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Marked Enhancement (marked + enhancement)
Selected AbstractsControlled release of argatroban from PLA film,Effect of hydroxylesters as additives on enhancement of drug releaseJOURNAL OF APPLIED POLYMER SCIENCE, Issue 5 2008Akira Mochizuki Abstract The aim of this study was to develop a drug eluting stent that prevents vein restenosis. For this, we selected argatroban as the study drug and poly(lactic acid) (PLA) as the matrix. To enhance the release of argatroban from PLA film, the addition of hydroxylesters (additives) was investigated. The additives investigated were diethyl tartrate (DET), diethyl malate (DEM), and triethyl citrate (TEC). Marked enhancement of drug release was observed in DET-added film, while TEC- or DEM-added film showed little enhancement. To clarify the effect of DET, the release profile based on the contents of the drug and DET in the film and the effect of alkyl chain length of tartrate were studied. Tartrates used were dimethyl, di- i -propyl, and di- n -butyl esters (DMT, DiPT, and DnBT, respectively), and the enhancement order was DMT , DET , DiPT , DBT , PLA alone. The reasons for enhancement were discussed from the viewpoint of drug release behavior, degradation of PLA, water uptake within the film, and SEM observations. It was concluded that enhancement of drug release was due to large amounts of water uptake within the film which resulted in the formation of open pores at its surface. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008 [source] Preparation, Characterization and Analytical Applications of a New and Novel Electrically Conducting PolymerELECTROANALYSIS, Issue 15 2006F. D'Eramo Abstract In this study, a glassy carbon electrode (GC) was modified with an electropolymerized film of 1-naphthylamine (1-NAP) with a subsequent overoxidation treatment in 0.2,M sodium hydroxide solution. This polymer p-1-NAPox film coated GC electrode was used for the selective determination of dopamine (DA) in the presence of a triple concentration of ascorbic acid (AA). These studies were performed using cyclic voltammetry and square-wave voltammetry at physiological pH. p-1-NAPox shows an attractive permselectivity, a marked enhancement of the current response and antifouling properties when compared to a bare GC electrode activated in basic media. With a preconcentration time of 3,minutes at open circuit, linear calibration plots were obtained for DA in buffer solution (pH,7.4) over the concentration range from 1×10,6,1×10,4 M with a detection limit of 1.59×10,7 M. [source] Anti-apoptotic effect of the basic helix-loop-helix (bHLH) transcription factor DEC2 in human breast cancer cellsGENES TO CELLS, Issue 4 2010Yang Liu DEC1 (BHLHB2/Stra13/Sharp2) and DEC2 (BHLHB3/Sharp1) are basic helix-loop-helix (bHLH) transcription factors that are involved in circadian rhythms, differentiation and the responses to hypoxia. We examined whether DEC1 and DEC2 are involved in apoptosis regulation, in human breast cancer MCF-7 cells. We found that siRNA-mediated knockdown of DEC2 resulted in marked enhancement of apoptosis compared with that in control cells transfected with nonspecific siRNA. However, knockdown of DEC1 by siRNA did not affect cell survival. Knockdown of DEC2 affected the expression of mRNA or proteins related to apoptosis, such as Fas, c-Myc, caspase-8, poly (ADP-ribose) polymerase (PARP) and Bax. We also showed that tumor necrosis factor-, (TNF-,) up-regulates the expression of DEC1 and DEC2. DEC2 over-expression caused by the transfection of an expression vector reduced the amounts of cleaved PARP and caspase-8 induced by TNF-, treatment, whereas DEC1 over-expression increased it. Finally, we revealed that treatment with double knockdown against both DEC1 and DEC2 decreased the amounts of cleaved PARP and caspase-8 induced by DEC2 siRNA with or without TNF-,. These data indicate that DEC2 has an anti-apoptotic effect, whereas DEC1 has a pro-apoptotic effect, which are involved in the balance of survival of human breast cancer MCF-7 cells. [source] Defective regulation of cholangiocyte Cl,/HCO,3 and Na+/H+ exchanger activities in primary biliary cirrhosisHEPATOLOGY, Issue 6 2002Saida Melero Primary biliary cirrhosis (PBC) is a disorder of unknown origin with autoimmune features. Recently, impaired biliary secretion of bicarbonate has been shown in patients with PBC. Here we have investigated whether bile duct epithelial cells isolated from PBC patients exhibit defects in transepithelial bicarbonate transport by analyzing the activities of 2 ion exchangers, Cl,/HCO,3 anion exchanger 2 (AE2) and Na+/H+ exchanger (NHE) in isolated cholangiocytes. AE2 and NHE activities were studied