Prominent Effect (prominent + effect)

Distribution by Scientific Domains

Selected Abstracts

Insulin resistance in type 2 diabetes: role of fatty acids,

Peter Arner
Abstract Insulin resistance is one of the key factors responsible for hyperglycaemia in type 2 diabetes and can result in a number of metabolic abnormalities associated with cardiovascular disease (insulin resistance syndrome), even in the absence of overt diabetes. The mechanisms involved in the development of insulin resistance are multifactorial and are only partly understood, but increased availability of free fatty acids (FFAs) is of particular importance for the liver and skeletal muscle. The role of FFAs in type 2 diabetes is most evident in obese patients who have several abnormalities in FFA metabolism. Because of a mass effect, the release of FFAs from the total adipose tissue depot to the blood stream is increased and the high concentration of circulating FFAs impairs muscle uptake of glucose by competitive inhibition. In upper-body obesity, which predisposes individuals to type 2 diabetes, the rate of lipolysis is accelerated in visceral adipose tissue. This results in a selective increase in FFA mobilisation to the portal vein, which connects visceral fat to the liver. A high ,portal' FFA concentration has undesirable effects on the liver, resulting in dyslipidaemia, hyperinsulinaemia, hyperglycaemia and hepatic insulin resistance. Recently, a new class of antidiabetic agents, the thiazolidinediones (TZDs) or ,glitazones' has been developed. A prominent effect of these agents is the lowering of circulating FFA levels and it is believed, but not yet proven, that this interaction with FFAs constitutes a major mechanism behind the glucose-lowering effect of the TZDs. Copyright © 2002 John Wiley & Sons, Ltd. [source]

Down-regulation of reduced folate carrier may result in folate malabsorption across intestinal brush border membrane during experimental alcoholism

FEBS JOURNAL, Issue 24 2007
Abid Hamid
Folate plays a critical role in maintaining normal metabolic, energy, differentiation and growth status of all mammalian cells. The intestinal folate uptake is tightly and diversely regulated, and disturbances in folate homeostasis are observed in alcoholism, attributable, in part, to intestinal malabsorption of folate. The aim of this study was to delineate the regulatory mechanisms of folate transport in intestinal absorptive epithelia in order to obtain insights into folate malabsorption in a rat model of alcoholism. The rats were fed 1 g·kg,1 body weight of ethanol daily for 3 months. A reduced uptake of [3H]folic acid in intestinal brush border membrane was observed over the course of ethanol administration for 3 months. Folate transport exhibited saturable kinetics and the decreased intestinal brush border membrane folate transport in chronic alcoholism was associated with an increased Km value and a low Vmax value. Importantly, the lower intestinal [3H]folic acid uptake in ethanol-fed rats was observed in all cell fractions corresponding to villus tip, mid-villus and crypt base. RT-PCR analysis for reduced folate carrier, the major folate transporter, revealed that reduced folate carrier mRNA levels were decreased in jejunal tissue derived from ethanol-fed rats. Parallel changes were observed in reduced folate carrier protein levels in brush border membrane along the entire crypt,villus axis. In addition, immunohistochemical staining for reduced folate carrier protein showed that, in alcoholic conditions, deranged reduced folate carrier localization was observed along the entire crypt,villus axis, with a more prominent effect in differentiating crypt base stem cells. These changes in functional activity of the membrane transport system were not caused by a general loss of intestinal architecture, and hence can be attributed to the specific effect of ethanol ingestion on the folate transport system. The low folate uptake activity observed in ethanol-fed rats was found to be associated with decreased serum and red blood cell folate levels, which might explain the observed jejunal genomic hypomethylation. These findings offer possible mechanistic insights into folate malabsorption during alcoholism. [source]

