bluuebunny/crossref_metadata_2025 huggingface dataset:
Experimental determination of dietary carbon turnover in bovine hair and hoof
Authors: Zazzo A. , Harrison S. M. , Bahar B. , Moloney A. P. , Monahan F. J. , Scrimgeour C. M. , Schmidt O.
Published: January 2008

Stable isotopes measured in keratinized tissues like hair or hoof have proven to be a useful tool for reconstructing the dietary history of animals with a weekly to daily resolution. Quantitative reconstruction of dietary preferences requires a precise estimate of tissue turnover by means of controlled feeding experiments. We determined the turnover rates of carbon in hoof and tail hair of growing steers ( Bos taurus L., 1758) fed a C3-based diet, followed by a C4-based diet, for 168 d. As with horses, turnover in steer hair was successfully described by a three-pool modelling approach, with apparent half-lives of 1.7, 7.7, and 69.1 d for each of the pools, each contributing 53%, 20%, and 28% of the total signal, respectively. Two pools only were identified in bovine hoof, which recorded the diet switch more slowly than hair with a reduction in the amplitude of short-term isotope changes. We interpreted this result as a sampling artefact and found that the hooves reflected the same pools as the hair if growth geometry is taken into account. The model parameters defined in this study allowed us to quantitatively reconstruct previous diets of steers of different breeds and individual history with a precision of ±1‰.
IMPLEMENTATION OF FERTILIZER POLICY IN BANGLADESH UNDER ALTERNATIVE SCENARIOS: AN APPLICATION OF MULTICRITERIA ANALYSIS MODELING
Authors: BEGUM MOSS ANJUMAN ARA , MANOS BASIL , MANIKAS IOANNIS
Published: January 2008

The analysis of the effects of fertilizer pricing on fertilizer-intensive agriculture and farms behavior ought to be an important topic of research for agricultural and environmental economists in Bangladesh. Several possibilities for fertilizer policy have been debated, in particular for the pricing of fertilizer. Following this observation, this study contributes to that discussion by simulating the impact that various policies based upon the price of fertilizer could have on agricultural production. Specifically, the study analyzes the economic, social and environmental implications of alternative fertilizer policies using a multicriteria model of farmers' behavior under different scenarios. The future agricultural and fertilizer scenarios are described in terms of the combination of policy instruments, policy style and configuration of actors. For the purpose of scenario analysis, narratives and quantitative indicator values have been compiled for each scenario. The quantitative estimates are used as input values in the modeling of fertilizing systems under policy changes. The results show that the increase of fertilizer price causes almost similar impacts as observed in the status quo scenario. The results also stress that fertilizer pricing, as a single instrument for controlling fertilizer use is not a satisfactory tool for significantly reducing fertilizer consumption in agriculture.
A MULTICRITERIA OPTIMIZATION MODEL FOR QUALITY OF MODULAR SOFTWARE SYSTEMS
Authors: ZACHARIAH BABU , RATTIHALLI R. N.
Published: January 2008

This paper discusses a decision-making problem related to software creation through Commercial-off-the-shelf (COTS) modules. When different alternatives of the same module are available with variations in the attributes of quality (like reliability, execution time, etc.) and cost, the problem is to select appropriate alternatives and integrate them into a software such that the objectives of the software developer (with respect to the attributes of quality) are satisfied. This calls for the use of multiple criteria decision-making techniques. The possible inconsistency between the objectives calls for prioritization of the objectives. Hence goal-programming (GP) approach is used to formulate the problem. We present a Branch and Bound (B&B) algorithm to solve this problem.
SIMPLE PROCEDURES FOR FINDING MEAN FIRST PASSAGE TIMES IN MARKOV CHAINS
Authors: HUNTER JEFFREY J.
Published: January 2008

The derivation of mean first passage times in Markov chains involves the solution of a family of linear equations. By exploring the solution of a related set of equations, using suitable generalized inverses of the Markovian kernel I - P, where P is the transition matrix of a finite irreducible Markov chain, we are able to derive elegant new results for finding the mean first passage times. As a by-product we derive the stationary distribution of the Markov chain without the necessity of any further computational procedures. Standard techniques in the literature, using for example Kemeny and Snell's fundamental matrix Z, require the initial derivation of the stationary distribution followed by the computation of Z, the inverse of I - P + eπT where eT = (1, 1, …, 1) and πT is the stationary probability vector. The procedures of this paper involve only the derivation of the inverse of a matrix of simple structure, based upon known characteristics of the Markov chain together with simple elementary vectors. No prior computations are required. Various possible families of matrices are explored leading to different related procedures.
NON-METRIC GRAVITY: A STATUS REPORT
Authors: KRASNOV KIRILL
Published: January 2008

We review the status of a certain (infinite) class of four-dimensional generally covariant gravity theories propagating two degrees of freedom that are formulated without any direct mention of the metric. General relativity itself (in its Plebański formulation) belongs to the class, so these theories are examples of modified gravity. We summarize the current understanding of the nature of the modification, of the renormalizability properties of these theories, of their coupling to matter fields, and describe some of their physical properties.
STABILITY OF 3D BLACK HOLE WITH TORSION
Authors: CVETKOVIĆ B. , BLAGOJEVIĆ M.
Published: January 2008

