVE: The classical studies of epidermal barrier function in infants have relied on measurement of transepidermal water loss by evaporimetry. This technique, although valuable, is, in practice, slow, expensive, and susceptible to error because of convective air currents. In this prospective study, we evaluated gestation-dependent and postnatal age-dependent changes in epidermal barrier function by measurement of skin surface electrical capacitance (SEC) in 40 newborn infants ranging from 25 to 40 weeks' gestational age. SEC was measured in picofarads with a dermal phase meter. METHODOLOGY: The measurements were recorded continuously during a 12-second period from the forehead at 12 to 24 hours of life. The baseline (CBL) surface hydration at 1 second and the rate of change of SEC during probe occlusion (CSL) were used as measures of surface hydration and transepidermal water movement, respectively. In the most premature infants (< 30 weeks), these measurements were repeated daily for 5 days. Data were analyzed by analysis of variance after logarithmic (Ln) transformation. RESULTS: We found a significant difference in Ln(CBL) in infants born before and after 30 weeks' gestation (4.91 +/- 0.36 Ln[pF] vs 2.67 +/- 0.21 Ln[pF], respectively). Similarly, CSL was significantly different in infants born before and after 30 weeks' gestation (16.42 +/- 5.55 pF/s vs 1.59 + 0.22 pF/s, respectively). In infants born at less than 27 weeks, both Ln(CBL) and CSL decreased significantly by postnatal day 5. In the term group (n = 25), CSL was significantly greater in white than in black infants (1.96 +/- 1.32 pF/s vs. 0.95 +/- 0.55 pF/s, respectively). CONCLUSION: These results demonstrate impaired epidermal barrier properties in immature infants, less than 30 weeks' gestation, and reveal a remarkable rate of barrier maturation of this group in the first few days of postnatal life. Also, the finding of decreased CSL in black infants supports the hypothesis of differences in barrier function attributable to skin types. Overall, these findings demonstrate the feasibility of bedside SEC measurements in the evaluation of epidermal barrier properties in the newborn infant.

Black People↗

Effect of insulated skin probes to increase skin-to-environmental temperature gradients of preterm infants cared for in convective incubators.

Thermal support systems for premature infants that are based on skin servocontrol depend on accurate measurement of skin surface temperature. We examined prospectively the effect of probe insulation to alter measured skin temperature in 10 preterm infants. The use of insulated probes resulted in significant alteration in incubator servocontrol, with lower incubator air temperatures and higher skin-to-environment temperature gradients.

Equipment Design↗

Measurement of transcutaneous carbon dioxide in low birthweight infants during the first two weeks of life.

With the advent of pulse oximetry, there has been a general decrease in the use of transcutaneous (Tc) blood gas monitoring in intensive care environments. The available data, however, suggest that arterial carbon dioxide pressure (PCO2) levels are best estimated by Tc methods. In this study, we report our experience using routine Tc PCO2 monitoring in 32 consecutive infants less than 2 weeks of age with birthweights less than 1500 g. A total of 644 simultaneous pairs (Tc PCO2 versus arterial PCO2) were obtained. Pairs were categorized according to a 2 x 2 matrix design based on sensor temperature (40 degrees or 43 degrees C) versus site of arterial sampling (umbilical [UAC] or peripheral artery catheter [PAC]). Sampling via the UAC resulted in excellent correlation between sample pairs at both sensor temperatures with similar regressions between groups. Sampling via the PAC, however, yielded poor correlation between sample pairs and a significantly different regression from both UAC groups. Based on these findings, we advocate the use of a sensor temperature of 40 degrees C in very low birthweight infants for tracking Tc PCO2 values. In addition, we suggest that inaccuracies in PAC sampling may lead to erroneous PCO2 determinations. We conclude that routine monitoring of Tc PCO2 is accurate and serves a useful and continuing role in the neonatal intensive care environment.

Arteries↗

Human newborn skin: the effect of isopropanol on skin surface hydrophobicity.