Skin friction features of drilled CIP piles in sand from pile segment analysis

Sungjune Lee
Abstract Numerical pile segment analysis is conducted in this study with an advanced soil model to investigate the skin friction behaviour of a drilled Cast-In-Place (CIP) pile installed in sand. Although the interface between the sand and pile is considered rough, thin elements adjacent to the pile are used to include effects of localized shear. Unit weights of fluid concrete and accompanied changes in stress are considered as the effects of pile installation. Changes in effective stresses are the most prominent effect due to pile installation with a change in direction of the major principal stress from the vertical to the radial direction. Shear behaviour of the sand at the interface during the early shear stage is related to the contractive tendency of the sand at small strain levels. Changes in the stress field around the pile with little changes in volumetric strain take place during the early shear stage. Stress redistributions during the early shear stage depend on the direction of the major principal stress before shear. Results of the pile segment analyses for drilled CIP piles show good agreement with design methods. Parametric studies are used to characterize the effects of sand density and pile diameter on the skin friction behaviour of drilled CIP piles. Copyright © 2007 John Wiley & Sons, Ltd. [source]

Zonal circulations over the Indian and Pacific Oceans and the level of lakes Victoria and Tanganyika

Laurent Bergonzini
Abstract Level records of two East African Great Lakes, Lake Victoria and Lake Tanganyika, which are considered as hydro-climatic proxies, are analysed. Comparisons between the two lake signals show synchronisms, which can only be accounted for by large-scale mechanisms. Lake-level variations associated with the short rains season (October,January) appear to have a prominent effect on the annual lake levels. The relations between lake-level variations and atmospheric circulation indexes are then investigated. Over the period 1946,2000, four indexes are selected to characterize the October,December zonal circulation over the Pacific and Indian Oceans. Over the Indian Ocean two surface zonal wind indexes (ZWIs) are used. For the Pacific, the southern oscillation index (SOI) and the Niño3 index are held to account for the El Niño,southern oscillation (ENSO). It is shown that significant overall negative correlations of level fluctuations are preferentially obtained with Indian Ocean circulation indexes. Although ZWI is highly correlated with the ENSO indexes, the latter display weaker relations with East African lake levels. It is shown that, for the 1946,2000 period, the October,December zonal circulation cell over the Indian Ocean plays a key role in the equatorial lake-level anomalies, thus demonstrating their influence on the hydro-climatic interannual variability of a large region. However, lake-level variation is a function not only of regional hydro-climatic conditions, but also of the initial (October) absolute lake level. Higher correlations are evident in a multiple correlation approach taking into account the initial lake level status in addition to the ZWI and ENSO indexes. Copyright © 2004 Royal Meteorological Society [source]

Synthesis of oligopeptides with the sequence SXWS and their chemotactic effects on a ciliated protozoan Tetrahymena pyriformis,

Eszter Illyés
Abstract In this paper, the solid phase synthesis and chemical characterization of members of an SXWS sub-library (SAWS, SDWS and SKWS) as well as the comparison of their chemotactic properties with those of SEWS, which exhibits a prominent effect at 10,12M on a ciliated protozoan, Tetrahymena pyriformis, are described. We found that the chemotaxis of cells induced with the SXWS peptides varied according to the nature of the amino acid residue (Ala, Asp, Lys) in position X. The chemotactic activity of SEWS was not surpassed by any of three new tetrapeptides, although SAWS was also chemoattractant. Interestingly, SDWS, with an acidic side chain at position X, could not elicit any chemotactic response. SKWS, however, showed mild but significant chemorepellent activity over a wide concentration range. Chemotactic selection studies showed that the two chemoattractant peptides (SAWS and SEWS) had an expressed ability to select high-responder offspring cell populations. Peptides with neutral (SDWS) or chemorepellent (SKWS) properties were not able to select such subpopulations from the mixed cultures of Tetrahymena, indicating that the chemotactic response elicited by SXWS peptides is ligand-specific. For ligand-binding experiments N -terminally labelled fluorescent derivatives of SXWS peptides were prepared, applying [4-[7-hydroxycoumaryl]]acetic acid (Hca -OH) or 4-ethoxymethylene-2-[1]-naphthyl-5(4H)-oxazolone (naOx -OEt) as markers. Hca -OH was introduced using an active ester technique as the last step of SPPS, or after cleavage in solution. The oxazolone naOx -OEt reacted with the amino group of the peptide by liberation of EtOH. The binding characteristics of fixed Tetrahymena cells with the naOx -labelled peptides showed good correlation between binding profiles and chemotactic responsiveness (SEWS > SAWS > SDWS , SKWS). A similar binding pattern was observed in the case of Hca -peptides (SEWS > SAWS > SDWS). Hca -SKWS, however, bound remarkably to the cell surface. The binding activity of the Hca -peptides was less pronounced than that of the naOx -peptides, indicating the importance of the fluorophores applied. Copyright © 2002 European Peptide Society and John Wiley & Sons, Ltd. [source]

