Wash or wipe? A comparative study of skin physiological changes between water washing and wiping after skin cleaning.

BACKGROUND/PURPOSE: Presently, skin-cleaning agents that claim to be removed by water or wiping alone are commercially available and have been used for the purpose of bed baths. However, there is a lack of knowledge on how water washing and wiping differently affect skin physiological functions or ceramide content. The aim of this study was to compare the effects of water washing and wiping on skin physiological functions and ceramide content. METHODS: Three kinds of the cleaning agents with different removal techniques (ie, water washing and wiping) were used in this study. Skin physiological functions (ie, transepidermal water loss, skin hydration, and skin pH) and skin ceramide content were measured before and after seven consecutive days of the application of each cleaning agent. RESULTS: No significant differences in skin physiological functions or ceramide content were observed between water washing and wiping. CONCLUSION: Cleaning agents that claim to be removed by water washing or wiping do not affect skin physiological functions or ceramide content by either removal method.

Detection of unruptured ovarian pregnancy subsequently successfully treated by conservative laparoscopic surgery: a case report and review of the literature.

Early detection of ovarian pregnancy (OP) is essential for successful laparoscopic conservative surgery. However, early preoperative ultrasonography-based diagnosis is often difficult when fetal cardiac activity or the yolk sac is absent. The authors report a case of OP diagnosed at eight weeks gestational age in a natural pregnancy. The patient presented with amenorrhea and transient vaginal bleeding, and slight tenderness in the right ovary was noted during vaginal ultrasonography. Furthermore, ultrasonography showed a gestational sac (GS) without fetal cardiac activity or yolk sac, consistent with OP, and an adjacent compressible lutein cyst. The uterus, fallopian tubes, and left ovary were normal, and no cul-de-sac blood or ascites were found. Laparoscopy showed a two-cm mass partially covering the right ovary, which contained an unruptured GS. Subsequently, the mass was removed, and OP was histologically confirmed.

Experimental determination of in-medium cluster binding energies and Mott points in nuclear matter.

In-medium binding energies and Mott points for d, t, 3He and α clusters in low-density nuclear matter have been determined at specific combinations of temperature and density in low-density nuclear matter produced in collisions of 47A MeV 40Ar and 64Zn projectiles with 112Sn and 124Sn target nuclei. The experimentally derived values of the in-medium modified binding energies are in good agreement with recent theoretical predictions based upon the implementation of Pauli blocking effects in a quantum statistical approach.

Laboratory tests of low density astrophysical nuclear equations of state.

Clustering in low density nuclear matter has been investigated using the NIMROD multidetector at Texas A&M University. Thermal coalescence modes were employed to extract densities, ρ, and temperatures, T, for evolving systems formed in collisions of 47A MeV (40)Ar+(112)Sn, (124)Sn and (64)Zn+(112)Sn, (124)Sn. The yields of d, t, (3)He, and (4)He have been determined at ρ=0.002 to 0.03 nucleons/fm(3) and T=5 to 11 MeV. The experimentally derived equilibrium constants for α particle production are compared with those predicted by a number of astrophysical equations of state. The data provide important new constraints on the model calculations.

Symmetry energy of dilute warm nuclear matter.

The symmetry energy of nuclear matter is a fundamental ingredient in the investigation of exotic nuclei, heavy-ion collisions, and astrophysical phenomena. New data from heavy-ion collisions can be used to extract the free symmetry energy and the internal symmetry energy at subsaturation densities and temperatures below 10 MeV. Conventional theoretical calculations of the symmetry energy based on mean-field approaches fail to give the correct low-temperature, low-density limit that is governed by correlations, in particular, by the appearance of bound states. A recently developed quantum-statistical approach that takes the formation of clusters into account predicts symmetry energies that are in very good agreement with the experimental data. A consistent description of the symmetry energy is given that joins the correct low-density limit with quasiparticle approaches valid near the saturation density.

Studies on the Cl + C2H5I reaction; site specific abstraction reactions and thermodynamics of adduct formation studied by observation of HCL product.