The development of a hydrophobic skin surface in newborn mammals such as the rat plays an important role in promoting adaptation to the abrupt change in the environment that occurs at birth. To determine whether the skin surface plays a similar role in the human neonate, we performed tests of water sorption and desorption on the chest wall of 13 term newborns. These tests were performed within the first 24 h of life on unperturbed skin (controls) and after perturbation of a contralateral site with isopropanol. The degree of surface hydration was determined by measurement of skin surface electrical capacitance, and desorption rates were calculated by 1st-order kinetic analysis. The unperturbed surface of the newborn skin exhibited a peak sorption value (change from baseline after water loading) of 435 +/- 83 pF (mean +/- SEM) and a desorption rate of 0.048 +/- 0.009 s-1. After exposure to isopropanol, the peak sorption value increased to 594 +/- 79 pF (p < 0.05) and the desorption rate decreased to 0.024 +/- 0.004 s-1 (p < 0.01). Paired sorption values were positively correlated (r2 = 0.8, p < 0.001). These results support the hypothesis that the skin surface of the human newborn, by limiting the sorption of water (or amniotic fluid) on the skin, may play a role in the adaptation to the change in environment at birth.

1-Propanol↗

Rate of stratum corneum formation in the perinatal rat.

During late gestation, the fetal rat exhibits marked hyperplasia of the interfollicular epidermis and accelerated cornification in preparation for birth. In this study, we utilized simple morphometric techniques to provide quantitative estimates of the rate of stratum corneum (SC) formation during the perinatal period. Cryostat sections of dorsal epidermis from rat pups between -48 and +72 h of age were expanded under alkaline conditions and the number of corneocyte interfaces counted from photomicrographs. This method yielded the following regression lines: prenatal, y = 0.19x + 13.07, r = 0.93; postnatal, y = 0.13x + 13.00, r = 0.93, where y = number of SC layers and x = age in hours. Lack of desquamation was assured by the postnatal persistence of the granular periderm. Adhesive stripping of the epidermis followed by phase-contrast microscopy revealed intact monolayer sheets of SC. Quantitation using a computerized image analysis system gave an average corneocyte surface area in the newborn rat of 1908 +/- 36 mu 2 (mean +/- SEM). Treatment of neonatal rats with epidermal growth factor (500 ng/g BW) increased the number of SC layers over the first 24 h of life (p < 0.05) and resulted in marked hyperkeratosis by one week of age. These results allow the following conclusions: 1) in the prenatal rat, SC forms at a rate of one layer every 5 h; 2) postnatally, SC formation slows to one layer every 8 h; 3) to support normal corneum synthesis at birth, dorsal keratinocytes must enter transition at a rate of approximately 3 cells/second/cm2 of body surface; and 4) treatment with exogenous EGF augments the rate of terminal differentiation of perinatal rat epidermis.

Animals↗

Ontogeny of water sorption-desorption in the perinatal rat.

In mammals, birth marks a transition to a cold and gaseous environment that requires rapid physiologic adaptations limiting heat and water loss. In this study, the perinatal Sprague-Dawley rat was utilized as a model to study the behavior of water binding to the external body surface following birth. Water sorption and desorption were quantified by measurement of skin surface capacitance following water loading using a dry ring electrode system. The results indicate that the external body surface of the newborn rat is highly hydrophobic. This hydrophobicity is manifested by the rapid desorption of water (amniotic fluid) following birth as well as marked limitation of water sorption after birth. Post-natally, this hydrophobic effect is gradually lost over the first 3 d of life. Somatic growth retardation results in retention of this surface property, whereas extraction of the skin surface with acetone abolishes it. Morphologic and functional (water binding) studies performed after stripping the stratum corneum with acrylic adhesive strongly suggest a physiologic role for the periderm in determining this postnatal hydrophobic effect. These data are interpreted as evidence for a novel thermoregulatory mechanism in the rat during adaptation to post-natal life.

Absorption↗

Changes in static and dynamic skin fold measurements in the first 60 hours of life: higher values following cesarean delivery.

Infants born by cesarean section (CS) have been reported to have increased intracellular and total body water and have a slower postnatal decline in cell water content compared to vaginally delivered infants. These findings support the hypothesis that delivery-related changes in water compartmentalization will result in postnatal differences in tissue compressibility. In order to test this hypothesis, static and dynamic skin fold thicknesses (SFTs) were obtained in 60 healthy, term, appropriate for gestational age infants between 1 and 60 h of life. Thirty infants were delivered vaginally and 30 by CS. Midtriceps, subscapular and abdominal skin folds were measured twice daily during the first 3 days of life. There were no differences between groups in birth weight, length, head circumference, gestational age, sex or ponderal index. Our results showed that static SFTs were significantly greater in CS than in vaginally delivered infants at birth and remained so throughout the study period. In both groups, static SFTs increased while weight decreased over time. At birth, dynamic SFTs were significantly greater in infants delivered by CS. We speculate that skin fold differences between CS and vaginal deliveries may reflect a different dynamic of perinatal body water distribution. The mechanism underlying the paradoxical increase in static SFTs in both groups is unknown.

