Association of caesarean delivery with child adiposity from age 6 weeks to 15 years.

OBJECTIVES: o assess associations of caesarean section with body mass from birth through adolescence. DESIGN: ongitudinal birth cohort study, following subjects up to 15 years of age. SETTING AND PARTICIPANTS: Children born in 1991-1992 in Avon, UK who participated in the Avon Longitudinal Study of Parents and Children (ALSPAC) (n=10 219). PRIMARY OUTCOME: standardized measures of body mass (weight-for length z-scores at 6 weeks, 10 and 20 months; and body mass index (BMI) z-scores at 38 months, 7, 9, 11 and 15 years). Secondary outcome: categorical overweight or obese (BMI: 85th percentile) for age and gender, at 38 months, 7, 9, 11 and 15 years. RESULTS: Of the 10 219 children, 926 (9.06%) were delivered by caesarean section. Those born by caesarean had lower-birth weights than those born vaginally (-46.1 g, 95% confidence interval(CI): 14.6-77.6 g; P=0.004). In mixed multivariable models adjusting for birth weight, gender, parental body mass, family sociodemographics, gestational factors and infant feeding patterns, caesarean delivery was consistently associated with increased adiposity, starting at 6 weeks (+0.11 s.d. units, 95% CI: 0.03-0.18; P=0.005), through age 15 (BMI z-score increment+0.10 s.d. units, 95% CI: 0.001-0.198; P=0.042). By age 11 caesarean-delivered children had 1.83 times the odds of overweight or obesity (95% CI: 1.24-2.70; P=0.002). When the sample was stratified by maternal pre-pregnancy weight, the association among children born of overweight/obese mothers was strong and long-lasting. In contrast, evidence of an association among children born of normal-weight mothers was weak. CONCLUSION: Cesarean delivery is associated with increased body mass in childhood and adolescence. Research is needed to further characterize the association in children of normal weight women. Additional work is also needed to understand the mechanism underlying the association, which may involve relatively enduring changes in the intestinal microbiome.

Infant antibiotic exposures and early-life body mass.

OBJECTIVES: To examine the associations of antibiotic exposures during the first 2 years of life and the development of body mass over the first 7 years of life. DESIGN: Longitudinal birth cohort study. SUBJECTS: A total of 11 532 children born at 2500 g in the Avon Longitudinal Study of Parents and Children (ALSPAC), a population-based study of children born in Avon, UK in 1991-1992. MEASUREMENTS: Exposures to antibiotics during three different early-life time windows (<6 months, 6-14 months, 15-23 months), and indices of body mass at five time points (6 weeks, 10 months, 20 months, 38 months and 7 years). RESULTS: Antibiotic exposure during the earliest time window (<6 months) was consistently associated with increased body mass (+0.105 and +0.083 s.d. unit, increase in weight-for-length Z-scores at 10 and 20 months, P<0.001 and P=0.001, respectively; body mass index (BMI) Z-score at 38 months +0.067 s.d. units, P=0.009; overweight OR 1.22 at 38 months, P=0.029) in multivariable, mixed-effect models controlling for known social and behavioral obesity risk factors. Exposure from 6 to 14 months showed no association with body mass, while exposure from 15 to 23 months was significantly associated with increased BMI Z-score at 7 years (+0.049 s.d. units, P=0.050). Exposures to non-antibiotic medications were not associated with body mass. CONCLUSIONS: Exposure to antibiotics during the first 6 months of life is associated with consistent increases in body mass from 10 to 38 months. Exposures later in infancy (6-14 months, 15-23 months) are not consistently associated with increased body mass. Although effects of early exposures are modest at the individual level, they could have substantial consequences for population health. Given the prevalence of antibiotic exposures in infants, and in light of the growing concerns about childhood obesity, further studies are needed to isolate effects and define life-course implications for body mass and cardiovascular risks.

An overview of essential hypertension in Americans as a multifactorial phenomenon: interaction of biologic and environmental factors.

This paper reviews the current literature on essential/primary hypertension in terms of its expression as a multifactorial phenomenon. The genetic and environmental risk factors involved in expression of hypertension and their interactions are discussed. A specific mutation in epithelial sodium channels, T549M, is presented as a genetic risk factor for primary hypertension as expression of this mutation has been reported to result in hyperabsorption of sodium in homozygous individuals. T549M is used in this report to illustrate the multifactorial nature of primary hypertension. Possible interactions of T549M with environmental factors known to promote hypertension and the outcome of these interactions are discussed. Data indicates that both genetic and environmental risk factors must be considered to understand and intervene effectively with patients who have primary or essential hypertension.