Using N = 1+1 supersymmetric extension of the three-dimensional gravity with torsion, we show that a generic black hole has no exact supersymmetries, the extremal black hole has only one, while the zero-energy black hole has two. Combining these results with the asymptotic supersymmetry algebra, we are naturally led to interpret the zero-energy black hole as the ground state of the Ramond sector, and analogously, the anti-de Sitter solution as the ground state of the Neveu–Schwarz sector.
N = 2 SUPERSYMMETRIC QED RELATED TO N = 2 VOLKOV–AKULOV MODEL
Authors: SHIMA KAZUNARI , TSUDA MOTOMU
Published: January 2008

We discuss the relation between N = 2 Volkov–Akulov model and the spontaneously broken linear supersymmetry (LSUSY) interacting gauge theory for N = 2 vector and N = 2 scalar supermultiplets in two-dimensional spacetime (d = 2). The local gauge interaction of LSUSY is induced by the specific composite structure of the auxiliary fields and the consequent transformations.
The Ups and Downs of Bureaucratic Organization
Authors: Olsen Johan P.
Published: January 2008

Why do democracies give birth to bureaucracies and bureaucrats? How and why has a seemingly undesirable and unviable organizational form weathered relentless criticism over many years, and why do some see it experiencing a renaissance? Normative democratic theory, theories of formal organizations, and Weber's ideas are used in this essay to explore debureaucratization efforts since the late 1970s and the rediscovery of bureaucracy since the mid 1990s. One conclusion is that there has not been a monotonic development toward bureaucratization, as argued by Weber, or debureaucratization, as argued by his critics. Several normative and organizational components have coexisted; the significance of each component and their relationships has varied over time. Although elements of a theoretical framework are suggested, no great optimism for a comprehensive theory of bureaucratization and debureaucratization is offered. Institutions, agency, and macro forces all matter, but there is no agreement regarding the conditions under which one factor matters more than the others.
Regenerative response in the pig liver remnant varies with the degree of resection and rise in portal pressure
Authors: Mortensen Kim Erlend , Conley Lene Nagstrup , Hedegaard Jakob , Kalstad Trine , Sorensen Peter , Bendixen Christian , Revhaug Arthur
Published: January 2008

After parenchymal loss, the liver regenerates restoring normal mass and metabolic function. Prevailing theories on triggering events leading to regeneration include humoral, metabolic, and flow-mediated mechanisms, the latter emphasizing the importance of shear stress mediated nitric oxide regulation. We aimed to investigate whether the grade of resection and hence the portal venous pressure and sinusoidal shear stress increase would be reflected in the gene expression profiles in the liver remnant by using a global porcine cDNA microarray chip with ∼23,000 genes represented. Six pig livers were resected with 62% (low portal pressure resection) and 75% (high portal pressure resection), resulting in a portal venous pressure increase from a baseline of 6.1–8.2 and 12 mmHg, respectively. By sampling consecutive biopsies from the liver remnants, we found differentially expressed genes in the high portal pressure resection group to have functions related primarily to apoptosis, nitric oxide metabolism and oxidative stress, whereas differentially expressed genes in the low portal pressure resection group potentially regulate the cell cycle. Common to both groups was the upregulation of genes regulating inflammation, transport, cell proliferation, development, and protein metabolism. Also common to both groups was both up- and downregulation of genes regulating cell-cell signaling, signal transduction, cell adhesion, and translation. Genes regulating the metabolism of lipids, hormones, amines, and alcohol were downregulated in both groups. In conclusion, the genetic regenerative response in the liver remnant to varies according to the level of resection.
Decreased epithelial barrier function evoked by exposure to metabolic stress and nonpathogenicE. coliis enhanced by TNF-α
Authors: Lewis Kimberley , Caldwell Jackie , Phan Van , Prescott David , Nazli Aisha , Wang Arthur , Soderhölm Johan D. , Perdue Mary H. , Sherman Philip M. , McKay Derek M.
Published: January 2008

A defect in mitochondrial activity contributes to many diseases. We have shown that monolayers of the human colonic T84 epithelial cell line exposed to dinitrophenol (DNP, uncouples oxidative phosphorylation) and nonpathogenic Escherichia coli ( E. coli) (strain HB101) display decreased barrier function. Here the impact of DNP on macrophage activity and the effect of TNF-α, DNP, and E. coli on epithelial permeability were assessed. DNP treatment of the human THP-1 macrophage cell line resulted in reduced ATP synthesis, and, although hyporesponsive to LPS, the metabolically stressed macrophages produced IL-1β, IL-6, and TNF-α. Given the role of TNF-α in inflammatory bowel disease (IBD) and the association between increased permeability and IBD, recombinant TNF-α (10 ng/ml) was added to the DNP (0.1 mM) + E. coli (106colony-forming units), and this resulted in a significantly greater loss of T84 epithelial barrier function than that elicited by DNP + E. coli. This increased epithelial permeability was not due to epithelial death, and the enhanced E. coli translocation was reduced by pharmacological inhibitors of NF-κβ signaling (pyrrolidine dithiocarbamate, NF-κβ essential modifier-binding peptide, BAY 11–7082, and the proteosome inhibitor, MG132). In contrast, the drop in transepithelial electrical resistance was unaffected by the inhibitors of NF-κβ. Thus, as an integrative model system, our findings support the induction of a positive feedback loop that can severely impair epithelial barrier function and, as such, could contribute to existing inflammation or trigger relapses in IBD. Thus metabolically stressed epithelia display increased permeability in the presence of viable nonpathogenic E. coli that is exaggerated by TNF-α released by activated immune cells, such as macrophages, that retain this ability even if they themselves are experiencing a degree of metabolic stress.
Possible entrainment of ghrelin to habitual meal patterns in humans
Authors: Frecka Julie M. , Mattes Richard D.
Published: January 2008