The reaction of chlorine atoms with alkyl iodides can play a role in the chemistry of the marine boundary layer. Previous studies have shown that at room temperature the reaction takes place via a complex mechanism including adduct formation. For the Cl + ethyl iodide reaction results on the thermodynamics of adduct formation and on the product yields are inconsistent. The kinetics of the reaction Cl + C(2)H(5)I have been studied by the direct observation of the HCl product in real time flash photolysis/IR absorption experiments as a function of temperature from 273 to 450 K. At temperatures above 375 K kinetic measurements confirm a direct process and the rate coefficient determined (4.85 +/- 0.55) x 10(-11) exp((-363 +/- 51)/T) cm(3) molecule(-1) s(-1) is in good agreement with previous direct determinations. Product yield studies have also been undertaken by comparing the HCl signal from Cl + C(2)H(5)I with that from a calibration reaction which shows that HCl is the sole product of the reaction at these temperatures. Yield studies with selectively deuterated ethyl iodide demonstrate that abstraction occurs predominantly from the alpha site, with the selectivity decreasing with temperature. Extrapolation of the yield data to 298 K predicts an alpha:beta ratio of 0.68:0.32. At temperatures between 273 and 325 K a biexponential growth was observed for the HCl signal consistent with adduct formation. Analysis of the HCl time profiles allowed the extractions of the forward and reverse rate coefficients for adduct formation and hence the calculations of the thermodynamic properties of adduct formation. A third law analysis yields a value of Delta(r)H = (-54 +/- 4) kJ mol(-1). The value of Delta(r)H is in good agreement with a previous third law determination (J. J. Orlando, C. A. Piety, J. M. Nicovich, M. L. McKee, P. H. Wine, J. Phys. Chem. A, 2005, 109, 6659).

Effect of phosphate deficiency-induced anthocyanin accumulation on the expression of Solanum lycopersicum GLABRA3 (SlGL3) in tomato.

In Arabidopsis thaliana, the bHLH transcription factor, GLABRA3 (AtGL3), is an important regulator of epidermal cell differentiation and positively controls anthocyanin accumulation. In contrast, we previously showed that Solanum lycopersicum GLABRA3 (SlGL3), the AtGL3 homolog, suppressed anthocyanin accumulation in Arabidopsis. To clarify this functional discrepancy in anthocyanin accumulation, we analyzed the SlGL3 expression pattern in anthocyanin-induced tomato. The SlGL3 expression was significantly reduced in tomato seedlings rich in anthocyanin as a result of inorganic phosphate (Pi) starvation. This was consistent with the previous result obtained in Arabidopsis, wherein the overexpression of SlGL3 was shown to inhibit anthocyanin accumulation. Our study suggests that the function of SlGL3 is different from that of AtGL3, and it might inhibit anthocyanin accumulation in tomato.

CPC-ETC1 chimeric protein localization data in Arabidopsis root epidermis.

Intercellular movement of transcription factor proteins is essential for plant development. The R3 type MYB transcription factor protein, CAPRICE (CPC), moves from non-hair cells to root-hair cells where it promotes root hair formation in Arabidopsis root epidermis. In contrast, the CPC homolog of ENHANCER OF TRY AND CPC1 (ETC1) cannot move in root epidermal cells. In this work, we present protein localization data of CPC-ETC1 chimeric proteins. Localization of CPC-ETC1-GFP fusion proteins of chimera1 and chimera2 transgenic plants was observed using confocal laser scanning microscope. Insertion of ETC1-specific amino acids into CPC somewhat prevents normal protein localization of CPC in root epidermal cells. Cell-to-cell movement of chimera1 and chimera2 proteins from non-hair cells to root-hair cells was interfered. Nuclear localization was also inhibited, especially in chimera1.

Evidence for prevalent Z = 6 magic number in neutron-rich carbon isotopes.

The nuclear shell structure, which originates in the nearly independent motion of nucleons in an average potential, provides an important guide for our understanding of nuclear structure and the underlying nuclear forces. Its most remarkable fingerprint is the existence of the so-called magic numbers of protons and neutrons associated with extra stability. Although the introduction of a phenomenological spin-orbit (SO) coupling force in 1949 helped in explaining the magic numbers, its origins are still open questions. Here, we present experimental evidence for the smallest SO-originated magic number (subshell closure) at the proton number six in 13-20C obtained from systematic analysis of point-proton distribution radii, electromagnetic transition rates and atomic masses of light nuclei. Performing ab initio calculations on 14,15C, we show that the observed proton distribution radii and subshell closure can be explained by the state-of-the-art nuclear theory with chiral nucleon-nucleon and three-nucleon forces, which are rooted in the quantum chromodynamics.

A genetic model of substrate deprivation therapy for a glycosphingolipid storage disorder.