Human amylin stimulates inflammatory cytokine secretion from human glioma cells.

Chronic neurodegeneration in the brains of Alzheimer's disease (AD) patients may be mediated, at least in part, by the ability of amyloid beta (Abeta) to exacerbate inflammatory pathways in a conformation-dependent manner. In this regard, we previously reported that the Abeta-peptide-mediated potentiation of inflammatory cytokine secretion from interleukin-1beta (IL-1beta)-stimulated human astrocytoma cells was conformation dependent. Other amyloidogenic peptides, such as human amylin, which display similar conformation-dependent neurotoxic effects, may also elicit inflammatory cytokine secretion from glial cells. To test this hypothesis, we compared human and rat amylin for the effects on cytokine production in U-373 MG human astrocytoma cells. Human amylin alone stimulated U-373 MG cells to secrete IL-6 and IL-8 in a concentration-dependent manner with maximum effects seen at 10-25 microM peptide. In addition, human amylin markedly potentiated IL-1beta-stimulated cytokine production with a similar concentration dependence. In contrast, nonamyloidogenic rat amylin modestly stimulated cytokine secretion, either alone or combined with IL-1beta. Aging human amylin resulted in diminished cytokine secretion, probably due to the formation of large, less active aggregates. In agreement with our previous studies using Abeta, extracellular Ca(2+) was necessary for human amylin stimulation of cytokine secretion. Our data suggest that amyloidogenic peptides promote cytokine secretion through similar beta-sheeted secondary-structure- and extracellular-Ca(2+)-dependent mechanisms.

The influence of physical activity, socioeconomic status, and ethnicity on the weight status of adolescents.

OBJECTIVE: This study examined the effects of physical activity, television viewing, video game play, socioeconomic status (SES), and ethnicity on body mass index (BMI). RESEARCH METHODS AND PROCEDURES: The sample was 2389 adolescents, 10 to 16 years of age (12.7 +/- 1.0 years); 1240 (52%) females and 1149 (48%) males; 77% white and 23% African American; from rural (77%) and urban (23%) settings. BMI and skinfolds were directly assessed. All other data were obtained from questionnaires. RESULTS: Watching television on non-school days was related to being overweight (p < 0.005). However, when BMI analyses were adjusted for ethnicity and SES, there were no significant effects of television viewing on BMI (p > 0.061). Increased hours of video game play enhanced the risk of being overweight for both genders when analyses were adjusted for ethnicity and SES (p < 0.019). In males, participation in as little as one high-intensity physical activity 3 to 5 days a week decreased the ethnic- and SES-adjusted relative risk of being overweight (RR = 0.646; CI: 0.427 to 0.977). For females, the ethnic- and SES-adjusted relative risk for being overweight was not significantly altered by physical activity. The logistic analyses further indicated the influence of low SES and African American ethnicity overshadowed any direct effect of television or videos. DISCUSSION: Because weight status of male adolescents appears to be more related to exercise habits than to television or video game habits, increased participation in high-intensity exercise appears to be important. For females, neither videos nor exercise habits appear to be related to risk of being overweight. However, ethnicity and SES may be important factors that can influence body weight status, while television viewing may be of some importance. Thus, programs to reduce obesity in female adolescent should focus their efforts in lower SES communities.

Terbutaline increases open channel density of epithelial sodium channel (ENaC) in distal lung.

Neonatal and adult vertebrate respiration is facilitated by alveolar fluid and sodium (Na+) absorption driven by apical sodium channels (ENaC). ENaC are characterized in Xenopus laevis lung (XLL) epithelia using voltage clamping and fluctuation analysis to non-invasively examine macroscopic transepithelial current and resistance (I(SC), R(T)), single channel current (i(Na)) and total channel density (N(T)) responses to a beta adrenergic agonist (Terbutaline). Terbutaline addition to the basolateral bath of XLL increased Na entry to > 200% of control reflecting a doubling of open channel density (N(o). These data are consistent with the notion that XLL can serve as a useful model for investigation of distal lung ENaC response to agents of physiological interest.

Staging of malignant cutaneous wounds: a pilot study.