Ghrelin is reportedly a meal-initiation signal based on observations that concentrations increase before meals coincident with rising hunger. However, evidence that ghrelin peaks vary with feeding schedules suggests that it rises in anticipation of an expected meal, rather than eliciting feeding. To explore the entrainment of ghrelin profiles, this study investigated the association between varying habitual meal patterns and plasma ghrelin concentrations. Lean and obese adults following either a short intermeal interval (SII) pattern, with 2.5–3.5 h between their habitual breakfast and lunch times, or a long intermeal interval (LII) pattern, with 5.5–6.5 h between these eating occasions, participated. Food intake and appetite were recorded for 2 baseline days. On the subsequent test day, blood samples were collected over 8 h while participants ate a breakfast and lunch matched to their customary meals and pattern. Appetite ratings were obtained and ghrelin, insulin, glucose, and leptin concentrations were measured. Peak ghrelin concentrations differed significantly by group and occurred prior to each group's respective lunch time. Ghrelin concentrations directly correlated with subjective hunger. This association was stronger when hunger preceded ghrelin, a pattern inconsistent with ghrelin causing the hunger rise. Ghrelin concentrations were inversely correlated with insulin, and peak insulin concentrations preceded nadir ghrelin concentrations postprandially. Ghrelin concentrations periprandially, and over the entire test session, did not differ by meal group, likely because of similar intakes between groups. These data demonstrate that the timing of ghrelin peaks is related to habitual meal patterns and may rise in anticipation of eating rather than eliciting feeding.
Selectivity of ROCK inhibitors in the spontaneously tonic smooth muscle
Authors: Rattan Satish , Patel Chirag A.
Published: January 2008

The selectivity of different Rho kinase (ROCK) inhibitors in the spontaneously tonic smooth muscle has not been investigated. We examined this issue using Y-27632 [(R)-(+)- trans- N-(4-pyridyl)-4-(1-aminoethyl)-cyclohexanecarbox anecarboxamide, 2HCl], H-1152 [(S)-(+)-(2-methyl-5-isoquinolinyl) sulfonylhomopiperazine, 2HCl], HA-1077 [(5 isoquinolinesulfonyl) homopiperazine, 2HCl], and ROCK inhibitor II [ N-(4-pyridyl)- N′-(2,4,6-trichlorophenyl)urea]. We compared these inhibitors in the spontaneously tonic smooth muscle of the internal anal sphincter (IAS). ROCK, protein kinase C (PKC), and myosin light chain kinase (MLCK) activities were determined in the IAS, before and after different ROCK inhibitors. Y-27632 and H-1152 were ∼30-fold more potent in the IAS (IC50: 4.4 × 10−7and 7.9 × 10−8M, respectively) vs. the phasic rectal smooth muscle (RSM) (IC50: 1.3 × 10−5and 2.5 × 10−6M, respectively). HA-1077 and ROCK inhibitor II were equipotent in the IAS vs. RSM. In the IAS, H-1152 was the most potent whereas ROCK inhibitor II is the least. Y-27632 and H-1152 caused concentration-dependent decrease in the IAS tone that correlates directly with the decreases in ROCK activity, without significant effect in the PKC and MLCK activities. This specifically selective correlation between ROCK activity and decrease in the IAS tone was absent in the case of HA-1077 and ROCK inhibitor II, which also inhibited PKC and MLCK. We conclude that the IAS tone is critically dependent on ROCK activity, and H-1152 and Y-27632 are the most selective and potent ROCK inhibitors in the IAS.
Developmental effects on myonuclear domain size of rat diaphragm fibers
Authors: Mantilla Carlos B. , Sill Rowan V. , Aravamudan Bharathi , Zhan Wen-Zhi , Sieck Gary C.
Published: January 2008

During early postnatal development in rat diaphragm muscle (Diam), significant fiber growth and transitions in myosin heavy chain (MHC) isoform expression occur. Similar to other skeletal muscles, Diam fibers are multinucleated, and each myonucleus regulates the gene products within a finite volume: the myonuclear domain (MND). We hypothesized that postnatal changes in fiber cross-sectional area (CSA) are associated with increased number of myonuclei so that the MND size is maintained. The Diam was removed at postnatal days 14 (P-14) and 28 (P-28). MHC isoform expression was determined by SDS-PAGE. Fiber CSA, myonuclear number, and MND size were measured using confocal microscopy. By P-14, significant coexpression of MHC isoforms was present with no fiber displaying singular expression of MHCNeo. By P-28, singular expression was predominant. MND size was not different across fiber types at P-14. Significant fiber growth was evident by P-28 at all fiber types (fiber CSA increased by 61, 93, and 147% at fibers expressing MHCSlow, MHC2A, and MHC2X, respectively). The number of myonuclei per unit of fiber length was similar across fibers at P-14, but it was greater at fibers expressing MHC2X at P-28. The total number of myonuclei per fiber also increased between P-14 and P-28 at all fiber types. Accordingly, MND size increased significantly by P-28 at all fiber types, and it became larger at fibers expressing MHC2X compared with fibers expressing MHCSlow or MHC2A. These results suggest that MND size is not maintained during the considerable fiber growth associated with postnatal development of the Diam.
Measurement of gluconeogenesis using glucose fragments and mass spectrometry after ingestion of deuterium oxide
Authors: Chacko Shaji K. , Sunehag Agneta L. , Sharma Susan , Sauer Pieter J. J. , Haymond Morey W.
Published: January 2008