Body Water↗

Preservation of permeability barrier ontogenesis in the intrauterine growth-retarded fetal rat.

The epidermal permeability barrier is provided by intercellular lipids forming multiple membrane bilayers in the stratum corneum. In the fetal rat, the barrier to transepidermal water loss forms during the 20th d of gestation and is accompanied by 1) increasing stratum corneum thickness; 2) increasing stratum corneum lipid content, particularly nonpolar ceramide and cholesterol content; and 3) the formation of lamellar unit structures throughout the stratum corneum interstices. In this report, we demonstrate that among pups of 20 d gestational age increasing barrier competence is correlated with increasing fetal weight. It has been previously demonstrated that fetal rats subjected to intrauterine growth retardation (IUGR) exhibit a thinner stratum corneum and decreased content of differentiation-specific epidermal structural proteins. To determine whether IUGR fetal rats also exhibit immaturity of barrier function and the barrier membrane system, maternal rats underwent unilateral uterine vessel ligation on d 17 or 18 of gestation and IUGR and control littermates were harvested on d 20, 21, or 22 of gestation for determination of transepidermal water loss. Despite significant somatic growth retardation and a thinner stratum corneum, barrier function in IUGR fetal rats did not significantly differ from that in control littermates at any gestational age. In both IUGR and control fetal rat epidermis at 21 d gestational age, lipids were deposited in a membrane pattern as visualized by nile red fluorescence microscopy and formed lamellar unit membrane structures throughout the stratum corneum intercellular domains as observed by electron microscopy.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Epidermal growth factor stimulates insulin-like growth factor-binding protein-1 expression in the neonatal rat.

Insulin-like growth factors (IGFs) and the IGF-binding proteins (IGFBPs) appear to be important in the regulation of perinatal growth. We have shown previously that administration of epidermal growth factor (EGF) to newborn rat pups inhibits growth and decreases serum IGF-I concentrations. The experiments described here were designed to investigate the effect of EGF on the IGFBPs using ligand blots of serum and Northern analysis of hepatic RNA. EGF administration caused a rapid (within 2 h) 2-fold increase in the serum IGFBP-1 concentration. Hepatic IGFBP-1 mRNA increased even more rapidly, was increased at least 2-fold at 2 h, and remained elevated 4 h after EGF. The response to EGF was specific to IGFBP-1; IGFBP-2 hepatic mRNA content was not increased over the control value, and serum IGFBP-3 and -4 concentrations were not changed by ligand blot analysis. The IGFBP-1 response to EGF was most dramatic in the first few days of life. Although EGF lowered circulating insulin levels, EGF stimulated IGFBP-1 secretion in the presence of exogenously administered insulin. Thus, the increase in IGFBP-1 did not appear to be mediated by changes in serum insulin. These results demonstrate that EGF increases serum IGFBP-1 concentrations, probably by stimulating synthesis. The association of decreased growth and increased IGFBP-1 concentrations after EGF treatment suggests that elevated IGFBP-1 concentrations may restrict IGF bioactivity in the neonatal rat.

Aging↗

Early metabolic consequences of epidermal growth factor administration to neonatal rats.

Daily administration of epidermal growth factor (EGF) to neonatal rodents elicits a classic morphogenetic syndrome. In this study, we examined the early (minutes to hours) consequences of EGF treatment in the neonatal rat (age 0-72 h). Significant findings included a rapid reduction in resting heart rate 4 h after EGF treatment accompanied by a sensitive dose- and age-dependent decrease in systemic oxygen consumption (VO2). Midscapular skin temperature (MST) was measured as a putative noninvasive indicator of brown adipose tissue thermogenesis. As little as 10 ng EGF/g body wt elicited a significant reduction in MST. Both the decrease in VO2 evoked by EGF and the MST response were potentiated by environmental cold exposure. EGF treatment also resulted in rapid (90 min) reductions in circulating levels of glycerol, triglyceride, and cholesterol while increasing serum glucose and arachidonic acid. Other free fatty acids were unaffected. Serum lactate levels were increased by EGF with the same time course as the reduction in VO2. These results provide new biochemical data on the pharmacological actions of EGF and further characterize the EGF-treated neonatal rodent as an intriguing in vivo model of growth factor action.

Animals↗

Ontogeny of integumental calcium in relation to surface area and skin water content in the perinatal rat.