PURPOSE/OBJECTIVES: To determine the color, size, hydration, and general appearance of malignant cutaneous wounds (MCWs); the effectiveness of using digital imagery to quantify wound characteristics; and the feasibility of an MCW staging system. DESIGN: Descriptive pilot study. SETTING: A university-affiliated, comprehensive cancer center. METHODS: Assessment of each subject's wound (N = 13) using the Hopkins Wound Assessment Tool (HWAT) and digital analysis of photographs. Development of an MCW staging system from grouping and classifying the assessment data. A panel of experts used the assessment data and MCW staging system to determine each subject's wound stage and the feasibility of a staging system. Visual HWAT data and digital photographic assessment data were compared for consistency in size, color, and hydration status. MAIN RESEARCH VARIABLES: Characteristics and stages of MCW; digital imagery. FINDINGS: Investigators identified four stages of MCW using the wound characteristics. Digitally assessed wound measurements of size, color, and hydration status were consistent, reflecting the ability of this method to accurately capture malignant wound characteristics. CONCLUSIONS: An MCW staging system is feasible. Wound color, hydration status, the absence or presence of nodules, drainage, pain, odor, and tunneling indicate the stage of malignant wound progression. The two stages identified are distinctly different from pressure or diabetic wound progression. Stage 1N is characterized by fibrous desmoplasia (hard fibrous nodule) of cancer metastasis, and stage 4 is characterized by destruction of the basement membrane. Data comparisons indicate that digital assessment has potential for more accurately recording wound assessment indices. IMPLICATIONS FOR NURSING PRACTICE: Nurses can improve their assessment and management of a patient's MCW by understanding the wounds' stages and using a digital imaging protocol. Further research is needed to establish the reliability and validity of the MCW staging system and the digital assessment and quantification protocol.

Insulin increases sodium (Na+) channel density in A6 epithelia: implications for expression of hypertension.

Essential or primary hypertension is a multifactorial disease that is expressed as a result of complex interactions between genes and environmental influences. Several mutations in many different proteins are associated with expression of hypertension, including abnormalities in the epithelial sodium channel (ENaC) found in absorptive organs (i.e., distal colon, distal tubule of the nephron). Some of these mutations result in structural and/or functional alterations in ENaC-mediated Na+ entry in epithelia responsible for fluid and electrolyte balance and are associated with expression of hypertension. Studies support the notion that there is a link between ENaC and hypertension of both the monogenic (single gene mutation) and primary or essential type (a multifactorial disease). Alterations of other aspects of the environment of absorptive cells (e.g., hyperinsulinemia, hyperaldosteronemia, high plasma cortisol, high plasma Na+) have also been shown to elicit hyperabsorption of Na+ via ENaC and therefore could contribute significantly to expression of hypertension in people with intermediate phenotypes. This article describes an initial study in which the effects of an environmental factor, extracellular levels of insulin, on ENaC were examined in a normal kidney cell model. Electrophysiologic techniques revealed that ENaC density rapidly increased in response to addition of insulin to the basolateral bath. This autoregulatory recruitment of Na+ total channel density masked a slight decrease in open channel probability. Insulin's effect on ENaC function and implications on fluid and electrolyte balance and expression of primary hypertension is discussed.

The affinity of cholera toxin for Ni2+ ion.

Cholera toxin (CT) was shown to bind to immobilized Ni2+ ion. The affinity of CT for the complex required the presence of the Ni2+ ion, since CT was unable to bind in its absence. Binding was mediated by the B-subunit (CTB) as both CT and CTB bound to the resin, but not the A-subunit (CTA). Binding was reversible in the presence of imidazole and suggested that the affinity of CT for the Ni2+ ion was mediated by His residues. The heat-labile enterotoxin of Escherichia coli (LT), which is closely related to CT, was unable to bind to the Ni2+ ion. Comparison of amino acid sequences revealed the presence of three His residues in CT (positions 13, 57 and 94), but only one in LT (position 57). To confirm that the residues at positions 13 and 94 of CTB were responsible for the binding, they were changed to residues found in LTB. Changing His13-->Arg completely abrogated the ability of CTB to bind to Ni2+ ion. In contrast, the mutation of His 94-->Asn reduced, but did not abrogate, the ability of CTB to bind to Ni2+ ion. Based on calculated interatomic distances, it is unlikely that His13 and His94 are part of the same complex. There appear to be two separate binding sites, with the principal site involving His13 and a much weaker site involving His94. This latter site can only participate in binding if the complex involving His13 has formed.

Steroid hormone-dependent expression of blocker-sensitive ENaCs in apical membranes of A6 epithelia.