in basal conditions and after stimulation with cyclic adenosine monophosphate (cAMP) and extracellular adenosine triphosphate (ATP), respectively. Cholangiocytes were grown from needle liver biopsies from 12 PBC patients, 8 normal controls, and 9 patients with other liver diseases. Also, intrahepatic cholangiocytes were cultured after immunomagnetic isolation from normal liver tissue (n = 6), and from recipients undergoing liver transplantation for end-stage PBC (n = 9) and other forms of liver disease (n = 8). In needle-biopsy cholangiocytes, basal AE2 activity was significantly decreased in PBC as compared with normal livers and disease controls. In addition, we observed that though cAMP increased AE2 activity in cholangiocytes from both normal and non-PBC livers, this effect was absent in PBC cholangiocytes. Similarly, though in cholangiocytes from normal and disease control livers extracellular ATP induced a marked enhancement of NHE activity, cholangiocytes from PBC patients failed to respond to purinergic stimulation. In conclusion, our findings provide functional evidence that PBC cholangiocytes exhibit a widespread failure in the regulation of carriers involved in transepithelial H+/HCO,3 transport, thus, providing a molecular basis for the impaired bicarbonate secretion in this cholestatic syndrome. [source] Histamine induces Toll-like receptor 2 and 4 expression in endothelial cells and enhances sensitivity to Gram-positive and Gram-negative bacterial cell wall componentsIMMUNOLOGY, Issue 2 2004Jaya Talreja Summary Histamine is a major inflammatory molecule released from the mast cell, and is known to activate endothelial cells. However, its ability to modulate endothelial responses to bacterial products has not been evaluated. In this study we determined the ability of histamine to modulate inflammatory responses of endothelial cells to Gram-negative and Gram-positive bacterial cell wall components and assessed the role of Toll-like receptors (TLR) 2 and 4 in the co-operation between histamine and bacterial pathogens. Human umbilical vein endothelial cells (HUVEC) were incubated with lipopolysaccharide (LPS), lipoteichoic acid (LTA), or peptidoglycan (PGN) in the presence or absence of histamine, and the expression and release of interleukin-6 (IL-6), and NF-,B translocation were determined. The effect of histamine on the expression of mRNA and proteins for TLR2 and TLR4 was also evaluated. Incubation of HUVEC with LPS, LTA and PGN resulted in marked enhancement of IL-6 mRNA expression and IL-6 secretion. Histamine alone markedly enhanced IL-6 mRNA expression in HUVEC, but it did not stimulate proportional IL-6 release. When HUVEC were incubated with LPS, LTA, or PGN in the presence of histamine marked amplification of both IL-6 production and mRNA expression was noted. HUVEC constitutively expressed TLR2 and TLR4 mRNA and proteins, and these were further enhanced by histamine. The expression of mRNAs encoding MD-2 and MyD88, the accessory molecules associated with TLR signalling, were unchanged by histamine treatment. These results demonstrate that histamine up-regulates the expression of TLR2 and TLR4 and amplifies endothelial cell inflammatory responses to Gram-negative and Gram-positive bacterial components. [source] Modifications of the fibroblast growth factor-2 gene led to a marked enhancement in secretion and stability of the recombinant fibroblast growth factor-2 proteinJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 6 2007Shin-Tai Chen Abstract Progress in FGF-2 gene therapy has been hampered by the difficulty in achieving therapeutic levels of FGF-2 secretion. This study tested whether the addition of BMP2/4 hybrid secretion signal to the FGF-2 gene and mutation of cys-70 and cys-88 to serine and asparagine, respectively, would increase the stability and secretion of active FGF-2 protein in mammalian cells using MLV-based vectors. Single or double mutations of cys-70 and cys-88 to ser-70 and asp-88, respectively, markedly increased the amounts of FGF-2 protein in conditioned media and cell lysates, which may be due to glycosylation, particularly at the mutated asp-88 residue. Addition of BMP2/4 secretion signal increased FGF-2 secretion, but also suppressed FGF-2 biosynthesis. The combination of BMP2/4 secretion signal and double cys-70 and cys-88 mutations increased the total amount of secreted FGF-2 protein >60-fold. The modifications did not alter its ability to stimulate cell proliferation and Erk1/2 phosphorylation in marrow stromal cells or its ability to bind heparin in vitro, suggesting that the modified FGF-2 protein was functionally as effective as the unmodified FGF-2. An ex vivo application of rat skin fibroblasts (RSF) transduced with the modified FGF-2 vector in a subcutaneous implant model showed that rats with implants containing cells transduced with the modified FGF-2 vector increased serum FGF-2 level >15-fold, increased growth of the implant, and increased vascularization within the implant, compared to rats that received implants containing ,-galactosidase- or wild-type FGF-2-transduced control cells. This modified vector may be useful in FGF-2 gene therapy investigations. J. Cell. Biochem. 