Inherited defects in the degradation of glycosphingolipids (GSLs) cause a group of severe diseases known as GSL storage disorders. There are currently no effective treatments for the majority of these disorders. We have explored a new treatment paradigm, substrate deprivation therapy, by constructing a genetic model in mice. Sandhoff's disease mice, which abnormally accumulate GSLs, were bred with mice that were blocked in their synthesis of GSLs. The mice with simultaneous defects in GSL synthesis and degradation no longer accumulated GSLs, had improved neurologic function, and had a much longer life span. However, these mice eventually developed a late-onset neurologic disease because of accumulation of another class of substrate, oligosaccharides. The results support the validity of the substrate deprivation therapy and also highlight some limitations.

Edg-1, the G protein-coupled receptor for sphingosine-1-phosphate, is essential for vascular maturation.

Sphingolipid signaling pathways have been implicated in many critical cellular events. Sphingosine-1-phosphate (SPP), a sphingolipid metabolite found in high concentrations in platelets and blood, stimulates members of the endothelial differentiation gene (Edg) family of G protein-coupled receptors and triggers diverse effects, including cell growth, survival, migration, and morphogenesis. To determine the in vivo functions of the SPP/Edg signaling pathway, we disrupted the Edg1 gene in mice. Edg1(-/-) mice exhibited embryonic hemorrhage leading to intrauterine death between E12.5 and E14.5. Vasculogenesis and angiogenesis appeared normal in the mutant embryos. However, vascular maturation was incomplete due to a deficiency of vascular smooth muscle cells/pericytes. We also show that Edg-1 mediates an SPP-induced migration response that is defective in mutant cells due to an inability to activate the small GTPase, Rac. Our data reveal Edg-1 to be the first G protein-coupled receptor required for blood vessel formation and show that sphingolipid signaling is essential during mammalian development.

Predictive population pharmacokinetic/pharmacodynamic model for a novel COX-2 inhibitor.

The objectives of these analyses were to (1) develop a population pharmacokinetic/pharmacodynamic model for a novel COX-2 inhibitor (CS-706) using data from primarily Caucasian subjects, (2) predict responses in subpopulations of interest (including Japanese subjects), and (3) correlate pharmacodynamic parameters to safety outcomes. The model was developed using data from 130 healthy adults following single or multiple doses of CS-706. Serial plasma concentrations of CS-706 and ex vivo whole-blood cyclooxygenase-1 (COX-1) and COX-2 activity were determined up to 72 hours postdose. An E(max) model described relationships between CS-706 plasma concentrations and COX-1 and COX-2 inhibition. CS-706 potency (EC(50)) was 397 ng/mL for COX-1 and 20 ng/mL for COX-2. None of the tested covariates influenced the pharmacodynamics of CS-706. Japanese subjects are expected to show a slightly reduced response to CS-706, consistent with lower exposure following the same dose given to Caucasian subjects. Predictive pharmacokinetic/pharmacodynamic modeling for COX-1 and COX-2 inhibition indicates a 20-fold potency ratio that is expected to be similar in Japanese and Caucasians. There was good correlation between COX-1 inhibition and the incidence of 7-day gastroduodenal mucosal injury. A dose of less than 25 mg bid could be adequate to inhibit COX-2 activity with a low risk of gastrointestinal mucosal injury.

Development of a predictive pharmacokinetic model for a novel cyclooxygenase-2 inhibitor.

A predictive population pharmacokinetic model was developed for a novel cyclooxygenase-2 (COX-2) inhibitor CS-706, using data from 130 subjects in 3 phase 1 trials after single or multiple doses of CS-706 (2- to 800-mg doses daily, up to 14 days) and validated using sparse data from a separate study. A 2-compartment model described the data. Typical apparent clearance (CL/F) was 47.2 L/h and was reduced by 43% at doses greater than 200 mg. Apparent clearance was decreased by 38% in female subjects and by 64% and 15%, respectively, in poor/intermediate CYP 2D6 and poor CYP 2C9 metabolizers. Typical apparent volume of the central compartment was 166 L and increased with body weight. Bioavailability increased by 42% after nighttime doses and decreased saturably with increasing dose (50% reduction at 221 mg). Predicted exposures in Japanese subjects were reduced relative to whites because of a lower frequency of poor metabolizers. The model may aid in optimizing the design of future studies and predicting exposures in other subpopulations.

Differentiation of human neuroblastoma by phenylacetate is mediated by peroxisome proliferator-activated receptor gamma.