Weak channel blocker-induced noise analysis was used to determine the way in which the steroids aldosterone and corticosterone stimulated apical membrane Na+ entry into the cells of tissue-cultured A6 epithelia. Among groups of tissues grown on a variety of substrates, in a variety of growth media, and with cells at passages 73-112, the steroids stimulated both amiloride-sensitive and amiloride-insensitive Na+ transport as measured by short-circuit currents in chambers perfused with either growth medium or a Ringer solution. From baseline rates of blocker-sensitive short-circuit current between 2 and 7 microA/cm2, transport was stimulated about threefold in all groups of experiments. Single channel currents averaged near 0.3 pA (growth medium) and 0.5 pA (Ringer) and were decreased 6-20% from controls by steroid due to the expected decreases of fractional transcellular resistance. Irrespective of baseline transport rates, the steroids in all groups of tissues stimulated transport by increase of the density of blocker-sensitive epithelial Na+ channels (ENaCs). Channel open probability was the same in control and stimulated tissues, averaging approximately 0.3 in all groups of tissues. Accordingly, steroid-mediated increases of open channel density responsible for stimulation of Na+ transport are due to increases of the apical membrane pool of functional channels and not their open probability.

Ca2+-sensing receptors in intestinal epithelium.

Expression of Ca2+-sensing receptors (CaR) was demonstrated in several human intestinal epithelial cell lines (T84, HT-29, and Caco-2) and in rat intestinal epithelium by both reverse transcriptase-polymerase chain reaction (PCR) and Northern blotting of RNA. Restriction patterns of the PCR products were of the sizes predicted by the human and rat sequences. CaR agonists (Ca2+, poly-L-arginine, protamine) mediated an increase in intracellular Ca2+ in HT-29-18-C1 cells (monitored by changes in fura 2 fluorescence), which was dependent on release from thapsigargin-sensitive stores. U-73122, an inhibitor of phosphatidylinositol-phospholipase C, eliminated the CaR agonist-mediated rise in intracellular Ca2+, whereas its inactive analog, U-73343, had no effect. Pertussis toxin pretreatment had no effect on CaR agonist-mediated modulation of intracellular Ca2+. Taken together, these studies demonstrate that CaR are expressed in intestinal epithelial cells and couple to mobilization of intracellular Ca2+. The presence of CaR in intestinal epithelial cells presents a new locus for investigations into the role(s) of extracellular Ca2+ in modulating intestinal epithelial cell differentiation and transepithelial Ca2+ transport.

The role of social physique anxiety and other variables in predicting eating behaviors in college students.

Early identification of potentially harmful eating patterns is critical in the effective remediation of such behaviors. The purpose of this investigation was to examine the degree to which various factors including gender, family history, and athletic status predict disordered eating behavior; social physique anxiety and percent body fat were added as potential predictor variables. The eating behaviors of student-athletes and nonathlete students were also compared. One hundred eighty undergraduate students (males = 49, females = 131) provided demographic information and completed the Eating Attitudes Test (EAT) and the Social Physique Anxiety Scale (SPAS). Stepwise multiple-regression analysis indicated that social physique anxiety, gender, and body fat (%Fat) combined to predict 34% of disordered eating behaviors: EAT = 0.921 SPA - 1.05 %Fat + 10.95 Gender (1 = M, 2 = F) - 17.82 (R2 = .34, SE = 4.68). A one-way ANOVA comparing the eating behaviors of athletes and nonathletes revealed no significant difference between these groups.

The medical and epidemiologic effects on workers of the levels of airborne Thermoactinomyces Spp. spores present in Australian raw sugar mills.

The objectives of the study were to determine whether there was a significant risk of members of the work force of raw sugar mills developing bagassosis. Airborne Thermoactinomyces sacchari spores were measured to determine whether they were sufficient to cause acute bagassosis, and whether there was any evidence of previous exposure to sufficient airborne T. sacchari spores to cause the development of chronic bagassosis in any of the work force. Monitoring of total airborne bacteria spore concentrations was undertaken in and around two cane sugar mills before, during, and after the 1992 cane processing season. Viable airborne bacteria counts were also obtained to confirm the presence of Thermoactinomyces sacchari. Area or zone samples at various sites around the mills and personal breathing zone samples from selected workers were obtained. The results showed that the total airborne bacteria spore count was lower than similar counts reported in other industries, such as cotton milling and wood chip handling, during normal operations. It was also found that the airborne counts during specific activities that generated higher than usual airborne spore levels were lower than expected from literature reports of handling similar material. Complementary medical examination of the entire full-time work forces of the two mills was carried out on a number of occasions during 1992. The medical data showed that no cases of acute bagassosis were detected, and that there was no evidence of the development of chronic bagassosis in any members of the work forces of either mill. Therefore, there is no significant risk of workers in the Australian sugar industry developing bagassosis.