We report a new method to measure the fraction of glucose derived from gluconeogenesis using gas chromatography-mass spectrometry and positive chemical ionization. After ingestion of deuterium oxide by subjects, glucose derived from gluconeogenesis is labeled with deuterium. Our calculations of gluconeogenesis are based on measurements of the average enrichment of deuterium on carbon 1, 3, 4, 5, and 6 of glucose and the deuterium enrichment in body water. In a sample from an adult volunteer after ingestion of deuterium oxide, fractional gluconeogenesis using the “average deuterium enrichment method” was 48.3 ± 0.5% (mean ± SD) and that with the C-5 hexamethylenetetramine (HMT) method by Landau et al. (Landau BR, Wahren J, Chandramouli V, Schumann WC, Ekberg K, Kalhan SC; J Clin Invest 98: 378–385, 1996) was 46.9 ± 5.4%. The coefficient of variation of 10 replicate analyses using the new method was 1.0% compared with 11.5% for the C-5 HMT method. In samples derived from an infant receiving total parenteral nutrition, fractional gluconeogenesis was 13.3 ± 0.3% using the new method and 13.7 ± 0.8% using the C-5 HMT method. Fractional gluconeogenesis measured in six adult volunteers after 66 h of continuous fasting was 83.7 ± 2.3% using the new method and 84.2 ± 5.0% using the C-5 HMT method. In conclusion, the average deuterium enrichment method is simple, highly reproducible, and cost effective. Furthermore, it requires only small blood sample volumes. With the use of an additional tracer, glucose rate of appearance can also be measured during the same analysis. Thus the new method makes measurements of gluconeogenesis available and affordable to large numbers of investigators under conditions of low and high fractional gluconeogenesis (∼10 to ∼90) in all subject populations.
A new method for the noninvasive determination of abdominal muscle feedforward activity based on tissue velocity information from tissue Doppler imaging
Authors: Mannion A. F. , Pulkovski N. , Schenk P. , Hodges P. W. , Gerber H. , Loupas T. , Gorelick M. , Sprott H.
Published: January 2008

Rapid arm movements elicit anticipatory activation of the deep-lying abdominal muscles; this appears modified in back pain, but the invasive technique used for its assessment [fine-wire electromyography (EMG)] has precluded its widespread investigation. We examined whether tissue-velocity changes recorded with ultrasound (M-mode) tissue Doppler imaging (TDI) provided a viable noninvasive alternative. Fourteen healthy subjects rapidly flexed, extended, and abducted the shoulder; recordings were made of medial deltoid (MD) surface EMG and of fine-wire EMG and TDI tissue-velocity changes of the contralateral transversus abdominis, obliquus internus, and obliquus externus. Muscle onsets were determined by blinded visual analysis of EMG and TDI data. TDI could not distinguish between the relative activation of the three muscles, so in subsequent analyses only the onset of the earliest abdominal muscle activity was used. The latter occurred <50 ms after the onset of medial deltoid EMG (i.e., was feedforward) and correlated with the corresponding EMG onsets ( r = 0.47, P < 0.0001). The mean difference between methods was 20 ms and was likely explained by electromechanical delay; limits of agreement were wide (−40 to +80 ms) but no greater than those typical of repeated measurements using either technique. The between-day standard error of measurement of the TDI onsets (examined in 16 further subjects) was 16 ms. TDI yielded reliable and valid measures of the earliest onset of feedforward activity within the anterolateral abdominal muscle group. The method can be used to assess muscle dysfunction in large groups of back-pain patients and may also be suitable for the noninvasive analysis of other deep-lying or small/thin muscles.
Cyclic strain induces mouse embryonic stem cell differentiation into vascular smooth muscle cells by activating PDGF receptor β
Authors: Shimizu Nobutaka , Yamamoto Kimiko , Obi Syotaro , Kumagaya Shinichiro , Masumura Tomomi , Shimano Yasumasa , Naruse Keiji , Yamashita Jun K. , Igarashi Takashi , Ando Joji
Published: January 2008

Embryonic stem (ES) cells are exposed to fluid-mechanical forces, such as cyclic strain and shear stress, during the process of embryonic development but much remains to be elucidated concerning the role of fluid-mechanical forces in ES cell differentiation. Here, we show that cyclic strain induces vascular smooth muscle cell (VSMC) differentiation in murine ES cells. Flk-1-positive (Flk-1+) ES cells seeded on flexible silicone membranes were subjected to controlled levels of cyclic strain and examined for changes in cell proliferation and expression of various cell lineage markers. When exposed to cyclic strain (4–12% strain, 1 Hz, 24 h), the Flk-1+ES cells significantly increased in cell number and became oriented perpendicular to the direction of strain. There were dose-dependent increases in the VSMC markers smooth muscle α-actin and smooth muscle-myosin heavy chain at both the protein and gene expression level in response to cyclic strain, whereas expression of the vascular endothelial cell marker Flk-1 decreased, and there were no changes in the other endothelial cell markers (Flt-1, VE-cadherin, and platelet endothelial cell adhesion molecule 1), the blood cell marker CD3, or the epithelial marker keratin. The PDGF receptor β (PDGFRβ) kinase inhibitor AG-1296 completely blocked the cyclic strain-induced increase in cell number and VSMC marker expression. Cyclic strain immediately caused phosphorylation of PDGFRβ in a dose-dependent manner, but neutralizing antibody against PDGF-BB did not block the PDGFRβ phosphorylation. These results suggest that cyclic strain activates PDGFRβ in a ligand-independent manner and that the activation plays a critical role in VSMC differentiation from Flk-1+ES cells.
AMPK activation attenuates S6K1, 4E-BP1, and eEF2 signaling responses to high-frequency electrically stimulated skeletal muscle contractions
Authors: Thomson David M. , Fick Christopher A. , Gordon Scott E.
Published: January 2008