Phenylacetate (PA) is a member of a class of aromatic fatty acids that has demonstrated antitumor activity in experimental models and in humans. Previous reports have shown that PA and its analogues can act as ligands for the peroxisome proliferator-activated receptor (PPAR) and thereby regulate certain gene expression through peroxisome proliferator response elements. The role of this activity in the antitumor activity of PA has not been determined. To address this question, we have used the human neuroblastoma cell line LA-N-5, which expresses PPARgamma and can be induced to differentiate with PA and with classical PPARgamma ligands. Our results indicated that the PPARgamma ligands 15-deoxy- prostaglandin J2 and GW1929 as well as PA induced LA-N-5 cells to differentiate to a similar phenotype as evidenced by inhibition of cell proliferation, neurite outgrowth, increased acetylcholinesterase activity, and decreased N-myc gene expression. Furthermore, induction with all of the compounds was accompanied by up-regulation of mRNA levels of the nuclear retinoic acid receptor beta (RARbeta) and specific activation of a reporter gene construct (SVbetaRE-CAT) that contains the canonical RA response element located in the RARbeta promoter. All of the assessed functional and molecular effects of PA on LA-N-5 cells, as well as those of the classical PPARgamma ligands, were inhibited by cotreatment with specific PPARgamma antagonists (GW9662 and/or GW0072). Taken together, these studies have confirmed a role for PPARgamma in neuroblastoma cell biology and indicated that the PPARgamma signaling pathway plays a direct role in the PA-induced differentiation response of this cell type.

Expression of brain-derived neurotrophic factor and p145TrkB affects survival, differentiation, and invasiveness of human neuroblastoma cells.

A large number of poor prognosis neuroblastoma (NB) tumors constitutively express brain-derived neurotrophic factor (BDNF) and variably express the gene for its tyrosine kinase (Trk) receptor TrkB. Good prognosis NB tumors typically express high levels of TrkA mRNA, which encodes the signal transducing receptor for nerve growth factor, p140TrkA. These neurotrophins are necessary for neural cell survival and differentiation. This study evaluates the effects of activation of the BDNF-TrkB signal transduction pathway on the growth, survival, morphology, and invasive capacity of NB cells. We find that the addition of BDNF to SY5Y cells induced to express p145TrkB by retinoic acid treatment does not significantly affect cell proliferation yet will support cell survival. Activation of the BDNF-TrkB signal transduction pathway stimulates disaggregation of cells and extension of neuritic processes which can be blocked by a BDNF-neutralizing antibody. Treatment of cells with K252a, an inhibitor of Trk, reverses the cellular disaggregation. An evaluation of the effects of BDNF and nerve growth factor on the ability of NB cells to penetrate basement membrane proteins indicated that BDNF stimulated a 2-fold increase while nerve growth factor inhibited RA-SY5Y cell invasion. Thus, activation of the p145TrkB signal transduction pathway stimulates NB cell survival, disaggregation, and invasion; all characteristics of metastatic cells. Furthermore, these studies indicate that activation of different Trk signal transduction pathways in NB cells results in distinct differences in tumor cell biology and these may be relevant to the clinical course of the patients.

Inhibition of N-myc expression and induction of apoptosis by iron chelation in human neuroblastoma cells.

Neuroblastoma is the second most common solid malignancy of childhood. Enhanced expression of the amplified N-myc gene in the tumor cells may be associated with poor patient prognosis and may contribute to tumor development and progression. The use of deferoxamine mesylate (DFO), an iron chelator, to treat neuroblastoma is being investigated in national clinical studies. We show here by TUNEL assay and DNA laddering that DFO induces apoptosis in cultured human neuroblastoma cells, which is preceded by a decrease in the expression of N-myc and the altered expression of some other oncogenes (up-regulating c-fos and down-regulating c-myb) but not housekeeping genes. The decrease in N-myc expression is iron-specific but does not result from inhibition of ribonucleotide reductase, because specific inhibition of this iron-containing enzyme by hydroxyurea does not affect N-myc protein levels. Nuclear run-on and transient reporter gene expression experiments show that the decrease in N-myc expression occurs at the level of initiation of transcription and by inhibiting N-myc promoter activity. Comparison across neuroblastoma cell lines of the amount of residual cellular N-myc protein with the extent of apoptosis measured as pan-caspase activity after 48 h of iron chelation reveals no correlation, suggesting that the decrease in N-myc expression is unlikely to mediate apoptosis. In conclusion, chelation of cellular iron by DFO may alter the expression of multiple genes affecting the malignant phenotype by multiple pathways. Given the clinical importance of N-myc overexpression in neuroblastoma malignancy, decreasing N-myc expression by DFO might be useful as an adjunct to current

Cell type-specific activity of the N-myc promoter in human neuroblastoma cells is mediated by a downstream silencer.