Development of UHMWPE modified PP/PET blends and their mechanical and abrasive wear behavior

Navin Chand
In this study, polypropylene and polyethylene terephthalate blend were modified by incorporating different percentages of ultrahigh molecular weight polyethylene (UHMWPE) ranging from 1 to 5 phr. Modified blends were prepared by melt mixing the PP/PET blend and UHMWPE. Ultimate tensile strength of UHMWPE filled blend was determined at 10, 20, 50, and 100 mm/min cross head speeds of testing. It was found that increase of cross head speed from 10 to 100 mm/min increases the tensile strength of PP/PET/UHMWPE blends. Maximum ultimate tensile strength is exhibited by the blend containing 2 phr UHMWPE. Breaking strain of the UHMWPE modified and unmodified PP/PET blend increased with the increase of cross head speed due to the highly entangled chain structure of UHMWPE. Shore A hardness of the filled blends also increased from 341 to 356, which is highest for 2 phr UHMWPE. High stress abrasive wear of UHMWPE modified blend was determined by using Suga abrasion tester, model NUS-1 Japan. Wear rate of the PP/PET(90/10) blends having 1, 2, and 5 phr of UHMWPE was determined at different loads such as 1, 3, 5, and 7 N and sliding distances from 6.4 m to 25.6 m. Wear rate values show that UHMWPE has prominent effect on abrasive wear of PP/PET blends. Addition of 2 and 5 phr UHMWPE improved the wear resistance of PP/PET blends at different loads, which has been explained on the basis of improved bonding as compared with pure PP/PET blend and increased hardness. Maximum abrasive wear rate reduction was achieved by adding 2 phr UHMWPE in PP/PET(90/10) blend. POLYM. COMPOS. 28:267,272, 2007. © 2007 Society of Plastics Engineers [source]

Interferon-, mediates suppression of C-reactive protein: Explanation for muted C-reactive protein response in lupus flares?

Helena Enocsson
Objective C-reactive protein (CRP) is synthesized by hepatocytes in response to interleukin-6 (IL-6) during inflammation. Despite raised IL-6 levels and extensive systemic inflammation, serum CRP levels remain low during most viral infections and disease flares of systemic lupus erythematosus (SLE). Because both viral infections and SLE are characterized by high levels of interferon-, (IFN,), the aim of this study was to determine whether this cytokine can inhibit the induction of CRP. Methods The interference of all 12 IFN, subtypes with CRP promoter activity induced by IL-6 and IL-1, was studied in a CRP promoter, and luciferase reporter,transfected human hepatoma cell line, Hep-G2. CRP secretion by primary human hepatocytes was analyzed by enzyme-linked immunosorbent assay. Results CRP promoter activity was inhibited by all single IFN, subtypes, as well as by 2 different mixtures of biologically relevant IFN, subtypes. The most prominent effect was seen using a leukocyte-produced mixture of IFN, (56% inhibition at 1,000 IU/ml). The inhibitory effect of IFN, was confirmed in primary human hepatocytes. CRP promoter inhibition was dose dependent and mediated via the type I IFN receptor. Transferrin production and Hep-G2 proliferation/viability were not affected by IFN,. Conclusion The current study demonstrates that IFN, is an inhibitor of CRP promoter activity and CRP secretion. This finding concords with previous observations of up-regulated IFN, and a muted CRP response during SLE disease flares. Given the fundamental role of both IFN, and CRP in the immune response, our results are of importance for understanding the pathogenesis of SLE and may also contribute to understanding the differences in the CRP response between viral and bacterial infections. [source]