Amyloid beta peptide potentiates cytokine secretion by interleukin-1 beta-activated human astrocytoma cells.

Neurodegenerative processes in Alzheimer disease (AD) are thought to be driven in part by the deposition of amyloid beta (A beta), a 39- to 43-amino acid peptide product resulting from an alternative cleavage of amyloid precursor protein. Recent descriptions of in vitro neurotoxic effects of A beta support this hypothesis and suggest toxicity might be mediated by A beta-induced neuronal calcium disregulation. In addition, it has been reported that "aging" A beta results in increased toxic potency due to peptide aggregation and formation of a beta-sheet secondary structure. In addition, A beta might also promote neuropathology indirectly by activating immune/inflammatory pathways in affected areas of the brain (e.g., cortex and hippocampus). Here we report that A beta can modulate cytokine secretion [interleukins 6 and 8 (IL-6 and IL-8)] from human astrocytoma cells (U-373 MG). Freshly prepared and aged A beta modestly stimulated IL-6 and IL-8 secretion from U-373 MG cells. However, in the presence of interleukin-1 beta (IL-1 beta), aged, but not fresh, A beta markedly potentiated (3- to 8-fold) cytokine release. In contrast, aged A beta did not potentiate substance P (NK-1)- or histamine (H1)-stimulated cytokine production. Further studies showed that IL-1 beta-induced cytokine release was potentiated by A beta-(25-35), while A beta-(1-16) was inactive. Calcium disregulation may be responsible for the effects of A beta on cytokine production, since the calcium ionophore A23187 similarly potentiated IL-1 beta-induced cytokine secretion and EGTA treatment blocked either A beta or A23187 activity. Thus, chronic neurodegeneration in AD-affected brain regions may be mediated in part by the ability of A beta to exacerbate inflammatory pathways in a conformation-dependent manner.

Pharmacological characterization of LY303870: a novel, potent and selective nonpeptide substance P (neurokinin-1) receptor antagonist.

LY303870 [(R)-1-[N-(2-methoxybenzyl)acetylamino]-3-(1H-indol-3-yl)-2-[N-(2-(4- (piperidin-1-yl)piperidin-1-yl)acetyl)amino]propane] is a new, potent and selective nonpeptide neurokinin-1 (NK-1) receptor antagonist. LY303870 bound selectively and with high affinity to human peripheral (Ki = 0.15 nM) and central (Ki = 0.10 nM) NK-1 receptors. LY303870 inhibited [125I]substance P (SP) binding to guinea pig brain homogenates with similar affinity; however, it had approximately 50-fold lesser affinity for rat NK-1 sites. The less active enantiomer, LY306155 [(S)-1-[N-(2-methoxybenzyl)acetylamino]-3-(1H-indol-3-yl)-2-[N-(2-(4- (piperidin-1-yl)piperidin-1-yl)acetyl)amino]-propane], was 1,000- to 15,000-fold less potent in all the species examined. LY303870 antagonized in vitro NK-1 receptor effects as demonstrated by blockade of SP-stimulated phosphoinositide turnover in UC-11 MG human astrocytoma cells (Ki = 1.5 nM) and interleukin-6 secretion from U-373 MG human astrocytoma cells (Ki = 5 nM). In addition, LY303870 inhibited SP-induced rabbit vena cava contractions (pA2 = 9.4) with high (50,000-fold) selectivity vs. NK-2 or NK-3 receptor-mediated responses. In vivo, LY303870 inhibited [Sar9,Met(O2)11]-SP induced guinea pig bronchoconstriction (ED50 = 75 micrograms/kg i.v.) and pulmonary microvascular leakage in the bronchi (ED50 = 12.8 micrograms/kg i.v.) and trachea (ED50 = 18.5 micrograms/kg i.v.). Therefore, LY303870 is a potent and selective NK-1 receptor antagonist in vitro and in vivo. The use of LY303870 will facilitate a better understanding of NK-1 receptors in physiological processes.

Transpiration as a function of soil temperature and soil water stress.

An apparatus was developed for the measurement of transpiration rates of Trifolium repens. The transpiration rates were measured under controlled conditions of soil water stress and soil temperature. Other environmental parameters such as air temperature, relative humidity, light intensity and air speed were held constant. Diffusive resistances were calculated and stomatal aperture changes were recorded for all treatment combinations. A significant interaction between soil water stress and soil temperature was observed for stomatal closures. Stomatal closure was observed even in the so-called wet range of soil water stress. An increase in mesophyll resistance or incipient drying was observed for several treatment combinations. The mesophyll resistance was shown to increase as soil water stress increased.