100: 1493,1508, 2007. © 2007 Wiley-Liss, Inc. [source] ISOLATION AND CHARACTERIZATION OF A CELL WALL-DEFECTIVE MUTANT OF CHLAMYDOMONAS MONOICA (CHLOROPHYTA),JOURNAL OF PHYCOLOGY, Issue 6 2003Cesar Fuentes Cell wall,defective strains of Chlamydomonas have played an important role in the development of transformation protocols for introducing exogenous DNA (foreign genes or cloned Chlamydomonas genes) into C. reinhardtii. To promote the development of similar protocols for transformation of the distantly related homothallic species, C. monoica, we used UV mutagenesis to obtain a mutant strain with a defective cell wall. The mutant, cw-1, was first identified on the basis of irregular colony shape and was subsequently shown to have reduced plating efficiency and increased sensitivity to lysis by a non-ionic detergent as compared with wild-type cells. Tetrad analysis of crosses involving the cw-1 mutant confirmed 2:2 segregation of the cw:cw+ phenotypes, indicating that the wall defect resulted from mutation of a single nuclear gene. The phenotype showed incomplete penetrance and variable expressivity. Although some cells had apparently normal cell walls as viewed by TEM, many cells of the cw-1 strain had broken cell walls and others were protoplasts completely devoid of a cell wall. Several cw-1 isolates obtained from crosses involving the original mutant strain showed a marked enhancement of the mutant phenotype and may prove especially useful for future work involving somatic cell fusions or development of transformation protocols. [source] Loud noise enhances nigrostriatal dopamine toxicity induced by MDMA in miceMICROSCOPY RESEARCH AND TECHNIQUE, Issue 4 2004Marco Gesi Abstract The neurotoxicity of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) has been intensely investigated due to the widespread abuse of this drug and its neurotoxic effects. In mice, MDMA neurotoxicity has been demonstrated for striatal dopamine (DA) terminals. However, the current literature has reported great variability in the effects induced by MDMA; this is partially due to changes in environmental conditions. For instance, elevated temperature and a crowded noisy environment markedly increase the neurotoxic effects induced by MDMA. The environmental factor loud noise is often present during ecstasy intake; however, only a few studies have analysed the consequence of a concomitant exposure to loud noise and ecstasy intake. In the present experimental work, we investigated whether nigrostriatal DA toxicity occurring after MDMA administration was potentiated in the presence of loud noise (100 dBA). We administered MDMA to C57/Black mice using a "binging" pattern for two durations of white noise exposure. We found a marked enhancement of MDMA toxicity (7.5 mg/Kg ×4, 2 hours apart, i.p.) in the presence of white noise exposure lasting for at least 6 hours. The striatal damage was assessed by assaying DA levels as well as the loss of tyrosine hydroxylase (TH) and the increase in striatal glial fibrillary acidic protein (GFAP) immunohistochemistry. Since loud noise often accompanies ecstasy intake, the present findings call for more in-depth studies aimed at disclosing the fine mechanisms underlying this enhancement. Microsc. Res. Tech. 64:297,303, 2004. © 2004 Wiley-Liss, Inc. [source] ,Chimeric' Grafts Assembled from Multiple Allodisparate Donors Enjoy Enhanced Transplant SurvivalAMERICAN JOURNAL OF TRANSPLANTATION, Issue 3 2009D. R. Saban Certain components of a graft that provoke alloimmunity may not be vital for graft function or critical as targets of rejection. Corneal transplantation is an example of this, because graft epithelium plays a role in allosensitization, whereas corneal graft endothelium,which shares the same alloantigens,is the critical target in allorejection. In this study, we found that exploiting this biology by replacing donor epithelium of an allograft with an allodisparate third-party epithelium yields a marked enhancement in transplant survival. Such ,chimeric' allografts consisted of a C3H/He (H-2k) corneal epithelium over a C57BL/6 (H-2b) epithelial-denuded cornea (or v.v.) and orthotopically placed on BALB/c (H-2d) hosts. Conventional corneal allografts (C3H/He or C57BL/6) or