Regulation of protein translation through Akt and the downstream mammalian target of rapamycin (mTOR) pathway is an important component of the cellular response to hypertrophic stimuli. It has been proposed that 5′-AMP-activated protein kinase (AMPK) activation during muscle contraction may limit the hypertrophic response to resistance-type exercise by inhibiting translational signaling. However, experimental manipulation of AMPK activity during such a stimulus has not been attempted. Therefore, we investigated whether AMPK activation can attenuate the downstream signaling response of the Akt/mTOR pathway to electrically stimulated lengthening muscle contractions. Extensor digitorum longus muscles ( n = 8/group) were subjected to a 22-min bout of lengthening contractions by high-frequency sciatic nerve electrical stimulation (STIM) in young adult (8 mo) Fischer 344 × Brown Norway male rats. Forty minutes before electrical stimulation, rats were subcutaneously injected with saline or 5-aminoimidazole-4-carboxamide-1–4-ribofuranoside (AICAR; 1 mg/g body wt), an AMPK activator. Stimulated and contralateral resting muscles were removed at 0, 20, and 40 min post-STIM, and AMPK, acetyl CoA carboxylase (ACC), Akt, eukaryotic initiation factor 4E-binding protein (4E-BP1), 70-kDa ribosomal protein S6 kinase (S6K1), and eukaryotic elongation factor 2 (eEF2) phosphorylations were assessed by Western blot. AICAR treatment increased ( P ≤ 0.05) post-STIM AMPK (Thr172) and ACC phosphorylation (Ser79/221), inhibited post-STIM S6K1 (Thr389) and 4E-BP1 (gel shift) phosphorylation, and elevated post-STIM eEF2 phosphorylation (Thr56). These findings suggest that translational signaling downstream of Akt/mTOR can be inhibited after lengthening contractions when preceded by AMPK activation and that energetic stress may be antagonistic to the hypertrophic translational signaling response to loaded muscle contractions.
Determination of protein synthesis in vivo using labeling from deuterated water and analysis of MALDI-TOF spectrum
Authors: Xiao Gary Guishan , Garg Meena , Lim Shu , Wong Derek , Go Vay Liang , Lee Wai-Nang Paul
Published: January 2008

This paper describes a method of determining protein synthesis and turnover using in vivo labeling of protein with deuterated water and analysis of matrix-assisted laser desorption time-of-flight mass spectrometer (MALDI-TOF) spectrum. Protein synthesis is calculated using mass isotopomer distribution analysis instead of precursor to product amino acid enrichment ratio. During protein synthesis, the incorporation of deuterium from water changes the mass isotopomer distribution (isotope envelop) according to the number of deuterium atoms (0, 1, 2, 3, etc.) incorporated, and the distribution of the protein with 0, 1, 2, 3,… atoms of deuterium follows a binomial distribution. A mathematical algorithm by which the distribution of deuterium isotopomers can be extracted from the observed MALDI-TOF spectrum is presented. Since deuterium isotopomers are unique to newly synthesized proteins, the quantitation of their distribution provides a method for the quantitation of newly synthesized proteins. The combined use of postsource decay sequence identification and mass isotopomer distribution analysis makes the use of in vivo labeling with deuterated water a precise method to determine specific protein synthesis.
Endurance exercise training reduces gallstone development in mice
Authors: Wilund Kenneth R. , Feeney Laura A. , Tomayko Emily J. , Chung Hae R. , Kim Kijin
Published: January 2008

Gallstones form when the ratio of bile cholesterol to bile acids and phospholipids is elevated, causing cholesterol to precipitate. Physical inactivity is hypothesized to increase gallstone development, but experimental evidence supporting this is lacking, and potential mechanisms for the antilithogenic effects of exercise have not been described. The purpose of this study was to examine the effect of endurance exercise training on gallstone formation and the expression of genes involved in bile cholesterol metabolism in gallstone-sensitive (C57L/J) mice. At 10 wk, 50 male mice began a lithogenic diet and were randomly assigned to an exercise-training (EX) or sedentary (SED) group ( n = 25 per group). Mice in the EX group ran on a treadmill at ∼15 m/min for 45 min/day for 12 wk. At the time animals were euthanized, gallstones were collected, pooled by group, and weighed. The weight of the gallstones was 2.5-fold greater in the SED mice compared with EX mice (143 vs. 57 mg, respectively). In the EX mice, hepatic expression of the low-density lipoprotein receptor (LDLr), scavenger receptor class B type 1 (SRB1), and sterol 27 hydroxylase (Cyp27) was increased by ∼2-fold ( P < 0.05 for each). The LDLr and SRB1 increase cholesterol clearance by low-density lipoprotein and high-density lipoprotein particles, respectively, while Cyp27 promotes the catabolism of cholesterol to bile acids. Taken together, these data indicate that exercise promotes changes in hepatic gene expression that increase cholesterol uptake by the liver but simultaneously increase the catabolism of cholesterol to bile acids, effectively reducing cholesterol saturation in the bile. This suggests a mechanism by which exercise improves cholesterol clearance from the circulation while simultaneously inhibiting gallstone formation.
Properties of Ceramides and Their Impact on the Stratum Corneum Structure:
Authors: Kessner D. , Ruettinger A. , Kiselev M.A. , Wartewig S. , Neubert R.H.H.
Published: January 2008