The N-myc oncogene is actively transcribed in many neuroblastoma tumors, but is not expressed in mature, normal tissue of any type. Chloramphenicol acetyl transferase (CAT) assays of constructs containing N-myc sequence transfected into N-myc expressing LA-N-5 neuroblastoma cells or non-expressing HeLa carcinoma cells have revealed a 201 base pair (bp) regulatory region mediating the cell type-specific activity of the promoter. While located downstream from 5' mRNA cap sites, the region appears to function by preventing transcriptional initiation. This downstream region is capable of suppressing promoter activity independently of position, and contains an element having 100% homology with the 9 bp consensus sequence of a transcriptional silencer found in the upstream region of the lysozyme gene. DNA gel retardation assays have shown that this sequence is involved in a specific DNA-protein interaction with nuclear extract from HeLa cells that is distinct from that occurring with extract from LA-N-5 cells. These results suggest that the N-myc promoter's cell type-specific activity is regulated by a downstream silencer, and that differential binding of regulatory protein from that present in non-expressing cells may result in the constitutive N-myc expression seen in neuroblastoma.

Cell type-specific expression and negative regulation by retinoic acid of the human N-myc promoter in neuroblastoma cells.

Expression of the N-myc oncogene is an important determinant of tumor behavior in human neuroblastoma. To study the regulation of N-myc, we have subcloned fragments of the 5' flanking region of the human N-myc gene upstream of the chloramphenicol acetyl transferase (CAT) reporter gene, and assayed for promoter activity in transient transfections into neuroblastoma and other cell lines. Upstream sequences were found to possess promoter activity to within 121 bp of the major cap site (-121). Negative regulatory elements were identified in regions approximately 2 kb and 500 bp upstream from the major cap site, as well as 150-1000 bp downstream. Promoter constructs containing downstream elements from bp +150 to +1000 were active in N-myc-expressing neuroblastoma cell lines, but not in non-expressing Epstein-Barr virus (EBV)-transformed 729-6 B-cell or HeLa cell lines, while those lacking this element were active in all cell types tested. All tested constructs retaining promoter activity showed decreased activity in parallel with the down-regulation of endogenous N-myc in response to treatment of transfected cells with retinoic acid. These studies suggest that N-myc regulation may be controlled at different levels, and provide a basis for further characterization of N-myc regulation in neuroblastoma.

Pharmacokinetics of chronically administered all-trans-retinoyl-beta-glucuronide in mice.

After the subcutaneous injection of retinoyl beta-glucuronide (RAG), both RAG and retinoic acid (RA), formed by the hydrolysis of RAG in vivo, achieved peak plasma concentrations within 1-2 h. Thereafter, RA was rapidly cleared from the plasma whereas RAG was eliminated much more slowly. No significant changes were noted in the peak (2 h) plasma levels of RAG for treatment periods up to 56 days (one injection of RAG/day), in the clearance rate of RAG from plasma, or in plasma retinol concentrations. Similarly, no consistent decrease in plasma levels of the RA hydrolysis product was observed. Mice undergoing these long-term chronic treatments with RAG did not show any clinical manifestations of retinoid toxicity. Taken together, our findings that chronic dosing with RAG produces sustained levels of both the parent compound and the RA hydrolysis product, combined with the apparent low toxicity of RAG, suggest that RAG could be a safe and useful alternative to some retinoids which are presently being utilized in the clinic.

Galactosemic neuropathy in transgenic mice for human aldose reductase.

We studied the functional consequences of an enhanced polyol pathway activity, elicited with galactose feeding, on the peripheral nerve of transgenic mice expressing human aldose reductase. Nontransgenic littermate mice were used as controls. With a quantitative immunoassay, the expression level of human aldose reductase in the sciatic nerve was 791 +/- 44 ng/mg protein (mean +/- SE), about 25% of that in human sural nerve. When the transgenic mice were fed food containing 30% galactose, significant levels of galactitol accumulated in the sciatic nerve. Galactose feeding of nontransgenic littermate mice led to a 10-fold lower accumulation of galactitol. Galactose feeding for 16 weeks caused a significant and progressive decrease in motor nerve conduction velocity in transgenic mice to 80% of the level of galactose-fed littermate mice, which was not significantly different from that of galactose-free littermate mice. A morphometric analysis of sciatic nerve detected > 10% reduction of mean myelinated fiber size but no alterations of myelinated fiber density in galactose-fed transgenic mice compared with other groups. The functional and structural changes that develop in galactose-fed transgenic mice are similar to those previously reported in diabetic animals. The results of these studies suggest that transgenic mice expressing human aldose reductase may be a useful model not only for defining the role of the polyol pathway in diabetic neuropathy but also for identifying and characterizing effective inhibitors specific for human aldose reductase.