isografts (BALB/c) were also transplanted on BALB/c hosts. Alloreactive T-cell frequencies (CD4+ interferon [IFN]-,+) primed to the graft endothelium were strongly diminished in chimeric hosts relative to conventionally allografted hosts. This was corroborated by a decreased T-cell infiltration (p = 0.03) and a marked enhancement of allograft survival (p = 0.001). Our results represent the first successful demonstration of chimeric tissue, epithelial-denuded allograft plus third-party allodisparate epithelium, in the promotion of allograft survival. Moreover, chimeric grafting can be readily performed clinically, whereby corneal allograft rejection remains a significant problem particularly in inflamed graft beds. [source] Effect of millimeter wave irradiation on tumor metastasisBIOELECTROMAGNETICS, Issue 4 2006Mahendra K. Logani Abstract One of the major side effects of chemotherapy in cancer treatment is that it can enhance tumor metastasis due to suppression of natural killer (NK) cell activity. The present study was undertaken to examine whether millimeter electromagnetic waves (MMWs) irradiation (42.2 GHz) can inhibit tumor metastasis enhanced by cyclophosphamide (CPA), an anticancer drug. MMWs were produced with a Russian-made YAV-1 generator. Peak SAR and incident power density were measured as 730,±,100 W/kg and 36.5,±,5 mW/cm2, respectively. Tumor metastasis was evaluated in C57BL/6 mice, an experimental murine model commonly used for metastatic melanoma. The animals were divided into 5 groups, 10 animals per group. The first group was not given any treatment. The second group was irradiated on the nasal area with MMWs for 30 min. The third group served as a sham control for group 2. The fourth group was given CPA (150 mg/kg body weight, ip) before irradiation. The fifth group served as a sham control for group 4. On day 2, all animals were injected, through a tail vein, with B16F10 melanoma cells, a tumor cell line syngeneic to C57BL/6 mice. Tumor colonies in lungs were counted 2 weeks following inoculation. CPA caused a marked enhancement in tumor metastases (fivefold), which was significantly reduced when CPA-treated animals were irradiated with MMWs. Millimeter waves also increased NK cell activity suppressed by CPA, suggesting that a reduction in tumor metastasis by MMWs is mediated through activation of NK cells. Bioelectromagnetics 27:258,264, 2006. © 2006 Wiley-Liss, Inc. [source] Effect of millimeter waves on natural killer cell activationBIOELECTROMAGNETICS, Issue 1 2005V.R. Makar Abstract Millimeter wave therapy (MMWT) is being widely used for the treatment of many diseases in Russia and other East European countries. MMWT has been reported to reduce the toxic effects of chemotherapy on the immune system. The present study was undertaken to investigate whether millimeter waves (MMWs) can modulate the effect of cyclophosphamide (CPA), an anticancer drug, on natural killer (NK) cell activity. NK cells play an important role in the antitumor response. MMWs were produced with a Russian-made YAV-1 generator. The device produced modulated 42.2,±,0.2 GHz radiation through a 10,×,20 mm rectangular output horn. Mice, restrained in plastic tubes, were irradiated on the nasal area. Peak SAR at the skin surface and peak incident power density were measured as 622,±,100 W/kg and 31,±,5 mW/cm2, respectively. The maximum temperature elevation, measured at the end of 30 min, was 1 °C. The animals, restrained in plastic tubes, were irradiated on the nasal area. CPA injection (100 mg/kg) was given intraperitoneally on the second day of 3-days exposure to MMWs. All the irradiation procedures were performed in a blinded manner. NK cell activation and cytotoxicity were measured after 2, 5, and 7 days following CPA injection. Flow cytometry of NK cells showed that CPA treatment caused a marked enhancement in NK cell activation. The level of CD69 expression, which represents a functional triggering molecule on activated NK cells, was increased in the CPA group at all the time points tested as compared to untreated mice. However, the most enhancement in CD69 expression was observed on day 7. A significant increase in TNF-, level was also observed on day 7 following CPA administration. On the other hand, CPA caused a suppression of the cytolytic activity of NK cells. MMW irradiation of the CPA treated groups resulted in further enhancement of CD69 expression on NK cells, as well as in production of TNF-,. Furthermore, MMW irradiation restored CPA induced suppression of the cytolytic activity of NK cells. Our results show that MMW irradiation at 42.2 GHz can up-regulate NK cell functions. Bioelectromagnetics 26:10,19, 2005. © 2004 Wiley-Liss, Inc. [source] | |||||||||||||