The stratum corneum (SC) represents the outermost layer of the mammalian skin, exhibits the main skin barrier and plays an important role in the water penetration pathway through the SC. Knowing the structure and properties of the SC at the molecular level is essential for studying drug penetration through the SC and for the development of new dermal drug delivery systems. Therefore, research interest is focused on the SC lipid matrix and on water diffusion through it. Thus, the ultimate aim is to design a lipid mixture that mimics the barrier properties of the human SC to a high extent and that can substitute the SC in drug delivery systems. This review summarizes various studies performed on either isolated animal or human ceramide based SC model systems, coming to the result that using synthetic lipids with a well-defined architecture allows good extrapolation to the in vivo situation. This review is the continuation of part 1 that is focused on a detailed description of the thermotropic and/or lyotropic phase behaviour of single ceramide types obtained by various experimental techniques. The objective of part 2 is to reflect the numerous studies on SC lipid model systems, namely binary, ternary and multicomponent systems, during the last decade. In this context, neutron diffraction as a prospective tool for analyzing the internal membrane structure is addressed in particular. Based on these new insights, current SC models are presented, whose validations are still under discussion. A profound knowledge about SC lipid organization at the molecular level is still missing.
The Role of Emollients in the Management of Diseases with Chronic Dry Skin
Authors: Proksch E.
Published: January 2008

Dry skin is a common skin condition as well as a key aspect of a number of diseases such as atopic dermatitis and psoriasis but also of other diseases and systemic conditions. Dry skin has an impact on the patient in terms of discomfort, pruritus and impaired quality of life. Within the overall treatment regimen for these diseases, the use of emollients to manage dry skin plays a considerable role in managing skin conditions. In atopic dermatitis and psoriasis, emollients help to improve skin condition and to reduce pruritus alongside more potent pharmacological agents. It is important to choose an emollient that not only soothes and rehydrates the skin but also offers numerous other dermatological supporting roles, especially induction of proper epidermal differentiation. This review will explain the role of emollients within the management of diseases with dry skin as a major symptom and the components of an ideal emollient.
Improvement of the Experimental Setup for Skin Absorption Screening Studies with Reconstructed Skin EPISKIN®
Authors: Grégoire S. , Patouillet C. , Noé C. , Fossa I. , Benech Kieffer F. , Ribaud C.
Published: January 2008

Percutaneous penetration studies are usually performed in human skin samples set up in a Franz® cell device. The ability to perform these studies may depend on the availability of skin samples. Reconstructed skin models are an interesting alternative to overcome such limitations but are less easily mounted in diffusion cell devices. Previous data showed that EPISKIN® was a highly performing model to carry out such studies. However, the setup in a PermeGear® cell device is time consuming and therefore unsuitable for screening purposes. Another approach could be using EPISKIN in its cell culture insert. The aim of this study was to compare cutaneous penetration of chemicals applied to EPISKIN samples in a PermeGear cell versus in their own insert. Eight chemicals having widely different chemical structures and penetration potentials were studied. Six test chemicals showed a similar penetration level in both devices. Using the PermeGear cell device, the penetration level was overestimated for the other 2 tested chemicals. The results demonstrated that percutaneous studies with EPISKIN samples could be easily performed using the insert setup. The EPISKIN model has been greatly improved in the recent years and it is now possible to develop screening tests for the evaluation of skin penetration with a higher reliability.
Differences in the ICD-10 Diagnostic Subtype of Depression in Bipolar Disorder Compared to Recurrent Depressive Disorder
Authors: Kessing Lars Vedel , Jensen Hans Mørch , Christensen Ellen Margrethe
Published: January 2008

Background: The aim of the study was to investigate whether patients with bipolar depression and patients with recurrent depressive disorder present with different subtypes of depressive episode as according to ICD-10. Sampling and Methods: All patients who got a diagnosis of bipolar affective disorder, current episode of depression, or a diagnosis of recurrent depressive disorder, current episode of depression, in a period from 1994 to 2002 at the first outpatient treatment or at the first discharge from psychiatric hospitalization in Denmark were identified in a nationwide register. Results: Totally, 389 patients got a diagnosis of bipolar disorder, current episode of depression, and 5.391 patients got a diagnosis of recurrent depressive disorder, current episode of depression, at first contact. Compared with patients with a diagnosis of recurrent depressive disorder, patients with bipolar disorder, current episode of depression, were significantly less often outpatients (49.4 vs. 68.0%), significantly more often got a diagnosis of severe depression (42.7 vs. 23.3%) or a diagnosis of depression with psychotic symptoms (14.9 vs. 7.2%). The rate of subsequent hospitalization was increased for patients with bipolar disorder, current episode of depression, compared with patients with a current depression as part of a recurrent depressive disorder (HR = 1.50, 95% CI = 1.20–1.86). Conclusions: The results consistently indicate that a depressive episode is severer and/or more often associated with psychotic symptoms when it occurs as part of a bipolar disorder than as part of a recurrent depressive disorder.
Phenomenological Investigation of Despair in Depression
Authors: Bürgy Martin
Published: January 2008