Calcium is an important regulator of epidermal differentiation and skin biomechanics in many vertebrate species. In this study, we measured total epidermal calcium in the perinatal Sprague-Dawley rat. Values ranged from 12 to 15 mg per 100 g of tissue. These levels were elevated compared with dermis and other soft (nonbone) organs, including brain, kidney, heart, and liver. Administration of radioactive calcium to the pregnant rat resulted in high rates of 45Ca2+ localization in the fetal epidermis 24 h later. From gestational day 20 to postnatal day 3, the epidermis showed progressive dehydration with water content decreasing from 79 to 73%. Dermal hydration over the same period decreased from 91 to 81%. In the neonatal rat (age 0-3 days), linear regression analysis of surface area vs. body weight on a log-log plot yielded a slope of 1.04. This finding contrasts with an expected slope of 0.67 based on simple surface area-to-volume relationships and differs from the empirical 0.75-power law observed in adult bioenergetics. In summary, these results show the perinatal rat is encapsulated by a continuous differentially hydrated calcium-rich epidermal envelope that increases in surface area over the early postnatal period directly as the first power of body mass.

Animals↗

Effects of maternally administered epidermal growth factor on placental permeability.

Epidermal growth factor is a well-studied modulator of epithelial membrane structure and function. Mammalian placentas are a rich source of epidermal growth factor receptors, but the role of epidermal growth factor in placental pathophysiologic conditions is unclear. To determine whether epidermal growth factor could affect mechanisms of placental transfer, we used an in situ rat placental perfusion model. Fourteen Sprague-Dawley rats that were 20 days pregnant were randomized to epidermal growth factor or placebo during placental transport experiments. We chose ethylenediaminetetraacetate tagged with chromium 51 as a marker of placental permeability. Epidermal growth factor treatment led to a dramatic increase of maternofetal clearances of chromium 51-ethylenediaminetetraacetate. We conclude that maternally administered epidermal growth factor has a potent action on placental permeability.

Animals↗

Suppression of insulin-like growth factor I during epidermal growth factor-induced growth retardation.

Epidermal growth factor (EGF) attenuates growth when administered to rats less than 2 wk of age but lacks growth-retarding properties when given to older animals. Because the insulin-like growth factors (IGF) are postulated to be important regulators of somatic growth during the perinatal period, we examined the effect of exogenous EGF on serum and tissue concentrations of IGF-I and hepatic expression of mRNA for IGF-I and IGF-II. A single injection of EGF (500 ng/g body wt) produced a significant (P less than 0.01) decline in serum IGF-I concentration within 4 h in newborn rat pups [controls, 46.2 +/- 9.1 (SD) ng/ml; EGF treated, 29.4 +/- 4.0 ng/ml] but was ineffective in 2-wk-old animals (control IGF-I, 72.8 +/- 15.1 vs. 64.0 +/- 13.7 ng/ml). When the EGF was given on days 0-3 of life, circulating IGF-I concentrations were suppressed further (control, 61.4 +/- 8.6; EGF treated, 32.5 +/- 8.6 ng/ml). Despite the change in circulating IGF-I levels in the newborn rats, the amount of IGF-I extractable from liver and kidney of growth-retarded animals was not significantly different from control. Likewise, IGF-I and IGF-II mRNA expression in liver, as assessed by blot hybridization, was unchanged by the EGF treatment. The rapid decline in IGF-I concentration after EGF administration, coupled with the restriction of this phenomenon the first 2 wk of extrauterine life, implies that changes in IGF-I are involved in the pathogenesis of EGF-induced growth retardation.

Animals↗

Considerations on the role of surface tension and epidermal growth factor in the mechanism of integumental pattern formation.

The formation of the posterior parietal hair whorl during normal human development is proposed as a morphogenetic problem in which the effects of surface tension and the appearance of singularities figure prominently. Surface tension is considered in the sense of "Langer's lines" which define local contours of tension in the skin of the organism. According to this view, an analysis of the organism's skin tension field is fundamental to problems of integumental pattern formation. A computational analysis of the skin tension field is proposed, potentially using methods from finite element theory applied to molecular and cellular mechanisms within the skin which resist deformation. To this end, surface tension is provisionally defined as the differential adsorption (adhesion) of molecular and supramolecular binding elements within the skin. In practical applications, it is suggested that epidermal growth factor (EGF) and similar molecules have the physicochemical features and the biological effects required to experimentally probe surface tension phenomena at supramolecular levels. In this regard, the concept of topological discontinuities is introduced as a potential theoretical bridge across levels of organization. Specific examples of these discontinuities are given and discussed in terms of the development of singularities in control surfaces. It is hoped that these considerations will be useful in the mechanistic analysis of hair whorl formation during human embryo-genesis and in other problems of integumental pattern formation and nonequilibrium surface behavior.