In current psychopathological literature, the concept of despair is almost redundant. At most, the term is applied in a behavioral biological context as a synonym for helplessness and hopelessness. In light of the fact that the subjective experience of despair is neglected, the present paper adopts a phenomenological approach. The selection and hermeneutic investigation of philosophical concepts serve as tools for an initial delineation of the core structure of despair. On the basis of a growing deviation between desire and reality, target and actual status, an alternating development is initiated which increasingly constricts and leads to hopelessness and suicide. This phenomenological core structure is identified from a number of integral characteristics of depression and further developed. Despair, thus, becomes a psychopathological key term through which access can be gained to the subjective experience of the depressive individual and which can provide the basis for promoting understanding and communication as well as developing successful therapeutic interventions.
Peritoneal Membrane Evaluation in Routine Clinical Practice
Authors: Rodrigues Anabela S. , Silva Sandra , Bravo Fernanda , Oliveira Jose C. , Fonseca Isabel , Cabrita Antonio , Krediet Raymond T.
Published: January 2008

Background/Aims: Establishment of reference values for small solute transport, sodium sieving and effluent CA125 with 3.86% (4 h) peritoneal equilibration test (PET), and comparison with fast-fast PET with regard to small solute transport categories. Methods: Cross-sectional study; 69 prevalent patients. Sodium sieving corrected for sodium diffusion with a formula applicable to the PET. CA125 appearance rate (AR) was measured. Expected and observed 60 min D/Pcreatinine were compared by Bland and Altman. Results: Means (95% CI): D/Pcreatinine 0.73 (0.70–0.76), MTACcreatinine 9.6 (8.4–10.9) ml/min, D/D₀ glucose 0.30 (0.28–0.31), corrected dip 0.17 (0.15–0.18), CA125 150 (125–176) U/min. Both corrected and uncorrected sodium sieving were informative. Peritoneal transport was faster at 60 min dwell. UFF patients presented very low corrected dip and CA125 AR. Conclusion: 3.86% (4 h) PET provided results similar to those from SPA. Correction for diffusion of sodium sieving is dispensable for simple clinical evaluations. D/Pcreatinine at 60 min overestimated small solute transport rate. Effluent CA125 was consistently lower in UFF patients.
High Incidence of Familial Gastric Cancer in Tuscany, a Region in Italy
Authors: Roviello Franco , Corso Giovanni , Pedrazzani Corrado , Marrelli Daniele , De Falco Giulia , Suriano Gianpaolo , Vindigni Carla , Berardi Anna , Garosi Lorenzo , De Stefano Alfonso , Leoncini Lorenzo , Seruca Raquel , Pinto Enrico
Published: January 2008

Objectives: Only 1% of diffuse gastric cancers occur in families with autosomal dominant gastric cancer susceptibility. Germline mutations in the E-cadherin gene account for the hereditary diffuse gastric cancer (HDGC) syndrome. We studied a large cohort of gastric cancer patients from Tuscany, a region in Italy, to evaluate the presence of familial clustering of gastric cancer. Methods: 238 pedigrees were retrospectively studied by structured interviews. All probands with diagnosed gastric cancer were contacted in-person or by phone and tumor types were assessed in first- and second-degree relatives. Familial aggregation was investigated in order to search for families with suspected HDGC. Results: Familial aggregation for gastric cancer was observed in 79 of 238 cases (33.2%). Among these, there were 64 families (81%) with one gastric cancer other than the proband, 10 families with two gastric cancers (12.7%) and 5 families with three gastric cancers (6.3%). Fourteen families fulfilled the HDGC clinical criteria, one of them presenting with a pathogenic germline mutation in the E-cadherin gene (7.1%). Conclusions: The prevalence of familial HDGC appears extremely high. Since only one pathogenic germline mutation was noted in a family fulfilling the HDGC clinical criteria, factors other than E-cadherin gene mutations may contribute to the familial clustering of HDGC.
UFT as Maintenance Therapy in Patients with Advanced Colorectal Cancer Responsive to the FOLFOX4 Regimen
Authors: Scalamogna R. , Brugnatelli S. , Tinelli C. , Sagrada P. , Gattoni E. , Tronconi M.C. , Riccardi A. , Luchena G. , Corazza G.R.
Published: January 2008

Background: In advanced colorectal cancer (ACC), FOLFOX4 has been accepted as a standard chemotherapeutic regimen. Due to the neurotoxicity induced by oxaliplatin, which occurs in about 50% of patients during the 6-month FOLFOX4 regimen, and the frequent need for hospitalization, alternative regimens may be required. We aimed to determine whether a ‘maintenance’ therapy with oral UFT (uracil-tegafur) in patients responding to FOLFOX4 is able to maintain the response and improve the quality of life (QoL) as a result of the outpatient regimen and lower psychological distress. Methods: Untreated patients with ACC who did not progress after 6 months of FOLFOX4 received oral UFT until disease progression or unacceptable toxicity. The aim of the study was to maintain the response obtained with the FOLFOX4 regimen for at least 6 months. The secondary objective was to evaluate QoL during the two different treatment regimens utilizing the 36-item Short Form Health Survey (SF-36). Results: From January 2003 to August 2004, out of the enrolled 30 patients [22 males and 8 females; 2 patients with a complete response (CR), 14 patients with a partial response (PR) and 6 patients in stable disease (SD) after 6 months of FOLFOX4] 22 continued therapy with UFT until progression without significant toxicity; the remaining 8 patients (27%) had progressive disease (PD) during or at the end of FOLFOX4 and were treated with other regimen. After 6 months of UFT, 4 patients (13%) had CR, 6 patients (20%) PR and 4 patients (13%) SD; 16 patients (53%) progressed. Median follow-up was 31 months [interquartile range (IQR): 20–31 months]; 14 patients died of PD. The median time to progression was 13.9 (IQR: 7.7–20.1) months and the median survival time was 31 months (IQR: 20–31 months). Evaluation of QoL demonstrated a trend towards better QoL during UFT treatment. Conclusions: These results support the feasibility of maintaining good response and improving QoL (measured by SF-36) with an oral fluoropyrimidine after combination chemotherapy in ACC patients; moreover, since UFT can be used orally, patient compliance is increased and the duration of hospitalization can be decreased.
Education and Employment in Long-Term Survivors of High-Grade Osteosarcoma: A Japanese Single-Center Experience
Authors: Yonemoto T. , Ishii T. , Takeuchi Y. , Kimura K. , Hagiwara Y. , Tatezaki S.
Published: January 2008

Objective: To investigate the status of education and employment of long-term survivors who became physically handicapped after treatment for high-grade osteosarcoma. Methods: Of the osteosarcoma patients treated at our hospital, 41 patients aged less than 18 years at the initial presentation who were free of disease for 10 years or longer after the end of treatment were studied. The status of their education and employment was investigated via a questionnaire. Results: Twenty-seven patients responded to the questionnaire (response rate, 65.9%). Of these patients, 73.1% (19/26) could return to the school they had attended before the disease, and 52% (13/25) graduated from college or university. The percentage of those who went to college or university was higher in the limb-sparing group. Seventy-two percent of the patients were engaged in clerical work, and the mean annual income was 4.01 million JPY (corresponding to about 24,000 EUR). No difference was noted in the status of employment between the amputation and limb-sparing groups. Conclusions: The percentage of patients who went to college or university was similar to the percentage in all Japanese. However, the status of the diseased limb appeared to affect school attendance. The mean annual income of the patients was comparable to that of the national average, and they experienced no major problems in their employment. Physical disabilities posed few problems in their daily living.
The Role of Adjuvant Chemotherapy for Patients with Resected Pancreatic Cancer: Systematic Review of Randomized Controlled Trials and Meta-Analysis
Authors: Boeck Stefan , Ankerst Donna Pauler , Heinemann Volker
Published: January 2008

Background: In patients undergoing surgery for resectable pancreatic cancer prognosis still remains poor. The role of adjuvant treatment strategies (including chemotherapy and chemoradiotherapy) following resection of pancreatic cancer remains controversial. Methods: A Medline-based literature search was undertaken to identify randomized controlled trials that evaluated adjuvant chemotherapy after complete macroscopic resection for cancer of the exocrine pancreas. Five trials of adjuvant chemotherapy were eligible and critically reviewed for this article. A meta-analysis (based on published data) was performed with survival (median survival time and 5-year survival rate) being the primary endpoint. Results: For the meta-analysis, 482 patients were allocated to the chemotherapy group and 469 patients to the control group. The meta-analysis estimate for prolongation of median survival time for patients in the chemotherapy group was 3 months (95% CI 0.3–5.7 months, p = 0.03). The difference in 5-year survival rate was estimated with 3.1% between the chemotherapy and the control group (95% CI –4.6 to 10.8%, p > 0.05). Conclusion: Currently available data from randomized trials indicate that adjuvant chemotherapy after resection of pancreatic cancer may substantially prolong disease-free survival and cause a moderate increase in overall survival. In the current meta-analysis, a significant survival benefit was only seen with regard to median survival, but not for the 5-year survival rate. The optimal chemotherapy regimen in the adjuvant setting as well as individualized treatment strategies (also including modern chemoradiotherapy regimens) still remain to be defined.
Serum Bone Turnover Markers in Patients with Primary Bone Tumors
Authors: Wang Jingsheng , Pei Fuxing , Tu Chongqi , Zhang Huaixian , Qiu Xueyong
Published: January 2008

Objectives: It was the aim of this study to investigate parameters of bone turnover such as serum bone-specific alkaline phosphatase (BALP) and N-terminal midfragment of osteocalcin (N-MID), as well as serum C-terminal telopeptide of type I collagen (CTX) in patients with primary bone tumors and to investigate their validity in differentiating malignant from benign bone tumors. Methods: A total of 219 patients with primary bone tumors entered the study. The patients were divided into 2 groups according to their age, including a teenage (10–19 years old) and an adult group (≧20 years old). In each group, the patients were divided into several subgroups (osteosarcoma, benign bone tumors or tumor-like lesions, giant cell tumor, and other primary malignant bone tumors). An age- and gender-matched control population was also studied in each group. Blood samples were taken for measurement of serum BALP, N-MID and CTX. Results: The serum BALP levels in patients with osteosarcoma were significantly higher than those of patients in the other subgroups and the controls, both in the teenage (p = 0.01) and the adult group (p = 0.000). The serum N-MID and CTX levels did not significantly differ among patients of different subgroups and the controls, both in the teenage (p = 0.773 and p = 0.747, respectively) and the adult group (p = 0.163 and p = 0.074, respectively). Conclusions: A high serum BALP level is valuable for the diagnosis of adult osteosarcoma, but its use in the development of a differential diagnosis in the teenage patients is not advised because serum BALP levels are also affected by age, pubertal stage and growth velocity. Both serum N-MID and serum CTX are hardly useful in the differential diagnosis of primary bone tumors.