Animals↗

Sensory transduction and the mammalian epidermis.

This paper constitutes, in its main intent, an introduction to the mammalian epidermis as a surface for biosensor applications. In particular, the structure and function of the epidermis of the newborn rat are examined as a model for studies of the human state. Data are presented illustrating an anisotropic organization of the dorsal surface of the neonatal rodent with regard to line of tension and thermal gradients. The dependence of the mechanical properties of the epidermis upon calcium is examined by means of an in-vitro assay of epidermal retraction. The potential role of keratin tonofilaments as piezoelectric and pyroelectric elements in the epidermis is introduced and the spatial alignment of these macromolecular arrays is demonstrated to be a function of physiological tensions. These findings are discussed in the context of noninvasive epidermal sensors utilized to understand mechanisms of sensory development and physiological regulation. Optoelectronic (infrared) imaging of the dorsal temperature field and the alteration in this field by treatment with epidermal growth factor are presented as examples of this methodologic approach. It is concluded that a detailed examination of the material and physical properties of mammalian epidermis is a reasonable goal of biosensor development and research. Hypothetically, such studies may reveal important molecular and cellular mechanisms by which sensory data are transmitted or transduced at the organism-environmental interface.

Animals↗

Epidermal development in the growth retarded fetal rat.

Intrauterine growth retardation (IUGR) due to vascular insufficiency in humans results in newborn infants with marked loss of subcutaneous fat and a poorly characterized "dysmature" appearance of the epidermis. In this study, we examined selected indices of epidermal development in 20 and 21 day old growth retarded fetal rats. IUGR was produced by unilateral ligation of the uterine artery and vein on gestational day 17. Littermate rats from the opposite uterine horn were utilized as pair matched experimental controls. A total of 49 consecutive fetal pairs were examined. Mean body weight (+/- SEM) for controls was 4.2 +/- 0.1 g versus 2.6 +/- 0.2 g for the treatment group on gestational day 20 (n = 74, P less than 0.01) and 6.0 +/- 0.1 versus 4.0 +/- 0.2 g, respectively, on the day 21 (n = 24, P less than 0.01). Examination by light and electron microscopy showed marked diminution in overall epidermal thickness in the growth retarded animals, particularly of the stratum granulosum and stratum corneum. Epidermal DNA content was decreased in IUGR pups on day 20 (0.99 +/- 0.05 versus 1.26 +/- 0.07 micrograms DNA/mg wet weight, P less than 0.05). Soluble epidermal proteins showed a similar reduction in IUGR animals (30.2 + 0.8 versus 34.7 +/- 1.6 micrograms protein/mg wet weight, P less than 0.05). IUGR also decreased the total amount of epidermal protein extractable in 8 M urea. Differentiation-specific epidermal proteins (keratins, filaggrin) were markedly reduced in the growth retarded animals following normalization to epidermal surface area and analysis by polyacrylamide gel electrophoresis. Overall, these changes in the growth retarded fetal rat lead to formation of a thin, hypoplastic, and poorly keratinized epidermal covering.

Animals↗

Surface tension in the developing mammal: anisotropic tension generation in the dorsal skin of the perinatal rat.

It is common knowledge that skin biopsies retract following excision. The direction and the magnitude of this retraction is thought to be related to the field of tension previously experienced by the skin sections in vivo. We utilized this phenomenon to investigate the ontogeny, directionality, and regulation of skin tension in the perinatal rat from gestational day 20 to postnatal day 6. In this study, geometrically-precise biopsies (circles and rectangles) were excised from the dorsal skin of perinatal rats and placed in tissue culture media. The excised skin sections rapidly exhibited changes in shape (to ellipses and helices). These resulting conformations were characterized with regard to selected spatial attributes; i.e., the ratio of major to minor axes for elliptical figures and the "winding number" for helices. This simple methodological approach allowed the following conclusions: 1) skin retraction in the rat is anisotropic and is maximal in the rostral-caudal direction; 2) skin retraction is inversely related to postnatal age and to ambient temperature; 3) retraction is inhibited by in vivo treatment with epidermal growth factor (EGF) as well as by metabolic poisons such as sodium azide; 4) retraction is augmented in vitro by calcium chloride. Overall, these data support the hypothesis of a metabolically active, temperature-dependent, anisotropically organized retractile mechanism in the dorsal skin of the perinatal rat.

Aging↗